Antiretroviral therapy

Antiretroviral therapy (art) is the standard treatment for human immunodeficiency virus infection: combinations of drugs that block distinct stages of the viral life cycle. Combination provides greater antiviral potency and a higher barrier to resistance — HIV's reverse transcriptase is error-prone and its replication rate enormous, so any single agent selects a resistant variant within weeks, while simultaneous blockade at several steps requires more mutations than the virus can readily accumulate. The classes are nucleoside and nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and integrase strand transfer inhibitors, the last — exemplified by dolutegravir — now anchoring most regimens worldwide for their potency, tolerability and high barrier to resistance. Suppressing plasma HIV RNA below detection prevents progressive immunodeficiency, protects against opportunistic infection, and blocks sexual transmission entirely, the finding behind "undetectable equals untransmittable". The same drugs given to uninfected people at risk work as pre-exposure prophylaxis.

art has turned a uniformly fatal disease into a chronic condition with near-normal life expectancy when suppression is maintained — the qualification that matters, since benefit depends on sustained adherence, and interruption brings both viral rebound and the risk of resistance. Long-acting injectable regimens given every one or two months address exactly that constraint.

What art does not do is cure. Provirus integrates into the host genome of long-lived CD4+ T cells, including CD4+ effector memory T cells, within days of infection, and this reservoir is transcriptionally silent, invisible to immune surveillance and untouched by drugs that act only on replication — so rebound follows interruption within weeks. Chronic immune activation persists despite suppression, driven partly by residual antigen, microbial translocation and coinfection, raising inflammatory markers such as C-reactive protein (CRP) and dysregulating the Mechanistic target of rapamycin (mTOR) pathway, and linking treated HIV to accelerated aging, cardiometabolic disease and neurological injury. These residual pathologies, along with weight gain seen with integrase inhibitors, define the frontier of current research and motivate work toward functional cure and art-free remission.