Optimizing Regimen Selection in Virologically Suppressed Patients With HIV

AJMC: Why might a virologically suppressed patient switch HIV regimens?

BOURGI: Each year, perhaps 10% to 15% of virologically suppressed patients on a stable regimen explore treatment switching.

Most patient-initiated requests are motivated by interest in new treatment modalities; increasingly, patients are interested in long-acting injectables, which have gained visibility through direct-to-consumer advertising. Other patients inquire about switching to smaller pills for ease of swallowing or simplifying therapy from multitablet regimens.

Adverse effects (AEs) from current antiretroviral therapy (ART) are another, though less common, driver. Older regimens are associated with central nervous system effects such as insomnia and depression. More recent HIV therapies have been associated with significant weight gain and gastrointestinal intolerance. Any complaints during an office visit may prompt discussion of regimen switching.

By contrast, providers more often initiate discussions in response to laboratory or clinical findings. For example, patients taking protease inhibitors or older formulations of tenofovir may show metabolic dysfunction or kidney impairment, both of which warrant consideration of a switch. Providers also increasingly recommend switching from regimens containing abacavir, given its association with cardiovascular risk. Pregnancy remains a key point to reassess regimen safety. Finally, any concern about drug-drug interactions—including with common over-the-counter or other recently initiated medications—can prompt a provider to recommend switching to an alternative ART regimen.

AJMC: How do cardiovascular and metabolic health influence ART regimen decisions for this population?

BOURGI: In virologically suppressed patients with HIV, I avoid ART regimens containing abacavir due to its association with cardiovascular risk. Otherwise, I select the best ART regimen to maintain a patient’s viral suppression while simultaneously but separately managing comorbid cardiovascular and metabolic conditions.

For ART, I prioritize the first-line regimens recommended by HHS guidelines. Many of these contain second-generation integrase inhibitors associated with weight gain, particularly in combination with tenofovir alafenamide, and I frequently see metabolic complications including weight gain, dyslipidemia, and fatty liver disease in virally suppressed patients. Unfortunately, no evidence supports switching ART to combat weight gain. Lifestyle interventions and weight-suppressive therapies such as GLP-1 receptor agonists have shown promise in combatting weight gain in people living with HIV, as they have in the general population.

The management approach for dyslipidemia and fatty liver disease depends upon disease severity. Some data suggest that switching away from agents such as tenofovir alafenamide can partially reduce triglycerides by about 10% to 15%. If triglyceride elevations are mild, that modest improvement may be clinically meaningful, and switching ART could be considered.

Routine laboratory testing helps guide these decisions. A comprehensive metabolic panel provides creatinine levels to assess kidney function, which might prompt discontinuing tenofovir. The same panel includes liver function tests (alanine aminotransferase, aspartate aminotransferase), for which unexplained elevations may signal fatty liver disease. I also monitor lipid panels and fasting plasma glucose in all my patients at least annually to provide a broader snapshot of their metabolic health.

AJMC: How can providers simplify HIV treatment while balancing pill burden, patient preferences, and clinic capacity?

BOURGI: A regimen switch must not compromise virologic outcomes, even if the intention is to improve quality of life (QOL). Fortunately, most patients are now candidates for simple, single-tablet regimens that are taken once daily. This includes many patients with drug-resistant HIV who previously required complex multitablet regimens. For patients who are not candidates for single-tablet regimens, combining long-acting injectables with 1 or 2 oral agents can simplify ART. While not pill-free, this represents a substantial improvement in QOL compared with 5 or 6 daily medications.

However, switching regimens is rarely straightforward. Patients who have long tolerated and trusted their current therapy may be resistant to change. Providers must consider the potential for new AEs, the impact on adherence, and the logistics of the new regimen. Particularly for long-acting injectables, patient commitment and adherence to multiple annual clinic visits is critical, as all FDA-approved injectable HIV therapies must be administered by a licensed professional. This requirement substantially increases the workload of clinic staff who must manage injection visits and monitor patient adherence to those appointments.

For these reasons, regimen simplification requires careful patient-provider discussion to balance clinical effectiveness, convenience, and the practical realities of delivering care.

AJMC: How do clinical trial data guide treatment decisions?

BOURGI: When evaluating a new HIV regimen, I first consider whether the clinical trial sample is reflective of the patient population that I treat. Even strong clinical trial evidence must translate to the real-world setting of my practice. Fortunately, HIV medicine benefits from a wealth of high-quality data and clear, clinically meaningful trial outcomes.

Trial data also guide my conversations with patients. Many trials provide patient-friendly summaries or brief videos that explain the study design, goals, and outcomes in plain language. I often share these with patients ahead of a discussion so they can consider the findings in their own time. During visits, we review the evidence together, and I explain why I think a regimen change may be beneficial while encouraging patients to voice concerns. This process allows us to reach a shared decision, whether that means switching regimens or remaining on a well-tolerated therapy.

Trust-building is central to this approach. Patients should feel empowered to evaluate evidence themselves rather than being moved to switch simply because a new drug is available. I only recommend changes when there is strong, convincing evidence that the alternative offers meaningful benefits over their current regimen.

AJMC: For new ART regimens, how should noninferior virologic outcomes be interpreted?

