Human Immunodeficiency (HIV)
Human immunodeficiency virus (HIV) is a sexually transmitted lentivirus that causes acquired immunodeficiency syndrome (AIDS), a condition that leads to progressive failure of the immune system. It is spread through contact with blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, or breast milk of a person with HIV. If left untreated, it is almost always fatal.
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Human Immunodeficiency (HIV)
There are two major types of HIV, type 1 (HIV-1) and type 2 (HIV-2). HIV-1 viruses are further divided into groups M, N, O, P. Group M viruses are the most common group and are predominately responsible for the AIDS pandemic. Group M is further subdivided into clades based on their genetic sequences, which tend to concentrate within specific geographic regions. The clade that an individual becomes infected with can be a major factor in the rate of progression to AIDS; specifically clades C, D and G are 8 times more likely to develop AIDS.
HIV-2 is mostly found in West Africa and it is also divided into groups (A to H). It is less easily transmitted than HIV-1 and the time between infection and symptoms tends to be longer. Despite its relative geographic confinement, HIV-2 should be considered in all patients exhibiting symptoms of HIV.
HIV is divided into three main stages:
Acute Retroviral Syndrome: Early symptoms of HIV are defined as acute retroviral syndrome and they appear 3-6 weeks after infection and can easily be confused with the symptoms of the flu or other milder diseases. As a result, most infections remain undiagnosed until they progress to more advanced stages.
Clinical Latency (inactivity or dormancy): This period is sometimes called asymptomatic HIV infection or chronic HIV infection. During this phase HIV is active but reproduces at very low levels. People who are on antiretroviral therapy may live with clinical latency for several decades. Toward the middle and end of this period, the viral load begins to rise and the CD4+ cell count begins to drop. The World Health Organization (WHO) sub-classifies this period into three stages based on the CD4+ cell count of the individual:
STAGE 1: the CD4+ cell count is at least 500 cells per microliter
STAGE 2: the CD4+ cell count is 350 to 499
STAGE 3 (advanced HIV disease, or AHD): The CD4+ cell count is 200 to 349
AIDS (Acquired Immunodeficiency Syndrome): This is the stage of infection that occurs when the immune system is badly damaged and an infected individual become vulnerable to opportunistic illnesses. The CD4+ cell count is less than 200 or the percent of CD4+ cells is less than 15% of all lymphocytes. Without treatment, people who are diagnosed with AIDS typically survive about 3 years. Once a dangerous opportunistic illness is acquired, life expectancy without treatment falls to about 1 year.
Laboratory diagnosis is the only way to confirm an HIV infection and there are specific serologic markers that can be detected early in the course of an infection:
- HIV RNA: detectable by molecular methods, 11 days from the time of HIV infection
- HIV-1 P24 ANTIGEN: detectable 16 days from the time of infection
- HIV ANTIBODIES: detectable 22 days from the time of infection.
During the early infection stage (acute retroviral syndrome) the flu-like symptoms are accompanied by a burst of viral replication that can be detected in the blood. The detection of p24 antigen (viral capsid protein) is directly correlated to the amount of virus (viral load) circulating in the infected individual.
Antibodies against specific HIV proteins and glycoproteins (e.g. p24, gp41, gp120) are produced between 2-8 weeks after infection and remain detectable in the blood thereafter.
The screening test most widely used to detect exposure to HIV is the “HIV Antibody Test”. The first test was approved in 1985 by the FDA and it still remains one of the WHO recommended HIV diagnostics. Advances in technologies and critical reagents have enabled the development of new generation HIV Antibody Tests, which are able to detect an infected individual earlier and with greater accuracy. The 4th generation HIV Antibody Test is capable of diagnosing an HIV infection 3-4 weeks after transmission by simultaneously detecting both HIV antibody and p24 antigen. In addition, many of these tests can also distinguish between acute and established HIV infections, as well as detect antibodies to HIV groups M and O, and HIV-2.
The commercial HIV diagnostic testing market has expanded to include several testing formats such as Western blot, immunofluorescence (IFA), and lateral flow as well as self-collection sample types such as saliva, and urine. Regardless of the type of screening test used, a positive result requires follow up with a second test to confirm a diagnosis of HIV.
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