Pathogenesis of HIV: Key Mechanisms Explained

HIV targets CD4 immune cells, uses them as factories, then destroys them — slowly weakening the immune system over years. The virus enters the body through blood, semen, vaginal fluid, or breast milk and locks onto a CD4 T-cell through the CD4 receptor and a co-receptor called CCR5 (or sometimes CXCR4). Once inside, HIV converts its RNA into DNA using an enzyme called reverse transcriptase and inserts that DNA permanently into the cell's own genome. The infected cell then produces thousands of new virus copies before dying, and each new copy goes on to infect other CD4 cells. This is why HIV cannot be cleared by the immune system on its own — once integrated, the viral DNA stays for the cell's lifetime.

CD4 count measures the number of healthy CD4 immune cells per microlitre of blood — the lower it drops, the more vulnerable a person becomes to infections. A healthy adult usually has a CD4 count between 500 and 1,500 cells/µL. HIV progressively kills CD4 cells, and when the count falls below 200, the person is at high risk of opportunistic infections like tuberculosis, pneumocystis pneumonia, cryptococcal meningitis and certain cancers — this is the point at which HIV becomes AIDS. Antiretroviral therapy (ART) stops the virus from replicating, so the CD4 count can recover to normal levels within months to years. CD4 counts are checked every 3–6 months to monitor treatment response and immune recovery.

ART drugs block the virus at different stages of its life cycle, so it cannot multiply — but they cannot remove HIV DNA already hidden inside cells. There are several drug classes, each attacking a different step: entry inhibitors block the virus from binding to CD4 cells; reverse transcriptase inhibitors (both nucleoside and non-nucleoside) stop the virus from converting RNA into DNA; integrase inhibitors stop the DNA from being inserted into the host genome; and protease inhibitors block the assembly of new virus particles. Modern ART combines three or more drugs from different classes to prevent resistance. Consistent daily ART reduces the amount of virus in the blood (viral load) to undetectable levels — at which point the person cannot transmit HIV to sexual partners (U=U, undetectable equals untransmittable).

The virus hides its DNA inside long-lived immune cells in tissues where drugs can't fully reach — these hidden reservoirs are what prevents a true cure. Even when ART suppresses HIV in the blood to undetectable levels, latent virus persists inside a small number of resting CD4 memory cells, in lymph nodes, gut lining and the brain. If ART is stopped, these reservoirs reactivate within weeks and the virus rebounds. Research is exploring several cure strategies: "shock and kill" (waking up latent virus so drugs can eliminate it), gene editing (removing CCR5 or excising HIV DNA), and stem-cell transplants (the approach that cured a handful of patients with HIV plus leukaemia). A widely available cure is still years away, but ART now makes HIV a manageable long-term condition with near-normal life expectancy.