Long-Term Suppression of HIV Infection: Benefits and Limitations of Current Treatment Options

HIV type 1, a causative agent of AIDS, is a source of worldwide morbidity and mortality. There are an estimated 1 million people in North America currently living with HIV infection, and more than 40,000 new cases occur annually. Before the advent of highly active antiretroviral therapy (HAART), the mortality rate of HIV infection was nearly 100%, and life expectancy was short. However, successful HAART delays the onset of AIDS, allowing patients to live with chronic HIV infection for 20 years or more. HAART usually consists of a combination of protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs). Although these agents are highly efficacious in delaying the onset of AIDS, their clinical utility is limited by viral resistance, nonadherence to therapy, and drug toxicity. Consequently, multidrug regimens are necessary for successful treatment. Initial NNRTI-based HAART regimens are effective at reducing viral load and boosting CD4⁺ cell counts. NNRTI resistance is uncommon, but should it occur, the NNRTI-based therapy needs to be quickly replaced by a PI-based therapy. Triple NRTI-based regimens are recommended only if NNRTI- or PI-based regimens cannot be used. When developing a multidrug regimen, it is also important to select HAART agents with limited adverse effects. Because each HAART agent has its own unique adverse effect profile, selecting a regimen with a favorable profile may be difficult. For example, certain PIs produce adverse metabolic effects that may increase the risk of developing cardiovascular disease. In contrast, NNRTI-based therapies have a different side effect profile. Because each HAART agent has specific limitations, tailoring a regimen to the individual patient is of paramount importance for achieving optimal outcomes.