Dr. Mark Jacobson
Antiretroviral therapy (ART) for the treatment of HIV infection has improved steadily since the advent of potent combination therapy in 1996 and it has transformed HIV infection into a manageable chronic condition. However, fewer than one-third of HIV-infected individuals in the United States have suppressed viral loads, mostly due to undiagnosed HIV infection and failure to link or retain diagnosed patients in care.
The period of acute HIV infection is particularly problematic with respect to transmission of the disease. Acute HIV infection may have no signs at all or can present itself as a nonspecific viral illness within 2-6 weeks of infection. This is also the most infectious phase of the disease and is often undiagnosed. After exposure to HIV, it can take as many as 3-4 weeks for antibodies to be detectable. Advanced fourth-generation HIV tests (also known as “combo tests”) have been developed to detect HIV during the acute window period before antibody is detectable and during established HIV.
There has been a progressive shift toward earlier initiation of ART in patients with HIV infection. It is well recognized that the key to successful ART in maintaining viral suppression is adherence to the prescribed regimen. Evidence indicates that drug resistance and consequent loss of viral suppression occurs more frequently in individuals who initiate therapy later in the course of infection than in those who initiate ART earlier. Initiation of ART is now recommended for all HIV-infected individuals, regardless of CD4 cell count, to reduce the morbidity and mortality associated with HIV infection and to prevent HIV transmission. More than 25 antiretroviral (ARV) drugs in 6 mechanistic classes are approved for treatment of HIV infection. These include nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), a fusion inhibitor (FI), a CCR5 antagonist, and integrase strand transfer inhibitors (INSTIs). In addition, two drugs (pharmacokinetic [PK] enhancers or boosters) are used to improve the PK profiles of some ARV drugs. The initial ARV regimen for a treatment-naive patient generally consists of two NRTIs, usually abacavir plus lamivudine or tenofovir disoproxil fumarate plus emtricitabine, plus a drug from one of three drug classes: an INSTI, an NNRTI, or a PK-enhanced PI.
Pre-exposure prophylaxis (PrEP) should be considered for individuals who are HIV-negative and at very high risk for HIV infection. When taken every day, PrEP with the combination of tenofovir and emtricitabine has been shown to reduce the risk of HIV infection in people who are at high risk by >90%. A recent study also suggests that “on demand” PrEP is also effective; in this scenario, a drug dose is taken three times: 2-24 hours before anticipated unprotected sex, and then at 24 and 48 hours afterwards. This “on demand” regimen reduced HIV acquisition by nearly 90%.