The science of Durban,AIDS 2016

Introduction : The science presented at the 21st International AIDS Conference in Durban, South Africa, in July 2016, addressed the state of the field across basic, clinical, prevention, law and policy and implementation science. Methods and Results : The AIDS response has seen remarkable achievements in scientific advances, in translation of those advances into prevention, treatment and care for affected individuals and communities, and in large scale implementation – reaching 18 million people with antiviral therapy by mid‐year 2016. Yet incident HIV infections in adults remain stubbornly stable and are increasing in some regions and among adolescents and adults in some key populations, challenging current science, policy and programming. There have been important advances in both preventive vaccines and in cure research, but both areas require ongoing investment and innovation. Clinical research has flourished with new agents, regimens, delivery modes and diagnostics but has been challenged by aging and increasingly complex patient populations, long‐term adherence challenges, co‐infections and co‐morbidities, and unresolved issues in TB management and epidemic control. It is an extraordinary period of innovation in prevention, yet the promise of new tools and combination approaches have yet to deliver epidemic HIV control. Conclusions : Proven interventions, most notably pre‐exposure prophylaxis, PrEP, have been limited in rollout and impact. Treatment as prevention has the promise to improve clinical outcomes but remains uncertain as a prevention tool to reduce population‐level HIV incidence. The improvement of legal, policy and human rights environments for those most at risk for HIV acquisition and most at risk for lack of access to essential services; sexual and gender minorities, sex workers of all genders, people who inject drugs, and prisoners and detainees remain among the greatest unmet needs in HIV/AIDS. Failure to do better for these individuals and communities could undermine the HIV response.     

Novel glucagon receptor antagonists with improved selectivity over the glucose-dependent insulinotropic polypeptide receptor

Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closely related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a >1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperglycemia in Sprague-Dawley rats. Furthermore, the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.     

Motivated Reasoning and HIV Risk? Views on Relationships,Trust, and Risk from Young Women in Cape Town,South Africa,and Implications for Oral PrEP

In high prevalence environments relationship characteristics are likely to be associated with HIV risk, yet evidence indicates general underestimation of risk. Furthermore uncertainty about partner‘s risk may challenge PrEP demand among young African women. We conducted quantitative and qualitative interviews with women before and after HIV discussions with partners, to explore how partner’s behavior affected risk perceptions and interest in PrEP. Twenty-three women were interviewed once; twelve had a follow-up interview after speaking to their partners. Fourteen women were willing to have their partner contacted; yet two men participated. Several themes related to relationships and risk were identified. These highlighted that young women’s romantic feelings and expectations influenced their perceptions of risk within their relationships, consistent with the concept of motivated reasoning. Findings emphasize challenges in using risk to promote HIV prevention among young women. Framing PrEP in a positive empowering way that avoids linking it to relationship risk may ultimately encourage greater uptake.     

Expanding the space: inclusion of most-at-risk populations in HIV prevention, treatment, and care services

The provision of appropriate HIV prevention, treatment, and care services for most-at-risk populations (MARP) will challenge many health care systems. For people who sell sex or inject drugs and for men who have sex with men, stigma, discrimination, and criminalization can limit access to care, inhibit service uptake, and reduce the disclosure of risks. Several models for provision of HIV services to MARP may address these issues. We discuss integrated models, stand-alone services, and hybrid models, which may be appropriate for some MARP in some settings. Both public health and human rights frameworks concur that those at greatest risk should have expanded access to services.