HIV/AIDS

HIV/AIDS

1 Overview

Summary and Quick Facts

  • Human immunodeficiency virus (HIV) attacks and destroys the cells of the immune system responsible for fighting infection. Without proper treatment, HIV can eventually advance to AIDS.
  • This protocol reviews how HIV is transmitted and treated, along with some intriguing therapies and natural interventions that may lessen the unwanted side effects associated with traditional antiretroviral therapy.
  • Combining antiretroviral therapies with a healthy diet and lifestyle may help you overcome some of the challenges associated with traditional antiretroviral therapies. The supplements described in this protocol may complement traditional medical approaches and support healthy immune cell counts as well.
  • Probiotics and omega-3 fatty acids from fish oil have immune enhancing and anti-inflammatory properties that may benefit people with HIV.

What is HIV/AIDS?

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) by destroying CD4+ helper T cells, thus weakening the host’s immune system. When HIV invades a host cell, it integrates its viral genetic material into the cell’s genome. As the viral load increases, the patient’s immune system weakens, and becomes susceptible to opportunistic infection.

Thankfully, many treatment options now exist for people with HIV, and quality of life and mortality rates continue to improve. Conventional antiretroviral therapies, however, can have troubling side effects such as lipodystrophy, insulin resistance, and even diabetes and increased cardiovascular risk.

Natural interventions such as green coffee extract and multivitamins may complement antiretroviral therapy to further improve quality of life and reduce unwanted side effects.

What are the Risk Factors for HIV/AIDS?

  • Exposure to contaminated body fluids:
    • Blood (eg, transfusions, sharing intravenous drug needles)
    • Semen (eg, sexual intercourse)
    • Breast milk
  • Presence of sexually-transmitted diseases such as gonorrhea and chlamydia
  • Uncircumcised men have a higher risk than circumcised men

What are the Signs and Symptoms of HIV/AIDS?

Note: HIV stages progress from acute, to latent, to late/advanced stages and AIDS.

Early symptoms can last a few weeks and may include:

  • Headache
  • Nausea
  • Sore throat
  • Fever
  • Swollen lymph nodes
  • Muscle pain
  • Oral and/or esophageal sores

The latent phase may last months or even years and present no symptoms. Symptoms reappear at later stages and can include:

  • Fatigue
  • Night sweats
  • Susceptibility to various infections

What are Conventional Medical Treatments for HIV/AIDS?

Note: Conventional treatment regimens generally combine multiple antiretroviral drugs. Some antiretroviral therapies include:

  • Entry inhibitors (eg, maraviroc)
  • Fusion inhibitors (eg, enfuvirtide)
  • Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/ NtRTIs) (eg, abacavir)
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) (eg, etravirine)
  • Integrase inhibitors (eg, raltegravir)
  • Protease inhibitors (eg, ritonavir)

What are Emerging Therapies for HIV/AIDS?

  • *Metformin, the diabetes drug, can maintain glucose metabolism and reduce cardiovascular risk factors associated with antiretroviral therapy.
  • Cytokine therapy is being researched to restore normal cytokine signaling that is essential for immunologic activity and is disrupted by HIV infection.
  • Hormone restoration therapy, including growth hormone, sex hormones, and dehydroepiandrosterone (DHEA), may benefit patients with HIV.
  • Attempts to create an HIV vaccine have been ongoing.

What Dietary and Lifestyle Changes Can Be Beneficial for HIV/AIDS?

  • Eat a healthy, well-balanced diet to ensure adequate intake of essential nutrients
  • Engage in a regular form of moderate exercise
  • Avoid unhealthy lifestyle habits such as illicit drug use, smoking, and drinking alcohol excessively

What Natural Interventions May Be Beneficial for HIV/AIDS?

  • *Green coffee extract. Extracts from green coffee beans, high in chlorogenic acid, suppress excess blood glucose levels; therefore, they may benefit HIV patients on antiretrovirals who develop insulin resistance or diabetes.
  • Multivitamins. Multivitamins, including vitamins A, B complex, C, D, and E, have been shown to reduce the risk of HIV progression, improve pregnancy outcomes in HIV-positive mothers, and alleviate comorbidities.
  • Antioxidants. Oxidative damage participates in the progression of HIV to AIDS. Antioxidants such as carotenoids, glutathione, N-acetlycysteine, green tea, lipoic acid, and carnitine have all been shown to benefit patients with HIV.
  • Omega-3 fatty acids. Omega-3 fatty acid supplementation may improve lipid profiles in HIV patients.
  • Other natural interventions may help promote immune system function and improve well-being for HIV patients, including whey protein, selenium, lactoferrin, zinc, coenzyme Q10, reishi, and probiotics.

*Metformin and green coffee extract may not be a good choice for patients with malabsorption. Always speak to your doctor before adding to your treatment regimen.

2 Introduction

Quality of life for HIV/AIDS patients has dramatically improved in recent years with the advent of sophisticated new therapies, and scientific innovation is unraveling the mysteries of the human immunodeficiency virus at an expeditious rate. Cutting-edge treatments under investigation at the frontiers of science are redefining the discussion of HIV/AIDS and “cure” is no longer a four-letter word in the minds of some leading HIV researchers.1

Having identified multiple aspects pivotal in controlling HIV infection and developing antiretroviral drugs to target many of them, the scientific community has made tremendous strides in the management of latent HIV. The mortality rate for HIV-positive individuals has declined considerably and continues to do so.2-4

Alas, the indispensable antiretroviral drugs themselves cause a number of troubling side effects. Patients treated with long-term antiretroviral therapy usually develop, among other concerns, lipodystrophy, insulin resistance, and increased cardiovascular risk. Unfortunately, these drug-induced conditions diminish patients’ quality of life and contribute to an increased rate of cardiovascular events and diabetes.5-8

Life Extension believes that a major gap in conventional HIV treatment regimens is the failure to aggressively manage patients’ cardio-metabolic risk by using evidence-based drugs like metformin, and scientifically studied natural compounds like green coffee extract and omega-3 fatty acids from fish oil. Moreover, hormone restoration therapy appears to promote healthy fat redistribution and improve body composition in male HIV patients, and is associated with lower risk of death in HIV-positive women.

In this protocol you will learn some basics of the biology of the human immunodeficiency virus and how it destroys the immune system of its host. You will also discover a number of natural compounds that may improve your quality of life by targeting several antiretroviral drug-related side effects, and read about avant-garde medical therapies that aim to improve outlook for HIV patients even further in the not-so-distant future.

3 Understanding HIV/AIDS

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) by destroying CD4+ "helper T cells." In healthy individuals, helper T cells organize immune responses that protect the body from infection. When HIV invades the human system, it binds to co-receptors (typically CXCR4 or CCR5) on the surfaces of CD4+ cells and macrophages, and introduces viral genetic material into these cells.

Once HIV has gained entry into the host cell, viral RNA is reverse transcribed into viral DNA and combines with the DNA of the host cell—so as the infected cell replicates, so, too, does the virus.9 Reverse transcription from viral RNA to viral DNA is a target for some antiretroviral drugs. As CD4+ cell levels become depleted with advancing HIV infection, viral replication within macrophages, dendritic cells, and other cell types sustains viral load.

HIV can be categorized based on its interaction with surface co-receptors during attachment and entry into host cells. Three primary entry methods comprise a large percentage of HIV cases—R5, which utilizes the receptor CCR5 to gain entry; X4, which uses the CXCR4 co-receptor; and X4R5, which uses both.10

Given the dependency upon these cell-surface co-receptors for entry, some strains of HIV are unable to infect individuals who harbor mutations in the gene encoding the co-receptor. These people are resistant to the subtype(s) of HIV that would normally utilize a wild-type receptor to gain entry into host cells.

In addition to attacking the immune system, HIV has the ability to escape immune attack. During cell replication, some HIV viruses mutate at such a rapid rate that they become unrecognizable to the immune system. This enables the virus to keep multiplying and also allows for further mutations. Furthermore, viral DNA that enters the chromosome of the infected cell (where it combines with the cell's own DNA by the action of the HIV-integrase enzyme) may remain in a latent state. As a result, it can remain undetected by the immune system.9,11 This has presented a tremendous obstacle for achieving complete elimination of the disease.

As HIV continues to survive and replicate within its human host, it eventually weakens the immune system; this leaves the infected individual susceptible to opportunistic infections, including Pneumocystis pneumonia (PCP), tuberculosis, herpes simplex virus, and Kaposi's sarcoma.9,12

4 Distinguishing HIV-1 and HIV-2

The widely used term, "HIV," generally refers to HIV-1, the most prevalent form worldwide. However, two types have been identified: HIV-1 and HIV-2. Both are transmitted via the same routes,13 both are associated with similar opportunistic infections, and both cause AIDS.14 However, HIV-2 has a lower viral load,14-16 is less pathogenic,15,16 generally progresses more slowly than HIV-1,16,17 and is mostly confined to West Africa.

The breakdown of the immune system from HIV-2 infection is less dramatic and occurs at a slower rate than it does with HIV-1.18 Also, neutralization escape—that is, the ability to mutate and dodge an attack from neutralizing antibodies—is less common in HIV-2 infections.19 Thus, characteristics of HIV-1 including a higher viral load, greater pathogenicity, and the ability to escape neutralization more often, contribute to its widespread prevalence.

Both types of HIV appear to have originated from simian immunodeficiency viruses (SIV) in chimpanzees (Pan troglodytes) and sooty mangabeys (Cercocebus atys; SM).20,21 SIV are retroviruses that infect primates; certain strains of SIV are thought to have mutated into HIV and subsequently infected humans.20,22

5 Transmission

HIV can be transmitted via exposure to contaminated body fluids, such as blood,23,24 semen,23,25 or breast milk.26-29 Potential routes of transmission include blood transfusions,30 intravenous drug use,24,31 and unprotected sexual intercourse32; HIV-infected females can transmit the virus to their children in utero,33,34 during delivery,34 or via breastfeeding.35

Anal sex is associated with a much higher risk of HIV transmission than vaginal sex. One factor that may contribute to this is that the rectum contains a thin membrane (the lamina propria) that harbors an abundance of HIV target cells—and only one layer of tissue separates these target cells from the rectal lumen.36,37

Although oral sex generally presents a relatively low risk of HIV transmission,38 the risk of transmitting HIV increases if the mouth or genitals contain cuts or open sores (eg, recent dental work) that could provide an entryway for the virus.39 Similarly, the risk of transmission during anal or vaginal sex increases in the presence of sexually transmitted diseases, such as herpes or syphilis, that produce ulcers or sores that compromise mucosal integrity, leaving the individual more susceptible to infection.40,41 Additional risk factors include sexually transmitted infections such as gonorrhea or chlamydia, which produce genital inflammation that can weaken mucosal barriers that would normally help shield the body from infection. Gonorrhea also interferes with CD4 cell activation and proliferation, potentially increasing the opportunity for infection.42

Uncircumcised men are at higher risk of contracting HIV than those who are circumcised. This may be because the foreskin possesses numerous Langerhans cells, which contain a protein called Langerin. Langerin helps protect the body from HIV infection by quickly degrading the virus. However, if a viral onslaught occurs and the cells run out of available Langerin, these cells become viral transporters for infection and deliver the virus to lymph nodes. Thus, removing the foreskin diminishes the opportunity for the Langerhans cells to promote viral infection as transporters.43,44

6 Symptoms/Course of Disease

HIV progression comprises the acute, latent, and late/advanced stages. The acute stage comprises the first few weeks after infection, during which time the patient may experience "flu-like" symptoms including headache, nausea, sore throat, or fever45; other possible symptoms include swollen lymph nodes, muscle pain, and oral and esophageal sores. As HIV enters and replicates within CD4+ cells in the immune system, the viral load increases sharply, and there is a corresponding dip in the number of CD4+ cells, and an increase in CD8+ cells in the blood. During this stage, the patient is extremely infectious.

This phase usually ends a few weeks later, when the immune system is able to mount an effective response: The viral load decreases, and the number of CD4+ rises again, marking the beginning of the latent stage. At this point, the disease enters a period of clinical dormancy that could last for many years, although it can be much shorter in some patients. During this time, there may be no symptoms, and the carrier may be entirely unaware that he or she is carrying HIV. The virus, however, still continues to progress.

As CD4+ cell count decreases below 350 cells/µL, patients often develop constitutional symptoms, such as fatigue and night sweats, and become more prone to various infections. When the immune system is no longer able to fight off the infection, the advanced stage begins and is characterized by CD4+ cell counts below 200 cells/µL, the development of opportunistic infections, and a severely impaired immune system, all of which culminate into AIDS.45

7 Diagnosis

The diagnosis of HIV typically begins with a test that detects natural antibodies produced against the virus. If the antibody test result is positive, a more sensitive test is performed, such as a Western blot analysis or indirect immunofluorescence assay (a test that uses fluorescent compounds so that HIV antibodies present in the blood glow fluorescent green when placed under ultraviolet light).

The human body generally does not produce HIV antibodies until several weeks after infection, so if antibody tests are administered prior to that point, they may return false-negative results. This is particularly worrisome given that people with HIV appear to be most infectious during the acute stage.47-49 Consequently, patients with a negative test result are encouraged to be tested again three months later, as well as six months later. Virologic tests, which detect the actual virus or components thereof, are useful for identifying acute infection in patients who test negative for HIV antibodies.50

Current diagnostic options for detecting HIV include:

Viral Load Tests

These tests measure the quantity of HIV in the blood. Examples include the polymerase chain reaction (PCR) test, which can identify HIV by detecting its genetic material.

P24 Antigen Test

This test detects the p24 antigen, a protein produced by HIV. Detectable levels of p24 are produced during the early stages of HIV infection, making this a useful test in cases where an asymptomatic patient is suspected to have HIV (because of high-risk behaviors, for example) and tests negative for antibodies.51

Fourth Generation Assay

In 2010, the FDA approved a new, "fourth generation" test, called the ARCHITECT HIV Ag/Ab Combo Assay. This test detects both the p24 antigen and HIV antibodies, with the goal of facilitating early diagnosis of the infection. It has demonstrated high diagnostic sensitivity and specificity in detecting HIV.52-54

Nucleic Acid Tests

Nucleic acid tests (NAT) can identify HIV infection approximately 12 days before antibodies become detectable.55 This allows for earlier detection of the virus, which could prevent the spread of the infection due to early awareness. In a study of more than 3,000 people who were tested for HIV, using NAT improved the detection yield by 23% compared with a rapid HIV test.56

Rapid Tests

Rapid HIV tests present an affordable option that allows for easy sample collection (eg, via oral swab or finger prick) and produces results in just 15 minutes. However, they are associated with a high rate of false-positive results. Consequently, patients who test positive with a rapid test should then be checked via a conventional HIV test to confirm the diagnosis.

Once an HIV infection has been diagnosed, key measures used for evaluation and monitoring are:

CD4+ Cell Count

This is considered the hallmark of disease progression. In healthy individuals, CD4 count usually range from 500 to more than 1,000 cells/µL; when these levels drop below 200, it is a criterion for AIDS.57 In addition to being an indicator of disease progression, CD4 count can help to assess when to start antiretroviral therapy. A recent trial found that a combination of clinical monitoring and CD4+ cell count testing was the most effective strategy for monitoring HIV progression.58

The World Health Organization recommends that patients with HIV begin treatment when their CD4 count falls to ≤350 cells/µL, even if they don't have symptoms. Although, recent evidence indicates that if HIV-infected individuals initiate antiretroviral therapy sooner they are much less likely to transmit the disease to others.59

Viral Load

If the patient adheres to his/her medication regimen and the antiretroviral therapy is effective, the viral load will generally drop to less than 50 copies/mL in 16 to 24 weeks, depending on the level before treatment was initiated.60 If viral load does not appear to decrease with treatment, this could be a sign of drug resistance.

Drug Resistance

These tests determine whether a strain of HIV is resistant to any anti-HIV medications. During genotypic testing, for example, the genetic structure of the HIV sample is studied for mutations that are recognized as creating HIV resistance to certain drugs. During phenotypic testing, the HIV is exposed to different concentrations of various antiretrovirals to determine resistance.

