HAART
Summary
HAART (Highly Active Antiretroviral Therapy) is combination drug therapy for HIV infection, typically using ≥3 drugs from ≥2 different classes to maximally suppress viral replication and prevent resistance. It reduces HIV viral load to undetectable levels, restores immune function (CD4 count), and prevents progression to AIDS.
Detail
HAART, now more commonly called ART (antiretroviral therapy) or cART (combination ART), targets multiple steps of the HIV replication cycle to achieve durable viral suppression while minimizing resistance development. Standard regimens combine drugs from different classes: 2 NRTIs (e.g., tenofovir + emtricitabine) plus a third agent from another class - typically an integrase strand transfer inhibitor (INSTI, e.g., dolutegravir, bictegravir), a non-nucleoside reverse transcriptase inhibitor (NNRTI, e.g., efavirenz), or a boosted protease inhibitor (PI, e.g., darunavir/ritonavir). Other classes include entry/fusion inhibitors (enfuvirtide, maraviroc) and CD4 post-attachment inhibitors. Mechanism rationale: HIV reverse transcriptase lacks proofreading, causing high mutation rates; monotherapy rapidly selects resistant strains, so combination therapy with different mechanisms of action is required to achieve synergistic suppression and genetic barrier to resistance. Clinical goals include achieving undetectable viral load (<20-50 copies/mL), CD4 count recovery, reduced transmission risk (U=U, undetectable = untransmittable), and prevention of opportunistic infections. Monitoring involves viral load and CD4 counts at baseline and periodically. Key considerations for boards: know major drug toxicities (e.g., NRTIs - lactic acidosis, lipodystrophy; PIs - hyperlipidemia, insulin resistance, GI upset; NNRTIs - rash, hepatotoxicity; INSTIs - weight gain, generally well-tolerated). Initiation is recommended for all HIV-positive patients regardless of CD4 count. Drug resistance testing guides regimen selection. HAART has transformed HIV from a fatal illness to a manageable chronic disease, dramatically reducing mortality and opportunistic infections (e.g., PCP, toxoplasmosis, CMV, MAC) since its introduction in the mid-1990s. Immune reconstitution inflammatory syndrome (IRIS) can occur upon starting therapy in patients with low CD4 counts, causing paradoxical worsening of opportunistic infections as immune function recovers.
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- UpToDate - Antiretroviral therapy for HIV
- CDC HIV Treatment Guidelines
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