A New Era in HIV Treatment: Single-Pill Regimens Offer Hope to Aging Population

A significant shift in HIV care is on the horizon, promising to revolutionize daily treatment for older adults living with the virus. New investigational single-pill and simplified regimens are emerging from clinical trials, offering the potential to dramatically reduce the burden of complex multi-drug therapies that have long challenged this growing demographic. These advancements address the unique needs of an aging HIV population, for whom managing numerous medications often presents a formidable obstacle to consistent adherence and overall well-being.

The Aging Face of HIV and the Burden of Pills

The landscape of HIV is rapidly evolving, with a substantial and increasing proportion of individuals living with the virus now over the age of 50. Projections indicate that by 2030, approximately 75% of people with HIV in the United States will be 50 years or older. This demographic shift is largely a testament to the success of antiretroviral therapy (ART), which has transformed HIV from a fatal diagnosis into a manageable chronic condition. However, longevity brings its own set of challenges. Older individuals with HIV often contend with multiple comorbidities, such as cardiovascular disease, kidney disease, diabetes, and hypertension, that require additional medications. This phenomenon, known as polypharmacy, frequently involves taking five or more non-ART medications alongside their HIV treatment.

The resulting high pill burden can be staggering. Many older adults with HIV currently manage regimens consisting of a median of three antiretroviral pills daily, with some taking as many as 11, and nearly 40% requiring doses twice a day. Such complex schedules increase the risk of poor adherence, leading to suboptimal viral suppression and potential drug resistance. Furthermore, the likelihood of harmful drug-drug interactions between ART and other medications is significantly elevated in this population, which can compromise treatment efficacy or lead to adverse side effects. Older adults are inherently more susceptible to these adverse events due to age-related physiological changes affecting drug metabolism, such as declining renal and hepatic function. These intertwined issues underscore the urgent need for simpler, more manageable treatment options.

A New Horizon: Bictegravir-Lenacapavir Offers Simplification

A novel single-tablet regimen (STR) combining bictegravir (an integrase strand transfer inhibitor) and lenacapavir (an HIV-1 capsid inhibitor) is showing significant promise in addressing these challenges. Recently, Phase 3 clinical trials, known as ARTISTRY-1 and ARTISTRY-2, demonstrated that this investigational daily oral pill provided viral suppression comparable to existing complex multi-pill regimens among older adults living with HIV.

The trials included 557 adults with HIV-1 infection, many of whom were older than typically represented in HIV studies, with a median age of 60 years. These participants had extensive treatment histories, averaging 28 years on ART, and a significant proportion had developed resistance to prior HIV treatments. At 48 weeks, 96% of participants who switched to the bictegravir-lenacapavir single-tablet regimen maintained viral suppression (HIV-1 RNA levels below 50 copies/mL), a result similar to the 94-96% viral suppression observed in those who continued their complex multi-pill therapies. Importantly, no new drug resistance emerged during the trial.

Beyond efficacy, the new regimen delivered additional benefits critical for older patients. Participants who transitioned to bictegravir-lenacapavir reported significantly greater treatment satisfaction and showed improvements in their lipid profiles, a crucial advantage given the higher prevalence of cardiovascular conditions among older adults with HIV. The regimen was generally well-tolerated, with adverse event rates comparable to those of the more complex treatments, offering a promising, streamlined alternative for long-term HIV management.

Expanding Options: Doravirine-Islatravir and Long-Acting Injectables

Further advancements are broadening the spectrum of simplified HIV treatments. Doravirine-islatravir (DOR/ISL), an investigational once-daily, two-drug oral regimen, has also shown strong results in Phase 3 trials. Merck, the developer, announced that DOR/ISL met its primary endpoints, demonstrating non-inferior efficacy and a comparable safety profile to other standard oral antiretroviral therapies. This includes studies involving both previously untreated adults and those who switched from existing regimens, maintaining high rates of viral suppression at both 48 and 96 weeks. The U.S. Food and Drug Administration has set an action date of April 28, 2026, for the application of DOR/ISL, signaling its potential availability in the near future.

Alongside these oral developments, long-acting injectable regimens, such as cabotegravir and rilpivirine (CAB/RPV), represent another significant innovation. Approved for administration every one to two months, CAB/RPV has demonstrated high virologic suppression in older adults, even in those with a higher burden of comorbidities. Studies indicate that older adults on injectable regimens exhibit better treatment adherence compared to their younger counterparts. However, considerations for older patients regarding existing comorbidities, potential for polypharmacy, and drug resistance profiles remain important factors in determining eligibility for such treatments.

Beyond Pills: The Broader Impact on Patient Lives

The introduction of simplified, single-pill or less frequent regimens holds transformative potential for older adults living with HIV. Reducing the daily pill burden not only enhances treatment satisfaction but also significantly improves adherence, which is critical for long-term viral suppression and preventing drug resistance. For individuals who have managed HIV for decades, often navigating complex and demanding treatment schedules, these new options offer a profound improvement in their quality of life. The psychological relief of taking fewer pills, or even a single daily tablet, can foster greater independence and reduce the constant mental and logistical burden associated with chronic illness management.

From a broader healthcare perspective, improved adherence translates into better long-term health outcomes for patients, potentially reducing hospitalizations and the costs associated with managing complications arising from poor adherence or complex drug interactions. As regulatory bodies review the data, these developments underscore a patient-centered evolution in HIV care, acknowledging the diverse and complex needs of a population that continues to age gracefully with HIV.

These advancements represent a pivotal moment in the fight against HIV. For older adults who have steadfastly adhered to demanding multi-pill regimens for years, the promise of a simpler, equally effective daily treatment signals a new era of enhanced quality of life, greater adherence, and a more manageable future with HIV. The scientific community continues to push boundaries, offering renewed hope and practical solutions to an ever-growing, resilient population.