VIRTUAL WORKSHOP ON POSTNATAL PROPHYLAXIS TO REACH ELIMINATION OF HIV VERTICAL TRANSMISSION: OPTIMIZING RESEARCH AND ACCELERATING ACCESS TO INNOVATION 11 MAY–10 DECEMBER 2021 MEETING REPORT
VIRTUAL WORKSHOP ON POSTNATAL PROPHYLAXIS TO REACH ELIMINATION OF HIV VERTICAL TRANSMISSION: OPTIMIZING RESEARCH AND ACCELERATING ACCESS TO INNOVATION 11 MAY–10 DECEMBER 2021 MEETING REPORT Virtual workshop on postnatal prophylaxis to reach elimination of HIV vertical transmission: optimizing research and accelerating access to innovation, meeting report, 11 May-10 December 2021 ISBN 978-92-4-005287-1 (electronic version) ISBN 978-92-4-005288-8 (print version) © World Health Organization 2022 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. 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The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. iii ACKNOWLEDGEMENTS ................................................................................................................................................ iv 1. BACKGROUND ......................................................................................................................................................... 1 2. OBJECTIVES ............................................................................................................................................................. 2 3. WORKSHOP FORMAT AND METHODS ................................................................................................................... 2 4. KEY OUTCOMES ...................................................................................................................................................... 3 5. CONCLUSIONS AND NEXT STEPS ............................................................................................................................ 7 Annex: Agendas and Participants .................................................................................................................................... 9 CONTENTS WHO thanks all workshop participants for offering their expertise and advice, especially speakers and group work facilitators. Special thanks to Elaine Abrams (ICAP at Columbia University and IMPAACT), Theodor Ruel (University of California, San Francisco (UCSF)) and Martina Penazzato (WHO) for their technical leadership as well as Jennifer Zech for her critical contribution to planning and conducting the four meetings. This work was implemented with generous contributions from Unitaid and IMPAACT. ACKNOWLEDGEMENTS iv 1The global community has made exceptional progress in preventing the vertical transmission of HIV, halving the number children newly infected and rapidly expanding access to antiretroviral (ARV) drugs for pregnant women living with HIV (1). Although only a few countries have validated the elimination of vertical transmission, several others are developing a vision and a path to a future in which no child is born with HIV (2). Despite decades of progress in reducing the rates of vertical transmission, some children continue to acquire HIV. Even with expanded treatment coverage for women with HIV, perinatal transmission continues to occur among infants born to women with HIV diagnosed in pregnancy or at delivery. Infants are also at risk of acquiring HIV during breastfeeding to viraemic women with HIV; roughly half of all children newly infected acquire HIV during breastfeeding. Although countries continue to make progress, challenges remain in retaining women living with HIV in healthcare services and on effective antiretroviral therapy (ART) throughout pregnancy and the breastfeeding period and in detecting and preventing new HIV infections among women during pregnancy and breastfeeding. Guidelines on infant feeding in relation to HIV reaffirm the position of World Health Organization (WHO) that the best way to prevent transmission in the postpartum period and optimize infant survival is to ensure that mothers living with HIV are diagnosed, receive effective treatment and are able to breastfeed their infants for up to two years, with the infant being exclusively breastfed in the first six months of life. If a mother receiving ART maintains suppressed viral loads, the risk of transmitting HIV through breast milk is very low, and infant prophylaxis accordingly confers minimal additional benefit beyond 4–6 weeks of life. However, some women with HIV face new challenges in adherence while breastfeeding, presenting periods of risk for transmission that are difficult to foresee. WHO recommends enhanced postnatal prophylaxis for infants who are assessed to be at increased risk of HIV transmission at the time of birth and is being implemented in several countries. However, challenges persist with identifying infants at high risk and providing enhanced prophylaxis with existing formulations. Given the uncertainty about best practices, countries have adopted a variety of different approaches to enhanced postnatal prophylaxis: enhanced postnatal prophylaxis for all breastfeeding HIV-exposed infants; enhanced postnatal prophylaxis for high-risk infants identified