Initial Treatment Regimens for HIV Infection

Core Principles of Initial HIV Therapy

The American Medical Association recommends antiretroviral therapy (ART) for all HIV-infected individuals with detectable plasma virus, regardless of CD4 cell count, to reduce morbidity and mortality 4, 5
Initial therapy typically consists of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a third active drug from a different class, usually an InSTI 3, 6
Treatment should be initiated as soon as possible after diagnosis, with some centers implementing same-day ART initiation 3, 7
Baseline resistance testing is recommended before starting therapy, though treatment may begin before results are available in some cases 3

InSTI-based regimens are recommended as first-line therapy due to higher rates of virologic suppression compared to other regimens 1, 2
The American College of Physicians recommends dolutegravir/abacavir/lamivudine, dolutegravir plus tenofovir alafenamide (TAF)/emtricitabine, elvitegravir/cobicistat/TAF/emtricitabine, or raltegravir plus TAF/emtricitabine as first-line regimens 1, 2, 3
Dolutegravir/abacavir/lamivudine has an evidence rating of AIa and requires HLA-B*5701 testing prior to abacavir use to prevent hypersensitivity reactions 1, 2
Dolutegravir plus TAF/emtricitabine has an evidence rating of AIa and is a good option for patients with or at risk for renal or bone disease 1, 2

TAF has fewer renal and bone toxicities compared to TDF, especially when used with pharmacological boosters 8
HLA-B5701 testing is mandatory before using abacavir, and approximately 50% of individuals positive for HLA-B5701 will experience potentially life-threatening hypersensitivity reactions 2
Patients with high viral load or low CD4 count require potent regimens, as some combinations have suboptimal virologic suppression in this setting 1, 3
Patients with comorbidities, such as HBV or HCV coinfection, require special consideration when selecting initial therapy 4, 5

Regular viral load monitoring is essential to identify treatment failures early and minimize resistance development 4, 5
Monitor for drug-specific toxicities, particularly during the first few months of therapy 3
Assess adherence at each visit, as this is critical for treatment success 1

Not testing for HLA-B*5701 before prescribing abacavir-containing regimens can lead to potentially life-threatening hypersensitivity reactions 2
Overlooking drug interactions, particularly with cobicistat-boosted regimens, can lead to adverse effects 8
Delaying ART initiation can lead to poorer outcomes, and early treatment is associated with better outcomes 3