Treatment Switching in Virologically Suppressed Patients With HIV

Rajesh Gandhi, MD

Professor of Medicine

Harvard Medical School

Director of HIV Education

Massachusetts General Hospital

Boston, MA

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

GANDHI: The main reasons patients and their clinicians consider switching are to simplify treatment, reduce drug interactions, and mitigate long-term safety risks. In my practice, roughly 50% of the patients have been in care long-term and were previously treated with older regimens with multiple pills or higher toxicity; among these, about 95% have transitioned to newer, simpler combinations that maintain viral suppression while reducing adverse effects (AEs). Specific examples include switching from protease inhibitors to integrase inhibitors, because protease inhibitors can cause nausea, vomiting, and elevated cholesterol. I also recommend switching patients off abacavir due to long-term cardiovascular risk. For patients who recently started therapy with modern, less-toxic regimens, switching is less common except for those interested in long-acting injectables to avoid daily pills. Overall, regimen switches are driven by the opportunity to maintain virologic suppression while reducing complexity, toxicity, and long-term health risks.

AJMC: For virologically suppressed patients, what considerations guide the choice between continuing a daily oral regimen and transitioning to a long-acting injectable?

GANDHI: The FDA-approved long-acting injectable, coformulated cabotegravir plus rilpivirine, is indicated for patients already suppressed on oral therapy. Its main appeal to patients is the ability to avoid a daily pill, which is helpful for those who find pill-taking stigmatizing, have difficulty swallowing, or simply prefer an alternative to daily therapy.

In practice, the current long-acting injectable option requires patients to visit the clinic every 2 months, which may be inconvenient for some patients. There is also a small risk of viral breakthrough with injectables, which occurs in roughly 1% of patients, potentially due to drug dispersal or technical administration issues, such as inadequate needle length in patients with obesity. Close monitoring is essential. Overall, the choice depends on balancing convenience, patient preference, and small risk of viral breakthrough. For example, patients who take other daily medications for comorbidities may prefer a daily oral HIV regimen for the simplicity of taking medications all at once.

AJMC: When considering whether to recommend treatment switching—especially to newer regimens—what clinical trial data do you consider?

GANDHI: Virologic efficacy is the top priority; any new regimen must reliably maintain viral suppression after a switch. Safety and tolerability are next. If approved, doravirine/islatravir would be a potential 2-drug regimen that lacks an integrase inhibitor; doravirine is a well-established non-nucleoside reverse transcriptase inhibitor, and islatravir would be a first-in-class nucleoside reverse transcriptase translocation inhibitor. Early switch studies in virologically suppressed patients show noninferiority to standard 3-drug regimens, which is reassuring for patients who have trouble with integrase inhibitors due to sleep disturbances, brain fog, or weight gain.

The combination also appears to have a favorable AE profile and minimal drug-drug interactions, which is important for patients with multiple chronic conditions. Hepatitis B–virus (HBV) status is a consideration, since many 2-drug regimens, including doravirine/islatravir, do not provide HBV coverage.

Many of my colleagues and I are awaiting head-to-head data comparing doravirine/islatravir to the 3-drug regimen bictegravir/emtricitabine/tenofovir alafenamide in treatment-naïve patients, which are expected next year. Favorable results in that context would support broader use beyond switch scenarios.

AJMC: How does HBV coinfection influence your recommendations regarding treatment switches in virologically suppressed patients?

GANDHI: About 5% to 10% of people with HIV in the US have HBV coinfection, with higher rates in endemic regions. For patients with chronic HBV, switching to a 2-drug regimen that lacks HBV activity requires independently prescribing tenofovir or entecavir to maintain HBV suppression while keeping HIV controlled.

For patients without chronic HBV, confirming immunity before discontinuing tenofovir-containing regimens is essential. Vaccination, regular monitoring, and coordinated HIV/HBV management are key when simplifying therapy or switching regimens.

AJMC: What other considerations influence your treatment decisions regarding switching?

GANDHI: Cardiovascular disease is another key consideration. We prefer to switch patients to lipid-neutral regimens, which is one reason we recommend patients move off protease inhibitors that are known to affect cholesterol.