Patients who test positive for HIV should also undergo screening for other conditions that are associated with HIV, including other sexually transmitted diseases, tuberculosis, and hepatitis B.61

8 Treatment

Antiretroviral Drugs

Patients today have access to an arsenal of powerful antiretroviral drugs to decrease the viral load.

Entry inhibitors. Entry inhibitors bind to CCR5 receptors on immune cells, preventing HIV from attaching to them and initiating infection. Example: maraviroc (Selzentry).

Fusion inhibitors. Fusion inhibitors block the gp41 protein on the surface of HIV, which prevents it from fusing with the host cell.62 Example: enfuvirtide (Fuzeon).

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs). These medications interfere with HIV’s ability to be imported into the DNA of healthy immune cells by limiting reverse transcription of viral RNA into viral DNA. Examples: abacavir (Ziagen), emtricitabine (Emtriva), lamivudine (Zeffix), tenofovir (Viread), zidovudine (Retrovir).

Non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs also inhibit reverse transcription of viral RNA. Examples: etravirine (Intelence), efavirenz (Sustiva), nevirapine (Viramune).

Integrase inhibitors. These medications inhibit integrase, an enzyme that facilitates the insertion of viral DNA into the DNA of infected cells.63 Example: raltegravir (Isentress)

Protease inhibitors. These drugs inhibit protease, an enzyme that is used to help assemble HIV after it has been incorporated into host DNA. Examples: atazanavir (Reyataz), fosamprenavir (Lexiva), ritonavir (Norvir), darunavir (Prezista).

A variety of these drugs, and others, are often used in combination to manage HIV; this strategy is referred to as highly active antiretroviral therapy, or HAART. Drug regimens are typically chosen based on a number of factors, including patient tolerability, patient genetic background, and physician experience.

A Landmark Discovery

Antiretroviral drugs do not completely eliminate the virus—a patient receiving HAART can still infect others, for example, through needle sharing or sexual intercourse. However, breakthrough findings emerged in 2011 with the HIV Prevention Trials Network (HPTN) 052 clinical trial, which found that if a heterosexual with HIV initiates antiretroviral treatment early (prior to the advanced stages of the disease), this can reduce the likelihood of sexual transmission to uninfected partners by a staggering 96%. These monumental findings suggest that, in addition to treating HIV infection, antiretroviral drugs may also dramatically decrease the likelihood of transmission of HIV between heterosexual partners if taken early enough. The study compared "early" participants who began antiretroviral treatment immediately at the beginning of the study, versus those who initiated treatment when their CD4+ counts fell to 250 cells/mm³ or less, or when they experienced an AIDS-associated illness.59 As the authors carry out further research, these findings represent a groundbreaking discovery in HIV management.

Challenges of antiretroviral treatment include:

  • Drug resistance. Combining protease inhibitors and reverse transcriptase inhibitors into drug "cocktails" has been extremely effective at decreasing viral load in patients with HIV.64 As noted earlier, however, HIV can mutate at a rapid rate during cell replication; this can give rise to resistant strains of the virus that do not respond to treatment. Patients can mitigate this risk by adhering to their medication schedules, as non-adherence encourages the development of resistant strains of HIV. Inadequate drug treatment (ie, consisting of just one or two drugs, versus a broader combination) can also promote resistance.65-67 Drug resistance tests, which establish whether an HIV strain is resistant to certain medications, can provide guidance for selecting optimal drug combinations for each patient and could be useful for revising combination therapies in cases where treatments begin to fail.
  • Toxicity/side effects. A significant concern with antiretroviral drugs is their high toxicity and negative side effects, which range from nausea and diarrhea to more serious complications, including liver abnormalities and insulin resistance.68 In many cases, a patient may not be able to tolerate one or more drugs. Moreover, these medications have been found to increase oxidative stress, overwhelming the body's antioxidant supplies. Until less toxic therapies are developed, patients can support their health by optimizing other, more controllable areas of the overall treatment package, such as engaging in moderate physical activity and maintaining optimal nutrition.

Note: Some preliminary human data indicates milk thistle extract may support liver health in HIV/HCV co-infected patients.69 Additionally, a write-up of a single case involving a man with HIV/HCV co-infection reports eradication of both infections after two weeks of intravenous infusions of silymarin, a group of active constituents from milk thistle.70 More studies are needed before firm conclusions can be drawn.

  • Insulin resistance and other cardio-metabolic abnormalities. Long-term antiretroviral drug therapy has been associated with a number of metabolic side effects, including insulin resistance and diabetes.5-7 Impaired glucose metabolism in antiretroviral-treated HIV patients, in turn, contributes to an increased risk of cardiovascular disease and other major comorbidities. In order to maintain the best quality of life, HIV patients must strive to keep these metabolic risks in check by controlling their glucose levels.

Life Extension recommends the antidiabetic drug metformin to maintain optimal glucose metabolism during healthy aging, as well as in various disease states.71 Several studies suggest metformin effectively combats HAART-associated cardio-metabolic risk as well.

In a year-long trial involving 50 HIV-infected patients who had been treated with antiretroviral drugs for an average of six years and had developed metabolic syndrome, metformin treatment significantly slowed the rate of coronary artery calcification compared to lifestyle modification.72 Moreover, metformin alone significantly improved insulin sensitivity, and, when combined with lifestyle modification, boosted levels of HDL (“good”) cholesterol.

In addition to improving insulin sensitivity, metformin also appears to promote healthy fat distribution, which is typically deregulated in HAART-treated HIV patients. A small, six-month trial in non-diabetic HIV-positive patients revealed that metformin therapy reduced abdominal fat accumulation, lowered blood pressure, and raised HDL cholesterol, supporting the cardio-protective role of the drug in this population.73

Studies show that though some other diabetic drugs may control insulin sensitivity in HIV patients, they do not reduce overall cardiovascular risk as effectively as metformin. In one investigation involving 37 patients, rosiglitazone tampered insulin resistance similarly to metformin, but only metformin suppressed postprandial lipemia, an independent cardiovascular risk factor.74

A small study published in the Journal of the American Medical Association found that metformin was safe and well-tolerated in HIV patients at a dose of 500 mg twice daily.75 This trial further showed that metformin reduced visceral abdominal fat, which poses greater cardio-metabolic risk than subcutaneous abdominal fat, without affecting liver function and causing only mild gastrointestinal discomfort in some patients.

Green coffee extract has recently emerged as a powerful glucose control agent as well. Unroasted coffee beans, once purified and standardized, produce high levels of chlorogenic acid and other beneficial polyphenols that can suppress excess blood glucose levels. Human clinical trials support the role of chlorogenic acid-rich green coffee bean extract in promoting healthy blood sugar control and reducing disease risk.

Scientists have discovered that chlorogenic acid found abundantly in green coffee bean extract inhibits the enzyme glucose-6-phosphatase that triggers new glucose formation and glucose release by the liver.76,77 Glucose-6-phosphatase is involved in dangerous postprandial (after-meal) spikes in blood sugar.

In another significant mechanism, chlorogenic acid increases the signal protein for insulin receptors in liver cells.78 That has the effect of increasing insulin sensitivity, which in turn drives down blood sugar levels.

In a clinical trial, 56 healthy volunteers, were challenged with an oral glucose tolerance test before and after a supplemental dose of green coffee extract. The oral glucose tolerance test is a standardized way of measuring a person's after-meal blood sugar response. In subjects not taking green coffee bean extract, the oral glucose tolerance test showed the expected rise of blood sugar to an average of 144 mg/dL after a 30-minute period. But in subjects who had taken 200 mg of the green coffee bean extract, that sugar spike was significantly reduced, to just 124 mg/dL—a 14% decrease.79 When a higher dose (400 mg) of green coffee bean extract was supplemented, there was an even greater average reduction in blood sugar—up to nearly 28% at one hour.

Note: Metformin and green coffee extract may not be appropriate for patients who are experiencing malabsorption. Patients with malabsorption should consult a qualified healthcare provider before using metformin or green coffee extract.

Cytokine Therapy

Cytokines are cell-signaling proteins used by the immune system to orchestrate immunologic activity. By secreting cytokines, cells of the immune system are able to modify the number and/or activity of other immune cells throughout the body. Cytokines are needed to mediate responses to infection and injury, and to ensure hemostatic immune balance during healthy conditions. During HIV infection, however, cytokine signaling becomes irregular.80,81

CD8+ cytotoxic T cells are necessary to destroy HIV-infected cells, while CD4+ T-helper cells are necessary to organize defense against pathogens. In late-stage HIV, CD8+ cells become dysfunctional and CD4+ cell numbers decline dramatically, allowing HIV to replicate rampantly and impairing the body’s ability to respond to infections. Thus, upon progression to AIDS, most patients succumb to opportunistic infections. Recent research suggests suboptimal production and signaling of γ-chain cytokines (IL’s-2, -4, -7, -9, -15, and -21) contributes significantly to immunological failure in HIV infected patients.81

Armed with this knowledge, scientists have begun developing cutting-edge therapies that capitalize on the ability of exogenous recombinant cytokines to reinvigorate immune function lost to HIV infection. Currently, clinical trials with IL-2 and -7 have shown promising results,82-84 and preliminary data with IL-15 and -21 is encouraging.85-87 A growing body of evidence indicates that cytokines, especially in combination, may become an important tool in augmenting CD4+ cell populations and CD+8 function in HAART-treated HIV patients.

Moving forward, researchers hope to begin assessing efficacy of various combinations of recombinant γ-chain cytokines in HIV patients. Clinical trials are underway; any HIV patient interested in participating in a trial should speak with their healthcare provider(s) and visit www.clinicaltrials.gov to identify trials they may be eligible for.

Hormones: Striking the Right Balance

Hormones appear to have a profound impact on conditions associated with HIV.

Growth hormones. Body fat distribution disorders, including lipoatrophy (fat loss in select areas) and lipohypertrophy (fat accumulation in select areas), are common among people with HIV/AIDS.88,89 Lipoatrophy usually occurs in the patient's buttocks, limbs, and face, whereas lipohypertrophy is characterized by visceral fat accumulations, or fat accumulations in the abdomen, mid-upper neck, mammary area, and/or above the pubic region.88 These physical changes can have a negative impact on self-perception and quality of life. Moreover, antiretroviral drug therapy is associated with the development of these conditions, a factor that could dissuade patients from taking their medications.88-90 Prolonged exposure to thymidine analogs, for example, particularly stavudine (d4T), is considered a risk factor for developing lipohypertrophy and lipoatrophy.88

This disturbance in fat metabolism, commonly referred to as "lipodystrophy syndrome," is associated with various metabolic changes, including insulin resistance and dyslipidemia (excessive amounts of fat in the blood).88 Mounting evidence suggests growth hormone plays a role in the pathogeneses of these phenomena,89,91,92 and numerous study findings have indicated that using hormone replacement therapy may help to combat these metabolic challenges.

In HIV-infected individuals with accumulations of abdominal fat, an independent association was found between lowered secretions of growth hormone and higher levels of fasting glucose and triglycerides. This suggests enhancing the amount of growth hormone may be beneficial for such patients.93 Additional support for this hypothesis came from a study by Benedini and colleagues, who found that people with HIV who had syndromes of fat accumulation benefited from significant reductions in body fat, as well as increased lean tissue, following growth hormone treatment.94 A review of several randomized controlled trials revealed that the use of growth hormone axis drugs successfully decreases visceral fat tissue mass and increases lean body mass in people who have HIV-associated lipodystrophy.95 A review by Leung and Glesby found that analogs of the growth hormone/growth hormone-releasing hormone axis seemed particularly effective at decreasing visceral fat tissue in patients with HIV.96

Testosterone. Testosterone has many important functions in the body, including its roles in fat distribution and muscle mass.97-99 However, low testosterone levels are common in patients with HIV.100-102

Low testosterone levels are associated with the loss of lean body mass, lost muscle mass, and an increased incidence of wasting.101,103 In many studies, patients with HIV who received testosterone treatment found that it helped stop the loss of lean body and muscle mass.101 A study of HIV-infected male patients using HAART indicated that sex hormones participate in fat distribution changes, as well as insulin sensitivity, among male patients with HIV-lipodystrophy.104

The beneficial effects of testosterone treatment in HIV-infected patients have been reported in a number of studies. A systematic review and meta-analysis by Kong and Edmonds found that testosterone therapy increased lean body mass more than placebo, and that a greater increase occurred when the testosterone was administered intramuscularly.105 In a review of anabolic steroids for the treatment of weight loss in people with HIV, Johns and associates found a potential relationship between the use of anabolic steroids and small increases in lean body mass and body weight. However, the authors did not formally recommend testosterone treatment due to study limitations, as well as the lack of knowledge regarding potential benefits and adverse effects of long-term anabolic steroid use, target populations for the therapy, and the best regimen.106 In HIV-infected men with abdominal obesity and low testosterone, taking 10 grams of testosterone each day for 24 weeks corresponded with a greater reduction in total, whole body, and abdominal fat mass, as well as a more substantial increase in lean mass, compared with participants who took a placebo.107

DHEA. Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone that exerts influence within a variety of biological systems either directly, or via its metabolites, which include androgens and estrogens. With respect to the immune system, studies have shown that the number of CD4+ cells correlates positively with serum DHEA levels, and negatively with cortisol levels in HIV patients.108 Other data indicates antiretroviral drug therapy may cause a drop in serum DHEA levels.109 In a study that followed 34 HIV-positive men for nearly three years, lower DHEA, and higher cortisol levels were associated with increasing lipodystrophy severity.110

In clinical trials, DHEA treatment has enhanced overall quality of life,111 improved the steroid hormone profile,112 and eased depressive symptoms113 in HIV patients. The effects of DHEA administration on CD4+ and CD8+ levels in humans remain unclear, but DHEA treatment does not appear to result in negative outcomes in HIV trials.

Men and women who would like more information about maintaining healthy hormone levels should review Life Extension’s “Male Hormone Restoration” and “Female Hormone Restoration” protocols.

Female hormone restoration. In a review of patient data from 84 cases of HIV in women older than 40, use of hormone replacement therapy was associated with a strong reduction in risk of death.114 In fact, the risk reduction for hormone replacement therapy was as strong as that associated with antiretroviral drug use in this trial.

9 Developing a Cure

The medical community has not yet found a cure for HIV/AIDS, but a striking case from Berlin may provide valuable insights into potential treatment strategies: Due to a genetic mutation (known as CCR5-delta32), some people do not express chemokine receptor 5 (CCR5), a co-receptor for HIV, on their CD4+ cells. These individuals are naturally resistant to R5 HIV infection. In the Berlin case, a patient with leukemia and HIV received a stem cell transplant from an individual with this mutation.115 Since the stem cell treatment, which occurred several years ago, doctors have not found any evidence of HIV. This finding has prompted further study in an attempt to replicate these results and ultimately develop a cure.

In 2011, Sangamo BioSciences announced a cell-based method for reducing HIV viral load, harnessing the potential therapeutic power of the CCR5 mutation. The process involves the temporary cessation of antiretroviral treatment, the removal of T cells containing the CD4 receptor, and the exposure of these cells to an enzyme to knockout the gene for the CCR5 co-receptor. Following this treatment, the cells are re-introduced into the patient, where they appear to function normally. In preliminary experiments, this method has been found to boost CD4 cell counts in people with HIV and may also be useful for controlling viral load. One HIV-infected patient in these experiments was able to maintain a controlled viral load even without HAART.116

Numerous other investigations have been carried out to devise a cure, including attempts to produce an HIV vaccine. Kang and colleagues recently developed the SAV001 vaccine, which is now undergoing clinical trials. The SAV001 vaccine is made by genetically modifying the virus so that it is no longer pathogenic. From there, the virus undergoes further deactivation via radiation and chemical treatments. Testing this vaccine in clinical trials will take a few years, but if it proves successful, it will represent one of the greatest developments in the history of HIV/AIDS research.

