HomePEPFAR SAB Meeting Notes – April 5, 2024

# 									PEPFAR SAB Meeting Notes – April 5, 2024							

April 23, 2024

**Welcome**

**Time: 08.40**
        - *Call to order and FACA compliance*: Lindsey Yessick
        - *Welcome and other formalities*: mike Reid & Chairs Quarraisha Abdool-Karim & Carlos del Rio

Notes:
        - Dr. Lindsey Yessick, the designated federal officer for the PEPFAR Scientific Advisory Board, commences the meeting and reminds everyone of FACA provisions.
        - Dr. Mike Reid summarized the agenda, including the morning which focused on biomedical challenges and the afternoon covering strategic initiatives and sustainability.
        - Dr. Quarraisha Abdool-Karim. She thanked the American people for their ongoing support of PEPFAR and their generosity in saving lives across the least developed countries. She congratulated Amb. Nkengasong and his team for ensuring the efficient and effective delivery of this unprecedented program by any country. She thanked SAB members for taking the time to join in person or virtually. She reminded SAB members that there was a full agenda of updates on new areas e.g. sustainability, behavioral interventions, and new committees and importantly the guidance being sought from SAB on several key issues relating long-acting prevention and treatment agents and ARV drug resistance. She introduced and facilitated Session 1.

**Session 1: Introduction from AMB & Summary of PEPFAR’s funding**

**Time: 08.45**
        - Opening Comments, PEPFAR (Presenter: AMB Nkengasong)
        - Review of PEPFAR’s financial data (Presenter: Dr. Becky Bunnell, PEPFAR)
        - Brief Q&A

Notes:
        - The Ambassador reiterated that the one-year reauthorization is not a demonstration of diminished bipartisan support, but that we should continue to educate Congress and the public on PEPFAR. He also emphasized the role of the new Bureau to elevate the diplomatic engagement of HIV.           - Discussion             - SAB members thanked the Ambassador for reminding everyone how far we have come with treatment and attitudes towards treatment and how much remains to be done.
            - There are harmful changes happening in some environments, such as Uganda, that are politically complicated. SAB members asked how much they can hope that PEPFAR is able to make efforts in this area. They believe we should address these challenges in terms of how implementation science is conceptualized and how these issues come into that and what it means in terms of HIV prevention and access to treatment.
            - Amb. Nkengasong responded to question related to news of Ugandan Constitutional Court upholding most of the Anti-Homosexuality Act [AHA]               - Amb. Nkengasong noted we must not give up engagement and to directly address the issue of access to care for the LGBTQI community in Uganda and in other countries, including Ghana and Kenya
              - Amb. Nkengasong shared he had a recent phone conversation with Ugandan President Yoweri Musevni and that he and UNAIDS Executive Director Winnie Byanyima have recently also had dialogues with leadership in Ghana about ensuring LQBTQI+ persons and other key populations have continued access to essential HIV services.
              - Amb. Nkengsong reiterated that our HIV/AIDS response will not be successful if certain populations are neglected, noting “HIV/AIDS anywhere is HIV/AIDS everyone.” 
        - Dr. Bunnell provided an overview of the funding pipeline and the PEPFAR response to stagnant funding and the contributions she hoped the SAB would provide:           - Innovations available to PEPFAR
          - What implementation science should PEPFAR incorporate?
          - What is the sustainability roadmap for the science pillar of the strategy?
          - Discussion:             - What is the PEPFAR operational definition of equity? How will we know it when we see it? How is it measured?               - The strategy has a definition of equity. 

**Session 2: Dolutegravir Resistance – Implications for PEPFAR**

**Time: 09.15**
        - Review of PEPFAR DTG resistance data, including CADRE data (Presenter: Dr. Elliot Raizes, CDC)
        - Q&A and open discussion

