As 2026 Gets Underway, What’s in the Pipeline for HIV Prevention and Treatment?

The evolution of HIV treatment is one of the most remarkable stories in medicine. From handfuls of pills taken multiple times a day to injections administered twice a year, antiretroviral therapy has come a long way. But the quest for more effective, better tolerated and more convenient therapies continues, and as we enter the new year, the HIV pipeline is promising.

HIV Prevention

Twice-yearly lenacapavir pre-exposure prophylaxis (PrEP) was the big story of 2024 and 2025. Gilead Sciences’ capsid inhibitor was approved for PrEP last June after the two clinical trials showed that injections every six months dramatically reduced the risk of HIV acquisition for cisgender women in Africa (PURPOSE 1) and for gay and bisexual men and gender-diverse people in the United States and six other countries (PURPOSE 2).

But lenacapavir may prove even more durable for HIV prevention. Results from a Phase 1 study presented at last year’s Conference on Retroviruses and Opportunistic Infections (CROI) showed that people who received longer-acting formulations of lenacapavir maintained effective drug concentrations for at least 56 weeks, suggesting that once-yearly PrEP could be feasible. Gilead considers the results encouraging enough to skip directly to Phase 3 trials.

For people who would rather avoid injections, longer-acting oral PrEP also shows promise. At last summer’s International AIDS Society Conference on HIV Science, researchers reported that Merck’s MK-8527—a novel nucleoside reverse transcriptase translocation inhibitor—was safe, well tolerated and maintained protective drug levels for more than 28 days. Two Phase 3 trials of once-monthly MK-8527 PrEP are underway. EXPrESSIVE-10 is enrolling young cisgender women in Africa, while EXPrESSIVE-11 is recruiting gay men and bisexual men and transgender and nonbinary people in the U.S. and several other countries.

HIV Treatment

When it comes to HIV treatment, current antiretroviral regimens are safe and highly effective, so improved convenience and ease of use are a priority. Multiple studies are looking at new all-in-one combination pills and medications that can be taken less often than once a day.

Gilead is testing a once-daily single-tablet regimen containing lenacapavir—which comes in both oral and injectable formulations—plus its integrase inhibitor bictegravir, best known as a component of Biktarvy. The company recently reported that people who switched from a more complex multi-tablet regimen (in ARTISTRY 1) or from Biktarvy (in ARTISTRY 2) maintained viral suppression at least as well as those who stayed on their current regimen.

The first novel antiretroviral to emerge from the pipeline may be Merck’s islatravir, a nucleoside reverse transcriptase translocation inhibitor that works differently from existing drugs. Islatravir hit a snag in 2021 when participants in earlier trials saw declines in CD4 T cell or total lymphocyte counts, but scientists determined that the doses used were too high. Subsequent trials have tested lower doses and not seen similar side effects.

At CROI 2025, researchers reported that participants in two Phase 3 trials who switched to a once-daily islatravir/doravirine combination pill maintained an undetectable viral load for 48 weeks. Merck recently announced that the new combo pill is also safe and effective for people starting HIV treatment for the first time.

Merck and Gilead are collaborating on a once-weekly combination pill containing islatravir and lenacapavir. Phase 2 data presented at the European AIDS Conference in October showed that people who switched from daily Biktarvy to separate islatravir and lenacapavir pills maintained viral suppression at 96 weeks. The companies are now testing islatravir/lenacapavir as a weekly single-tablet regimen in the Phase 3 ISLEND-1 and ISLEND-2 trials, and it could become the longest-acting regimen that doesn’t require injections.

Merck is testing on its own once-weekly partner for islatravir, a next-generation non-nucleoside reverse transcriptase inhibitor dubbed ulonivirine. Although a Phase 2 study of ulonivirine and a higher dose of islatravir was halted due to the aforementioned side effects, ulonivirine itself was safe and effective, and development of the combination is ongoing using a lower islatravir dose.

For its part, Gilead is evaluating a once-weekly integrase inhibitor (GS-1720) plus a prodrug of lenacapavir (GS-4182) in the Phase 2 WONDERS-1 and WONDERS-2 trials. It is also testing a potential once-monthly oral HIV capsid inhibitor (GS-3107), two long-acting injectable integrase inhibitors (GS-1219 and GS-3242) and an injectable nucleoside reverse transcriptase translocation inhibitor (GS-1614) in Phase 1.

Also further back in the pipeline are ViiV Healthcare’s VH184, a third-generation integrase inhibitor with activity against resistant virus, and VH499, an experimental capsid inhibitor. At CROI 2025, researchers reported that oral versions of the two new antiretrovirals taken every three or five days were safe and showed potent antiviral activity in Phase 2 trials. But ultimately, long-acting regimens are the goal, and early studies are testing injectable formulations of the drugs that could potentially be administered every six months or less.

Finally, the Indian pharmaceutical company Hetero Labs is working on an HIV maturation inhibitor called HRF-10071. In laboratory studies, it showed activity against all HIV-1 subtypes, which is important for a drug intended for worldwide use. At the IAS meeting, researchers reported that HRF-10071 alone showed good antiviral activity in a small Phase 2 study, and it will next be tested in combination regimens. There are currently no approved maturation inhibitors, so HRF-10071 should work against HIV that has developed resistance to other types of antiretrovirals.

Broadly Neutralizing Antibodies

Beyond new antiretrovirals, researchers are also exploring broadly neutralizing antibodies (bnAbs) for HIV prevention, treatment and a functional cure. People with HIV normally produce HIV-specific antibodies that target parts of the virus that are hidden or highly variable. But a small proportion of individuals make more potent antibodies that target conserved parts of the virus that don’t change much. Therapies derived from these natural bnAbs have been enhanced to extend their durability. The drawback of bnAbs is that HIV can develop resistance, so they are best used in combination therapy, and people should be pre-screened for viral susceptibility to specific antibodies.

Gilead is studying a pair of bnAbs called teropavimab and zinlirvimab as potential twice-yearly partners for lenacapavir. Phase 2 data presented at the European AIDS Conference showed that nearly 90% of people who switched to lenacapavir injections plus IV infusions of the two bnAbs administered every six months maintained viral suppression for a year.

ViiV, too, is evaluating a bnAb, dubbed N6LS, as a partner for its long-acting integrase inhibitor cabotegravir (currently administered monthly or every other month in combination with rilpivirine). At CROI 2025, researchers reported that 96% of people who received monthly cabotegravir injections plus N6LS infusions every four months maintained viral suppression. The second part of the study will evaluate cabotegravir injections given every two months plus N6LS infusions every six months. In the future, N6LS might be paired with experimental ultra-long-acting formulations of cabotegravir or with injectable versions of VH184 or VH499.

Research on these and other candidates for HIV prevention and treatment continues apace, and we will likely hear updates at this year’s CROI in late February or the International AIDS Conference in July. But scientists and advocates fear that future advances are threatened by cuts to federal funding for HIV research, which lays the groundwork for the development of new therapies.