primarily based on maternal ART duration and, when available, maternal viral load close to delivery; enhanced postnatal prophylaxis for at least 12 weeks of prophylaxis, usually AZT + NVP for the first six weeks followed by NVP alone; extended enhanced postnatal prophylaxis over the entire breastfeeding period when viral suppression is not achieved or maintained; and triple prophylaxis with a fixed-dose combination of AZT + 3TC + NVP to address the challenges of procuring syrups. Overall, options for more effective regimens to prevent HIV infection among infants have been promoted (3), and several novel interventions are being introduced to allow for greater access to earlier treatment. However, the use of optimal ARV drug formulations for preventing and treating HIV infection among newborns and young infants remains a significant challenge. Limited availability of appropriate formulations and dosing schedules that account for prematurity and low birth weight continue to result in unavoidable complexity with which healthcare workers and families struggle. The scientific community has not identified a validated surrogate for postnatal transmission risk; consequently, trials proving efficacy to reduce the risk of children acquiring HIV are required. The cost and logistical challenges of developing such large clinical trials have effectively blocked the development and introduction of better prevention regimens for children since the early investigations of NVP and AZT among newborns and breastfeeding infants. Newer drugs are more potent, and novel technologies offer the potential to surmount many barriers to adherence and implementation of current postnatal prophylaxis. Further, innovation in adaptive study designs and mixed methods offer new ways to efficiently study infrequent outcomes such as postnatal transmission. For this reason, IMPAACT and WHO held a workshop to achieve consensus on the approach to investigating innovative strategies to prevent HIV vertical transmission perinatally and in the postnatal period and establish the next steps for implementing such studies. 1. BACKGROUND 22. OBJECTIVES The overall objective was to reach consensus on the approach to investigate innovative strategies to prevent HIV vertical transmission perinatally and in the postnatal period and establish the next steps for implementing such studies. Specific objectives included: • to review the rationale to optimize postnatal prophylaxis in the evolving maternal treatment landscape; • to identify scenarios to inform the development of innovative postnatal prophylaxis strategies and regimens; • to define the target drug characteristics and candidates to be used in postnatal prophylaxis; and • to reach consensus on an optimal research approach to investigate alternative postnatal prophylaxis strategies. 3. WORKSHOP FORMAT AND METHODS The virtual workshop comprised four meetings held over eight months from May to December 2021 (Fig. 1). The workshop brought together academic researchers, clinical experts, women living with HIV, regulators, industry representatives, HIV programme managers, funders and other key stakeholders involved in delivering and studying programmes to prevent the vertical transmission of HIV. The process was supported by a detailed desk review of current postnatal prophylaxis policies in countries, the perspective of community of women living with HIV in collaboration with mothers2mothers (m2m), pipeline analysis and targeted review of innovative methods for study design. Consensus was reached via plenary sessions and working group discussions. FIGURE 1: WORKSHOP STRUCTURE What is the status? Review the current status of implementation of maternal treatment and current transmission dynamics How can we do better? Explore scenarios for using novel agents as postnatal prophylaxis, their characteristics and their duration What products? Identify products to give priority for infants and define profiles for new technologies to be used for infants and young children How do we study? Consider new ways to study novel platforms with rare outcomes and efficiently compare new agents 1 2 3 4 Optimizing postnatal prophylaxis to move out: Refocusing the research agenda and advancing product development 34. KEY OUTCOMES Why: is postnatal prophylaxis still needed? (11 and 13 May 2021) The first meeting was attended by key stakeholders, including programme managers, academic researchers, women living with HIV, industry, funders and invited experts. The group reviewed the current status of services to prevent children from acquiring HIV, including where and why children are newly infected, scaling up optimized regimens as well as PrEP among pregnant and breastfeeding women and the impact of the COVID-19 pandemic on efforts to prevent vertical transmission. The meeting also reviewed the current use of postnatal prophylaxis, including implementation of enhanced postnatal prophylaxis, and collated the lessons learned from implementing programmes and research efforts to implement postnatal prophylaxis and early infant treatment. WHO postnatal prophylaxis guidelines have been