Robert Newells

Session included the announcement of a new anti-stigma award from ViiV, updates on HIV cure and vaccine research, review of integrase inhibitors for treatment and prevention, and a call for a "differentiated" prevention approach.

Dr. Pedro Cahn, Scientific Director of Fundacion Huesped in Argentina, discussed the use of Integrase Strand Transfer Inhibitors (InSTIs) such as dolutegravir in treatment and cabotegravir in PrEP; a drug class could help “succeed” with goals of 90-90-90 as they are superior or non inferior compared to today’s first line regimens. He reviewed current guidance questions related to a possible association between dolutegravir use in pregnancy and risk of neural tube defects identified in a Botswana study. What he called “unprecedented rollout in low-income countries” highlights the need for implementation research. Dr. Nduku Kilonzo of the National AIDS Control Council in Kenya talked about the need for differentiated models of HIV prevention, including scaled up primary prevention to address persistently high rates of HIV incidence, noting huge gap in harm reduction services in epidemics driven by drug use and that “success in VMMC [was] not celebrated enough or leveraged enough.”

With progress but significant time to go before a vaccine or a cure, there is urgent need for scaled up primary prevention and access to effective, well tolerated ART regimens. This work must happen in the context of research, monitoring and stakeholder engagement that addresses unanswered questions, identifies best practices to support informed choice, along with advocacy to ensure adequate funding for this work.

Shona Dalal

The plenary session today focused on innovative approaches in the search for a cure and vaccine for HIV, the use of integrase inhibitors as antiretrovirals, and approaches to HIV prevention that are needed to reduce the numbers of new HIV infections that continue to occur every year.

Brad Jones described a dynamic reservoir of virus with proliferating viral clones as a challenge in finding an HIV cure. Broadly neutralizing antibodies and adenovirus based vaccines show promise. Pedro Cahn discussed the movement towards broader use of integrase inhibitors and long-acting formulations. Cautions include their use as monotherapy, with TB drugs, and with dolutegravir for women of child-bearing age. Implementation research is needed to make the rollout of different ARV regimens effective. Nduku Kilonzo highlighted the need to rethink primary prevention, the lack of funding, and the need to increase access to services. Prevention is particularly important because of the transmission that occurs during acute infection before a person can conceivably be on treatment. Analyzing data at sub-national levels is important to capture heterogeneity in HIV prevalence for focused attention. A multi-sectoral, scaled response with sub-national prevention targets, routine data reviews, and political will is needed to show progress.

Broadly neutralizing antibodies and adenovirus-based vaccines show encouraging responses in animal models and non-human primates; their efficacy in human populations is an area to watch. Integrase inhibitors have many positive features and implementation research will aid rollout. Caution, contraception, and informed choice for women of childbearing age are recommended with dolutegravir until further surveillance data is available on causality of neural tube defects. Reductions in funding, flatlined new infections, and dramatic population increases in sub-Saharan Africa highlight a need to differentiate HIV prevention. Focusing interventions at finer geographic levels, strengthened data systems, and implementation research is needed for long-term success.

Julie Mitchell

In the first talk of the plenary session, Brad Jones discussed the advancements and challenges in biomedical research focused on developing a cure and a vaccine for HIV.

To prevent HIV rebound after ART discontinuation, we need to develop strategies that eliminate HIV-infected cells, boost the immune response to control replication, or, more likely, do both. While clinical trials are attempting to eliminate the viral reservoir have shown increased HIV expression in vivo, a reduction in reservoir size has not been seen. However, recent studies combining a TLR7 agonist and broadly neutralizing antibodies (bNAbs) have shown promise in inducing viral control in non-human primate models. In vaccine development, a goal is to elicite bNAbs, which are protective against infection in animal models. However, bNAbs have unique characteristics that make them difficult to develop so further studies are needed to design new vaccine strategies to elicit them. Finally, a new Ad26 mosaic HIV vaccine has shown safety and immunogenicity in early human trials comparable to parallel non-human primate trials, and an efficacy study has begun enrolling African women.

Dr. Jones made two important points regarding our continued efforts to develop a cure and vaccine. The first was that we need a better understanding of the size and dynamics of the viral reservoir. Without proper knowledge of the quantity of intact versus defective provirus, the latently infected cell types, and the anatomical locations harboring reservoir, we risk inappropriately interpreting results. The final point was that, while our focus is on HIV, the scientific discoveries we make in the process are seeds that will be used to save lives from other conditions long after the HIV epidemic is over.

Mosepele Mosepele

The plenary delivered by Pedro Cahn in this session was a compelling review of the integrase inhibitor (InSTI) class of drugs, emphasizing why this class is increasingly the preferred class of ARVs as evidenced by their widespread use globally, including across an estimated 50% of lower-and-middle income countries.

Among patients initiating ART, several trials favored InSTIs over NNRTIs and PIs. Benefits of InSTIs include rapid viral decay, better CD4 recovery, higher barrier to resistance and no evidence of increased IRIS, including in patients with TB. In ART switch studies, InSTIs maintain viral efficacy with better lipid indices among PI experienced patients. Among those experiencing virologic failure, an estimated 70-100% of patients attain viral suppression, when prescribed InSTIs containing ART. In terms of treatment simplification for virally suppressed patients, maintenance dual ART with 3TC-Dolutegravir (DTG) or DTG/rilpivirine seems as effective as the traditional triple ART regimen. In the near future, HPTN083 and HPTN084 trials will provide new data on the efficacy of long-acting Cabotegravir (LA CaB) in PrEP. Despite shift towards use of InSTIs globally, some questions remain, particularly safety in pregnancy and risk of InSTI resistance when DTG is used together with a compromised NRTI-backbone in routine care.

This plenary provided a clear and compelling overview of the role of InSTIs across different clinical settings globally, and a balanced report on what is less well known about InSTIs. Of note, the InSTI era seems promising for 2nd generation (DTG, BIC and CAB) but not for first generation agents (Raltegravir, Elvitegravir). It is likely that 2nd generation InSTIs era will usher in dual ART therapy (oral or even injectable) as a standard of care in many settings in the future