Drug-drug interactions are another critical factor. For example, dolutegravir can double metformin levels, so metformin doses should be limited to 1000 mg daily in patients with comorbid HIV and diabetes. We also see interactions between HIV medications and multivalent cations like calcium, iron, magnesium, aluminum, and zinc, all of which can be found in over-the-counter supplements and some of which are ingredients in osteoporosis medications. Multivalent cations can reduce integrase inhibitor absorption, so I counsel patients to space these multivalent cations about 6 hours apart from their HIV medications to maintain viral suppression, and I routinely reinforce this at each visit.

AJMC: What gaps exist in treatment-switching guidelines, and how do you negotiate these gaps?

GANDHI: How to address weight gain after initiating therapy is one gap. Some gain represents return to health, but about 10% of patients experience excessive gain linked to certain antiretroviral therapies (ARTs).

Switching regimens generally does not reverse this effect. Management focuses on lifestyle interventions—heart-healthy diet and regular exercise—which are especially important given elevated risks of cardiovascular disease, diabetes, and certain cancers in people with HIV. GLP-1 receptor agonists may be considered for patients with diabetes or obesity, but their use outside approved indications is not recommended. Monitoring and lifestyle support remain the mainstay for otherwise healthy patients.

AJMC: How do you approach prevention and management of comorbidities when switching ART in virologically suppressed patients?

GANDHI: For prevention, my focus is on reducing cardiovascular risk. I often recommend patients switch off abacavir because of its association with myocardial infarction and off protease inhibitors, which negatively affect lipid levels. I also emphasize early statin use due to higher baseline cardiovascular risk in patients with HIV. Results of the REPRIEVE trial (NCT02344290) showed that initiating statins in patients with HIV when their 10-year risk threshold exceeds 5% reduced cardiovascular events by about 35%.1 By contrast, in the general population of people without HIV, clinicians usually wait to prescribe statins until 10-year risk exceeds 10%. Together, regimen optimization and early statin initiation are powerful tools to prevent comorbidities in people with HIV.

For patients with established comorbidities, coordination of care is essential. Nearly half of the patients in my practice are now over 60 years of age, so collaboration with geriatricians helps us address frailty, falls, and polypharmacy. For those facing adherence challenges due to substance use, alcohol, or mental health conditions, we work closely with community health workers and integrate HIV care with behavioral health and addiction treatment. This multidisciplinary, team-based model is key to maintaining viral suppression and improving outcomes in patients with more complex disease.

AJMC: What obstacles impact optimization of ART regimens for virologically suppressed patients?

GANDHI: The biggest barriers are often tied to insurance coverage, especially for long-acting injectables. Some plans require medical benefit billing, others use pharmacy benefit channels, and the rules vary widely by insurer and state. This complexity creates delays that don’t exist for oral ART. Our team leans heavily on clinical pharmacists, who dedicate much of their time to navigating prior authorizations, buy-and-bill processes, and benefit logistics.

Policy and geographic differences also drive disparities. Patients in Massachusetts, for example, generally have smoother access to newer therapies than those in states with more restrictive Medicaid policies. At a systems level, limited access to streamlined regimens keeps patients on older therapies that can worsen adherence and AEs. Looking ahead, as agents like lenacapavir enter practice, we need consistent national policies, simplified benefit structures, and strong care coordination to ensure timely, equitable access.

AJMC: How do access disparities impact clinical outcomes for virologically suppressed patients with HIV?

GANDHI: In the US, only about 65% of people with HIV are virologically suppressed compared with closer to 90% in other parts of the world. This gap largely reflects our fragmented health care system, which contributes to persistent disparities and uneven access to treatment. Because nearly all new HIV transmissions occur from individuals who are not virologically suppressed, raising suppression rates is critical to ending the HIV epidemic.

Optimizing ART can help by ensuring uninterrupted access to effective regimens, expanding use of long-acting injectables for patients who struggle with daily adherence, and supporting innovative care models such as home administration of therapy. If we can raise suppression rates to 80% to 90%, we have the tools to dramatically reduce new infections. The challenge now is building the infrastructure and equity in access needed to make this a reality.

REFERENCE

1. Grinspoon SK, Fitch KV, Zanni MV, et al. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. 2023;389(8):687-699. doi:10.1056/NEJMoa2304146