widely implemented, with adaptations to the programme context. Some programmes with low rates of antenatal care attendance, maternal HIV testing, maternal ART coverage and viral load testing capacity have opted against risk stratification and provide an enhanced postnatal prophylaxis regimen for all infants exposed to HIV, whereas other programmes provide infant daily NVP prophylaxis for an extended duration to cover transmission risk throughout the breastfeeding period. A simplified risk-stratification approach may be more relevant for high-performing vertical transmission prevention programmes, whereas a simplified non-risk-stratified approach may be more appropriate for suboptimally performing programmes, given implementation challenges. In settings with concentrated epidemics, where the epidemic is often driven by key populations, infants exposed to HIV should be considered at high risk for acquiring HIV. It was agreed that all settings could benefit from newer technologies that promote retention during pregnancy and throughout the breastfeeding period. The group noted several challenges in enhanced and extended postnatal prophylaxis implementation, including ARV drug stock-outs, lack of appropriate formulations, lack of guidance on alternative ARV drug options for prophylaxis, poor adherence, poor documentation, inconsistent infant feeding practices and inadequate retention throughout the duration of breastfeeding. It was concluded that tailoring postnatal prophylaxis strategies to programmatic context may improve the access, adherence, retention and HIV-free outcomes of infants exposed to HIV. Newer ARV drug options and technologies that enable simplified regimens, non-toxic potent agents and convenient administration, including longer-acting formulations, should be given priority to optimize the effect of postnatal prophylaxis – especially throughout the breastfeeding period – in preventing vertical HIV transmission. 4Who and when: who should receive postnatal prophylaxis at birth or during breastfeeding? (8 and 10 June 2021) The second meeting was attended by country programme leaders, clinicians and researchers. Building on the outcomes of the first meeting, the group outlined the specific scenarios in which infants are at risk for vertical transmission, considering both current and future landscapes with the aim of informing new strategies and product characteristics that will address them. The potential role for novel ARV drug formulations and delivery platforms in these settings was considered. The group noted how several postnatal prophylaxis strategies could be considered to provide more effective and feasible options for infants and their mothers. In the short term, a risk-stratified approach combining legacy ARV drugs used for treatment appears to be the most rapid route to innovate postnatal prophylaxis. These strategies require rapid investigation of the most appropriate dosing for preterm and term neonates with pharmacokinetic modelling and studies. In the long term, pipeline products that enable less frequent administration open the door to a more integrated approach in which one well tolerated and effective strategy could be administered across the risk spectrum perinatally and postnatally (Fig. 2). The group acknowledged how these options will require building on the evidence generated in the adult population, defining clearly preferred product characteristics and actively investigating novel molecules among neonates and infants. FIGURE 2: POTENTIAL STRATEGIES FOR INNOVATIVE POSTNATAL PROPHYLAXIS Short-term options With existing ARV drugs and formulations once appropriate dosing is identified Long-term options With pipeline products depending on their successful approval for use in HIV prevention or treatment ALD (or ALL) perinatal* for high-risk and ZERO for low risk plus nothing postnatally for all ALD (or ALL) perinatal* for high-risk and 3TC for low risk + postnatal 3TC for all ALD (or ALL) perinatal* for high-risk and DTG for low risk + postnatal DTG for all Broadly neutralizing HIV antibodies perinatally and postnatally for all Long-acting ARV drugs perinatally and postnatally for all Broadly neutralizing HIV antibodies + long-acting ARV drugs perinatally and postnatally for all No postnatal prophylaxis ALD= ABC plus 3TC plus DTG 10 mg scored ALL= ABC plus 3TC plus LPV/r granules *For premature babies, AZT + NVP should be used 5What: what is the new generation of ARV drug formulations to be investigated and developed for postnatal prophylaxis? (1 October; included in PADO 5 meeting agenda) This third discussion leveraged the PADO5 group being convened in September 2021 to review the ARV drug pipeline, revise the PADO priority list, identify the remaining research questions and define a target product profile and product preferred characteristics for innovative technologies to develop new formulations for children to treat and prevent HIV among neonates, infants and older children. The PADO5 meeting (4) included a thematic session focused on postnatal prophylaxis and enabled the group to identify priority ARV drugs in