Pathophysiology of HIV, and the different groups and common side effects of anti-retroviral medications

Pathophysiology

HIV infects and progressively depletes CD4+ T cells (via direct cytopathic effect and immune-mediated destruction of infected cells), leading to progressive immunodeficiency - antiretroviral therapy targets distinct steps in the HIV replication cycle, with different drug classes blocking entry, reverse transcription, integration, or maturation
A chronic, lifelong infection without a cure (though functional cure/long-term remission strategies are an active area of research); with effective modern antiretroviral therapy, life expectancy approaches that of the general population
HIV binds CD4 and a co-receptor (CCR5 or CXCR4) to enter target cells, reverse-transcribes its RNA genome into DNA, integrates into the host genome (establishing latent reservoirs that persist despite treatment), then uses host machinery to produce new virions that bud and mature - progressive CD4+ T cell depletion from this cycle underlies the progressive immunodeficiency defining AIDS-stage disease

NRTIs/NNRTIs block reverse transcription; integrase strand transfer inhibitors block viral DNA integration into the host genome (now typically first-line given high efficacy, high resistance barrier, and good tolerability); protease inhibitors block viral maturation into infectious virions; entry/fusion inhibitors (e.g. CCR5 antagonists) block viral entry - combining agents from different classes (typically 2-3 drugs) prevents resistance emergence that would occur readily with any single agent alone

Modern first-line regimens are typically integrase inhibitor-based (e.g. bictegravir or dolutegravir with two NRTIs), reflecting high efficacy, high genetic barrier to resistance, and favourable tolerability compared with older regimens
The latent viral reservoir (established early in infection, resistant to current antiretroviral therapy) is the central barrier to cure - current treatment suppresses active replication but does not eliminate this reservoir, explaining why lifelong treatment (rather than a finite curative course) remains standard

Latent reservoir persistence (the cure barrier), CD4 count as a marker of immunodeficiency severity/opportunistic infection risk, drug class-specific adverse effect profiles, resistance mutation patterns guiding regimen selection after treatment failure

The HIV latent reservoir, established early in infection within resting CD4+ T cells, is not touched by antiretroviral therapy (which only blocks active replication) - this is the fundamental reason lifelong treatment remains necessary despite fully suppressed plasma viral load, and is the central obstacle current cure research is trying to overcome

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