AIDS 2026: New HIV drugs in the ART pipeline

4 August 2026. Related: Early access, Conference reports, Antiretrovirals, Intl AIDS 26th Rio 2026.

Simon Collins, HIV i-Base

AIDS 2026 included new data on the latest HIV drugs, most notably for once-weekly oral formulations and practical issues linked to treatment access.

Hyperlinks in the text are to open-access abstracts but links to the webcasts are also included in the references at the end.

In one of the plenary lectures, Monica Gandhi from UCSF California gave a comprehensive plenary talk about advances in long-acting ART. [1]

This included not only the development of new long-acting drugs but also new ways to use recently approved drugs, especially long-acting injectables.

Although long-acting cabotegravir/rilpivirine (CAB-LA/RPV-LA) is both effective and popular, when approved in 2021 this was only as a switch option for people with undetectable viral load from using oral ART. However, perhaps the greatest benefit of injectable ART is in supporting people who for complex reasons are unable to become undetectable on oral ART because of difficulties with adherence.

Several recent studies in high-income settings have reported promising results from this approach, including Monica Gandhi’s own research at Ward 86 in San Francisco. One outcome has been to find similarly high rates of viral suppression compared to switch studies and high acceptability, even in participants with complex needs that include housing insecurity, substance use and mental health. Many of these people became undetectable for the first-time after using injectable ART. [2]

It is notable that US treatment guidelines from HSS and IAS-USA since 2024 endorse the option to individualise use of CAB/RPV-LA in people who still have detectable viral load, even without results from randomised studies.

Other small studies are reporting benefits from using CAB-LA (two-monthly from ViiV) with lenacapavir (six-monthly from Gilead) off-label, especially when RPV-LA is contraindicated.

The talk also highlighted the problem of delayed access to long-acting injectable drugs in low- and middle-income settings – a key theme of AIDS 2026.

For example, independent researchers in these countries are unable to run their own studies because the drug manufacturers refuse to sell to them – even when the research includes funding to buy them at the regular price. These studies should already be collecting data to look at appropriate strategies in all countries, even when it combines drugs from different manufacturers in novel combinations.

A four-monthly formulation of cabotegravir (CAB-ULA) is also in development for ART and an annual formulation of lenacapavir for PrEP. Other compounds in early phase studies include new long-acting INSTIs (GS-3242 from Gilead and VH-184 from ViiV) and a capsid inhibitor (VH-499 from ViiV).

Once-weekly oral islatravir/lenacapavir

AIDS 2026 included studies for two different once-weekly oral ART.

These were oral presentations of the phase 3 ISLEND-1 and ISLEND-2 studies with simultaneous publication of ISLEND-1 in the NEJM. Both were large international phase 3 active-controlled non-inferiority switch studies that randomised people on stable ART to once-weekly ISL/LEN (2 mg/300 mg) or to remain on current ART.

ISLEND-1 was a double-blind study in 607 participants stable on B/F/TAF with matching placebo in each arm, with results presented by Jurgen Rockstroh from University of Bonn. ISLEND-2 was an open-label design that enrolled 626 people on a wider range of current ART, with results presented by Amy Colson from Community Research Initiative, Boston. [2, 3, 4]

Both studies found high rates of efficacy in all arms at week-48 with no significant differences in viral suppression or side effects in the active vs control arms of either study.

In ISLEND-1, viral load was detectable >50 copies/mL in 0 vs 1 participant (diff −0.3; 95% CI: −1.4 to 0.8), meeting pre-specified criteria for non-inferiority. Viral load was <50 copies/mL in 284 (93.4%) vs 280 (92.4%) (diff 1.0; 95% CI: −3.2 to 5.2), in ISL/LEN vs control groups, respectively. Tolerability was generally good and similar between arms with 6 (2.0%) vs 5 (1.7%) participants discontinuing due to adverse events in the ISL/LEN vs B/F/TAF groups with serious events in 16 (5.3%) and 14 (4.6%), respectively. This included one unvaccinated participant in the ISL/LEN arm who became HBsAg+ that generated discussion about awareness of hepatitis B vaccination when previously reported earlier at CROI 2026.

Similar results in ISLEND-2 included detectable viral load >50 copies/mL in 1 vs 4 participants (diff –1.0%; 95% CI: –3.0 to +1.1), showing non-inferiority. Viral load was undetectable >50 copies/mL in 299 (95.2%) vs 298 (95.5%) participants (diff –0.3%; 95%CI: –3.9 to 3.2%). All comparisons are ISL/LEN vs control, respectively.

Once weekly oral islatravir/ulonivirine

Anne Luetkemeyer from UCSF presented week 24 results using islatravir in a once-weekly oral formulation with the investigational NNRTI ulonivirine (previously MK-8507).

This was a phase 2b open-label study that randomised 150 participants (1:1) on stable B/F/TAF to either islatravir + ulonivirine ULO (2 mg/200 mg) once-weekly or to remain on current once-daily ART. Primary and secondary endpoints included viral rebound at weeks 24 and 48 respectively. At week 48, participants in the B/F/TAF control arm switch to ISL/ULO. [5]

Results at week 24 included detectable viral load >50 copies/mL in 0/78 vs 1/78 (1.3%, 95%CI: –6.9 to +3.5). Viral load was <50 copies/mL in 94.9% vs 97.5% with slightly more missing data (5.1% vs 1.3%), in the ISL/ULO vs B/F/TAF arms respectively.

