Viral load monitoring for HIV

Previous treatment guidelines recommended that anyone with a viral load greater than 100,000 copies/mL of blood should begin treatment. It is now standard of care in the United States to begin anti-retroviral treatment upon discovery of HIV positive status. HIV is a retrovirus, an RNA virus that enters a host cell and uses the host DNA replication machinery and the enzyme reverse transcriptase to produce DNA from the viral RNA genome. HIV also produces an integrase enzyme which is used to integrate the newly produced viral DNA into the host's DNA. The virus is then replicated every time the host cell's DNA replicates. Due to the nature of the virus the drugs used to treat HIV are called antiretroviral medicines, and the course of treatment is called antiretroviral therapy (ART). These potent medicines cannot cure an individual; they can however manage the virus and slow the progression of the HIV infection. Strict compliance with the prescribed ART regimen is vital to controlling the disease.

Highly active antiretroviral therapy (HAART) is the current recommended treatment for HIV. HAART entails taking a combination (regimen) of three or more ART medications from at least two different classes of drugs. There are six classes of ART medications:

• non-nucleoside reverse transcriptase inhibitors (NNRTIs)
• Nucleoside reverse transcriptase inhibitors (NRTIs)
• protease inhibitors (PIs)
• entry inhibitors
• Fusion inhibitors
• Integrase inhibitors

Each class of medications uses a different mode of action to blocks the virus. Treatment is more effective in controlling the virus when a combination of medications from different classes is used. HAART also reduces the risk of developing drug resistance. Viral load tests are used to monitor the effects ART, to track viral suppression, and detect treatment failure. Successful combination ART should give a fall in viral load of 1.5 to 2 logs (30-100 fold) within six weeks, with the viral load falling below the limit of detection within four to six months.[4]

Laboratory monitoring schedule for patients using ART:

Viral load monitoring for HIV complements the CD4 count, which is another sort of test associated with monitoring HIV. Confusion about when to take a CD4 test is common.[1] The results of a viral load test help determine when a CD4 count is indicated.[1] CD4 cells are the primary target of HIV. A CD4 test quantifies Helper T cells and is often combined with viral load testing to monitor the progression of HIV. CD4 testing shows the strength of the immune system, but does not report viral activity. As established by the Centers for Disease Control and Prevention (CDC), a person with HIV and a CD4 count below 200 or a CD4 percentage below 14% is considered to have AIDS.[5] An increased CD4 count can result from an immune response to an infection or a recent vaccination. A decreased CD4 count, in combination with higher numbers on a viral load test, indicates an increased risk of getting sick from opportunistic diseases.

While receiving ART some patients with undetectable viral load measurements may experience an increase in viral load, to a low level (usually below 400 copies/mL blood), and then returned to an undetectable level. These transient blips do not indicate that the virus is developing resistance to drug therapy. Blips appear to be more common in the winter, suggesting a connection with illness such as colds and influenza.[6] Viral load blips are partially explained by various patient related factors, and thought to be relatively common. High level and sustained increases in viral load are frequently related to the development of drug resistance and/or viral mutations, and often dictate changes in ART.

The window period for a test is the amount of time from the initial infection event until the disease can be detected.[7] Exposure to HIV, followed by replication of the virus, may take as long as six months to reach a level detectable in many testing methods. An HIV antibody test usually detects the HIV antibodies within two to eight weeks, but can have a valid negative result for a long as 2 to 6 months after initial infection. Viral load tests can also be used to diagnose HIV infection, especially in children under 18 months born to mothers with HIV, where the presence of maternal antibodies prevents the use of antibody-based (ELISA) diagnostic tests.[8] Pooled viral RNA testing shortens the window period to a median of 17 days (95% CI, 13-28 Days).[9] Although it is not the standard of care to use this test for diagnosis, in communities with high HIV prevalence, this test has a significantly improved negative predictive value over 3rd and 4th generation tests for detecting acute HIV infections.[10][11]

The higher the viral load value, the more viral elements there are in blood and other body fluids. For example, individuals with HIV are most contagious during the earliest (acute) stages of the infection, sometimes with millions of copies of HIV per centiliter of blood. According to one estimate, the majority of transmissions among gay men in the UK occur during primary infection.[16] This is because, at this phase, the immune response is still developing. Antibody levels against the virus during acute infection are often too low to be detected, meaning that an antibody test for a highly infectious individual can come back negative.

There is at least one documented case of an HIV-positive individual with an undetectable viral load infecting his partner.[17] Nevertheless, two recent major studies of serodiscordant couples in which the positive partner had an undetectable viral load have found no linked transmission events despite at least some unprotected sex among the couples.[18][19] HPTN 052, a third study, found one linked transmission event in a test group of 886 couples,[20] although it is unclear whether the originally infected partner in this case had achieved an undetectable viral load at the time of transmission.[21]

Viral load in blood corresponds imperfectly to viral load in other parts of the body. Individuals with undetectable viral loads in their blood might not have undetectable viral loads in other bodily fluids, such as semen or vaginal secretions. In one recent study, of 83 men with undetectable viral loads, 21 had very slight but not undetectable viral loads in their semen.[22] However, it is unclear how much this actually increases transmission risk.

Nucleic acid tests are a typical way to measure viral load, including for HIV.

ExaVir™ Load Version 3 from Cavidi AB is a largely manual test, which has the European regulatory approval (CE-Mark) for clinical use and is also used for viral load monitoring. Virus-associated reverse transcriptase (RT) activity is measured and can therefore detect all types and subtypes of HIV.[2] The technology does not require sophisticated laboratories.[34][35]