HHS broadens two-drug HIV treatment options in major guideline update

Clinical takeaway: Initial HIV treatment with dolutegravir/lamivudine can now be considered regardless of baseline viral load, while additional two-drug regimens have been added for selected clinical scenarios, reflecting continued movement toward simplified antiretroviral therapy (ART).

The US Department of Health and Human Services (HHS) has updated its Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV, expanding recommendations for two-drug ART and adding new guidance on regimen optimization, long-acting therapies, hepatitis B coinfection, and special populations.

The headline change is a broadened recommendation for the two-drug regimen dolutegravir/lamivudine. Based on findings from the DOLCE study, the regimen is now recommended as an initial treatment option regardless of baseline HIV viral load, removing a prior limitation and potentially expanding eligibility for treatment-naive patients.

The guideline panel also added boosted darunavir plus lamivudine or emtricitabine as two-drug options in certain clinical scenarios, further increasing flexibility in regimen selection.

What's changed

• Dolutegravir/lamivudine is now recommended as an initial ART regimen regardless of baseline HIV viral load.
• Boosted darunavir plus lamivudine or emtricitabine has been added as an initial treatment option for certain clinical scenarios.
• Doravirine/islatravir was added as a regimen optimization strategy for virologically suppressed patients without prior virologic failure or resistance to either agent.
• New guidance advises against switching to dolutegravir/lamivudine or a boosted protease inhibitor plus lamivudine/emtricitabine in patients with historical M184V/I mutations.
• The drug-drug interaction section was updated to address islatravir interactions and long-acting ART, while formal interaction tables were removed in favor of referral to the Liverpool HIV Drug Interaction Checker.
• Updated recommendations were added for management of HIV/hepatitis B coinfection, including hepatitis D screening and considerations when using tenofovir-sparing regimens.
• Expanded guidance addresses long-acting injectable ART, treatment interruptions, substance use disorders, pregnancy, and care transitions for adolescents and young adults with HIV.

The update also introduces a new section outlining core principles of antiretroviral therapy and adds “Knowledge Gaps” summaries to selected guideline chapters. In addition, the panel expanded discussions on cost-related barriers to care and added new ART cost comparison tables to support treatment decision-making.

Although FDA approved bictegravir/lenacapavir (Bixlenvo) in August 2026, the panel said it is still reviewing the available evidence and plans to address the regimen in a future guideline update.

Source: Panel for the Use of Antiretroviral Agents in Adults and Adolescents With HIV (2026 Sep 24). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV: What's New in the Guidelines