Six-monthly injectable lenacapavir + 2 bNAbs

James McMahon from the Alfred Hospital and Monash University in Melbourne presented week-104 results from a phase 2 study that randomised 80 participants (2:1) on currently stable ART to either 6-monthly ART using lenacapavir plus two bNAbs (teropavimab and zinlirvimab) or to continue current ART. Viral suppression at weeks 24 and 52 were the primary and secondary endpoints respectively. At week 52, the control arm could switch to LEN + bNAbs.

Results at week 104, reported viral suppression of 98% (40/41) and 100% (19/19) in continuous vs late-switch arms respectively. However, this M=F analysis (missing=failure) excludes results for 20/80 participants who didn’t contribute to week 104 data. [6]

CD4 differences between arms were reported as a new safety signal though with median CD4 changes at week 104 of +34 (–71 to +111) vs –38 (–159 to +140) in the early vs late switch groups, respectively.

Two phase 3 switch studies with this combination are now enrolling people on stable oral ART, using control arms of continued oral ART or injectable CAB-RPV-LA. (NCT07683000 and NCT07682961 respectively). [7, 8]

Cabotegravir-LA plus lotivibart (bNAb aka N6LS and VH109)

Although no new clinical data was presented on an investigational combination using cabotegravir-LA injections (possible in a 4-monthly version) with the bNAb lotivibart, AIDS 2026 did include a poster reporting participant preferences for an IV rather than SC formulation. [9]

comment

The ART pipeline includes many exciting developments, with once-weekly oral ART likely to have a big impact on quality of life by reducing the need for daily dosing, and easier distribution and likely cost compared to injectable ART.

However, scientific advances need to be matched with equitable access – a point made by Monica Gandhi and many others throughout the conference. This includes access for independent research, especially for management of advanced HIV in low- and middle-income countries.

There are at least six studies that are already funded to study the combination of CAB/LEN but are unable to start because neither ViiV nor Gilead will sell CAB-LA or lenacapavir to the researchers.

LANCET (ACTG A5433) currently planned for Botswana, Brazil, and South Africa.
PALACE (ACTG A5431) planned as a small pilot study in the US.
CHAPAS 5: a paediatric platform; plan to evaluate CAB/LEN in children in Uganda.
An EU-funded EDCTP study in Uganda to study ART-naive people at high risk of poor adherence.
An MSF study in people with low CD4 counts <200 cells/mm3.
SUPPRESS-LA (Gates-funded) in pregnant women in several countries in Africa, compared to DTG-based ART.

Another alternative would be to use drugs that are becoming available in PrEP programmes, but this also seems to be blocked.

References

Monica Gandhi. Beyond pills: The future of long-acting and curative therapies. Symposium SY05.
https://programme.aids2026.org/Programme/Session/23 (Abstract)
https://conference.aids2026.org/media-325-beyond-pills-the-future-of-long-acting-and-curative-therapies (Webcast)
Spinelli M et al. HIV Viral Suppression With Use of Long-Acting Antiretroviral Therapy in People With and Without Initial Viremia. JAMA Apr 22;333(16):1451-1453. doi: 10.1001/jama.2025.0109. (22 April 2025).
https://pubmed.ncbi.nlm.nih.gov/40048173
Rockstroh JK et al. Once-weekly oral islatravir/lenacapavir (ISL/LEN) versus daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed adults with HIV-1: Week 48 results of the ISLEND-1 phase 3 trial. Late-breaking oral abstract OAB1406LB.
https://programme.aids2026.org/Abstract/Abstract/?abstractid=12349
Colson AE et al. Once-weekly oral islatravir/lenacapavir (ISL/LEN) versus daily standard-of-care therapy in virologically suppressed adults with HIV-1: week 48 results of the ISLEND-2 phase 3 trial. Late breaking oral abstract OAX1106LB.
https://programme.aids2026.org/Abstract/Abstract/?abstractid=12363
Rockstroh JK et al for the ISLEND-1 Study Team. Phase 3 Trial of Weekly Oral Islatravir–Lenacapavir for HIV-1 Treatment, for the ISLEND-1 NEJM. DOI: 10.1056/NEJMoa2607973. (29 July 2026).
https://www.nejm.org/doi/full/10.1056/NEJMoa2607973
Luetkemeyer AF et al. Randomized active-controlled phase 2b study evaluating efficacy and safety of switch to islatravir (ISL) 2 mg with ulonivirine (ULO) 200 mg once weekly in virologically suppressed adults living with HIV-1. Late-breaking oral abstract OAB1405LB.
https://programme.aids2026.org/Abstract/Abstract/?abstractid=12324 (abstract)
https://conference.aids2026.org/media-348-artistic-strategies-2-the-long-game (webcast)
McMahon J et al. Efficacy and safety of twice-yearly lenacapavir, teropavimab, and zinlirvimab as an HIV-1 treatment for up to 104 weeks. Oral abstract OAB1403.
https://programme.aids2026.org/Abstract/Abstract/?abstractid=9973 (abstract)
https://conference.aids2026.org/media-348-artistic-strategies-2-the-long-game (webcast)
ClinicalTrials.gov. Study of Lenacapavir, Teropavimab, and Zinlirvimab in Virologically Suppressed Adults With HIV-1 on Stable Oral Treatment Regimens.
https://clinicaltrials.gov/study/NCT07683000
ClinicalTrials.gov. Study of Lenacapavir, Teropavimab, and Zinlirvimab Versus Cabotegravir and Rilpivirine in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy.
https://clinicaltrials.gov/study/NCT07682961
Gutner C et al. Participants report positive experiences switching from subcutaneous to intravenous lotivibart (LVB, N6LS, VH3810109) and cabotegravir long-acting injections for HIV-1 treatment in EMBRACE study. Poster abstract WEPEB097.
https://programme.aids2026.org/Abstract/Abstract/?abstractid=5995