10 Dietary and Lifestyle Considerations

Optimal nutrition is important for maintaining a healthy immune system and preserving overall general health. However, several factors make this a challenge for people with HIV. Weight loss and malnutrition are common due to complications such as anorexia, changes in metabolism, malabsorption, and chronic diarrhea.117 HIV-related factors such as depression, loss of appetite, impaired taste or smell, or stomach upset (from treatment or from co-infections) may prevent affected individuals from eating enough.117,118 Even people with HIV who consume adequate diets may experience chronic diarrhea and/or vomiting from drug treatments or opportunistic infections, leading to nutrient loss.117 Combined, these factors can lead to nutrient deficiency, which can impair immune function and lower the body's resistance to infection.118,119 New infections, in turn, can further impair nutritional status, creating a vicious cycle that promotes the progression of the disease.118 Moreover, some individuals with HIV may have increased nutrient requirements for other reasons, including pregnancy, or because they are infants or growing children. These issues underscore the importance of ensuring adequate intake of vitamins and other nutrients to maintain health.

Other steps toward optimal health include maintaining a healthy lifestyle—avoiding the use of illicit drugs, alcohol, and tobacco, as well as engaging in moderate physical activity. In moderation, being active has been found to support immune function, reduce the potential for metabolic abnormalities, and decrease the risk of acute infection. It can also boost muscle mass, which may be useful for countering HIV-related lipodystrophy.118 Regular physical activity is associated with decreased levels of skeletal muscle inflammatory proteins, as well as reductions in several other important markers of inflammation. These markers bear strong correlations with adverse conditions such as cardiovascular and metabolic diseases (eg, insulin resistance), underscoring the value of moderate physical activity. Moderate activity can also eliminate obesity. This presents additional health-related benefits, particularly since obesity is associated with impaired immune function, along with a host of other health problems.120 Prolonged (more than 1.5 hours), high-intensity exercise is not recommended for people with HIV, as it may have an immune-suppressing effect.121

11 Targeted Natural Interventions

Given the deteriorating effects of HIV/AIDS progression on the immune system and nutrient status, it is not surprising that nutritional supplements have been shown to be extremely beneficial in patients with HIV. Taking vitamin supplements lowered the risk of HIV disease progression in several studies.122-126 The use of vitamin supplements has also been associated with improved pregnancy outcomes in HIV-infected pregnant women,122,127 increased appetite in HIV-infected children,128 and better health and survival of children with HIV.129-131

In addition, nutritional supplements have been found to improve comorbidities associated with HIV. In HIV-infected patients being treated for tuberculosis (TB), for example, the consumption of micronutrients (vitamins A, B complex, C, and E, plus selenium) corresponded with a lower risk of TB recurrence and a significantly lower incidence of peripheral neuropathy (a side effect of TB treatment); this treatment also raised CD4+ and CD3+ counts.132 In a recent study of children with HIV, a daily supplement of vitamins A, B complex, C, D, E, and folic acid, plus zinc, iron, and copper (at levels based on recommended daily allowances) corresponded with faster recovery from diarrheal episodes and pneumonia.133

Antioxidants

Antioxidants are widely known for their health benefits and may be particularly important for people with HIV. In 1985, Life Extension was among the first organizations to propose that patients with HIV/AIDS would benefit from taking high doses of antioxidants. Since then, many scientific studies have examined a wide range of nutrients and supplements for use in HIV/AIDS.

Under normal circumstances, metabolic processes in the body generate free radicals. At low/moderate concentrations, these reactive oxygen species are not harmful, but instead have a variety of beneficial functions. At high concentrations, however, they become extremely destructive. Normally, the human body keeps these levels in check by neutralizing free radicals with its own natural antioxidant defense system. However, some conditions can boost the production of free radicals and create oxidative stress—a condition in which the body's antioxidant defenses are unable to neutralize the overwhelming quantity of free radicals being produced. This can lead to cellular damage and the development of disease.134

HIV is associated with substantial oxidative stress,135-142 and reactive oxygen species participate in the progression of HIV to AIDS.139 As HIV progresses, antioxidant levels decline.143,144 Compounding this problem further is the fact that various HIV treatments have been shown to increase oxidative stress.141,145-147 Combined, these factors create an unhealthy environment that could be further exacerbated by the inadequate intake or poor absorption of nutrients that are commonly associated with HIV.148,149 Antioxidant micronutrient deficiencies are common among people with HIV.150 Reduced serum levels of vitamins E (a powerful antioxidant) have been associated with a higher risk of developing AIDS.151

Antioxidant supplements have been found to counteract some of the damaging effects associated with HIV. Taking supplements of vitamin E (800 IU per day) and vitamin C (1,000 mg per day) for three months lowered oxidative stress among patients with HIV and produced a trend toward a decrease in viral load.150 High serum levels of vitamin E have been linked with a slower progression of HIV.151 In large study in Tanzania involving 1,075 pregnant women with HIV, taking a daily multivitamin combination consisting of vitamins C (500 mg), E (30 mg), and various B vitamins and folic acid improved CD4, CD3, and CD8 cell counts and lowered the risk of fetal death, low birth weight, preterm birth, and small size for gestational age.127

Other antioxidants have also shown beneficial effects in people with HIV. A study involving 331 AIDS patients found that when patients received supplements including various carotenoids (natural pigments with antioxidant properties), as well as multivitamins and minerals, mortality rates were lower, and CD4 T-cell counts were higher, compared with patients who received the same supplementation without the carotenoids.152 In HIV-infected patients following a stable HAART regimen, the use of broad-spectrum, high-dose micronutrient supplementation with antioxidants corresponded with a 24% increase in CD4 cell count.153 Other important antioxidants that have been highlighted in the HIV literature include:

Glutathione. Glutathione is thought to be an extremely important antioxidant for HIV-infected patients, because it appears to interfere with HIV’s entry into its target cells.154 Glutathione deficiency—a common finding in HIV—is associated with compromised T-cell function and decreased survival.155-156 Some nutrients that offer a host of health benefits also assist in the production of glutathione. One of these is N-acetylcysteine.

N-acetylcysteine. N-acetylcysteine (NAC) is of particular interest for people with HIV/AIDS, because it reinstates glutathione levels and has been found to maintain glutathione concentrations,123,157 improve T-cell counts, and reduce viral load in patients with advanced AIDS.157-159 In many studies, the use of NAC oral supplements has correlated with better quality of life and patient well-being.160 A study involving 81 HIV-infected patients showed that eight weeks of oral NAC supplementation correlated with significant improvements in whole blood glutathione concentrations, as well as increased T-cell glutathione levels.161 NAC is known for exerting antioxidant effects against the activity of glycoprotein 120 (gp120), an HIV protein that induces oxidative stress during the infection of macrophages (a type of white blood cell).162

Green tea. Green tea leaves contain compounds called catechins, which have powerful antioxidant properties. The most abundant catechin in green tea, epigallocatechin gallate (EGCG), has also been found to suppress HIV.163 Kawai and colleagues found that EGCG can bind to T-cells and block the virus from attaching to them.164 When HIV comes into contact with a helper T cell in the human body, gp120 on its surface binds to a CD4 receptor on the surface of the T cell, ultimately leading to infection.165 In several studies, EGCG blocked the attachment of gp120 to CD4 cells with varying degrees of inhibition.164,166 EGCG also appears to lower the risk of HIV transmission—normally, fibrils in human sperm collect HIV viruses and deliver them to target cells. EGCG inhibits this activity and degrades the fibrils, thereby lowering transmission risk.167 EGCG has also been found to inhibit a variety of HIV subtypes at physiologic concentrations without damaging human cells.165 When coupled with other nutrients (vitamin C or lysine), green tea extract inhibited the production of HIV in chronically infected T cells; in latently infected cells, combining the green tea extract with vitamin C and amino acids resulted in significantly greater suppressive action than when any of the three were applied individually.168

Lipoic acid. This powerful antioxidant plays a central role in the defense against free radicals. It also recycles other important antioxidants, including glutathione,169 and decreases intracellular signaling that promotes inflammation.170 Taking a 300 mg supplement of alpha-lipoic acid three times per day for six months significantly elevated blood glutathione levels in a group of HIV-infected men and women aged 44‒47 years.171 In the lab, alpha-lipoic acid has been shown to inhibit HIV replication.172 Its ability to scavenge reactive oxygen species has been found to block nuclear factor-kappa B, a transcriptional activator that is instrumental in the regulation of HIV gene expression.173 In a study by Merin and associates, applying alpha-lipoic acid to cells infected with HIV completely stopped “initiation of HIV-1 induction by [tumor necrosis factor-alpha]."174

Carnitine (acetyl-L-carnitine). Acetyl-L-carnitine (ALC), also an antioxidant, boosts immune function and helps the body convert fat into energy. A number of studies have reported positive effects of ALC supplementation in people with HIV, especially its positive impact on the side effects of certain antiretroviral drugs. People with HIV who use the NRTIs zalcitabine, didanosine, or stavudine often experience peripheral neuropathy (peripheral nerve damage) and myopathy (muscle tissue disease). These outcomes have been observed in other NRTIs as well and can discourage patients from adhering to their medication regimens.175 However, ALC may help to mitigate these effects.

ALC is known to be involved with peripheral nerve regeneration.176 In a small study by Osio and associates (n=20), taking 2,000 mg of oral ALC each day for a month led to significant reductions in pain intensity scores among HIV-infected patients taking antiretroviral therapy.177 A larger study involving 90 HIV-positive patients with antiretroviral toxic neuropathy found that taking 500 mg of ALC intramuscularly twice per day for 14 days resulted in statistically significant improvements in weekly mean pain ratings versus placebo. When these patients subsequently took 1,000 mg of oral ALC twice per day for six weeks, symptomatic improvements were observed.178 A cohort study involving 21 HIV patients with NRTI-related neuropathy who were reviewed after receiving acetyl-L-carnitine for a mean of 4.3 years, 13 of the 16 patients who completed the study reported "very much or moderate" symptomatic improvement, and nine were pain-free.179 Hart and associates observed that when HIV-infected patients with antiretroviral toxic neuropathy took ALC treatment, 76% of patients experienced reductions in neuropathic pain.176 In a small study involving 21 participants, receiving 3,000 mg of ALC daily for 24 weeks corresponded with improvements in subjective pain ratings.180 A very small review and meta-analysis of 14 studies that described various analgesics did not find a significant benefit of taking 1 gram of ALC daily in treating HIV-associated sensory neuropathy; the authors pointed out that this review was limited by the small number of eligible studies, as well as the differences in study designs and size, which made comparisons across studies difficult.181

Vitamins

Certain vitamins have amassed a notable amount of clinical evidence to highlight their potential supplemental value in people with HIV.

Vitamin D. Vitamin D has a multitude of important functions within the human body, including its roles in supporting proper immune function, regulating bone metabolism, and maintaining calcium and phosphorus homeostasis.182,183 In people with HIV, vitamin D deficiency is common, as is lower-than-normal bone mineral density.4,184-191 Additionally, people with HIV appear to be at an increased risk of osteopenia and osteoporosis.184,190,192 In a recent review of the medical literature, McComsey and colleagues concluded that HIV infection should be regarded as a risk factor for bone disease.193

Deficient levels of vitamin D in HIV-infected individuals may be due to the virus itself185,190 as well as to the effects of antiretroviral treatment.184,185,189,190,194-197 Tenofovir, for example, is a widely used NRTI that is associated with low bone mineral density,198-201 as well as increased levels of parathyroid hormone (PTH). (Increased PTH levels are associated with decreased bone mineral density).202 Non-nucleoside reverse transcriptase inhibitors (NNRTI) have also been implicated in vitamin D deficiency; one in particular—efavirenz—has been linked to low concentrations of 25-hydroxyvitamin D (the form of vitamin D that is measured to determine vitamin D status in the human body).187,189,203

As people with HIV continue to live longer, bone loss prevention becomes an even more prominent consideration in this aging population.192 Some studies have shown a correlation between vitamin D status and CD4 counts,186,203-206 while others did not find this relationship.187,207 Interestingly, some studies that detected vitamin D deficiencies in HIV patients found that uninfected individuals also had low levels of vitamin D.186,187 In the United States, vitamin D deficiency is highly prevalent in the general population, regardless of HIV status.187

Beta-carotene/vitamin A. Beta-carotene is a plant pigment found in colorful fruits and vegetables and is converted into vitamin A in the body. It plays important roles in human growth, vision, and its support of the immune system. In people with HIV who were given 100,000 IU of vitamin A from beta-carotene daily for four weeks, white blood cell counts rose 66%, and T-helper cells rose slightly. Six weeks after cessation of the beta-carotene treatment, the immune-cell measurements returned to pretreatment levels.208 In a Uganda study involving 181 children with HIV, vitamin A supplementation was associated with significantly lower mortality rates, as well as improvements in chronic diarrhea and persistent cough.129 In another study, 687 children in Tanzania with pneumonia received 400,000 IU of vitamin A at baseline, as well as four months after discharge, and, then eight months after discharge. None of the children showed any signs of vitamin A deficiency when they started treatment. Vitamin A supplementation was associated with a 49% drop in mortality and a 92% decrease in diarrhea-related deaths. Plus, AIDS-related deaths plummeted 68%.130 In a population in South Africa that is not generally vitamin A deficient, children with HIV-infected mothers received 50,000 IU of vitamin A at ages 1 month and 3 months, 100,000 IU at 6 months and 9 months, and then 200,000 IU at 12 months and 15 months; this resulted in a significant reduction in morbidity from diarrheal disease.131 In a U.S. study involving HIV-infected children, the use of vitamin A supplementation prior to influenza vaccination muted the increase of HIV viral load post-immunization.209

Kennedy-Oji and associates observed improved weight retention among South African HIV-infected women with vitamin A supplementation.210 Conversely, vitamin A deficiency in HIV-positive women has been associated with increased mother-to-child transmission of the infection.211 However, the potential value of vitamin A supplements in pregnant women with HIV remains questionable, particularly as some studies have indicated that vitamin A supplementation may increase the HIV load in breast milk212 and may potentially elevate the risk of HIV transmission from mother to child.213 A recent review of studies encompassing 6,517 women with HIV in South Africa, Zimbabwe, Malawi, and Tanzania found that vitamin A supplement use among HIV-infected pregnant women correlated with improved birth weights; although the review found no evidence that vitamin A supplements increase the risk of mother-to-child transmission of HIV, the authors pointed out the moderate quality of scientific evidence in these studies.

