Objective:

To critically appraise the role of dual antiretroviral therapy (2DR) versus triple antiretroviral therapy (3DR) in aging and comorbid people with HIV (PWH), integrating evidence from randomized trials and real-world studies.

Approach:

Key Findings:

• Three-drug antiretroviral regimens (3DR) have long been the standard of care due to their efficacy and resistance barrier.
• Aging PWH face increased risks of comorbidities and polypharmacy, necessitating a shift in HIV care goals.
• Dual antiretroviral therapy (2DR) has emerged as a clinically investigated alternative, with specific strategies endorsed by international guidelines based on randomized controlled trials demonstrating non-inferior virological efficacy compared with 3DR.

Interpretation:

The demographic shift in the HIV population necessitates a broader approach to care that includes managing multimorbidity and reducing polypharmacy-related risks.

Limitations:

• Randomized controlled trials often exclude individuals with multimorbidity and advanced frailty, limiting generalizability.
• Real-world studies may have confounding factors and variability in monitoring intensity.

Conclusion:

A patient-centered framework is proposed for antiretroviral therapy selection, considering geriatric dimensions alongside virological endpoints.

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