Notes:
        - Dr. Raizes presented the results of four studies that show a variety of prevalence of dolutegravir resistance in people with elevated viral loads. His presentation sought to ask: is there a trend towards increased dolutegravir resistance since the TLD rollout, several years ago? Are there identifiable risk factors for DTG resistance? How well does DTG resistance in children track with adults? And do we need to be looking at unique risk factors for pediatric populations?
        - Discussion:           - Moderator opens discussion with comments on importance of additional research on dolutegravir resistance in terms of data sources; implications for first line treatment choices and advantages to TLD compared to previous first line treatment options. The cost effectiveness of routine screening of DTG resistance at this point in time and with limitations of available data is questionable.
          - Judy Auerbach: Supported moderator’s point on considering the resistance data in the context of treatment.             - Strategies to understand adherence before concerns about resistance are critical. How can we further evaluate adherence? 
          - Carlos del Rio: Underscored the importance of the DTG resistance data and highlighted that collaboration between PEPFAR and the ACTG in the A5381 study (An observational cohort to assess therapeutic efficacy and emergence of HIV drug resistance following initiation of tenofovir-Lamivudine-Dolutegravir (TLD) for first- or second-line ART) to generate needed data for informing PEPFAR policies and programming including the unanswered questions that the DTG resistance data is unmasking.
          - Connie Celum: This is data from a single study. This should be replicated in larger cohort to understand the complexities and implications of this observation.
          - Lejeune Lockett: For clarification: you mentioned Uganda can do resistance testing on 5000 individuals. What is that capacity based on?             - Uganda has a protocol in place for genotyping samples with a VL over 1000 through the lab system in the previous 3-6 months. Based on this, 5000 people per annum will be able to qualify. Turnaround times have been improving in the past 12 months. 
          - Susan Swindells: Elliot made the point that DTG prevalence is low. Enough to worry but not panic. One of the more useful approaches they could take is to understand risk factors. We should work out who and why to inform any decision moving forward.
          - Angela Mushavi: Regarding the data from South Africa, with DTG levels, is it a sign that people are not taking their drugs? The resistance it so much lower than other antivirals.
          - Juliana Da Silva: Regarding methodologies, for two of them they are based in a single clinic.             - For the multi-country analysis we are planning, we are going to have the results soon. Summary statement/Recommendation:  Ongoing monitoring of ARV drug resistance including for DTG through sentinel health facilities and community surveillance is important to monitor trends and needs to be integrated into insights from treatment outcomes in patients on TLD regimens. At this point in time routine testing for DTG resistance in patients on TLD regimens is not indicated. Targeted studies/analysis in patients with treatment failure on TLD is needed to differentiate between patients with treatment interruptions and those who are adherent or have recently been initiated on treatment using a TLD regimen. 

**Session 3: Role of Long-Acting Agents for Treatment in PEPFAR Programs**

**Time: 10.15**
        - Review of CARES Data (Presenter: Dr. Cissy Kityo, JCRC, Uganda)
        - PEPFAR presentation on the role of LAA for treatment (Presenter: Dr. Deborah Goldstein, USAID)
        - Q&A and open discussion

