Therapeutic management of HIV

Highly active antiretroviral therapy (HAART) has been used to treat HIV for several years with a reduction in mortality and morbidity. However, some patients fail to achieve complete viral suppression. Durability of therapy cannot be guaranteed and cross-resistance may arise, making second-line therapy a complex issue. Toxicity and pharmacokinetic interactions with other drugs may complicate long-term efficacy of regimens. The reduction of viral burden can prevent progressive immunodeficiency and may decrease the risk of selecting resistant viruses. Triple therapy with a protease inhibitor showed a decrease in morbidity, mortality and durability, but protease-sparing therapies might yield fewer side-effects. Lipid-related toxicity of protease inhibitors has resulted in the use of nonnucleoside reverse transcriptase inhibitors (NNRTI) in HAART. However, a single mutation for an NNRTI can confer cross-class resistance that limits further options for second-line therapy. When choosing HAART it is crucial to achieve durability and to structure doses to suit the patient's lifestyle, and it is important for patients to initiate therapy when they are ready. The decision to change drug regimens following treatment failure or rebound will depend on the initial choice of HAART. Viral load reduction occurs rapidly in most patients on HAART but immune reconstitution is slow and occurs almost unaided. Therefore prophylaxis against opportunistic infections should not be stopped prematurely.