HHS Updates Guidelines for Antiretroviral Treatment of HIV

Guidelines on antiretroviral treatment of HIV issued by the Department of Health and Human Services (HHS) were updated in September to reflect the recent, evidence-based consensus of the Panel for the Use of Antiretroviral Agents in Adults and Adolescents with HIV.¹

The guidelines do not yet include bictegravir/lenacapavir (Bixlenvo), which was approved by the FDA in August and is currently under review by the Panel for a future update.

A new section in the Principles of Antiretroviral Therapy discusses selection and optimization of antiretroviral therapy (ART), and offers considerations in the event of virologic failure.

In a departure from previous editions which have included tables of antiretroviral (ARV)-drug interactions, these updated guidelines refer to the Liverpool HIV Drug Interaction Checker for interaction guidance.²

A key update, based on the DOLCE study, is recommendation of the two-drug ARV regimen of dolutegravir/lamivudine (DTG/3TC) regardless of baseline plasma HIV viral load.³ In addition, the two-drug combinations of boosted darunavir with either lamivudine or emtricitabine (FTC) are included as options depending on the clinical scenario. The panel advises against DTG/3TC, however, or a boosted protease inhibitor plus 3TC or FTC as a switch strategy for those with historical M184V/1 mutations.

In considering approaches to optimize ART, the Panel recommends the two-drug regimen of doravirine/islatravir (DOR/ISL) as an optimization strategy for those with ongoing viral suppression and no history of prior virologic failure or resistance to either component.It advises against, however, several agents that have been associated with serious adverse effects, high pill burden, or low barrier to resistance.

The section on interrupted ART has been expanded to include considerations for interruptions of oral ART, long-acting injectable ART, and regimens containing both oral and LA ARVs.

The section for adolescents and young adults with HIV has been expanded to describe a range of issues beyond ART, including:

• Differences in management of persons with perinatally and non-perinatally acquired HIV
• The varied challenges that can present with HIV in this age group, from developmental changes, mental health and stubstance use to unstable housing and trauma
• Age- and population-specific treatment adherence strategies
• Transitions from pediatric to adult care

The section on substance use disorders (SUD) and HIV expands discussion in several areas, including:

• Emphasizing importance of routine screening for SUD and co-occurring mental health disorders, and that SUD does not contraindicate ART.
• Examining how SUD and related behaviors affect HIV care outcomes
• Describing the utility of LA ART for persons with SUD.
• Focusing on a particular adulterant in illicit opioids, medetomidine, and how it can interact with some ARV drugs

The section on women with HIV updates perinatal guidelines for ART use; discusses use of LA cabotegravir (CAB-LA) during pregnancy; and considers HIV care after menopause and with common comorbidities.

Additions to the section on hepatitis B virus (HBV)/HIV coninfection include notice thatISL- containing ARV regimens are contraindicated with 3TC and FTC.This section also expands considerations and recommendations when initiating or transitioning to tenofovir-sparing ART for persons with HBV/HIV.

Newly added to this section is the clarification that, in certain situations, tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) alone (without 3TC or FTC) can be used as the only drug with HBV activity.It notes, however, that TAF or TDF alone for HBV treatment is to be used in combination with an effective ARV regimen.

This updated guidelines also consider recent changes in costs and reimbursement, providing two new tables with cash-pay estimates for recommended initial and optimization ART regimens. The section includes recommendations on assessing and addressing cost-related barriers to ART, "while ensuring that cost-driven regimen changes do not compromise virologic efficacy."

References

1. Clinical Info HIV.gov. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. 2026, September 24. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/ .

2. University of Liverpool and Centre for Experimental Therapeutics. HIV Drug Interactions. 2026. https://www.hiv-druginteractions.org/.

3. Figueroa MI, Brites C, Cecchini D, et al. Efficacy and safety of dual therapy with dolutegravir/lamivudine in treatment-naive persons with CD4 counts <200/mm³: 48-week results of the DOLCE study. Clin Infect Dis. 2026; 82:122-131.