B vitamins. B vitamins are responsible for an array of important functions within the body, including proper functioning of the brain and immune system.214,215 A number of reports have documented the beneficial effects of B-vitamin supplementation in people with HIV. In a study involving 281 HIV-infected patients, taking vitamin B6 (more than two times the RDA), vitamin B1 (more than five times the RDA), or vitamin B2 (more than five times the RDA) was independently associated with improved survival.216 In 108 HIV-infected men tracked over an 18-month period, low B12 levels at the beginning of the study were significant predictors of faster disease progression (as determined by CD4 cell count); although the development of B12 deficiency corresponded with a drop in CD4 cell count, the normalization of vitamin B12 levels corresponded with higher CD4 cell counts.217

Additional Support

Compelling evidence has also been accumulating for the following:

Omega-3 fatty acids. Omega-3 fatty acids are essential oils—they are not made in the body and must be consumed from external sources. Their anti-inflammatory and immune-modulating capabilities make them a valuable component of general health218; additionally, they appear to have therapeutic value for people with HIV who suffer from high triglyceride levels. A number of published medical reports have described changes in lipid metabolism, increased levels of serum triglycerides, and low levels of HDL cholesterol in people with HIV; moreover, combination antiretroviral treatment is reported to be a risk factor.219-222 A combination of dieting and omega-3 supplements (6 grams per day) was found to cause a major drop in serum triglycerides and levels of arachidonic acid.223 A small systematic review found that varying doses of omega-3 fatty acids caused significant reductions in triglyceride concentrations in people with HIV who were taking antiretroviral therapy.224 A study involving 48 HIV-infected patients (47 males, one female) with HAART-associated hypertriglyceridemia found that a 12-week course of omega-3 fatty acids (4 grams per day) led to significant reductions in triglyceride levels compared with placebo.225 Wohl and associates found that omega-3 fatty acids (in the form of fish oil supplements), plus dietary and exercise counseling, lowered fasting triglyceride levels in HIV-infected patients with hypertriglyceridemia taking antiretroviral medication; however, the difference was not significant compared with participants who received counseling without the fish oil supplements.226 In other studies of HIV-infected patients with elevated triglyceride levels who were using antiretroviral therapy, omega-3 supplementation was associated with significant decreases in triglycerides.227-229

Whey protein. Whey protein contains all essential and nonessential amino acids, which are important for maintaining an adequate immune system response. Whey is also an important supplement to help boost the body’s synthesis of glutathione, and various therapeutic benefits, including its immune-enhancing properties, make it of great interest to people with HIV.230 In a study involving 41 HIV-infected patients, those who received 40 grams of whey protein each day benefitted from a CD4 count increase of 31 cells/µL, versus the control group, which showed a decline of 5 cells/µL over the same 12-week period.231 Whey protein has been found to improve immune function, elevate cellular glutathione levels, and maintain muscle mass.230,232 Although large randomized controlled trials will impart greater insights into the potential benefits of whey protein in patients with HIV, the results so far are encouraging.233

Lactoferrin. Lactoferrin is derived from whey protein. It has been found to inhibit viruses by binding to viral receptor sites, thus preventing the virus from infecting healthy cells.234 In vitro studies show that lactoferrin is an effective inhibitor of HIV entry.235-237 It may also effectively inhibit initial HIV infection by blocking uptake into epithelial cells and transfer from dendritic cells to CD4+ cells.238

One study that compared 22 asymptomatic and 45 symptomatic patients with HIV to 30 healthy control subjects found that plasma lactoferrin levels were decreased in patients infected with HIV.239 In a six-month trial involving 22 HIV-1-infected children, oral lactoferrin caused a small decrease in viral load and an increase in CD4+ cell numbers; lactoferrin plus antiretroviral therapy was more effective than lactoferrin alone.240

Coenzyme Q10 (CoQ10). CoQ10 is present in all cells of the human body and is essential for proper cell function. Low levels of CoQ10 have been detected in people with HIV, and one study found that the level of CoQ10 deficiency corresponds with the stage of HIV infection.241 CoQ10 supplementation increases a number of immune parameters, including T-cell counts,242,243 an important consideration in HIV. A known antioxidant, it has also been found to contribute to the improvement of antioxidant defenses in HIV-infected men when administered as part of a regimen consisting of various antioxidants.224 In a case study involving a 52-year-old man with HIV, the patient suffered from drug-related skeletal myopathy caused by zidovudine. Daily supplementation of CoQ10 led to recovery, allowing the patient to continue his HIV drug treatment.225 Cherry and associates tested a water-soluble formulation of CoQ10 on cultured rat cells and found that it was effective in preventing neurotoxicity caused by d4T (stavudine; the HIV medication most commonly associated with neuropathy).246 Although studies on the effects of CoQ10 in HIV are limited, findings so far highlight this as a promising area for further study.

Selenium. Selenium is required for proper immune system function247 and facilitates a multitude of antioxidant activities in the body.248,249 It also decreases the effect of inflammatory cytokines, which may reduce the risk of developing neurological damage, Kaposi's sarcoma (a common HIV-associated cancer), and wasting syndrome.250 In people with HIV, selenium deficiency has corresponded with disease progression to AIDS or death.247,250,251 Shor-Posner and colleagues found that, among HIV-infected drug users, low selenium was a significant risk factor for developing mycobacterial disease.252 The HIV-inhibiting effects of selenium have also been observed in human cell cultures.253,254 In human studies, selenium supplementation has been found to reduce the incidence of diarrhea and decrease the number of patient hospitalizations.255,256

Zinc and magnesium. On average, patients with HIV/AIDS who have low zinc levels have a higher viral load and lower T-cell counts.257,258 A U.S. study of 231 HIV-infected adults found that taking zinc supplements every day for 18 months reduced the rate of diarrhea by more than 50% compared with placebo and lowered the risk of immunological failure by 400% (CD4 T cell counts of <200 cells/µL). However, it did not affect viral load, nor did it have an impact on mortality.259,260 In a literature review of six human studies involving 1,009 participants, the use of zinc supplements appeared to decrease opportunistic infection among adults and children with HIV. Only the adults were found to have higher CD4 counts; no adverse events were reported for adults or children from using zinc supplementation.261

Some antiretroviral drugs appear to chelate magnesium post-interaction with integrase. Therefore, supplemental magnesium may ensure that magnesium levels are not depleted.262

Probiotics. The human gut contains naturally growing bacteria that possess an array of beneficial functions; these include their ability to provide essential nutrients to the body, break down foods that are otherwise indigestible, via fermentation reactions, for example, and prevent the growth of harmful pathogens.263,264 However, the gut is largely compromised in patients with HIV. Acute HIV infection is marked by the dramatic depletion of CD4+ cells from the gastrointestinal (GI) tract. The GI tract is believed to be a particularly attractive target for HIV replication because the CD4 cells it contains are primarily CD4+ memory cells, which are preferential targets for HIV replication. (CD4+ "memory" cells are named as such because they "remember" antigens they previously encountered; this allows them to mount a more rapid response in subsequent encounters.) Moreover, the CD4+ cells in the GI tract express substantial amounts of CCR5—a receptor commonly used by HIV to enter and infect cells.265,266 As HIV depletes the gut of immune cells, intestinal epithelial permeability generally increases, and the human host becomes increasingly vulnerable to microbial invasion and disease progression.267

Probiotics are living microorganisms that, when provided in sufficient quantities, impart health benefits. Certain strains of probiotics are associated with reduced inflammation268-270 and permeability,271-273 both of which are of notable interest for patients with HIV. In several studies involving people with HIV/AIDS, consuming probiotics was associated with improvements in CD4 cell counts.274-276 More recently, Hummelen and colleagues found that adding probiotics to micronutrient-fortified yogurt did not boost CD4 cell count after one month, versus the same preparation without the added probiotics; although the added probiotics were well tolerated, and no adverse events were reported.277 Larger clinical studies with longer follow-up periods are needed to fully assess the impact of probiotic supplementation on people with HIV, but results so far are promising.

Reishi extract. Reishi (Ganoderma lucidum, or lingzhi) is a mushroom native to Asia that has been a highly valued part of traditional herbal medicine for centuries.278 It has been used to treat a wide range of health problems and promote long life, but is most commonly used as an immune-enhancing supplement.278,279 Several studies have demonstrated reishi’s immune-potentiating ability.280 A preliminary study included five female monkeys with simian acquired immunodeficiency syndrome, caused by inoculation with a virus that is closely related to HIV, called simian immunodeficiency virus. Three of the monkeys received reishi extract and two received no treatment for one year. Treated monkeys had a higher survival rate (2/3 vs. 0/2) and the surviving monkeys experienced a decrease in viral load and less damage in lymphatic and other tissues.281

Reishi’s active constituents include triterpene compounds and polysaccharides; these constituents are central to reishi’s anti-viral and anticancer effects, as well as reishi’s ability to stimulate immune cells.282-284 Triterpenes and related compounds from reishi have been found to have specific anti-HIV-1 activity.285-287 Reishi also contains proteins, fibers, phenolic compounds, minerals, vitamins, and other potentially beneficial constituents.278,279 Extracts from reishi have been found in laboratory and animal studies to modulate both innate and adaptive immunity, stimulating macrophages, T cells (both CD4+ and CD8+ T lymphocytes, as well as others), B cells, dendritic cells, and natural killer cells, and altering the balance of other chemicals, called cytokines, that regulate immune cell activities.288,289 Both its antiviral and general immune-enhancing properties make reishi extract a good choice for individuals with HIV infection.

