Chapter 47: HIV – Antiretroviral Therapy

HIV pathogenesis involves the viral destruction of CD4+ T lymphocytes, leading to immune deficiency. Diagnosis relies on fourth-generation immunoassays and is monitored using two critical laboratory parameters: the CD4+ T-cell count, which indicates the extent of immune system damage, and the plasma HIV Ribonucleic Acid (RNA) viral load, which quantifies viral replication and monitors treatment effectiveness. Treatment goals center on achieving maximal and sustained suppression of the viral load to undetectable levels, restoring immune function, and significantly reducing morbidity, mortality, and the risk of HIV transmission (Treatment as Prevention, TasP). Antiretroviral Therapy (ART) is recommended for all patients regardless of CD4+ count, though initial regimen selection requires individualization based on genotypic resistance testing, comorbidities, and potential drug interactions. Current initial regimens predominantly utilize a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone paired with a potent third agent, typically an Integrase Strand Transfer Inhibitor (INSTI). NRTIs, such as tenofovir alafenamide (TAF) and emtricitabine, halt viral DNA production via chain termination and competitive inhibition, but caution is advised regarding specific adverse effects like lactic acidosis (a class effect), or hypersensitivity reaction (with abacavir, requiring HLA-B*5701 screening). Protease Inhibitors (PIs) are often pharmacokinetically "boosted" to enhance concentration, but they are associated with class effects including lipodystrophy, hyperlipidemia, and hyperglycemia. Specialized agents, including fusion inhibitors, CCR5 antagonists, and attachment inhibitors, are generally reserved for highly treatment-experienced patients with drug resistance. Finally, prevention strategies include Pre-exposure Prophylaxis (PrEP) and Post-exposure Prophylaxis (PEP), while successful management hinges on intensive patient education to mitigate nonadherence, the primary cause of treatment failure and development of drug resistance.