Rappourteur’s report – Symposium (SY04): ARVs for Prevention: Extrapolating from Data to Clinical Practice

Symposium (SY04): ARVs for Prevention: Extrapolating from Data to Clinical Practice

The first presentation in the session by Marta Boffito highlighted the importance of both pharmacokinetic and pharmacodynamic studies in the evaluation of novel PrEP agents. She highlighted the important role of animal models, as well as Phase 1, 2 and 3 studies in providing data to guide dosing strategies but stressed the importance of understanding cellular pharmacology considerations for these drugs, which include drug penetration into relevant tissues and cell types, race/ethnicity/pharmacogenetics, gender and appropriate dosing strategies based on pharmacokinetic principles. Further, she highlighted, that while drug concentrations in animal models and in vivo human tissues may correlate well with efficacy (e.g. for TDF/FTC), some drugs do not always show optimal tissue exposure (e.g. Cabotegravir LA), thus understanding what and how new PrEP agents may be effective extends beyond just tissue concentrations.

Charles Dobard of the Centers for Disease Control and Prevention (CDC) discussed the use of animal models in preclinical studies of ARVs for PrEP. These models, particularly humanized mouse models and nonhuman primate models using macaques, allow for the assessment of biological efficacy of PrEP under highly controlled conditions, thus playing a key role in defining relationships between pharmacokinetics and pharmacodynamics of experimental agents. Dobard highlighted recent exciting advances including the elucidation of a Rhesus macaque model of penile SHIV transmission as well as animal model studies showing high efficacy against rectal, vaginal and penile SHIV using both Tenofovir Alafenamide (TAF) and long-acting cabotegravir regimens.

The second two presentations of the session focused on practical aspects of PrEP implementation. Irene Mukui, systematically described the impressive progress and lessons learned from the national roll-out of a PrEP program in Kenya. In May of 2017, 1425 Kenyans were currently on PrEP compared to 17,466 in August 2018. She described how this has been achieved through the coordinated effort of multiple national and international stakeholders, integration into existing systems (e.g. Existing ARV supply chains) as well as through community involvement and demand creation. Efficient, strategic information systems and epidemiologic mapping enabled focusing on specific geographic areas (high incidence clusters) and populations.

The last presentation from civil society activist Emily Bass reviewed the interplay between advocacy and implementation. She opted for a “power-point-less” presentation, but providing, nonetheless, a well-articulated, self-reflective examination of PrEP roll-out throughout most of SSA and the current and future role of advocates/activists in this. Bass and colleagues also described the importance of ensuring that demand creation for PrEP and other novel prevention methods was undertaken creatively, meaningfully and with intent.

Rappourteur summary – Oral abstract (OA04): Entry into the PrEP Continuum

Oral abstract (OA04): Entry into the PrEP Continuum

In the oral abstract session, “Entry into the PrEP Continuum,” speakers highlighted the critical roles of monitoring PrEP outcomes and determining individuals’ motivations for initiating PrEP with respect to promoting PrEP scale-up among key populations globally.

Laura Fitch presented data from AVAC’s Global PrEP tracker (available at PrEPWatch.org) that includes a comprehensive database of information ongoing and planned demonstration projects, implementation initiatives, and national programs worldwide. Data from the first quarter of 2018 indicate that 309,525 people have been initiated on PrEP globally. North America and Sub-Saharan Africa currently have the highest overall number of initiations, accounting for 71% and 15% of the total number of users respectively. In the US, the majority of users are men who have sex with men (MSM), while the majority of users in sub-Saharan Africa are adolescent girls and young women (AGYW).

Kristi Gamarel and Nicholas Thuo both discussed important findings regarding individual motivations to use PrEP. Gameral provided information collected from MSM in New York, in primary partnerships. She found that those who had sexual goals congruent with those of their partner were 2-times more likely to initiate PrEP. Among young women in Kenya, Thuo et al. found, through qualitative interviews with PrEP initiators, that young women were self-aware and able to accurately identify risk in their relationships and interactions. The primary factors influencing their uptake of PrEP included a fear of acquiring HIV, their own perceived risk of HIV, and PrEP recommendations from health care workers and trusted peers.

Rosemary Delabre provided data on risk, risk-reduction behaviors and interest in using PrEP among transgender persons participating in a community-based, online survey in Europe. Among 245 transgender respondents (145 identifying as transgender women [TW] and 100 identifying as transgender men [TM] ); more than half of TW (n=74, 54.4%) and almost one-third of TM (n=28, 28.9%) reported interest in using PrEP. She emphasized the importance of engaging transgender persons in research and in tailored PrEP programs. From a local perspective, Albert Liu provided data from two population-based studies of HIV-uninfected TW and MSM conducted in San Francisco. Using this data, 97% of MSM and 79% of TGW in San Francisco were awae of PrEP, yet only 40% of MSM and 15% of TGW had used PrEP despite high levels of health insurance coverage and engagement in health care.

Rappourteur summary – Oral abstract (OA01): Location, Location, Location: Mucosal Mediators of Risk

Oral abstract (OA01): Location, Location, Location: Mucosal Mediators of Risk

This session addressed the importance of understanding the role of the mucosal female genital tract (FGT) in the risk of HIV acquisition and the efficacy of PrEP.