  1. Singh A et al. Cure for HIV: New possibility on horizon. J Pharm Bioallied Sci. 2011 Jul;3(3):461-4.
  2. Killian, M. S., Levy, J. A. "HIV/AIDS: 30 Years of Progress and Future Challenges." Eur J Immunol 41.12 (2011): 3401-11.
  3. Bhaskaran, K., Hamouda, O., Sannes, M., et al. "Changes in the Risk of Death After HIV Seroconversion Compared with Mortality in the General Population." JAMA 300.1 (2008): 51-9.
  4. Giusti, A., Penco, G., Pioli, G. "Vitamin D Deficiency in HIV-Infected Patients: a Systematic Review."Nutr Diet Supp 3 (2011): 101–111.
  5. Escote X et al. Lipodystrophy and insulin resistance in combination antiretroviral treated HIV-1-infected patients: implication of resistin. J Acquir Immune Defic Syndr. 2011 May;57(1):16-23.
  6. Tien PC et al. Antiretroviral therapy exposure and insulin resistance in the Women's Interagency HIV study. J Acquir Immune Defic Syndr. 2008 Dec 1;49(4):369-76.
  7. Tebas P. Insulin resistance and diabetes mellitus associated with antiretroviral use in HIV-infected patients: pathogenesis, prevention, and treatment options. J Acquir Immune Defic Syndr. 2008 Sep 1;49 Suppl 2:S86-92.
  8. Palios J et al. The Pathophysiology of HIV-/HAART-Related Metabolic Syndrome Leading to Cardiovascular Disorders: The Emerging Role of Adipokines. Exp Diabetes Res. 2012;2012:103063. Epub 2011 Dec 8.
  9. Campbell N. A., Reece, J. B., Urry, L. A., et al. Biology. 8th ed. San Francisco: Benjamin Cummings; 2008.
  10. Coakley E et al. Assessing chemokine co-receptor usage in HIV. Curr Opin Infect Dis. 2005 Feb;18(1):9-15.
  11. Agosto LM, Liszewski MK, Mexas A, et al. Patients on HAART often have an excess of unintegrated HIV DNA: implications for monitoring reservoirs. Virology. 2011 Jan;409(1):46-53.
  12. Onyancha, O. B., Ocholla, D. N. "Is HIV/AIDS in Africa Distinct? What Can We Learn From an Analysis of the Literature?" Scientometrics 79.1 (2009): 000–000.
  13. Markovitz, D. M. "Infection with the Human Immunodeficiency Virus Type 2." Ann Intern Med 118.3 (1993): 211-8. http://www.annals.org/content/118/3/211.abstract
  14. de Silva, T. I., Cotten, M., Rowland-Jones, S. L. "HIV-2: the Forgotten AIDS Virus." Trends Microbiol 16.12 (2008): 588-95. http://www.ncbi.nlm.nih.gov/pubmed/18964021
  15. Popper, S. J., Sarr, A. D., Travers, K. U., et al. "Lower Human Immunodeficiency Virus (HIV) Type 2 Viral Load Reflects the Difference in Pathogenicity of HIV-1 and HIV-2." J Infect Dis. 1999;180(4):1116-21.z
  16. MacNeil, A., Sankale, J. L., Meloni, S. T., et al. "Long-Term Intrapatient Viral Evolution during HIV-2 Infection." J Infect Dis 195.5 (2007): 726-33.
  17. Foxall, R. B., Albuquerque, A. S., Soares, R. S., et al. "Memory and Naïve-Like Regulatory CD4+ T Cells Expand During HIV-2 Infection in Direct Association with CD4+ T-Cell Depletion Irrespectively of Viremia." AIDS 25.16 (2011): 1961-70. http://www.ncbi.nlm.nih.gov/pubmed/21811143
  18. Pepin, J., Morgan, G., Dunn, D., et al. "HIV-2-Induced Immunosuppression among Asymptomatic West African Prostitutes: Evidence That HIV-2 Is Pathogenic, but Less So Than HIV-1." AIDS 5.10 (1991): 1165-72. http://www.ncbi.nlm.nih.gov/pubmed/1786143
  19. Shi, Y., Brandin, E., Vincic, E., et al. "Evolution of Human Immunodeficiency Virus Type 2 Coreceptor Usage, Autologous Neutralization, Envelope Sequence and Glycosylation." J Gen Virol 86.Pt 12 (2005): 3385-96.
  20. Chan, M. L., Petravic, J., Ortiz, A. M., et al. "Limited CD4+ T Cell Proliferation Leads to Preservation of CD4+ T Cell Counts in SIV-Infected Sooty Mangabeys." Proc Biol Sci 277.1701 (2010): 3773-81.
  21. Hahn, B. H., Shaw, G. M., De Cock, K. M, et al. "AIDS as a Zoonosis: Scientific and Public Health Implications." Science 287.5453 (2000): 607-14. http://www.ncbi.nlm.nih.gov/pubmed/10649986
  22. Gao, F., Bailes, E., Robertson, D. L., et al. "Origin of HIV-1 in the Chimpanzee Pan troglodytes troglodytes." Nature 397.6718 (1999): 436-41. http://www.ncbi.nlm.nih.gov/pubmed/9989410
  23. Pilcher, C. D., Joaki, G., Hoffman, I. F., et al. "Amplified Transmission of HIV-1: Comparison of HIV-1 Concentrations in Semen and Blood during Acute and Chronic Infection." AIDS 21.13 (2007): 1723-30. http://www.ncbi.nlm.nih.gov/pubmed/17690570
  24. Cohen, M. S., Hellmann, N., Levy, J. A., et al. "The Spread, Treatment, and Prevention of HIV-1: Evolution of a Global Pandemic." J Clin Invest 118.4 (2008): 1244-54. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276790/
  25. Kaul, R., Pettengell, C., Sheth, P. M., et al. "The Genital Tract Immune Milieu: an Important Determinant of HIV Susceptibility and Secondary Transmission." J Reprod Immunol 77. 1 (2008): 32-40. http://www.ncbi.nlm.nih.gov/pubmed/17395270
  26. Salazar-Gonzalez, J. F., Salazar M. G., Learn, G. H., et al. "Origin and Evolution of HIV-1 in Breast Milk Determined by Single-Genome Amplification and Sequencing." J Virol 85.6 (2011): 2751-63. http://www.ncbi.nlm.nih.gov/pubmed/21191008
  27. Gantt, S., Carlsson, J., Heath, L., et al. "Genetic Analyses of HIV-1 Env Sequences Demonstrate Limited Compartmentalization in Breast Milk and Suggest Viral Replication within the Breast That Increases with Mastitis." J Virol 84.20 (2010): 10812-9. http://www.ncbi.nlm.nih.gov/pubmed/20660189
  28. Permar, S.R., Kang, H.H., Wilks, A.B., et al. "Local Replication of Simian Immunodeficiency Virus in the Breast Milk Compartment of Chronically Infected, Lactating Rhesus Monkeys." Retrovirology 7 (2010): 7. http://www.retrovirology.com/content/7/1/7
  29. Gray, R. R., Salemi, M., Lowe, A., et al. "Multiple Independent Lineages of HIV-1 Persist in Breast Milk and Plasma." AIDS 25.2 (2011): 143-52. http://www.ncbi.nlm.nih.gov/pubmed/21173592
  30. Dwyre, D. M., Fernando, L. P., Holland, P. V. "Hepatitis B, Hepatitis C and HIV Transfusion-Transmitted Infections in the 21st Century." Vox Sang 100.1 (2011): 92-8. http://www.ncbi.nlm.nih.gov/pubmed/21175659
  31. Raguin, G., Lepretre, A., Ba, I., et al. "Drug Use and HIV in West Africa: a Neglected Epidemic." Trop Med Health 16.9 (2011): 1131-3. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3156.2011.02806.x/full
  32. Boily, M. C., Baggaley, R. F., Wang, L., et al. "Heterosexual Risk of HIV-1 Infection per Sexual Act: Systematic Review and Meta-Analysis of Observational Studies." Lancet Infect Dis 9.2 (2009): 118-29.
  33. Marinda, E. T., Moulton, L. H., Humphrey, J. H., et al. "In Utero and Intra-Partum HIV-1 Transmission and Acute HIV-1 Infection during Pregnancy: Using the BED Capture Enzyme-Immunoassay as a Surrogate Marker for Acute Infection." Int J Epidemiol 40.4 (2011): 945-54. http://ije.oxfordjournals.org/content/early/2011/04/05/ije.dyr055.abstract
  34. Arya, M., Levison, J., Giordano, T. P. "Ongoing Barriers to HIV Testing During Pregnancy: A Need for Media Campaigns Addressing Low Knowledge about Perinatal HIV Transmission among Women in the United States." AIDS Patient Care STDs 24.2 (2010): 71-2.
  35. Liang K, Gui X, Zhang YZ, et al. "A Case Series of 104 Women Infected With HIV-1 via Blood Transfusion Postnatally: High Rate of HIV-1 Transmission to Infants through Breast-Feeding." J Infect Dis 200.5 (2009): 682-6.
  36. Royce, R. A., Seña, A., Cates, W. Jr., et al. "Sexual Transmission of HIV." N Engl J Med 336.15 (1997): 1072-8.
  37. McGowan I. Rectal microbicides: a new focus for HIV prevention. Sex Transm Infect. 84.6 (2008): 413-7.
  38. Baggaley, R. F., White, R. G., Boily, M. C. "HIV Transmission Risk through Anal Intercourse: Systematic Review, Meta-Analysis and Implications for HIV Prevention." Int J Epidemiol 39.4 (2010):1048-63. http://ije.oxfordjournals.org/content/39/4/1048.full
  39. Saini R, Saini S, Sharma S. "Oral Sex, Oral Health and Orogenital Infections." J Glob Infect Dis 2.1 (2010): 57-62. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840968/
  40. Sandlin, M. I., Johnston, C., Bowe, D., et al. "Clinician and Patient Recognition of Anogenital Herpes Disease in HIV Positive Men Who Have Sex with Men." Sex Transm Dis 38.9 (2011): 833-6.
  41. Corbett, E. L., Steketee, R. W., ter Kuile, F. O., et al. "HIV-1/AIDS and the Control of Other Infectious Diseases in Africa." Lancet 359.9324 (2002): 2177-87.
  42. Boulton, I. C., Gray-Owen, S. D. "Neisserial Binding to CEACAM1 Arrests the Activation and Proliferation of CD4+ T Lymphocytes." Nat Immunol 3.3 (2002): 229-36.
  43. Pask, A. J., McInnes, K. J., Webb, D. R., et al. "Topical Oestrogen Keratinises the Human Foreskin and May Help Prevent HIV Infection." PLoS One 3.6 (2008): e2308. http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0002308
  44. Donoval, B. A., Landay, A. L., Moses, S., et al. "HIV-1 target cells in foreskins of African men with varying histories of sexually transmitted infections." Am J Clin Pathol 125.3 (2006): 386-91.
  45. Bell, S.K., McMickens, C.L., Selby, K. Biographies of Disease: AIDS. USA: Sigall K. Bell; 2011.
  46. Pantaleo G, et al. New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med. 1993 Feb 4;328(5):327-35.
  47. Hollingsworth, T. D., Anderson, R. M., Fraser, C. "HIV-1 Transmission, by Stage of Infection." J Infect Dis 198.5 (2008): 687-93.
  48. Wawer, M. J., Gray, R. H., Sewankambo, N. K., et al. "Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda." J Infect Dis 191.9 (2005): 1403-9. http://www.ncbi.nlm.nih.gov/pubmed/15809897
  49. Pilcher, C. D., Tien, H. C., Eron, J. J., Jr, et al. "Brief but Efficient: Acute HIV Infection and the Sexual Transmission of HIV." J Infect Dis 189.10 (2004): 1785-92. http://jid.oxfordjournals.org/content/189/10/1785.long
  50. Read, J. S.; Committee on Pediatric AIDS, American Academy of Pediatrics. "Diagnosis of HIV-1 Infection in Children Younger Than 18 Months in the United States." Pediatrics 120.6 (2007): e1547-62. http://www.ncbi.nlm.nih.gov/pubmed/18055670
  51. Pilcher, C. D., Christopoulos, K. A., Golden, M. "Public Health Rationale for Rapid Nucleic Acid or P24 Antigen Tests for HIV." J Infect Dis 201 Suppl 1 (2010): S7-15.
  52. Chavez, P., Wesolowski, L., Patel, P., et al. "Evaluation of the Performance of the Abbott ARCHITECT HIV Ag/Ab Combo Assay." J Clin Virol 52 Suppl 1 (2011):S51-5. http://www.ncbi.nlm.nih.gov/pubmed/21983253
  53. Bischof, J. J., Kuruc, J. D., Embry, J. A., et al. "Prospective Study of the ARCHITECT HIV Ag/Ab Combo Fourth Generation Assay to Detect HIV Infection in Sexually Transmitted Infection Clinics." AIDS 25.15 (2011): 1927-9. http://www.ncbi.nlm.nih.gov/pubmed/21811138
  54. Pandori MW, Hackett J Jr, Louie B, et al. "Assessment of the Ability of a Fourth-Generation Immunoassay for Human Immunodeficiency Virus (HIV) Antibody and P24 Antigen Detect Both Acute and Recent HIV Infections in a High-Risk Setting." J Clin Microbiol 47.8 (2009): 2639-42. http://jcm.asm.org/content/47/8/2639.full
  55. Fiebig, E. W., Wright, D. J., Rawal, B. D., et al. "Dynamics of HIV Viremia and Antibody Seroconversion in Plasma Donors: Implications for Diagnosis and Staging of Primary HIV Infection." AIDS 17.13 (2003): 1871-9.
  56. Morris, S. R., Little, S. J., Cunningham, T., et al. "Evaluation of an HIV Nucleic Acid Testing Program with Automated Internet and Voicemail Systems to Deliver Results." Ann Intern Med 152.12 (2010): 778-85.
  57. Schneider, E., Whitmore, S., Glynn, K. M., et al. "Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years--United States, 2008." MMWR Recomm Rep 57.RR-10 (2008): 1-12.
  58. University of California, San Francisco (UCSF). "Blood Cell Test For HIV Treatment Monitoring Is Cheaper But Just As Effective." Medical News Today. MediLexicon, Intl., 2 Dec. 2011. Web. 13 Jan. 2012. http://www.medicalnewstoday.com/releases/238550.php
  59. Cohen, M. S., Chen, Y. Q., McCauley, M., et al. "Prevention of HIV-1 infection with early antiretroviral therapy." N Engl J Med 365.6 (2011): 493-505. http://www.ncbi.nlm.nih.gov/pubmed/21767103 http://www.nih.gov/news/health/dec2011/niaid-22.htm
  60. Rizzardi, G. P., De Boer, R. J., Hoover, S., et al. "Predicting the duration of antiviral treatment needed to suppress plasma HIV-1 RNA." J Clin Invest105.6 (2000): 777-82. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC377467/
  61. Aberg, J. A., Kaplan, J. E., Libman, H., et al. "Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus: 2009 Update by the HIV Medicine Association of the Infectious Diseases Society of America." Clin Infect Dis49.5 (2009): 651-81.
  62. Cervia, J. S., Smith, M. A. "Enfuvirtide (T-20): A Novel Human Immunodeficiency Virus Type 1 Fusion Inhibitor." Clin Infect Dis 37.8 (2003): 1102-6.
  63. Jegede, O., Babu, J., Di Santo, R., et al. "HIV Type 1 Integrase Inhibitors: from Basic Research to Clinical Implications." AIDS Rev 10.3 (2008): 172-89.
  64. Yazdanpanah, Y., Fagard, C., Descamps, D., et al. "High Rate of Virologic Suppression with Raltegravir Plus Etravirine and Darunavir/Ritonavir among Treatment-Experienced Patients Infected with Multidrug-Resistant HIV: Results of the ANRS 139 TRIO Trial." Clin Infect Dis 49.9 (2009): 1441-9.
  65. Graham, S. M., Masese, L., Gitau, R., et al. "Antiretroviral Adherence and Development of Drug Resistance Are the Strongest Predictors of Genital HIV-1 Shedding Among Women Initiating Treatment." J Infect Dis 202.10 (2010):1538-42.
  66. Lockman, S., Hughes, M. D., McIntyre, J., et al. "Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure." N Engl J Med 363.16 (2010): 1499-509.
  67. Volberding, P. A., Deeks, S. G. "Antiretroviral Therapy and Management of HIV Infection." Lancet 376.9734 (2010): 49-62.
  68. Sharma B. "Anti-HIV-1 Drug Toxicity and Management Strategies." Neurobehav HIV Med (2011): 327-40.
  69. McCord A et al. Milk thistle may help improve liver health in people with HIV and hepatitis C. Proj Inf Perspect. 2008 Sep;(46):18. No abstract available.
  70. Payer BA, Reiberger T, Rutter K, et al. Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV-HCV coinfected patient. J Clin Virol. 49.2 (2010):131-3.
  71. Goepp J. The Drug Virtually Everyone Should Ask their Doctor About. Life Extension Magazine, Nov. 2010.
  72. Fitch K et al. Effects of Lifestyle Modification and Metformin on Atherosclerotic Indices among HIV-Infected Patients with the Metabolic Syndrome. AIDS. 2011 Dec 7. [Epub ahead of print]
  73. Diehl La et al. Metformin increases HDL3-cholesterol and decreases subcutaneous truncal fat in nondiabetic patients with HIV-associated lipodystrophy. AIDS Patient Care STDS. 2008 Oct;22(10):779-86.
  74. van Wijk JP, Hoepelman AI, de Koning EJ, et al. Differential effects of rosiglitazone and metformin on postprandial lipemia in patients with HIV-lipodystrophy. Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):228-33.
  75. Hadigan C et al. Metformin in the treatment of HIV lipodystrophy syndrome: A randomized controlled trial. JAMA. 2000 Jul 26;284(4):472-7.