BOURGI: Most HIV clinical trials will demonstrate non-inferiority rather than superiority with respect to virologic outcomes. When evaluating new regimens, additional benefits—such as lower metabolic risk, improved QOL, or better patient-reported outcomes—should be considered.

Patient heterogeneity should also be considered. Although a regimen may be generally safe and effective, individual patients may require alternatives due to comorbidities, tolerability, or prior resistance. Additionally, long-term safety is critical; older generic regimens, while effective for viral suppression, may be associated with higher rates of metabolic or neuropsychiatric complications, negatively affecting QOL.

Thus, providers and other managed care professionals should consider not only virologic efficacy but also long-term adverse outcomes and patient-centered measures, reflecting the full spectrum of benefits and risks of HIV therapy.

AJMC: What practical considerations inform ART switching decisions in virologically suppressed patients?

BOURGI: Most importantly, the patient must agree to the switch. Additionally, preparations and routine assessments must be performed to ensure that patients will maintain virologic suppression after switching. These include a comprehensive medical history with specific notes about prior virologic failures, hepatitis B–virus immunity or coinfection status, and any concomitant medications patients are taking. Insurance coverage should be confirmed to avoid treatment interruptions that could lead to virologic failures.

Finally, a plan for follow-up care must be developed. Ideally, a patient should be reassessed about 4 weeks after a regimen switch to ensure they are tolerating and adhering to the new regimen. At this time, viral load testing should be repeated to ensure continued virologic suppression.

AJMC: What gaps exist in guidelines for virologically suppressed patients with HIV?

BOURGI: Because guidelines are often built around data from clinical trials, and because those trials often have very strict inclusion criteria, the patients in those studies don’t always reflect the patients I see in my clinic, including individuals with substantial barriers to care, substance use disorders, or mental health conditions; the recommendations may not be actionable. Fortunately, guidelines are evolving as more real-world evidence becomes available. For example, long-acting injectables were initially studied only in virologically suppressed patients, but emerging real-world and retrospective data have supported their use in viremic patients as well—a major clinical need in many settings.

Patients with very advanced HIV constitute another population frequently excluded from clinical trials; recommendations for this population constitute an important gap. Recent European data have begun to address this, but more guidance is needed. Finally, while guidelines tend to emphasize virologic and metabolic outcomes, they rarely incorporate patient-reported outcomes or QOL considerations. For many patients, what matters most is not just viral suppression, but how a regimen affects their daily life. Incorporating these perspectives more systematically into guidelines would help us make treatment decisions that are both clinically effective and patient-centered.

AJMC: What barriers to treatment switching exist for patients who are virologically suppressed?

BOURGI: The most significant barrier is insurance approval. Prior authorizations can take considerable time and vary widely between plans. In some cases, a regimen may not be reimbursed at all, which prevents us from making what we feel is the most appropriate switch.

In practice, we sometimes provide patients with samples to start the new regimen while awaiting insurance approval. But this approach has risks; if approval is delayed and the patient runs out of samples, they may face treatment interruptions. Overall, navigating different formularies and inconsistent prior authorization requirements across insurers represents the greatest challenge to timely and seamless treatment switching.

AJMC: How might the goals of the Ending the HIV Epidemic public health initiative¹ be advanced?

BOURGI: From a virologic standpoint, current first- and second-line ART regimens are highly effective at achieving and maintaining suppression. However, adherence remains a barrier to realizing public health goals and ending the HIV epidemic. ART regimens with the highest adherence rates—including long-acting injectables or simplified oral regimens—should be recommended. Barriers that might prevent adherence or interrupt medication supply—including socioeconomic concerns—must be considered.

Linking HIV care with broader primary care initiatives is critical to adherence and optimizing long-term health. To improve metabolic and cardiovascular outcomes, for instance, routine risk assessment and lifestyle interventions should be preferred over modifying ART.

Finally, we must ensure equitable access to treatment, reduce stigma, and streamline insurance approval to enable rapid initiation of therapy. Expanding equitable access to HIV prevention strategies, including PrEP (pre-exposure prophylaxis), is critical to reducing new infections and complementing the benefits of effective treatment.

AJMC: What developments would you like to see for future HIV treatment?

BOURGI: I’m particularly excited about ongoing research into long-acting therapies. Clinical trials are underway studying injectables that could be given every 6 months, which would significantly change how we deliver HIV treatment. There are also promising studies on long-acting oral agents, such as a once-weekly pill, that could be more appealing for patients who are hesitant about injections.

From a public health standpoint, I’d like to see innovation in how these therapies are delivered. Relying solely on clinic visits will not work for everyone, especially patients in health care deserts or those facing barriers like transportation, unstable housing, or incarceration. Mobile units that bring long-acting injectables directly to homeless encampments, treatment centers, or even patients’ homes could make a major difference. In Tennessee, for example, some patients must travel hours to reach an HIV specialist. Meeting patients where they are—not just expecting them to come to us—will be critical to ensuring these advances translate into better adherence and viral suppression.

REFERENCE

1. The White House. National HIV/AIDS Strategy for the United States 2022–2025. HIV.gov. 2021. Accessed June 6, 2025. https://files.hiv.gov/s3fs-public/NHAS-2022-2025.pdf