Notes:
        - Dr. Kityo provided a summary of results from the  CARES study  presented at CROI 2024. The aim of the study was to assess non inferiority of switching biologically suppressed adults to CAB and RPV every eight weeks versus continuing, maintenance therapy with oral standard of care in, sub–Saharan African population managed using a public health approach. At week forty-eight, CAB and RPV, given every eight weeks had high efficacy.           - Discussion:             - A SAB member asked for clarity about the exclusion for the Hepatitis virus antibody.               - Ivan: Many people who are excluded. After discovering patients were excluded because hepatitis B, we tested for viral load and the antibody. The patients were followed up for 2 years. 
            - Yogan Pillay: Was there any difference in patient satisfaction depending on the MMD differences (2-3 months vs say 6 MMD) and CAB/RPV?
            - Cissy Kityo: There was excitement around this trial. Those who came to be screened wanted the treatment arm. Irrespective, the issue of taking pills daily is difficult. They prefer injections. 
        - Dr. Goldstein presented on how the CARES results could be applied to the PEPFAR context. She summarized ongoing CAB/RPV studies ongoing. She outlined the remaining implementation questions related to efficacy, operational barriers, and cost barriers.           - Discussion:             - Yogan Pillay: Can we pressure ViiV and Gilead to get going with the research needed for the Cab/Len combo?
            - Susan Swindells: PEPFAR should sensibly get behind implementation. Cab is not ideal, but that’s what we have to begin with. I haven’t heard about trying to bring generic manufacturers on board to speed up bioequivalence process which takes a long time. The US FDA seems open to the idea. This may be an area where PEPFAR muscle can help.
            - Judith Currier: Waiting for products to be developed or outcomes from studies in the field and saying this combination doesn’t check the boxes so should be shelved is a mistake. We should focus on evaluating this combination in populations who are high risk for resistance on current first line oral regimens. The CARES study surprised everyone -some patients who had drug resistance to current oral first line regimens still achieved viral suppression.
            - Carol Treston: It will fall on nurses to roll-out this. Nurses, already have a lot on their plate – how can we be sure they are compensated appropriately? The scope of practice for nurses varies by country – now is a good time to assess what barriers to nurse administration of the injectable long acting barriers are. While the cab /rpv LA combination may be perceived as suboptimal regimens for mass scale-up, they can be utilized to work out the programmatic scale up issues are.
            - Fred Sawe: We (KEMRI) is one of the sites that conducted this study. There was an effort to harmonize for the purposes of equity. PEPFAR should facilitate WHO prequalification. Even for oral ART we relied on WHO prequalification. As we roll it out, we should start with high-capacity sites to give country lessons and time to inform scale up.
            - Angela Mushavi: Similar to family planning experience where injectables are preferred over oral methods, some women think injectable ARVs are preferable to daily oral ARV drugs. It would be good if we had innovations in other delivery mechanisms that took away the need for frequent clinic visits e.g. self-care options for self-administration like in diabetes and obesity management or HIV self-testing. The current DSD models with MMD mean people only have to come to the clinic/health facility once or twice a year. How can we support R&D on the innovative products? Costs of long-acting agents could make it an equity issue.
            - Susan Swindells: In terms of delivery of long-acting agents, microarray patches could work for small children and babies, but not adults. For the TB interaction issue, there is a group of investigators in South Africa who are proposing to study this but accessing product from the manufacturers is a challenge. The data on the nature of interactions with concurrent TB medications may help to inform strategies to overcome this interaction if antagonistic.
            - Deborah Goldstein: A lot of discussion about requiring patients to visit health facilities to receive their injections. We should explore service delivery methods to administer the long- acting injectable agents in the community eg through mobile clinics. We don’t want HRH burn out. 

**Summary Statement/Recommendation:** Long-acting treatment agents for those who are virally suppressed, or settings with increasing treatment interruptions or in instances of therapeutic failure together with emerging drug resistance patterns are an important new opportunity for retaining survival gains made to date. While the frequency of administration of the LA CAB/RPV combination may not be perfect it provides an opportunity to identify what the challenges and barriers are to programmatic scale-up. We recommend PEPFAR support some pilot implementation science studies, particularly in countries struggling with achieving their 95-95-95 targets, and additionally explore nurse-initiated and mobile/community delivery options. The TB interaction needs to be urgently investigated. PEPFAR should play a lead role in negotiating tiered pricing to ensure equitable access and access to product for addressing the urgent research questions that remain.

**Session 4: Updates on Lenacapavir and PEPFAR’s Scaleup Plans**

**Time: 11.30 (Facilitator: Mitchell Warren)**
        - Presentation: Update on the PURPOSE program (Presenter: Dr. Moupali Das, Gilead)
        - Presentation: Considerations for Lenacapavir Market Introduction in LMICs (Presenter: Dr. Kristine Torjesen, FHI360)
        - Q&A and open discussion

Notes:
        - Mr. Warren set the stage for a discussion on Lenacapavir, highlighting that there will always be more than one product, so we should instead focus on the pipeline.
        - Dr. Das provided an update on the PURPOSE Program, which is committed to implementation science and health equity. She highlighted a quantitative study evaluating the efficacy of two products to provide more choices for prevention if they’re both effective (i.e., LEN and Descovy).
        - Dr. Torjesen presented on the market introduction for Lenacapavir for prevention. There was uniform agreement that there would be demand for LenPrEP if the product was shown to be safe and effective.
        - Discussion:           - Chair Abdool Karim: Expressed appreciation for Gilead sharing the status of the trial and timelines for outcomes with PEPFAR and the PEPFAR SAB at this early stage in contrast to what is typically happening where manufacturers are presenting the data after results are known and there re long delays in public access to products. She sought clarity on how Gilead was thinking about positioning the product e.g. as additional choice for PrEP users or is Gilead thinking about some novel or intentional targeting by population or geography informed by the Gilead tagline of ‘ending AIDS for everyone everywhere and UN Ending AIDS 2030 goal?
          - Connie Celum: In comparing daily oral PrEP to long-acting agents – sometimes we think the drop off for oral prep use is a problem with the product but there may be other factors at play. With the long-acting agents, the challenge is going to be on providers to have conversations about tradeoffs on oral vs LAAs. With the introduction of LAAs there will need to be more intensive monitoring, or there will be a repeat of what happened after oral prep introduction.
          - Judy Auerbach: The more people hear about long-acting treatment, I think they will be less interested in long-acting PREP. Will treatments undermine prevention?
          - Jesse Milan: Have we created the environment that allows people to make the decision to take PREP? Who are the people on PREP vs at risk? How can we communicate that PREP is something they need?
          - Angela Mushavi: What are we doing to market PREP? Have we created a marketing strategy for PREP? There are people in communities who don’t know about PrEP. 