  76. Henry-Vitrac C, Ibarra A, Roller M, Merillon JM, Vitrac X. Contribution of chlorogenic acids to the inhibition of human hepatic glucose-6-phosphatase activity in vitro by Svetol, a standardized decaffeinated green coffee extract. J Agric Food Chem. 2010 Apr 14;58(7):4141-4.
  77. Andrade-Cetto A, Vazquez RC. Gluconeogenesis inhibition and phytochemical composition of two Cecropia species. J Ethnopharmacol. 2010 Jul 6;130(1):93-7.
  78. Rodriguez de Sotillo DV, Hadley M, Sotillo JE. Insulin receptor exon 11+/- is expressed in Zucker (fa/fa) rats, and chlorogenic acid modifies their plasma insulin and liver protein and DNA. J Nutr Biochem. 2006 Jan;17(1):63-71.
  79. Nagendran MV. Effect of green coffee bean extract (GCE), High in Chlorogenic Acids, on Glucose Metabolism. Poster presentation number: 45-LB-P. Obesity 2011, the 29th Annual Scientific Meeting of the Obesity Society. Orlando, Florida. October 1-5, 2011.
  80. Diallo M et al. Prospect of IL-2, IL-7, IL-15 and IL-21 for HIV immune-based therapy. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Nov;36(11):1037-45.
  81. Sirskyj D et al. Disruption of the gamma c cytokine network in T cells during HIV infection. Cytokine. 2008 Jul;43(1):1-14. Epub 2008 Apr 15.
  82. Martin BK et al. ty of life in a clinical trial of highly active antiretroviral therapy alone or with intravenous or subcutaneous interleukin-2 administration. J Acquir Immune Defic Syndr. 2005 Dec 1;40(4):428-33.
  83. Sabbatini F et al. Qualitative immune modulation by interleukin-2 (IL-2) adjuvant therapy in immunological non responder HIV-infected patients. PLoS One. 2010 Nov 29;5(11):e14119.
  84. Chahroudi A et al. Interleukin-7 in HIV pathogenesis and therapy. Eur Cytokine Netw. 2010 Sep;21(3):202-7. Epub 2010 Aug 20.
  85. Walter J et al. High concentrations of interleukin 15 in breast milk are associated with protection against postnatal HIV transmission. J Infect Dis. 2009 Nov 15;200(10):1498-502.
  86. d’Ettorre G et al. Interleukin-15 in HIV infection: immunological and virological interactions in antiretroviral-naive and -treated patients. AIDS. 2002 Jan 25;16(2):181-8.
  87. Williams LD et al. Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllers. J Virol. 2011 Mar;85(5):2316-24. Epub 2010 Dec 15.
  88. Moreno, S., Miralles, C., Negredo, E., et al. "Disorders of body fat distribution in HIV-1-infected patients." AIDS Rev 11.3 (2009): 126-34. http://www.ncbi.nlm.nih.gov/pubmed/19654854
  89. Stanley, T. L., Grinspoon, S. K. "GH/GHRH Axis in HIV Lipodystrophy." Pituitary 12.2 (2009): 143-52.
  90. Sweeney, L. L., Brennan, A. M., Mantzoros, C. S. "The Role of Adipokines in Relation to HIV Lipodystrophy." AIDS 21.8 (2007): 895-904.
  91. Rietschel, P., Hadigan, C., Corcoran, C., et al. "Assessment of Growth Hormone Dynamics in Human Immunodeficiency Virus-Related Lipodystrophy." J Clin Endocrinol Metab 86.2 (2001): 504-10.
  92. Grunfield, C., Thompson, M., Brown, S.J., et al. “Recombinant human growth hormone to treat HIV-associated adipose redistribution syndrome: 12 week induction and 24-week maintenance therapy.” J Acquir Immune Defic Syndr 45.3 (2007):286-97.
  93. Lo, J., You, S. M., Wei, J., et al. "Relationship of Peak Growth Hormone to Cardiovascular Parameters, Waist Circumference, Lipids and Glucose in HIV-Infected Patients and Healthy Adults." Clin Endocrinol (Oxf) 71.6 (2009): 815-22. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889024/
  94. Benedini, S., Terruzzi, I., Lazzarin, A., et al. "Recombinant Human Growth Hormone: Rationale for Use in the Treatment of HIV-Associated Lipodystrophy." BioDrugs 22.2 (2008): 101-12.
  95. Sivakumar, T., Mechanic, O., Fehmie, D. A., et al. "Growth hormone axis treatments for HIV-associated lipodystrophy: a systematic review of placebo-controlled trials." HIV Med 12.8 (2011): 453-62. http://www.medscape.com/viewarticle/748585
  96. Leung, V. L., Glesby, M. J. "Pathogenesis and Treatment of HIV Lipohypertrophy." Curr Opin Infect Dis 24.1 (2011): 43-9.
  97. Brown, M. "Skeletal Muscle and Bone: Effect of Sex Steroids and Aging." Adv Physiol Educ 32.2 (2008): 120-6. http://www.ncbi.nlm.nih.gov/pubmed/18539850,
  98. Blouin, K., Boivin, A., Tchernof, A. "Androgens and Body Fat Distribution." J Steroid Biochem Mol Biol 108.3-5 (2008): 272-80.
  99. Lang, T. F. "The Bone-Muscle Relationship in Men and Women." J Osteoporos 2011 (2011): 702735.
  100. Rochira, V., Zirilli, L., Orlando, G., et al. "Premature Decline of Serum Total Testosterone in HIV-Infected Men in the HAART-Era." PLoS One 6.12 (2011): e28512. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028512
  101. Dobs A. "Role of Testosterone in Maintaining Lean Body Mass and Bone Density in HIV-Infected Patients." Int J Impot Res 15 Suppl 4 (2003): S21-5.
  102. Rietschel, P., Corcoran, C., Stanley, T., et al. "Prevalence of Hypogonadism among Men with Weight Loss Related to Human Immunodeficiency Virus Infection Who Were Receiving Highly Active Antiretroviral Therapy." Clin Infect Dis 31.5 (2000): 1240-4.
  103. Kopicko, J. J., Momodu, I., Adedokun A., et al. "Characteristics of HIV-Infected Men With Low Serum Testosterone Levels." Int J STD AIDS 10.12 (1999): 817-20.
  104. Andersen, O., Pedersen, S. B., Svenstrup, B., et al. "Circulating Sex Hormones and Gene Expression of Subcutaneous Adipose Tissue Oestrogen and Alpha-Adrenergic Receptors in HIV-Lipodystrophy: Implications for Fat Distribution." Clin Endocrinol (Oxf) 67.2 (2007): 250-8. http://www.ncbi.nlm.nih.gov/pubmed/17524033
  105. Kong, A., Edmonds, P. "Testosterone Therapy in HIV Wasting Syndrome: Systematic Review and Meta-Analysis." Lancet Infect Dis 2.11 (2002): 692-9. http://www.ncbi.nlm.nih.gov/pubmed/12409050
  106. Johns, K., Beddall, M. J., Corrin, R. C. "Anabolic Steroids for the Treatment of Weight Loss in HIV-Infected Individuals." Cochrane Database Syst Rev 4 (2005): CD005483.
  107. Bhasin, S., Parker, R. A., Sattler, F., et al. "Effects of Testosterone Supplementation on Whole Body and Regional Fat Mass and Distribution in Human Immunodeficiency Virus-Infected Men with Abdominal Obesity." J Clin Endocrin Metabl 92.3 (2007): 1049-57.
  108. Christeff N et al. Serum cortisol and DHEA concentrations during HIV infection. Psychoneuroendocrinology. 1997;22 Suppl 1:S11-8.
  109. TreatmentUpdate. [no authors listed] Changes in DHEA levels in people taking anti-HIV therapy. TreatmentUpdate. 2001 Winter;12(10):6-7.
  110. Christeff N et al. Longitudinal evolution of HIV-1-associated lipodystrophy is correlated to serum cortisol:DHEA ratio and IFN-alpha. Eur J Clin Invest. 2002 Oct;32(10):775-84.
  111. Abrams DI et al. Dehydroepiandrosterone (DHEA) effects on HIV replication and host immunity: a randomized placebo-controlled study. AIDS Res Hum Retroviruses. 2007 Jan;23(1):77-85.
  112. Poretsky L et al. Metabolic and hormonal effects of oral DHEA in premenopausal women with HIV infection: a randomized, prospective, placebo-controlled pilot study. Horm Metab Res. 2009 Mar;41(3):244-9. Epub 2008 Sep 22.
  113. Rabkin JG et al. Placebo-controlled trial of dehydroepiandrosterone (DHEA) for treatment of nonmajor depression in patients with HIV/AIDS. Am J Psychiatry. 2006 Jan;163(1):59-66.
  114. Clark RA et al. Clinical manifestations and predictors of survival in older women infected with HIV. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Aug 15;15(5):341-5.
  115. Hütter, G., Nowak, D., Mossner, M., et al. "Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation." N Engl J Med. 360.7 (2009): 692-8. http://www.nejm.org/doi/full/10.1056/NEJMoa0802905
  116. Ando, D. Nichol, G. Abst.# H2-794a: "HAART Treatment Interruption following Adoptive Transfer of Zinc Finger Nuclease (ZFN) Modified Autologous CD4 T-cells (SB-728-T) to HIV-infected Subjects Demonstrates Durable Engraftment and Suppression of Viral Load." Late-Breaker Poster Session: Antiretroviral Therapy of HIV-1 Infection, 11:15 a.m. - 1:15 p.m. CT, Sunday, September 18, 2011. http://bit.ly/zoAOm0 http://www.technologyreview.com/biomedicine/38630/
  117. Fisher, K. "Wasting and Lipodystrophy in Patients Infected with HIV: A Practical Approach in Clinical Practice." AIDS Read 11.3 (2001): 132-3, 137-40, 147. http://www.medscape.com/viewarticle/410373
  118. Somarriba, G., Neri, D., Schaefer, N., Miller, T.L. "The Effect of Aging, Nutrition, and Exercise during HIV Infection." HIV AIDS (Aukl) 2 (2010): 191-201. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218696
  119. Ahoua, L., Umutoni, C., Huerga, H., et al. "Nutrition Outcomes of HIV-Infected Malnourished Adults Treated With Ready-to-Use Therapeutic Foodin Sub-Saharan Africa: a Longitudinal Study." J Int AIDS Soc 14 (2011):2. http://www.jiasociety.org/content/14/1/2
  120. Gleeson, M., McFarlin, B., Flynn, M. "Exercise and Toll-Like Receptors." Exerc Immunol Rev 12 (2006): 34-53.
  121. Gleeson, M. "Immune Function in Sport and Exercise." J Appl Physiol 103.2 (2007): 693-9. http://jap.physiology.org/content/103/2/693.full
  122. Kawai, K., Kupka, R., Mugusi, F., et al. "A Randomized Trial to Determine the Optimal Dosage of Multivitamin Supplements to Reduceadverse Pregnancy Outcomes Among HIV-Infected Women in Tanzania." Am J Clin Nutr 91.2 (2010): 391-7. http://www.ajcn.org/content/91/2/391.full
  123. Fawzi, W. W., Msamanga, G. I., Spiegelman, D., et al. "A randomized trial of multivitamin supplements and HIV disease progression and mortality." N Engl J Med 351.1 (2004): 23-32. http://www.ncbi.nlm.nih.gov/pubmed/15229304?dopt=Abstract
  124. Mehta, S., Giovannucci, E., Mugusi, F. M., et al. "Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality." PLoS One 5.1 (2010b): e8770.
  125. Tang, A. M., Graham, N. M., Kirby, A. J., et al. "Dietary Micronutrient Intake and Risk of Progression to Acquired Immunodeficiency Syndrome (AIDS) In Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Homosexual Men." Am J Epidemiol 138.11 (1993): 937-51. http://www.ncbi.nlm.nih.gov/pubmed/7903021
  126. Abrams, B., Duncan, D., Hertz-Picciotto, I. "A Prospective Study of Dietary Intake and Acquired Immune Deficiency Syndrome in HIV-Seropositive Homosexual Men." J Acquir Immune Defic Syndr 6.8 (1993): 949-58. http://www.ncbi.nlm.nih.gov/pubmed/8100273?dopt=Abstract
  127. Fawzi, W. W., Msamanga, G. I., Spiegelman, D, et al. "Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania." Lancet 351.9114 (1998): 1477-82.
  128. Mda, S., van Raaij, J. M., Macintyre, U. E., de Villiers, F. P., Kok, F. J. "Improved Appetite after Multi-Micronutrient Supplementation for Six Months in HIV-Infected South African Children." Appetite 54.1 (2010a): 150-5. http://www.sciencedirect.com/science/article/pii/S0195666309006370
  129. Semba, R. D., Ndugwa, C., Perry, R. T., et al. "Effect of Periodic Vitamin A Supplementation of Mortality and Morbidity of Human Immunodeficiency Virus-Infected Children in Uganda: A Controlled Clinical Trial." Nutrition 21.1 (2005): 25-31. http://www.ncbi.nlm.nih.gov/pubmed/15661475
  130. Fawzi, W. W., Mbise, R. L., Hertzmark, E., et al. "A Randomized Trial of Vitamin a Supplements in Relation to Mortality Among Human Immunodeficiency Virus-Infected and Uninfected Children in Tanzania." Pediatr Infect Dis J 18.2 (1999): 127-33. http://journals.lww.com/pidj/Abstract/1999/02000/A_randomized_trial_of_vitamin_A_supplements_in.9.aspx
  131. Coutsoudis, A., Bobat, R. A., Coovadia, H. M., et al. "The Effects of Vitamin A Supplementation on the Morbidity of Children Born to HIV-Infected Women." Am J Public Health 85.8 Pt 1 (1995): 1076-81. http://www.ncbi.nlm.nih.gov/pubmed/7625499
  132. Villamor, R., Mugusi, F., Urassa, W., et al. "A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis." J Infect Dis 197.11 (2008): 1499-505. http://www.ncbi.nlm.nih.gov/pubmed/18471061 VIT SUPPS and TB
  133. Mda, S., van Raaij, J. M., de Villiers, F. P., et al. "Short-Term Micronutrient Supplementation Reduces the Duration of Pneumonia and Diarrheal Episodes in HIV-Infected Children." J Nutr 140.5 (2010b): 969-74.
  134. Valko, M., Leibfritz, D., Moncol, J., et al. "Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease." Int J Biochem Cell Biol 39.1 (2007): 44-84. http://www.pinnaclife.com/assets/files/pdf/References/Diabetes/Human-disease.pdf
  135. Oguntibeju, O. O., Esterhuyse A. J., Trute E. J. "Possible Role of Red Palm Oil Supplementation in Reducing Oxidative Stress in HIV/AIDS and TB Patients: a Review." J Medicinal Plants Res 4.3 (2010): 188-196. http://www.academicjournals.org/JMPR/PDF/pdf2010/4Feb/Oguntibeju%20et%20al.pdf
  136. Srinivas, A., Dias, B. F. "Antioxidants in HIV Positive Children." Indian J Pediatr 75.4 (2008): 347-50.
  137. Wanchu, A., Rana, S. V., Pallikkuth, S., Sachdeva, R. K. "Short Communication: Oxidative Stress in HIV-Infected Individuals: a Cross-Sectional Study." AIDS Res Hum Retroviruses 25.12 (2009): 1307-11.
  138. Aquaro, S. Scopelliti, F., Pollicita, M., Perno, C. F. "Oxidative Stress and HIV Infection: Target Pathways for Novel Therapies?" Future HIV Therapy 2.4 (2008): 327-338.
  139. Kashou, A. H., Agarwal, A. "Oxidants and Antioxidants in the Pathogenesis of HIV/AIDS." The Open Reprod Sci J 3 (2011): 154-161. http://benthamscience.com/open/torsj/articles/V003/SI0001TORSJ/154TORSJ.pdf
  140. Bautista, A. P. "Free Radicals, Chemokines, and Cell Injury in HIV-1 and SIV Infections and Alcoholic Hepatitis." Free Radic Biol Med 31.12 (2001): 1527-32. http://www.ncbi.nlm.nih.gov/pubmed/11744325
  141. Deresz, L. F., Sprinz, E., Kramer, A. S., et al. "Regulation of Oxidative Stress in Response to Acute Aerobic and Resistance Exercise in HIV-Infected Subjects: a Case-Control Study." AIDS Care 22.11 (2010): 1410-7.
  142. Ogunro, P. S., Ogungbamigbe, T. O., Ajala, M. O., et al. "Total Antioxidant Status and Lipid Peroxidation in HIV-1 Infected Patients in a Rural Area of South Western Nigeria." Afr J Med Sci 34.3 (2005): 221-5. http://www.ncbi.nlm.nih.gov/pubmed/16749352
  143. Pasupathi P, Ramchandran T, Sindhu PJ, et al. “Enhanced Oxidative Stress Markers and Antioxidant Imbalance in HIV Infection and AIDS Patients. 2009;1(2): 370-80. http://www.banglajol.info/bd/index.php/JSR/article/viewArticle/2295
  144. Bilbis, L. S., Idowu, D. B., Saidu, Y., et al. "Serum Levels of Antioxidant Vitamins and Mineral Elements of Human Immunodeficiency Viruspositive Subjects in Sokoto, Nigeria." Ann Afr Med 9.4 (2010): 235-9.
  145. Wang, X., Chai, H., Yao, Q., et al. "Molecular Mechanisms of HIV Protease Inhibitor-Induced Endothelial Dysfunction." J Acquir Immune Defic Syndr 44.5 (2007): 493-9. http://www.ncbi.nlm.nih.gov/pubmed/17245228
  146. Masiá, M., Padilla, S., Bernal, E., et al. "Influence of Antiretroviral Therapy on Oxidative Stress and Cardiovascular Risk: A Prospective Cross-Sectional Study in HIV-Infected Patients." Clin Ther 29.7 (2007): 1448-55. http://www.ncbi.nlm.nih.gov/pubmed/17825696
