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