**Summary statement/Recommendation**: We look forward to the outcome of the Gilead PURPOSE trials of 6 monthly injectable lenacapavir and initiating discussions now about post-trial access to the product; introduction to current PrEP users and other novel approaches to use including pricing; manufacturing and timelines of implementation studies. There is a need for more broader discussions on the increasing array for LAA agents and what implementation studies are needed that engage health care workers; increase awareness in communities of PrEP and equitable and timely access issues.

**Session 5: Behavioral Science Interventions in PEPFAR Programs**

**Time: 13.30**
        - Presentation on PEPFAR’s plans to scale the use of behavioral science interventions (Presenter: Dr. Ingrid Katz, GHSD)
        - Q&A and open discussion

Notes:
        - Dr. Katz presented on harnessing behavioral strategies, evidence that we know already exists, and the data that we have at PEPFAR, through all of the work to sustain epidemic control.
        - Discussion:           - During this ‘last mile’ phase, a more tailored approached will be needed based on the challenges in different epidemic settings; local knowledge of drivers and optimizing the combination of interventions needed. This will require a more dynamic and tailored approach rather than a ‘one size fits all’ approach and lived experiences and knowledge to inform more community and people-centric approaches. Importantly we have the GIPA principles capture in ‘nothing for us without us’.
          - Jesse Milan: stated that this is an opportunity to link with people outside of the medical care system. Universities have good behavioral science groups. They might be keen to work on this. We should do this systematically in countries. It would be a good way to rely on experts in country.
          - Jen Kates: Fogarty is creating capacity in Africa for research focused on HIV and behavioral science.
          - Carol Treston: There are several professional nursing orgs that would be interested in this.
          - Mitchell Warren: When we think about demand creation and treatment/prevention, one needs behavioral science across PEPFAR. There are programs that existed in country prior to PEPFAR. We shouldn’t rely only on the HIV community but also tap into other systems in place in country and in communities.
          - Moupali Das: There is nested qualitative work within the PURPOSE trials that can be tapped into. Many of the advocates we work with are behavioral and qualitative researchers. Those advocates would be good in country.
          - Judy Auerbach: For the purpose of SAB subcommittees, we need to be narrow. These questions are the broader conversation. What are behavioral interventions? What is social science? Do we want to touch on both? Then there are questions with policy work that taps into social science expertise. We need to define which we want to do. With that in mind, let’s not reinvent wheels. We should tap into relevant expertise.
          - Kristen Tjorsen: There has been a huge amount of research in the public sector funded by PEPFAR through USAID. There is a disconnect in behavioral science, and the people on the ground doing SBC. This group could bridge that.
          - Chair Abdool Karim: There is distrust in science and government that was most apparent during Covid-19. The trust that was built in the HIV response e.g. through community engagement and treatment literacy and access is being eroded. Dr Bunnell specifically highlighted the modernization of health systems – we need to extend that modernization through generative AI and ML and LLM to HIV behavior change if we are to accelerate closing gaps before 2030. The bottom line is that we have more and expanding options, but that toolbox won’t be appropriate for every setting. It won’t be a one size fits all.
          - Lisa Fitzpatrick: a few people have said there is a wealth of data on these questions. What are the barriers to the work we already understand and implement? 

