Benjamin Bavinton

Today’s AIDS 2024 Co-Chair’s Choice Special Session (SS04) included one of the most highly anticipated presentations for Track C at this year’s conference: interim results from the PURPOSE 1 trial evaluating twice-yearly long-acting injectable Lenacapavir (LEN) in cisgender women.

In 5345 cis-women, PURPOSE 1 compared the efficacy of LEN to daily F/TAF, daily F/TDF, and background counterfactual HIV incidence, with the results presented by Linda-Gail Bekker. Baseline characteristics were similar, with ~6-7% having used PrEP previously. There were zero infections in the LEN arm, and LEN efficacy was superior to both background incidence and F/TDF. >90% of LEN injections were on-time. Although adherence to F/TAF and F/TDF was poor, lower likelihood of infection was associated with medium or high adherence to F/TAF compared to low adherence (OR=0.11, 95%CI=0.012-0.49) in a nested case-control study. Both LEN and F/TAF were safe and well-tolerated, while injection site reactions to LEN diminished with time and led to only 4 discontinuations. Pregnant women participated in the trial; available pregnancy outcomes were similar across the arms and to those expected for the population. To account for LEVI syndrome, RNA testing is being conducted in the trial and open-label extension (OLE), with no evidence to-date of masked infections (though the OLE data will continue to further inform this). While adherence to F/TAF was poor, Bekker noted that some women do prefer pills, and hopes the data will encourage regulatory approvals for F/TAF for cis-women.

PURPOSE 1 shows that twice-yearly LEN offers an efficacious, safe, and discreet choice to improve PrEP use among cis-women. Several important innovations were included in the trial design (e.g. inclusion of adolescents and pregnant women; using background incidence for comparison). We eagerly await the results for PURPOSE 2 in cis-MSM and gender diverse populations, as well as further data from the PURPOSE 1 OLE and on the pharmacokinetic tail. Equity of access and scale-up to LEN will be a major focus in the next few years, as “for global impact, we need both efficacy and access”. NEJM article: DOI 10.1056/NEJMoa2407001.

Andrea Olga Papadopoulos

Six landmark abstracts were selected by co-chairs, Lewin, Spinner and Klepikov, each offering groundbreaking interventions in the HIV epidemic, notably ‘The Next Berlin patient’, 100% efficacy of HIV prevention in African women using a novel injectable prep. The IAS president’s award was presented to none other than Prof Françoise Barré-Sinoussi.

A truly special session, Christian Gaebler described “The Next Berlin patient”, the first successful attempt utilizing heterozygous CCR5 WT/Δ32 genotype hematopoietic stem cell transplantation to co-cure HIV and acute myeloid leukemia. HIV cure was demonstrated here by sustained undetectable viral load, undetectable reservoir DNA and steady decline in antibody titres for five years after stopping ART treatment following transplantation. For HIV prevention, Linda Gail Bekker presented findings of the PURPOSE-1 study, in which six-monthly injectible Lenacapavir proved 100% effective PrEP for enrolled, sexually-active, young cis gender women, compared to less-effective, adherence-challenged daily pill PrEP. In the ART realm, Gary Blick showed potential for switching from three-drug to a two-drug regimen (DTG and 3TC) even in people bearing the M184V/I resistance mutation, questioning “Do we still need to use TDF in developing countries?”. Further, innovative point-of-care interventions show utility in enhancing treatment adherence by way of monthly urine testing for TFV in the STREAM trial presented by Nigel Garret of CAPRISA; and enhancing healthcare access via vending machines distributed by NGOs around Moldova, presented by Ruslan Poverga. Béatrice Bercot showed data that DoxyPEP increases resistance of N. gonorrhea to tetracycline at the tetM gene, an already-prevalent form of antimicrobial resistance.

Following 41 years since Prof Barré-Sinoussi identified HIV (this year’s recipient of the IAS president’s award), the six talks represent the promise of rapidly evolving, innovative HIV science. Each study pushed passed previous conventions and boundaries: achieving cure with heterozygous CCR5/Δ32 transplantation instead of homozygous; designing PreP and healthcare access around ‘putting people first’, simplifying adherence monitoring and the critical possibility of simplifying ART to just two drugs, ‘saving costs and saving lives.’ This calls for debate as to whether genotypic drug resistance always equates to clinical resistance, and needs to be tested in larger study groups.