CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

109 CONTRACEPTION AND HIV RISK: A CONUNDRUM NO MORE Renee Heffron , University of Washington, Seattle, WA, USA This talk will provide state-of-the-art evidence on why we have come to understand that injectable depot medroxyprogesterone acetate does not impact women’s susceptibility to HIV infection. It will also examine reasons why data from recent studies have had conflicting results, discuss biologic changes elicited by contraceptive initiation that are relevant for women’s health beyond HIV susceptibility, and point out consequential questions in this domain that are remaining to be addressed. 110 THE STATE OF SRHR & HIV SERVICES FOR CISGENDER WOMEN: A COMMUNITY PERSPECTIVE Wame Jallow , International Treatment Preparedness Coalition, Gaborone, Botswana Globally, 19.1 million of the 36.9 million people living with HIV are cisgender women and girls. Countries are failing to meet commitments to the 2016 United Nations Political Declaration on Ending AIDS among adolescent girls and young women (ages 15 to 24), including reducing new HIV infections to below 100,000 per year by 2020, eliminating gender inequalities and all forms of gender-based abuse and violence, encouraging and supporting leadership of young people, scaling up comprehensive sexual and reproductive health education, and protecting their human rights. In 2018, a potential safety signal associating peri-conception dolutegravir (DTG) use with neural tube defects (NTDs) was reported. It cast a harsh spotlight on chronic problems: access to and quality of essential sexual and reproductive health rights and services for women and girls at risk for or living with HIV - particularly among those ages 14-49. The policy and access fallouts from the DTG signal – including national sex-based treatment restrictions for women and adolescent girls - has underscored that they must be essential stakeholders in design, development, implementation, delivery and oversight of HIV research, guidelines, policies and services. In sub-Saharan Africa, which is home to the world’s highest HIV rate and the lowest prevalence of contraception, access to and quality of essential sexual and reproductive health rights and services are complicated by a range of gender, social, economic, geographic, provider-level, structural and other barriers, limited choices, and lack of information – especially for younger, unmarried and rural women. A survey to assess the current status of sexual and reproductive rights, and HIV services was conducted in January 2020 among women and girls living with HIV in sub-Saharan Africa. Survey participants shared barriers to, and quality of these services - including access to optimal HIV treatment, what should be included in a ‘package of care’ - and their research and policy recommendations for implementing and monitoring solutions. 111 RECENT ADVANCES IN THE DIAGNOSIS, TREATMENT AND PREVENTION OF TUBERCULOSIS Gavin Churchyard , The Aurum Institute, Johannesburg, South Africa Recent advances in the diagnosis, treatment, and prevention of tuberculosis (TB) will be summarized and the importance of these advances for people with HIV discussed. Gaps in current knowledge that need to be addressed to accelerate progress towards ending the TB epidemic will be identified. A roadmap for TB related presentations at CROI will be presented. Shane Crotty , La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA Understanding the immunology of helper T cells, germinal centers, and the human naive B cell repertoire to enable better vaccine design Most vaccines provide protection from infection through the generation of neutralizing antibodies (nAbs). The repertoire of naive B cells is the starting material fromwhich nAbs eventually arise. Immunization strategies are increasingly targeting precise B cell specificities to mimic nAbs generated during natural infection, in an effort to maximize the potency of the vaccine-elicited Ab response. An understanding of the human B cell specificities capable of immunogen recognition can aid in immunogen design and inform decision- making for clinical trial advancement. We have developed strategies to probe for antigen-specific B cells in the human naive B cell repertoire (Science 2016, Science Translational Medicine 2018, COI 2018, and Science 2019) Germinal centers (GCs) are the engines of affinity maturation and are the critical source of memory B cells and long-lived plasma cells. GCs are entirely dependent on T follicular helper (Tfh) CD4 T cells (Immunity 2019). Helping B 112 ENGINEERING VACCINE IMMUNITY

