HIV

In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids.^[5][6] Non-sexual transmission can occur from an infected mother to her infant during pregnancy, during childbirth by exposure to her blood or vaginal fluid, and through breast milk.^{[7][8][9][10]} Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. Research has shown (for both same-sex and opposite-sex couples) that HIV is untransmittable through condomless sexual intercourse if the HIV-positive partner has a consistently undetectable viral load.^[5][6]


HIV infects vital cells in the human immune system, such as helper T cells (specifically CD4⁺ T cells), macrophages, and dendritic cells.^[11] HIV infection leads to low levels of CD4⁺ T cells through a number of mechanisms, including pyroptosis of abortively infected T cells,^[12] apoptosis of uninfected bystander cells,^[13] direct viral killing of infected cells, and killing of infected CD4⁺ T cells by CD8⁺ cytotoxic lymphocytes that recognize infected cells.^[14] When CD4⁺ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to the development of AIDS.

Many HIV-positive people are unaware that they are infected with the virus.^[113] For example, in 2001 less than 1% of the sexually active urban population in Africa had been tested, and this proportion is even lower in rural populations.^[113] Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or received their test results.^[113] Again, this proportion is even lower in rural health facilities.^[113] Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV.^[114]


HIV-1 testing is initially done using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a non-reactive result from the initial ELISA are considered HIV-negative, unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate.^[115] If the result of either duplicate test is reactive, the specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., a polymerase chain reaction (PCR), western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or PCR or reactive by western blot are considered HIV-positive and indicative of HIV infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate western blot result, which may be either an incomplete antibody response to HIV in an infected person or nonspecific reactions in an uninfected person.^[116]


Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. In general, a second specimen should be collected more than a month later and retested for persons with indeterminate western blot results. Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations.^[115] In addition, a few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection.


Modern HIV testing is extremely accurate, when the window period is taken into consideration. A single screening test is correct more than 99% of the time.^[118] The chance of a false-positive result in a standard two-step testing protocol is estimated to be about 1 in 250,000 in a low risk population.^[119] Testing post-exposure is recommended immediately and then at six weeks, three months, and six months.^[120]


The latest recommendations of the US Centers for Disease Control and Prevention (CDC) show that HIV testing must start with an immunoassay combination test for HIV-1 and HIV-2 antibodies and p24 antigen. A negative result rules out HIV exposure, while a positive one must be followed by an HIV-1/2 antibody differentiation immunoassay to detect which antibodies are present. This gives rise to four possible scenarios: