– Dr Monica Gandhi
Recent advances in HIV treatment such as once-daily single-tablet regimens, long-acting injectable HIV therapy, and integrase inhibitor-based ART, have transformed clinical practice and patient quality of life. These shifts are reshaping adherence, metabolic management, and personalization of care for people living with HIV.
In this Q&A, Dr Monica Gandhi shares her insights on the most impactful therapeutic developments, how clinicians can optimize integrase inhibitor use, which patients benefit most from long-acting or simplified regimens, and the key findings from EACS 2025 that will guide the future of HIV care.
I think the most remarkable shifts are going to one-pill once a day regimens (with usually three or even two drugs in each tablet) and also the long-acting therapies which are injectable. Some patients like pills, some like injections, and the ability to have choice is very important when you are asking someone to be on lifelong therapy.
I always tell patients they shouldn’t have side effects on a regimen and we can always switch them around to make sure they get a combination treatment they like. The quality of life when you can slip one pill, once a day into your pocket or come into the clinic every two months for an injection is much improved than the days when patients had to take multiple pills a day, usually more than once daily.
Integrase inhibitors are definitely the most powerful and well-tolerated antiretrovirals we have at the moment so it makes sense for guidelines to recommend them as first-line therapy for most people with HIV. However, with their increasing use and especially when combine with tenofovir alafenamide (TAF), weight gain has been seen, either as a result of being off of earlier regimens which were “weight suppressive” (e.g. efavirenz and tenofovir disoproxil fumarate, TDF) or metabolic effects we are still unravelling.
This weight gain seems to be most pronounced in women of African descent. Moreover, switching antiretroviral treatment (ART) doesn’t seem to lead to weight loss in the trials to date, so we balance this possible effect with diet changes, exercise and GLP-1 agonists if indicated in order to balance the metabolic safety effects with the excellent efficacy of the integrase inhibitor
Although the clinical trials with long-acting ART are in people with HIV with virologic suppression on oral ART, the people who seem to most benefit from demonstration projects and other studies are those who have trouble taking oral ART on a daily basis.
Factors such as stigma, recall, housing insecurity, substance use, mental health disorders, or other conditions that make adherence to oral ART difficult, can indicate a need for long-acting ART. We at Ward 86 (the HIV clinic I direct at San Francisco General Hospital, CA, USA) and other clinics have seen great success in achieving and maintaining virologic suppression in people with HIV without virologic suppression with the use of long-acting ART. We call patients to remind them of injections, but have often found they are self-motivated to come in on time, especially as many are experiencing virologic suppression, sometimes for the first time.
For simplified two-drug regimens, I would encourage their use in those who don’t have any difficulties taking oral ART daily as the two drugs (instead of three) have a little less leeway to allow for missed doses. However, they can be very easy to take. For those who don’t have trouble taking daily oral ART and who don’t have viral resistance to any of the components, two drug regimens are great.
We need affordable viral load testing methods, which are currently in development, along with reliable ways to identify who requires HIV resistance screening. We are working on a project to implement a urine tenofovir assay to figure out who needs HIV resistance testing sent for example.
Tenofovir is the backbone of most ART regimens. If someone isn’t taking their ART at all, indicated by a negative urine tenofovir test, the problem leading to high viral loads is non-adherence – and adherence counselling is indicated. If tenofovir is present in the urine with a high viral load, resistance testing should likely be sent as this may indicate a problem with viral resistance. Low-cost surveillance algorithms such as this one may help us more cost-effectively determine who needs resistance screening.
I think some of the most exciting data presented at EACS 2025 is the effectiveness of the single pill of islatravir/doravirine once daily across multiple subgroups in the trials conducted with this regimen. The single pill should be available in April 2026 which will give us more options for new therapies.
There were also acceptability studies showing people with HIV do like the long-acting injectable combination of cabotegravir/rilpivirine, making access to these regimens worldwide important. The 48 week trial results of the phase II trial of once-weekly islatravir and lenacapavir as a switch therapy in those with virologic suppression were presented and showed high rates of maintenance of virologic suppression. The phase 3 trials of this once weekly therapy (ISLEND-1 and ISLEND-2) have launched.
The Clarity study showed cabotegravir intramuscular therapy may be more tolerable than lenacapavir subcutaneously for HIV prevention. However, the power of choice is important for those who need HIV prevention, the appropriate therapy will depend on the individual.
Finally, the combination of bictegravir and lenacapavir (once daily) is going to have a very high genetic barrier to resistance which is exciting for future therapeutic options.
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This content has been developed independently by Touch Medical Media for touchINFECTIOUS DISEASES. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Session: Gandhi M. ART now & near: how far have we come & how much further must we go? Plenary lecture. EACS 2025. October 15 – 18, 2025, Paris, France.
Editor: Katey Gabrysch, Editorial Director.
Disclosures: This short article was prepared by touchINFECTIOUS DISEASES in collaboration with Monica Gandhi. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchINFECTIOUS DISEASES utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat). Monica Gandhi has nothing to disclose in relation to this interview.
Cite: Monica Gandhi. Sustainable HIV prevention in 2025: New strategies for PrEP delivery in a shifting funding landscape. 18 November 2025.
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