The Rise of 2-Drug Strategies: Tailoring HIV Treatment for an Aging Population

As HIV care continues to evolve, 2-drug regimens are emerging as a key strategy to balance efficacy with long-term safety—particularly in an aging patient population. Insights from phase 3 DOR/ISL trials highlight how this combination may fit into a broader shift away from traditional 3-drug, tenofovir-containing regimens. By eliminating tenofovir, DOR/ISL offers a potential advantage for patients at risk of renal impairment or bone toxicity, concerns that become increasingly relevant as people with HIV live longer and accumulate comorbidities.

Older patients often face complex treatment challenges, including polypharmacy, metabolic disease, and drug-drug interactions. In this context, DOR/ISL’s favorable safety profile and minimal interaction burden make it an attractive option. Its efficacy, comparable to standard regimens, further supports its role in patients who may not tolerate or prefer to avoid certain components of existing therapies.

However, patient selection remains critical. Clinicians must consider factors such as hepatitis B coinfection, as current 2-drug regimens—including DOR/ISL—do not provide adequate HBV coverage. This underscores the importance of comprehensive screening and individualized treatment planning.

Looking ahead, experts emphasize the need for longer-term data—extending to 3 to 5 years—as well as more granular evidence in specific populations, including women, older adults, and those with metabolic comorbidities. While current findings are promising, these additional data will be essential to fully define the regimen’s role in clinical practice.

Ultimately, DOR/ISL reflects a broader movement toward more personalized, simplified HIV care—where treatment decisions are increasingly driven by patient-specific factors rather than a one-size-fits-all approach.