  147. Ngondi, J. L., Oben, J., Forkah, D. M., et al. "The Effect of Different Combination Therapies on Oxidative Stress Markers in HIV Infected Patients in Cameroon." AIDS Res Ther 3 (2006): 19.
  148. Tang, A. M., Lanzillotti, J., Hendricks, K, et al. "Micronutrients: Current Issues for HIV Care Providers." AIDS 19.9 (2005): 847-61. TANG 2005
  149. Drain, P. K., Kupka, R., Mugusi, F., et al. "Micronutrients in HIV-Positive Persons Receiving Highly Active Antiretroviral Therapy." Am J Clin Nutr 85.2 (2007): 333-45.
  150. Allard, J. P., Aghdassi, E., Chau, J., et al. "Effects of Vitamin E and C Supplementation on Oxidative Stress and Viral Load in HIV-Infected Subjects." AIDS 12.13 (1998): 1653-9. http://www.ncbi.nlm.nih.gov/pubmed/9764785
  151. Tang, A. M., Graham, N. M., Semba, R. D., et al. "Association between Serum Vitamin A and E Levels and HIV-1 Disease Progression." AIDS 11.5 (1997): 613-20.
  152. Austin, J., Singhal, N., Voigt, R., et al. "A Community Randomized Controlled Clinical Trial of Mixed Carotenoids and Micronutrient Supplementation of Patients with Acquired Immunodeficiency Syndrome." Eur J Clin Nutr 60.11 (2006): 1266-76.
  153. Kaiser, J. D., Campa, A. M., Ondercin, J. P., et al. "Micronutrient Supplementation Increases CD4 Count in HIV-Infected Individuals on Highly Active Antiretroviral Therapy: A Prospective, Double-Blinded, Placebo-Controlled Trial." J Acquir Immune Defic Syndr 42.5 (2006): 523-8. http://www.ncbi.nlm.nih.gov/pubmed/16868496
  154. Markovic, I., Clouse, K. A. "Recent Advances in Understanding the Molecular of HIV-1 Entry and Fusion: Revisiting Current Targets and Considering New Options for Therapeutic Intervention." Curr HIV Res 2.3 (2004): 223-34.
  155. Morris, D., Guerra, C., Donohue, C., et al. "Unveiling the Mechanisms for Decreased Glutathione in Individuals with HIV Infection." Clin Dev Immunol 2012 (2012). http://www.hindawi.com/journals/cdi/2012/734125/
  156. Herzenberg, L. A., De Rosa, S. C., Dubs, J. G., et al. "Glutathione Deficiency Is Associated with Impaired Survival in HIV Disease." Proc Natl Acad Sci U S A 94.5 (1997): 1967-72. http://www.pnas.org/content/94/5/1967.full.pdf
  157. McComsey, G., Southwell, H., Gripshover B, et al. "Effect Of Antioxidants On Glucose Metabolism And Plasma Lipids In HIV-Infected Subjects With Lipoatrophy." J Acquir Immune Defic Syndr33.5 (2003): 605-7.
  158. Standish, L. J., Greene, K. B., Bain, S., et al. "Alternative Medicine Use in HIV-Positive Men and Women: Demographics, Utilization Patterns and Health Status." AIDS Care13.2 (2001): 197-208.
  159. Tantcheva, L. P., Stoeva, E. S., Galabov, A. S., et al. "Effect of Vitamin E and Vitamin C Combination on Experimental Influenza Virus Infection." Methods Find Exp Clin Pharmacol25.4 (2003): 259-64.
  160. Atkuri KR, Mantovani JJ, Herzenberg LA, et al. N-Acetylcysteine—a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 7.4 (2007): 355-9.
  161. De Rosa, S. C., Zaretsky, M. D., Dubs, J. G., et al. "N-Acetylcysteine Replenishes Glutathione in HIV Infection." Eur J Clin Invest 30.10 (2000): 915-29. http://www.ncbi.nlm.nih.gov/pubmed/11029607
  162. Visalli, V., Muscoli, C., Sacco, I., et al. "N-Acetylcysteine Prevents HIV Gp 120-Related Damage of Human Cultured Astrocytes: Correlation with Glutamine Synthase Dysfunction." BMC Neurosci 8 (2007): 106.
  163. Li, S., Hattori, T., Kodama, E. N. "Epigallocatechin Gallate Inhibits the HIV Reverse Transcription Step." Antivir Chem Chemother 21.6 (2011): 239-43. http://www.ncbi.nlm.nih.gov/pubmed/21730371
  164. Kawai, K., Tsuno, N. H., Kitayama, J., et al. "Epigallocatechin Gallate, the Main Component of Tea Polyphenol, Binds to CD4 and Interferes with Gp120 Binding." J Allergy Clin Immunol 112.5 (2003): 951-7. http://www.ncbi.nlm.nih.gov/pubmed/14610487
  165. Nance, C. L., Siwak, E. B., Shearer, W. T. "Preclinical Development of the Green Tea Catechin, Epigallocatechin Gallate, as an HIV-1 Therapy." J Allergy Clin Immunol 123. 2 (2009): 459-65.
  166. Williamson, M. P., McCormick, T. G., Nance, C. L., et al. "Epigallocatechin Gallate, the Main Polyphenol in Green Tea, Binds to the T-Cell Receptor, CD4: Potential for HIV-1 Therapy." J Allergy Clin Immunol 118.6 (2006): 1369-74. http://www.ncbi.nlm.nih.gov/pubmed/17157668
  167. Hauber, I., Hohenberg, H., Holstermann, B., et al. "The Main Green Tea Polyphenol Epigallocatechin-3-Gallate Counteracts Semen-Mediated Enhancement of HIV Infection." Proc Natl Acad Sci U S A 106.22 (2009): 9033-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683882/?tool=pubmed
  168. Jariwalla, R. J., Gangapurkar, B., Pandit, A., et al. "Micronutrient cooperation in the suppression of HIV production in chronically and latently infected cells." Mol Med Report 3.3 (2010): 377-85.
  169. Shay, K. P., Moreau, R. F., Smith, E. J. , et al. " Alpha-Lipoic Acid as a Dietary Supplement: Molecular Mechanisms and Therapeutic Potential." Biochim Biophys Acta 1790.10 (2009): 1149-60. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756298/
  170. Zhang, W.J., Wei, H., Hagen, T., et al. "Alpha-Lipoic Acid Attenuates LPS-Induced Inflammatory Responses By Activating the Phosphoinositide 3-Kinase/Akt Signaling Pathway." Proc Natl Acad Sci USA 104.10 (2007): 4077-82. ZHANG 2007
  171. Jariwalla, R. J., Lalezari, J., Cenko, D., et al. "Restoration of Blood Total Glutathione Status and Lymphocyte Function Following Alpha-Lipoic Acid Supplementation in Patients with HIV Infection." J Altern Complement Med 14.2 (2008): 139-46. http://www.ncbi.nlm.nih.gov/pubmed/18315507
  172. Baur, A., Harrer, T., Peukert, M., et al. "Alpha-Lipoic Acid Is an Effective Inhibitor of Human Immuno-Deficiency Virus (HIV-1) Replication." Klin Wochenschr 69.15 (1991): 722-4. http://www.ncbi.nlm.nih.gov/pubmed/1724477
  173. Suzuki, Y. J., Aggarwal, B. B., Packer, L. " Alpha-Lipoic Acid Is a Potent Inhibitor of NF-Kappa B Activation in Human T Cells." Biochem Biophys Res Commun 189.3 (1992): 1709-15. http://www.ncbi.nlm.nih.gov/pubmed/1482376
  174. Merin, J. P., Matsuyama, M., Kira, T., et al. "Alpha-Lipoic Acid Blocks HIV-1 LTR-Dependent Expression of Hygromycin Resistance in THP-1 Stable Transformants." FEBS Lett 394.1 (1996): 9-13. http://www.ncbi.nlm.nih.gov/pubmed/8925935
  175. Youle, M. "Acetyl-L-Carnitine in HIV-Associated Antiretroviral Toxic Neuropathy." CNS Drugs 21 Suppl 1 (2007a): 25-30; discussion 45-6. http://www.ncbi.nlm.nih.gov/pubmed/17696590
  176. Hart, A. M., Wilson, A. D., Montovani, C., et al. "Acetyl-L-Carnitine: a Pathogenesis Based Treatment for HIV-Associated Antiretroviral Toxic Neuropathy." AIDS 18.11 (2004): 1549-60. http://www.ncbi.nlm.nih.gov/pubmed/15238773
  177. Osio, M., Muscia, F., Zampini, L., et al. "Acetyl-L-Carnitine in the Treatment of Painful Antiretroviral Toxic Neuropathy in Human Immunodeficiency Virus Patients: An Open Label Study." J Peripher Nerv Syst 11.1 (2006): 72-6. http://www.ncbi.nlm.nih.gov/pubmed/16519785
  178. Youle, M., Osio, M, ALCAR Study Group. "A Double-Blind, Parallel-Group, Placebo-Controlled, Multicentre Study of Acetyl L-Carnitine in the Symptomatic Treatment of Antiretroviral Toxic Neuropathy in Patients with HIV-1 Infection." HIV Med 8.4 (2007b): 241-50.
  179. Herzmann, C., Johnson, M. A., Youle, M. "Long-Term Effect of Acetyl-L-Carnitine for Antiretroviral Toxic Neuropathy." HIV Clin Trials 6.6 (2005): 344-50. http://www.ncbi.nlm.nih.gov/pubmed/16566084
  180. Valcour, V., Yeh, T. M., Bartt, R., et al. "Acetyl-L-Carnitine and Nucleoside Reverse Transcriptase Inhibitor-Associated Neuropathy in HIV Infection." HIV Med 10.2 (2009): 103-10.
  181. Phillips, T. J., Cherry, C. L., Cox, S., et al. "Pharmacological Treatment of Painful HIV-Associated Sensory Neuropathy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials." PLoS One 5.12 (2010): e14433. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014433
  182. Bikle D. D. "Vitamin D and Immune Function: Understanding Common Pathways." Curr Osteoporos Rep 7.2 (2009): 58-63.
  183. Holick M. F. "High Prevalence of Vitamin D Inadequacy and Implications for Health." Mayo Clin Proc 81.3 (2006): 353-73. http://171.67.112.83/content/81/3/353.full
  184. Rodríguez, M., Daniels, B., Gunawardene, S., et al. "High Frequency of Vitamin D Deficiency in Ambulatory HIV-Positive Patients." AIDS Res Hum Retroviruses. 25.1 (2009): 9-14.
  185. Conrado, T., Miranda-Filho, Dde B., Ximenes, R. A., et al. "Vitamin D Deficiency in HIV-Infected Women on Antiretroviral Therapy Living in the Tropics."J Int Assoc Physicians AIDS Care (Chic)10.4 (2011): 239-45. http://jia.sagepub.com/content/10/4/239.short
  186. Adeyemi, O. M., Agniel, D., French, A.L., et al. "Vitamin D Deficiency in HIV-Infected and HIV-Uninfected Women in the United States." J Acquir Immune Defic Syndr 57.3 (2011): 197-204.
  187. Dao, C. N., Patel, P., Overton, E. T., et al. "Low Vitamin D Among HIV-Infected Adults: Prevalence of and Risk Factors for Low Vitamin D Levels in A Cohort of HIV-Infected Adults And Comparison to Prevalence Among Adults in the US General Population." Clin Infect Dis. 2011 Feb 1;52(3):396-405. http://cid.oxfordjournals.org/content/52/3/396.short
  188. Kim, J. H., Gandhi, V., Psevdos, G., et al. "Evaluation of Vitamin D Levels Among HIV-Infected Patients in New York City. AIDS Res Hum Retroviruses." (2011). [Epub ahead of print]
  189. Fox, J., Peters, B., Prakash, M., et al. "Improvement in Vitamin D Deficiency Following Antiretroviral Regime Change: Results from the MONET Trial." AIDS Res Hum Retroviruses 27.1 (2011): 29-34. http://www.liebertonline.com/doi/abs/10.1089/aid.2010.0081
  190. Gutiérrez, F., Masiá, M. "The Role of HIV and Antiretroviral Therapy in Bone Disease." AIDS Rev 13.2 (2011): 109-18. http://www.aidsreviews.com/files/2011_13_2_109-118.pdf
  191. Guillemi, S., Harris, M., Bondy, G. P., et al. "Prevalence of Bone Mineral Density Abnormalities and Related Risk Factors in an Ambulatory HIV Clinic Population." J Clin Densitom 13.4 (2010): 456-61.
  192. Post F. A. McCloskey, E. V., Compston J. E. "Prevention of Bone Loss and Management of Fracture Risk in HIV-Infected Individuals: Case Studies and Recommendations for Different Patient Subgroups." Future Virol 6.6 (2011): 769-782.
  193. McComsey, G. A., Tebas, P., Shane, E., et al."Bone Disease in HIV Infection: a Practical Review and Recommendations for HIV Care Providers." Clin Infect Dis. 51.8 (2010): 937-46.
  194. Lake, J. E., Adams, J. S. "Vitamin D in HIV-Infected Patients." Curr HIV/AIDS Rep 8 (2011): 133-141.
  195. Conesa-Botella, A., Florence, E., Lynen, L., et al. "Decrease of Vitamin D Concentration in Patients with HIV Infection on A Non Nucleoside Reverse Transcriptase Inhibitor-Containing Regimen." AIDS Res Ther 7 (2010): 40.
  196. Mueller, N. J., Fux, C. A., Ledergerber, B., et al. "High Prevalence of Severe Vitamin D Deficiency in Combined Antiretroviral Therapy-Naive and Successfully Treated Swiss HIV Patients." AIDS 24.8 (2010): 1127–1134.
  197. Van Den Bout-Van Den Beukel, C. J., Fievez, L., Michels, M., et al. "Vitamin D Deficiency among HIV Type 1-Infected Individuals in the Netherlands: Effects of Antiretroviral Therapy." AIDS Res Hum Retroviruses. 2008;24(11):1375–1382.
  198. Stellbrink, H. J., Orkin, C., Arribas, J. R., et al. "Comparison of Changes in Bone Density and Turnover with Abacavir-Lamivudine versus Tenofovir-Emtricitabine in HIV-Infected Adults: 48-Week Results from the ASSERT Study." Clin Infect Dis 51.8 (2010): 963-72.
  199. Carr, A., Hoy, J. "Low Bone Mineral Density with Tenofovir: Does Statistically Significant Mean Clinically Significant?" Clin Infect Dis 51.8 (2010): 973-5.
  200. Grund, B., Peng, G., Gibert. C. L., et al. "Continuous Antiretroviral Therapy Decreases Bone Mineral Density." AIDS 23 (2009): 1519-1529
  201. Gallant, J. E., Staszewski, S., Pozniak, A. L., et al. "Efficacy and Safety of Tenofovir DF Vs Stavudine in Combination Therapy in Antiretroviral Naive Patients: a 3-Year Randomized Trial." JAMA 292 (2004): 191-201.
  202. Childs, K. E., Fishman, S. L., Constable, C., et al. "Short Communication: Inadequate Vitamin D Exacerbates Parathyroid Hormone Elevations in Tenofovir Users." AIDS Res Hum Retroviruses 26.8 (2010): 855-9. http://www.liebertonline.com/doi/abs/10.1089/aid.2009.0308
  203. Welz, T., Childs, K., Ibrahim, F., et al. "Efavirenz is Associated with Severe Vitamin D Deficiency and Increased Alkaline Phosphatase." AIDS 24.12 (2010): 1923-8. http://journals.lww.com/aidsonline/Fulltext/2010/07310/Efavirenz_is_associated _with_severe_vitamin_D.14.aspx?WT.mc_id=HPxADx20100319xMP
  204. Villamor E. "A Potential Role for Vitamin D on HIV Infection?" Nutr Rev 64.5 Pt 1 (2006): 226-33.
  205. Stein, E. M., Yin, M. T., McMahon, D. J., et al. "Vitamin D Deficiency in HIV-Infected Postmenopausal Hispanic and African-American Women." Osteoperos Int 22.2 (2011): 477-87.
  206. Ross, A. C., Judd, S., Kumari, M., et al. "Vitamin D Is Linked to Carotid Intima-Media Thickness and Immune Reconstitution in HIV-Positive Individuals." Antivir Ther 16.4 (2011): 555-63.
  207. Arpadi, S. M., McMahon, D., Abrams, E. J., et al. "Effect of Bimonthly Supplementation with Oral Cholecalciferol on Serum 25-Hydroxyvitamin D Concentrations in HIV-Infected Children and Adolescents." Pediatrics 123.1 (2009): e121-6. http://www.ncbi.nlm.nih.gov/pubmed/19117833
  208. Fryburg, D. A., Mark, R. J., Griffith, B. P., et al. "The Effect of Supplemental Beta-Carotene on Immunologic Indices in Patients with AIDS: a Pilot Study." Yale J Biol Med 68.1-2 (1995): 19-23. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2590840/pdf/yjbm00037-0022.pdf
  209. Hanekom, W. A., Yogev, R., Heald, L. M., et al. "Effect of Vitamin A Therapy on Serologic Responses and Viral Load Changes after Influenza Vaccination in Children Infected with the Human Immunodeficiency Virus." J Pediatr 136.4 (2000): 550-2. http://www.ncbi.nlm.nih.gov/pubmed/10753259
  210. Kennedy-Oji, C., Coutsoudis, A., Kuhn, L., et al. "Effects of Vitamin A Supplementation during Pregnancy and Early Lactation on Body Weight of South African HIV-Infected Women." J Health Popul Nutr 19.3 (2001): 167-76.
  211. Semba, R. D., Miotti, P. G., Chiphangwi, J. D., et al. Maternal vitamin A deficiency and mother-to-child transmission of HIV-1. Lancet 343.8913 (1994): 1593-7. http://www.ncbi.nlm.nih.gov/pubmed/7911919
  212. Villamor, E., Koulinska, I. N., Aboud, S., et al. "Effect of Vitamin Supplements on HIV Shedding in Breast Milk." An J Clin Nutr 92.4 (2010): 881-6. http://www.ajcn.org/content/92/4/881.full
  213. Wiysonge, C. S., Shey, M., Kongnyuy, E. J., et al. "Vitamin A Supplementation for Reducing the Risk of Mother-to-Child Transmission of HIV Infection." Cochrane Database Syst Rev 1 (2011): CD003648.
  214. Kaplan, B. J., Crawford, S. G., Field, C. J., et al. "Vitamins, Minerals, and Mood." Psychol Bull 133.5 (2007): 747-60. http://www.healthwatcher.net/Quackerywatch/Synergy/Kaplan/Research/Vitamins,%20Minerals%20and%20Mood.pdf
