CROI 2024 Abstract eBook

Abstract eBook

Invited Session

48

Why Is Cabotegravir Rollout So Slow? Rupa Patel Washington University in St Louis, St Louis, MO, USA

impact on the viral reservoir in humanized mice and ongoing studies in non human primates will be presented. These new developments have the potential to accelerate the application of this powerful approach to PLWH. Sex-Differences in Atherosclerotic CVD Risks and Mechanisms: Insights from REPRIEVE Markella Zanni Harvard University, Cambridge, MA, USA Background: The presentation highlights risks for atherosclerotic cardio- vascular disease, particularly myocardial infarction, among ART-treated people with HIV, with attention to sex-differences in such risks. Sex-differences in the pathophysiologic mechanisms contributing to risks for myocardial infarction among people with HIV are also explored. Finally, data supporting sex-specific risk mechanisms among women with HIV are presented. Immunomodulation and Cardiovascular Disease: Lessons Learned From HIV Priscilla Y Hsue University of California San Francisco, San Francisco, CA, USA Background: For this invited talk, the role of inflammation and cardiovascular disease will be reviewed both in the context of the general population and persons living with HIV. In particular, the impact of statin therapy on inflammation as part of the JUPITER (non-HIV) and REPRIEVE (HIV) trials will be compared. Among persons with HIV, proof-of-concept studies have provided insight by probing different targets in the inflammatory cascade. In the general population, anti-inflammatory interventions such as colchicine and canakinumab have significantly reduced clinical events. Differences in immmune-based therapeutics among persons with HIV and the general population will be discussed. Finally, future therapeutic strategies for immunomodulation which may be more relevant in the context of HIV disease pathogenesis will be considered. Implications for Implementing CVD Risk Prevention Strategies for Low- and Middle-Income Countries Mpiko Ntsekhe University of Cape Town, Cape Town, South Africa Background: The implications of the results of Reprieve trial for Low and Middle Income Countries (LMICs), where the global burden of HIV, and the number of PWH who would be eligible to receive a statin based on the trial entry criteria are highest, are not clear. At face value it would seem that the potential to derive significant benefit from CVD morbidity and mortality reduction in PWH, should make the decision to adopt a pharma based primary CVD prevention public health strategy straightforward. On the other hand there are a number of challenges to implementing such a strategy in LMICS for policy makers, clinicians and health finance authorities, particularly in sub-Saharan Africa where the largest number of PWH live and resources are lowest. Whereas ASCVD is now the major cause of morbidity and mortality in PWH in many HICS, the same is not be true in most LMICS. Despite modeling estimates which suggest both a high incident ASCVD rate and large fraction of ASCVD attributable to HIV, observational (real world) data and clinical practice paint a different picture. AIDS related opportunistic infections still dominate the list of major causes of overall morbidity and mortality and amongst the non-HIV related causes of morbidity and mortality, CVD contributes a small proportion. Finally, amongst those with CVD, non-ischemic causes predominate. This may explain the relatively low LMICS MACE rate in the trial and significantly limits the justification for allocation of scarce resources to this important cause over others. Second, there are significant challenges to the use of conventional ASCVD risk scoring tools such as the Pooled Cohort Estimate (PCE) used in the trial to both HIV and non-HIV populations in LMICs. For example whereas the anticipated MACE rate based in part on study baseline PCE scores in the REPRIEVE trial was 12/1000, the observed MACE in the placebo arm was less than 3.5/1000 in participating LMICs and less than 2 in SSA. Such a low event rate would almost double the number of participants needed to treat to benefit from a statin, and by extension add significant costs to already constrained healthcare budgets. Given these and related challenges, a focus on healthy lifestyle and optimization of traditional risk factors, is likely to remain the primary prevention strategy of choice in PWH living in LMICs for the near term future.

Background: Long-acting injectable cabotegravir as pre-exposure prophylaxis for HIV prevention (LAI CAB PrEP) has been FDA approved in the U.S. since December 2021. Approvals are in place or pending in many countries and regions globally, and it is being evaluated for programmatic implementation in a variety of contexts. Since FDA approval in the U.S., LAI CAB PrEP implementation and scale-up has been relatively slow across the nation. In this presentation, we will highlight the challenges and opportunities in LAI CAB PrEP program initiation and describe select strategies that have supported successful programs. The Ring Comes Full Circle: Navigating the Complex Landscape of Biomedical Prevention Post-Phase III Leila E Mansoor Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa Background: The biomedical prevention landscape enters a pivotal phase as dapivirine (DPV) vaginal ring progresses beyond Phase III clinical trials. This presentation explores: the role of open-label extension (OLE) studies in refining Phase III results, insights from recent PEPFAR-based data in Zimbabwe on real-world ring use, and the intricate balance required in shaping future target product profiles within a complex regulatory landscape. Topical HIV prevention methods offer not only localized defense but also systemic protection. DPV ring Phase III trials revealed a 30% efficacy point estimate, rising to a promising 50% in women over 21. While pivotal for safety data, OLE studies complement and refine Phase III outcomes. Incorporating real-world scenarios, diverse populations, and long-term observations, these studies provide essential insights for optimizing DPV ring deployment. DPV ring OLE studies found increased counterfactual efficacy estimates. Increased adherence and retention relative to the randomized controlled trials were also noted. WHO's endorsement propels DPV ring implementation in 11 countries, targeting empowerment for young women, who often face heightened vulnerability due to age-related power dynamics, influencing the cycle of transmission. Favorable views expressed by women in Zimbabwe, underscore the tangible impact of DPV ring implementation. Examining usage patterns, adherence challenges, and demographic factors bridges the gap between clinical trials and practical implementation in resource-limited settings. Additionally, local manufacturing in South Africa aims to reduce ring costs significantly. Navigating a complex regulatory environment, DPV ring demands careful consideration for future target product profiles. Despite Phase III outcomes, studies in adolescents (MTN-034/REACH), pregnant women (MTN-042/DELIVER), and breastfeeding women (MTN-043/B-Protected) affirm safety and acceptability. Emerging 90-day variants and multi-purpose prevention technologies (MPT) underscore the pivotal balance for widespread acceptance and global success. "The Ring Comes Full Circle" represents a crucial juncture in biomedical prevention. Through open-label studies, real-world insights, including vulnerable populations, and a nuanced regulatory approach, we pave the way for effective, user-friendly, and globally applicable interventions. Beyond Phase III perils, DPV ring, with evolving iterations, contributes to our global arsenal against HIV. Background: HIV is preventable with the use of daily oral PrEP or long-acting injectable PrEP for all populations regardless of sex or gender. Additionally, event-driven PrEP is an option for cisgender men who desire intermittent use of medications. The IPERGAY Trial provided an important answer, intermittent dosing of PrEP is an effective method to prevent HIV, and as the only randomized controlled trial of event-driven PrEP, we are left with a persistently unanswered question, does event-driven PrEP only work for cisgender men? Real-world data and observational studies in Paris, San Francisco, Bangkok, Johannesburg, Amsterdam, and Harlem suggest that event-driven PrEP is desired, effective, and cost-effective. Cisgender women in Southern and Eastern Africa have reported a preference for an HIV prevention method that did not require taking daily pills, which made event-driven dosing more user-friendly and acceptable. However, efficacy data on event-driven PrEP among cisgender women are lacking. Pharmacokinetic studies on drug levels in plasma, rectum, and genital samples from cisgender women, cisgender men, and transgender Challenging the Dogma of Event-Driven PrEP Jenell Stewart Hennepin Healthcare and University of Minnesota, Minneapolis, MN, USA

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Invited Session

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CROI 2024