**Session 6: PEPFAR Nursing Leadership Initiative (NLI)**

**Time: 14.15**
        - Presentation on PEPFAR’s NLI initiative (Presenter: Jerilyn Hoover RN, USAID)
        - Q&A and open discussion

Notes:
        - Ms. Hoover presented on the PEPFAR Nursing Leadership Initiative launched as a new central initiative in Africa. The initiative will elevate the nursing workforce in PEPFAR partner countries to sustain gains in the HIV response and equip the nursing workforce with leadership and technical skills to enhance their contributions and mitigate disruptions of HIV service delivery by emerging public health threats.
        - Discussion:           - The SAB discussed opportunities to link nursing schools in Africa with schools in the States. The Ambassador reminded everyone that NEPI does this work.
          - Lisa Fitzpatrick: One of the recommendations I make is that when students provided care to rural areas, nurses train students but that was not well received.
          - Angela Mushavi: There has been a brain drain. We need to address this impact.
          - Carol Treston: We must engage orgs in each country because each country is different in how they define nurses. 

**Session 7: Advancing PEPFAR’s Sustainability Agenda**

**Time: 15.00-16.30**
        - Updates from PEPFAR sustainability advisory group (Presenter: Mike Ruffner & Sarah Dominis, GHSD & Dr. Jen Kates, KFF)
        - Q&A and open discussion

Notes:
        - Mr. Ruffner provided an update on the sustainability agenda. UNAIDS has put out a primer that clarifies that sustainability does not mean the end of donor assistance, but a response embedded in country systems. In addition, the roadmap is not a single document or event,           - Discussion:             - Peter Berman: Sustainability can be thought of as a politically concerning idea by some.
            - Jesse Milan: We should reframe the narrative to continue to frame it as a humanitarian crisis. If we do not sustain, people will die. What do we risk?               - We need to try and integrate then look for those weaknesses and program to those weaknesses. 
            - Fred Sawe: Sustainability means to do whatever needs to be done to keep the program going without losing gains. As we work with sustainability, we need to monitor the red flags to make sure we do not lose ground. We do not pull out; we just continue strengthening. I worry about corruption. When you hand money to weak systems, they don’t stretch as much as they could have reached. We need commodity security and availability.
            - Carlos del Rio: We are sustaining suppression while going uphill. That’s hard to communicate. We need to stop talking about ending the HIV epidemic. We should give measurable goals. Because politicians think we are approaching the end and don’t need funding.
            - Judith Currier: We should continue to quantify the number of people saved and born without HIV as the return on investment.               - Maybe we can better deploy that story. 
            - Takeaway: protect commodities and human resources always. 
        - Ms. Dominis outlined what exactly is included in the definition of integration: including HIV as part of a larger health sector plan. Many countries are already moving on to integration. There is a perception out there that PEPFAR is already moving towards integration, but PEPFAR has many questions about this process and the realities to be considered.           - Discussion:             - Ken Mayer: There are various kinds of integration, and some are lower hanging fruit.
            - Mark Harrington: We should think about who we are treating and think about their needs. Take a differentiated approach to integration based on the greatest clinical needs (NCDs for the elderly, children who need vaccines, etc.)
            - Mitchell Warren: We should think big at the beginning. Not small incremental things. This is essentially being person centered. We don’t need a radical new narrative that can be misinterpreted as funding a public health system. We need a midterm statement that clarifies this. It should explain sustainability and integration.
            - Ambassador Nkengasong: PEPFAR has not taken a position on integration in country. We cannot escape it. We will synthesize these thoughts and bring our thoughts back to you. Our goal should be focused on HIV and the 3 95s.
            - Fred Sawe: We integrated HIV into the antenatal care clinic and found it effective. We should select what we integrate. We should start at the community and what they can integrate. 

**Open Comment & Closing Remarks**

**Time: 16.30**

Notes:
        - PEPFAR Watch – Naike/Asia Russell           - Most PEPFAR countries don’t have the political will to take on the treatment of key populations. PEPFARs work around sustainability should be around science. We request from the SAB:             - The cuts for FY25 KP programs are inequitable and the deteriorating environment for service deliveries feel unsustainable.
            - PEPFAR should prioritize the need to scale of investment in key populations in the context of increased discrimination. There should be standalone more expensive nongovernment owner programs for these KP.
            - The SAB should explore a new multiyear initiative with the context of social and legal issues. 
        - Sister Love – Dazon Dixon Diallo           - The conversation can be very macro but today focused on people.
          - Prevention – sometimes populations need to be considered in groups that are not tied to their demographics or how they interact with community. We have to center ourselves in these communities and understand them if we want sustainability. 
        - Ambassador thanks everyone for learning so much. You need to be engaged for a long time on pandemics to see them go away.
        - Chairs thanks Ambassador for his engagement.

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