  215. Rall, L. C., Meydani, S. N. "Vitamin B6 and Immune Competence. Nutr Rev 51.8 (1993): 217-25. http://www.ncbi.nlm.nih.gov/pubmed/8302491
  216. Tang, A. M., Graham, N. M., Saah, A. J. "Effects of Micronutrient Intake on Survival in Human Immunodeficiency Virus Type 1 Infection." Am J Epidemiol 143.12 (1996): 1244-56. http://aje.oxfordjournals.org/content/143/12/1244.full.pdf
  217. Baum, M. K., Shor-Posner, G., Lu, Y, et al. "Micronutrients and HIV-1 Disease Progression." AIDS 9.9 (1995): 1051-6. http://www.ncbi.nlm.nih.gov/pubmed/8527077
  218. Wall, R., Ross, R. P., Fitzgerald, G. F., et al. "Fatty Acids from Fish: the Anti-Inflammatory Potential of Long-Chain Omega-3 Fatty Acids." Nutr Rev 68.5 (2010): 280-9.
  219. Grinspoon, S., Carr, A. "Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults." N Engl J Med 352.1 (2005): 48-62.
  220. DAD Study Group, Friis-Møller, N., Reiss, P., et al. "Class of antiretroviral drugs and the risk of myocardial infarction." N Engl J Med 356.17 (2007): 1723-35. http://www.nejm.org/doi/full/10.1056/NEJMoa062744
  221. Hellerstein, M. K., Grunfeld, C., Wu, K., et al. "Increased De Novo Hepatic Lipogenesis in Human Immunodeficiency Virus Infection." J Clin End Metab 76 (1993): 559-65.
  222. d'Arminio, A., Sabin, C. A., Phillips, A. N. "Cardio- and Cerebrovascular Events in HIV-Infected Persons." AIDS 18.13 (2004): 1811-7.
  223. Woods, M. N., Wanke, C. A., Ling, P. R., et al. "Effect of a Dietary Intervention and N-3 Fatty Acid Supplementation on Measures of Serum Lipid and Insulin Sensitivity in Persons with HIV." Am J Clin Nutr 90.6 (2009): 1566-78. http://www.ncbi.nlm.nih.gov/pubmed/19846544
  224. Oliveira, J. M., Rondó, P. H. "Omega-3 Fatty Acids and Hypertriglyceridemia in HIV-Infected Subjects on Antiretroviral Therapy: Systematic Review and Meta-Analysis." HIV Clin Trials 12.5 (2011): 268-74.
  225. Peters, B. S., Wierzbicki, A. S., Moyle, G., et al. "The Effect of a 12-Week Course of Omega-3 Polyunsaturated Fatty Acids on Lipid Parameters in Hypertriglyceridemic Adult HIV-infected Patients Undergoing HAART: A Randomized, Placebo-Controlled Pilot Trial." Clin Ther (2011) [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/22212377
  226. Wohl, D. A., Tien, H. C., Busby, M., et al. "Randomized Study of the Safety and Efficacy of Fish Oil (Omega-3 Fatty Acid) Supplementation with Dietary and Exercise Counseling for the Treatment of Antiretroviral Therapy-Associated Hypertriglyceridemia." Clin Infect Dis 41.10 (2005): 1498-504.
  227. Carter, V. M., Woolley, I., Jolley, D., et al. "A Randomised Controlled Trial of Omega-3 Fatty Acid Supplementation for the Treatment of Hypertriglyceridemia in HIV-Infected Males on Highly Active Antiretroviral Therapy." Sex Health 4 (2006): 287-90. http://www.ncbi.nlm.nih.gov/pubmed/17112442
  228. Gerber JG, Kitch DW, Fictenbaum CJ, et al. Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186. J Acquir Immune Defic Syndr. 2008 Apr;47(4):459-66.
  229. De Truchis, P., Kirstetter, M., Perier, A., et al. "Reduction in Triglyceride Level with N-3 Polyunsaturated Fatty Acids in HIV-Infected Patients Taking Potent Antiretroviral Therapy: a Randomized Prospective Study." J Acquir Immune Defic Syndr 44.3 (2007): 278-85.
  230. Marshall, K. "Therapeutic Applications of Whey Protein." Altern Med Rev9.2 (2004): 136-56. http://www.megawecare.co.th/file/research/Therapeutic%20Applications%20of%20Whey%20Protein_36.pdf
  231. Sattler, F. R., Rajicic, N., Mulligan, K., et al. "Evaluation of high-protein supplementation in weight-stable HIV-positive subjects with a history of weight loss: a randomized, double-blind, multicenter trial." Am J Clin Nutr 88.5 (2008): 1313-21. http://www.ncbi.nlm.nih.gov/pubmed/18996868
  232. Micke, P., Beeh, K. M., Buhl. R. "Effects of Long-Term Supplementation with Whey Proteins on Plasma Glutathione Levels of HIV-Infected Patients." Eur J Nutr41.1 (2002): 12-8.
  233. Hummelen, R., Hemsworth, J., Reid, G. "Micronutrients, N-Acetyl Cysteine, Probiotics and Prebiotics, a Review of Effectiveness in Reducing HIV Progression." Nutrients2.6 (2010): 626-651.
  234. van der Strate BW, Beljaars L, et al. Antiviral activities of lactoferrin. Antiviral Res. 2001 Dec;52(3):225-39.
  235. Swart PJ, Kuipers ME, et al. Antiviral effects of milk proteins: acylation results in polyanionic compounds with potent activity against human immunodeficiency virus types 1 and 2 in vitro . AIDS Res Hum Retroviruses. 1996 Jun 10;12(9):769-75.
  236. Swart PJ, Kuipers EM, et al. Lactoferrin: antiviral activity of lactoferrin. Adv Exp Med Biol. 1998;443:205-13.
  237. Berkhout B et al. Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides. Antiviral Res. 2002 Aug;55(2):341-55.
  238. Carthagena L et al. Modulation of HIV Binding to Epithelial Cells and HIV Transfer from Immature Dendritic Cells to CD4 T Lymphocytes by Human Lactoferrin and its Major Exposed LF-33 Peptide. Open Virol J. 2011;5:27-34. Epub 2011 Apr 15.
  239. Defer MC, Dugas B, et al. Impairment of circulating lactoferrin in HIV-1 infection. Cell Mol Biol (Noisy-le-grand). 1995 May;41(3):417-21.
  240. Zuccotti GV et al. Oral lactoferrin in HIV-1 vertically infected children: an observational follow-up of plasma viral load and immune parameters. J Int Med Res. 2006 Jan-Feb;34(1):88-94.
  241. Folkers, K., Langsjoen, P., Nara, Y., et al. "Biochemical Deficiencies of Coenzyme Q10 in HIV-Infection and Exploratory Treatment." Biochem Biophys Res Commun 153.2 (1988): 888-96. http://www.ncbi.nlm.nih.gov/pubmed/3382410
  242. Folkers, K., Hanioka, T., Xia, L. J., et al. "Coenzyme Q10 Increases T4/T8 Ratios of Lymphocytes in Ordinary Subjects and Relevance to Patients Having the AIDS Related Complex." Biochem Biophys Res Commun176.2 (1991): 786-91.
  243. Yamashita S, Yamamoto Y. "Simultaneous Detection of Ubiquinol and Ubiquinone in Human Plasma as a Marker of Oxidative Stress." Anal Biochem250.1 (1997): 66-73.
  244. Batterham, M., Gold, J., Naidoo, D., et al. "A Preliminary Open Label Dose Comparison Using an Antioxidant Regimen to Determine the Effect Onviral Load and Oxidative Stress in Men with HIV/AIDS." Eur J Clin Nutr 55.2 (2001): 107-14. http://www.ncbi.nlm.nih.gov/pubmed/11305623
  245. Rosenfeldt, F. L., Mijch, A., McCrystal, G., et al. "Skeletal myopathy associated with nucleoside reverse transcriptase inhibitor therapy: potential benefit of coenzyme Q10 therapy." Int J STD AIDS 16.12 (2005): 827-9. http://www.ncbi.nlm.nih.gov/pubmed/16336769
  246. Cherry, C. L., Mobarok, M., Wesselingh, S. L., et al. "Ubisol-Aqua: Coenzyme Q10 Prevents Antiretroviral Toxic Neuropathy in an In Vitro Model." Curr HIV Res. 2010 Apr 1;8(3):232-9.
  247. Look, M. P., Rockstroh, J. K., Rao, G. S., et al. "Serum Selenium, Plasma Glutathione (GSH) and Erythrocyte Glutathione Peroxidase (GSH-Px)-Levels in Asymptomatic Versus Symptomatic Human Immunodeficiency Virus-1 (HIV-1)-Infection." Eur J Clin Nutr 51.4 (1997): 266-72. http://www.ncbi.nlm.nih.gov/pubmed/9104578
  248. Hoffmann, P. R., Berry, M. J. "The Influence of Selenium on Immune Responses." Mol Nutr Food Res 52.11 (2008): 1273-80.
  249. Tinggi, U. "Selenium: its role as antioxidant in human health." Environ Health Prev Med 13.2 (2008): 102-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698273/
  250. Baum, M. K., Miguez-Burbano, M. J., et al. "Selenium and Interleukins in Persons Infected with Human Immunodeficiency Virus Type 1." J Infect Dis 182 Suppl 1 (2000): S69-73. http://jid.oxfordjournals.org/content/182/Supplement_1/S69.long
  251. Campa, A., Shor-Posner, G., Indacochea. F., et al. "Mortality Risk in Selenium-Deficient HIV-Positive Children." J Acquir Immune Defic Syndr Hum Retrovirol 20.5 (1999): 508-13. http://www.ncbi.nlm.nih.gov/pubmed/10225235
  252. Shor-Posner, G., Miguez, M. J., Pineda, L. M., et al. "Impact of Selenium Status on the Pathogenesis of Mycobacterial Disease in HIV-1-Infected Drugusers the Era of Highly Active Antiretroviral Therapy." J Acquir Immune Defic Syndr 29.2 (2002): 169-73.
  253. Hori, K., Hatfield, D., Maldarelli, F., et al. "Selenium Supplementation Suppresses Tumor Necrosis Factor Alpha-Induced Human Immunodeficiency Virus Type 1 Replication in Vitro." AIDS Res Hum Retroviruses 13.15 (1997): 1325-32.
  254. Kalantari, P., Narayan, V., Natarajan, S. K., et al. "Thioredoxin Reductase-1 Negatively Regulates HIV-1 Transactivating Protein Tat-Dependent Transcription in Human Macrophages." J Biol Chem 283.48 (2008): 33183-90. NEED LINK
  255. Kupka, R., Mugusi, F., Aboud, S., et al. "Effect of Selenium Supplements on Hemoglobin Concentration and Morbidity among HIV-1-Infectedtanzanian Women." Clin Infect Dis 48.10 (2009): 1475-8.
  256. Burbano X, Miguez-Burbano MJ, McCollister K, et al. Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants. HIV Clin Trials. 3.6 (2002):483-91.
  257. Ferencik, M., Ebringer, L. "Modulatory Effects of Selenium and Zinc in the Immune System."Folia Microbiol (Praha)48.3 (2003): 417-26.
  258. Rousseau, M. C., Molines, C., Moreau, J, et al. "Influence of Highly Active Antiretroviral Therapy on Micronutrient Profiles in HIV-Infected Patients." Ann Nutr Metab44.5-6 (2000): 212-216.
  259. Baum, M. K., Lai, S., Sales, S., Page, J. B., Campa, A. "Randomized, Controlled Clinical Trial of Zinc Supplementation to Prevent Immunological Failure Inhiv-Infected Adults." Clin Infect Dis 50.12 (2010): 1653-60. http://cid.oxfordjournals.org/content/50/12/1653.short
  260. Mehta, S., Fawzi, W. W. "Micronutrient Supplementation as Adjunct Treatment for HIV-Infected Patients." Clin Infect Dis 50.12 (2010): 1661-3.
  261. Zeng, L., Zhang, L. "Efficacy and Safety of Zinc Supplementation for Adults, Children and Pregnant Women with Hivinfection: Systematic Review." Trop Med Int Health (2011). doi: 10.1111/j.1365-3156.2011.02871.x. [Epub ahead of print] http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3156.2011.02871.x/full
  262. Liao C et al. Tautomerism and magnesium chelation of HIV-1 integrase inhibitors: a theoretical study. ChemMedChem. 2010 Jul 5;5(7):1053-66.
  263. Hooper, L. V., Gordon, J. I. "Commensal Host-Bacterial Relationships in the Gut." Science 292.5519 (2001): 1115-8.
  264. Ley, R. E., Turnbaugh, P. J., Klein, S., et al. "Microbial Ecology: Human Gut Microbes Associated with Obesity." Nature 444.7122 (2006): 1022-3.
  265. Mehandru, S., Tenner-Racz, K., Racz, P., et al. "The Gastrointestinal Tract Is Critical to the Pathogenesis of Acute HIV-1 Infection." J Allergy Clin Immunol 116.2 (2005): 419-22.
  266. Johnson, R. P. "How HIV Guts the Immune System." N Engl J Med 358.21 (2008): 2287-9.
  267. Brenchley JM, Douek DC. HIV infection and the gastrointestinal immune system. Mucosal Immunol. 1.1 (2008): 23-30.
  268. Furrie, E., Macfarlane, S., Kennedy, A., et al. " Synbiotic Therapy (Bifidobacterium Longum/Synergy 1) Initiates Resolution of Inflammation in Patients with Active Ulcerative Colitis: a Randomised Controlled Pilot Trial." Gut 54.2 (2005): 242-9.
  269. O'Mahony, L., McCarthy, J., Kelly, P., et al. "Lactobacillus and Bifidobacterium in Irritable Bowel Syndrome: Symptom Responses and Relationship to Cytokine Profiles." Gastroenterology 128.3 (2005): 541-51.
  270. Braat, H., van den Brande, J., van Tol, E., et al. "Lactobacillus Rhamnosus Induces Peripheral Hyporesponsiveness in Stimulated CD4+ T Cells via Modulation of Dendritic Cell Function." Am J Clin Nutr 80.6 (2004): 1618-25.
  271. Isolauri, E., Majamaa, H., Arvola, T., et al. "Lactobacillus Casei Strain GG Reverses Increased Intestinal Permeability Induced by Cow Milk in Suckling Rats." Gastroenterology 105.6 (1993): 1643-50.
  272. Madsen, K., Cornish, A., Soper, P., et al. "Probiotic Bacteria Enhance Murine and Human Intestinal Epithelial Barrier Function." Gastroenterology 121.3 (2001): 580-91.
  273. Ukena SN, Singh A, Dringenberg U, et al. Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity. PLoS One. 2.12 (2007): e1308.
  274. Trois L, Cardoso EM, Miura E. "Use of Probiotics in HIV-Infected Children: a Randomized Double-Blind Controlled Study." J Trop Pediatr 54.1 (2008): 19-24.
  275. Anukam, K. C., Osazuwa, E. O., Osadolor, H. B., et al. " Yogurt Containing Probiotic Lactobacillus Rhamnosus GR-1 and L. Reuteri RC-14 Helps Resolve Moderate Diarrhea and Increases CD4 Count in HIV/AIDS Patients." J Clin Gastroenterol 42.3 (2008): 239-43.
  276. Irvine, S. L., Hummelen, R., Hekmat, S., et al. "Probiotic Yogurt Consumption Is Associated with an Increase of CD4 Count among People Living with HIV/AIDS." J Clin Gastroenterol 44.9 (2010): e201-5.
  277. Hummelen, R., Hemsworth, J., Changalucha, J., et al. "Effect of Micronutrient and Probiotic Fortified Yogurt on Immune-Function of Anti-Retroviral Therapy Naïve HIV Patients." Nutrients3 (2011): 897-909.
  278. Sanodiya BS, Thakur GS, Baghel RK, et al. Ganoderma lucidum: a potent pharmacological macrofungus. Current pharmaceutical biotechnology. Dec 2009;10(8):717-742.
  279. Batra P, Sharma AK, Khajuria R. Probing Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (higher Basidiomycetes): a bitter mushroom with amazing health benefits. International journal of medicinal mushrooms. 2013;15(2):127-143.
  280. Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. The Cochrane database of systematic reviews. 2012;6:CD007731.
  281. Lu YZ, Wu XX, Chen S, et al. [Effectiveness of Ganoderma lucidum preparation in treating simian acquired immune deficiency syndrome]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae. Jun 2011;33(3):318-324.
  282. Boh B. Ganoderma lucidum: a potential for biotechnological production of anti-cancer and immunomodulatory drugs. Recent patents on anti-cancer drug discovery. Sep 2013;8(3):255-287.
  283. Gill BS, Sharma P, Kumar R, Kumar S. Misconstrued versatility of Ganoderma lucidum: a key player in multi-targeted cellular signaling. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. Mar 2016;37(3):2789-2804.
  284. Kladar NV, Gavaric NS, Bozin BN. Ganoderma: insights into anticancer effects. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). Aug 27 2015.
  285. el-Mekkawy S, Meselhy MR, Nakamura N, et al. Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum. Phytochemistry. Nov 1998;49(6):1651-1657.
  286. Min BS, Nakamura N, Miyashiro H, et al. Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Chemical & pharmaceutical bulletin. Oct 1998;46(10):1607-1612.
  287. Akbar R, Yam WK. Interaction of ganoderic acid on HIV related target: molecular docking studies. Bioinformation. 2011;7(8):413-417.
  288. Lin ZB. Cellular and molecular mechanisms of immuno-modulation by Ganoderma lucidum. Journal of pharmacological sciences. Oct 2005;99(2):144-153.
  289. Guggenheim AG, Wright KM, Zwickey HL. Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology. Integrative medicine (Encinitas, Calif.). Feb 2014;13(1):32-44.