Mucosal inflammation for example can increase the risk of HIV infection by recruiting and activating immune target cells in the FGT. Fowke and colleagues presented data showing that when daily low dose acetylsalicylic acid (ASA) is administered to HIV-negative low risk women, there was a 35% and 28% reduction, respectively, in CCR5+ CD4+ T cells and Th17 cells in the FGT. They concluded that daily use of ASA could be a novel approach that, when combined other methods of prevention, might reduce the risk of HIV infection.

Hormonal contraception (HC) is among strategies used to prevent unwanted pregnancies. However, HC may affect HIV-1 risk through changes in FGT microbiota. Balle et al. examined the impact of three HC methods on the adolescent FGT microbiota and related mucosal cytokine levels in a randomized, crossover trial. Adolescent girls (n=131), aged 15 to 19 were enrolled and randomized into three study arms: 1. injectable norethisterone enanthate (NET-EN), 2. combined oral contraceptives (COCs) or 3. combined contraceptive vaginal ring (CCVR) for 16 weeks. Participants were then switched to a second HC for four months. Use of COCs was found to be associated with lower microbial diversity and decreased abundance of bacterial vaginosis (BV)-associated bacteria in the vagina correlating with lower inflammation and potentially a lower HIV risk.

Pre-exposure prophylaxis (PrEP) in women has been found to have highly variable efficacy which has recently been associated with dysbiotic vaginal microbiota. Cheu et al. investigated the mechanism(s) underlying how vaginal bacteria might alter PrEP drug levels through bacteria-mediated metabolism. By co-culturing Jurkat cells (HIV targets) with PrEP drugs (tenofovir [TFV], tenofovir alafenamide [TAF], and dapirivine [DPV]) the investigators found that vaginal dysbiosis can metabolize PrEP drugs including TFV and DPV. This highlights the role that the microbiome can play in drug uptake to target sites and systemic availability and how this may affect virus transmission and treatment for prevention. Thus, understanding the vaginal microbiome and prevention of BV are critical for improving HIV prevention strategies.

Track D rappourteurs’ report at 2018 HIV R4P – MEN-ding the Gaps

The MEN-ding the Gaps session started off with a poster discussion exploring barriers to HCT in men. Barriers included fear of knowing HIV status, the assumption that acquiring HIV is seen as inevitable in this setting, use of female partner’s HIV status as proxy for male HIV testing, social status, stigmatisation and masculinity. Introduction of the proposed technology and HIV self-testing (HIVST), was looked upon favourably as HIVST allows for privacy and linkage to care via mobile phones has potential to overcome barriers to HIV testing and linkage to care in men. A study describing awareness, willingness and barriers to HIVST use among 4136 MSM in Brazil who use a gay social networking app revealed that 22% never tested for HIV. Main reasons were fear of a positive result (39%), shame (24%) and lack of perceived HIV risk (12%). Awareness and willingness to use HIVST were low (32% and 44% respectively) among the MSM analysed. Factors associated with HIVST willingness included income, schooling, intention to use condoms, PrEP willingness, trust in HIVST in comparison to conventional tests and pre-test counselling and decreased marijuana use. A study conducted by CDC Zambia sought to profile demographic characteristics of uncircumcised males to help address gaps in increasing circumcision coverage in Zambia. It concluded that circumcision programs need to focus on provinces with the highest HIV rates and be tailored to increase circumcision uptake among young, unmarried Zambian males with some education, who are more likely to reside in rural areas and likely to have had recent unprotected sex with a non-marital partner.

Track D rappourteurs’ report at 2018 HIV R4P – Its all about choices

HIV prevention is all about choice, but if one chooses HPTN-077, a study by HIV Prevention Trials Network sought to test acceptability of long acting injectable Cabotegravir (CAB LA) in HIV uninfected, low-risk men and women in the U.S., Brazil, South Africa and Malawi. It was observed that herte was a strong preference for a LAI PrEP at both baseline and follow-up, with product attributes being moderately to highly acceptable to most of the participants in both cohorts. Furthermore, participants from non-U.S. versus U.S. sites were found to be more interested in future use of an injectable PrEP. However, given the large differences between geographic regions, introduction strategies will likely require tailoring.

A discrete choice experiment conducted by the Research Tringle Institute International on attribute preferences for long-acting PrEP among South African youths found that each attribute evaluated influenced preferences of the youth, but duration of effectiveness exerted the strongest influence on preferences. Location of where to obtain the product was more influential, overall, for females than males, with females preferring to access method at a health care facility.

Quatro, a study among young women in Zimbabwe and South Africa tested the acceptability of four vaginal delivery forms (vaginal gel, films, rings and insert) for preventing HIV. The findings from adherence marker evaluation confirmed that most women did use the product, at least two times during the month of use, over half of the women who chose an on-demand product used it with sex and older women were more adherent to product. Interestingly, most of the women using the IVR, used it for the full 30 days. The findings from preferences study highlighted that users desired multiple prevention options hence women should be given various options to choose from.

Another study, ‘Influencers of Use and Attitudes Towards the Dapivirine Vaginal Ring’ it was found that partners were the main influencers of ring use, however, partner support was largely obtained after vaginal ring information provision. The study concluded that partner engagement is important for support of products that might impact on sexual relationships and recommends community, partner and individual level messaging on ring use and side effects to improve adherent ring use.

It is all about choice, the uChoose study data suggest that long acting injectable PrEP would be a method of choice for prevention in adolescents.