innate and adaptive responses and to block inhibitory pathways. The targeting of the adaptive immune response may be particularly critical, since functional cure observed during spontaneous resolution of acute hepatitis B (sAg loss, sAb seroconversion) is heavily dependent on a brisk T cell response. In this regard, success using an anti-PD-1 approach has been observed in early studies of these agents in chronic hepatitis B. It is likely that some combination of these novel treatment approaches and existing approved agents will be necessary to achieve functional cure. Alan S. Perelson , Los Alamos National Laboratory, Los Alamos, NM, USA Current therapies for HBV infection generate a sterilizing or functional cure in a very small fraction of treated individuals. Thus, many new therapeutic approaches are under preclinical and clinical development. Here I will show how insights into these new therapies and HBV biology can be gained by mathematically modeling some of the accumulating experimental data. For example, by blocking new infections with the entry inhibitor Myrculdex B (Myr-B), one can gain insight into the lifespan of HBV-infected hepatocytes. Analysis of viral load decay after initiation of Myr-B therapy suggests that there may be heterogeneity in the lifespan of HBV infected cells in vivo, with some infected cells living much longer than others and producing less virus. As another example, I will show how newmathematical models are able to provide quantitative insights into the effects of monotherapy using a capsid inhibitor (CI) and combination therapies of a CI with a nucleic acid analog. Lastly, I will discuss howmodeling is providing new estimates of the plasma half-life of HbsAg (as well as that of other species such as HBV DNA and ALT) which may inform therapeutic progress and duration of therapy need to achieve a functional cure. Over half of individuals living with or at risk for HIV are of childbearing potential and in need of effective contraception to prevent unintended pregnancies. One barrier to effective hormonal contraception is drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormones. Interpreting the clinical impact of ARV-hormone DDI data is complicated by an inadequate understanding of hormone pharmacology, including the therapeutic range of different contraceptive products. For example, efavirenz decreases progestin exposure by 10-85%, depending on the progestin studied and the route of administration, yet the clinical impact of this reduction was not realized until subdermal contraceptive implants were scaled-up in combination with efavirenz-based antiretroviral therapy (ART). Specifically, data from a large cohort in Kenya described a 3-fold increase in the risk of pregnancy when progestin-releasing subdermal implants were combined with efavirenz-based ART, yet this excess risk was not observed with depot medroxyprogesterone or oral contraceptives. In addition, some data describe modestly lower ARV exposure when combined with hormones, suggesting the potential for bidirectional ARV-hormone DDIs. To investigate DDIs during ARV development, first, one study is conducted between the ARV and a combination of oral contraceptives in healthy volunteers. DDI information from that study is then extrapolated across contraceptives. This approach presumes that all types of exogenous progestins and estrogens have a similar pharmacokinetic disposition and that the route of administration does not influence the DDI potential of the combination. Recently, studies of non-oral hormones have observed differences in the extent of ARV-hormone DDIs compared to oral studies. Further, individual characteristics, including pharmacogenetics, are emerging as important determinants of the magnitude of DDIs. Taken together, applying a single oral DDI study across diverse populations, different hormones, and variable routes of administration greatly simplify the complex nature of these DDIs. As the field enters an era of HIV treatment and prevention with non-oral ARVs and ARV-hormone multi-purpose technologies to simultaneously prevent both HIV and pregnancy, there lies a critical gap in our understanding of how existing DDI data will extend to these new products across diverse patient populations.

106 THE MATHEMATICS OF HEPATITIS B CURE

Oral Abstracts

107 DRUG-DRUG INTERACTIONS: THE UPS AND DOWNS OF ANTIRETROVIRALS PLUS CONTRACEPTIVES Kimberly K. Scarsi , University of Nebraska, Omaha, NE, USA

108 CONTRACEPTIVE IMPLANT ROLLOUT IN SOUTH AFRICA Gregory Petro , University of Cape Town, Cape Town, South Africa

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CROI 2020