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 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
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.
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