specific formulations to investigate. The group noted that research gaps around term and preterm pharmacokinetics and dosing persist. RAL granule formulation was the first integrase inhibitor approved for term neonates, but it has a low barrier to resistance, and should resistance develop, it could compromise the viral response to DTG. Another critical research gap is pharmacokinetics data on dosing for premature infants. IMPAACT 2023 is studying DTG for infants in the first 4–6 weeks of life, with the results expected in 2023, but there are no pharmacokinetics or dosing data for premature neonates. There is a possibility of evaluating DTG generic (10 mg scored) tablets in a parallel study to increase the sample size, assess the globally available formulation and combine with the IMPAACT 2023 study findings. The new long-acting formulations discussed by the group were CAB-LA, ISL, LEN and broadly neutralizing HIV antibodies (Fig. 2). Broadly neutralizing HIV antibodies, particularly in combination, may have a role in preventing perinatal HIV transmission and during breastfeeding. In early HIV infection, broadly neutralizing HIV antibodies have the potential to reduce viral reservoir burden and are a potential pathway to a functional cure. Formulations and dosing information are still limited for infants, and urgent action is needed to ensure that these novel drugs are investigated among neonates as soon as possible. FIGURE 3: PRIORITY PRODUCTS AND TECHNOLOGIES FOR NEONATES AND INFANTS FOR POSTNATAL PROPHYLAXIS CAB LA PA DO 5 Fo cu s on Po st na ta l P ro ph yl ax is ISL bNabs LEN Ready for prime time for adults, being investigated for adolescents, no data for <12 years old Waiver for <4 weeks. Potential for bimonthly administration. Formulation for neonates potentially challenging due to low dose. All studies on hold (December 2021) No PIP/PSP. Consider development of a multimonth subcutaneous injection (three-monthly or more). Multimonth combination of two or more broadly Neutralizing HIV antibodies for subcutaneous injection (three-monthly or more). Some pharmacokinetic data, but the right cocktail is not ready yet Micro Array Patches All are potentially suitable for this delivery system Source: Paediatric Drug Optimization HIV (PADO HIV 5) Meeting, 25 September–10 October 2021 6How: what is the optimal study design to investigate the safety and efficacy of new postnatal prophylaxis strategies? (8 and 10 December 2021) This fourth and final meeting gathered statisticians, clinical and implementation researchers to develop and identify a trial design that will enable the study of potential interventions and strategies for postnatal prophylaxis. A key challenge of assessing postnatal prophylaxis strategies to get to zero is that the outcomes are relatively rare. Randomized controlled trials, often considered the gold standard to compare interventions, are too costly when operated on the scale needed to assess outcomes occurring at frequencies <5%. Further, strategies to get to zero at the community level must be evaluated in real-world large-scale settings and not the rarefied environment of a clinical trial. The design must also be able to accommodate and evaluate new products as they emerge, adapting to a constantly evolving standard of care. The group reviewed the experience of some of the most recent trials undertaken to assess the efficacy of strategies to prevent vertical transmission and reflected on some of the challenges and lessons learned that each had to offer. Experts were also invited to reflect on the opportunity that observational data collection as part of cohort studies or programme cohort monitoring may provide in collecting short- and long-term outcome data. Innovative study design and methods were brought to the attention of the group to inspire and spark a discussion on how these methods could be used to investigate new postnatal prophylaxis strategies. In particular, the group examined the advantages and disadvantages of applying cluster randomized trials, adaptive trials, basket trials and Bayesian methods. Provided the challenges of undertaking multiple trials exploring different options, the group agreed that the most efficient way of tackling this question is via an adaptive design that enables options to be included as soon as they become available and then uses Bayesian methods to increase efficiency when designing a trial with low transmission rates to start with. 7Overall, the workshop helped to confirm the importance of postnatal prophylaxis as a tool to prevent vertical transmission, identify opportunities to design a strategy that might fit multiple settings in the future and put forward several potential drugs and formulations to be tested to optimize postnatal prophylaxis in the future discussing the challenges and opportunity to investigate these new strategies with innovative methods and more efficient clinical trial designs. The outcomes of the workshop were shared in February 2022 at CROI 2022, and peer-reviewed articles are being developed to fully disseminate the outcomes within the scientific community. Additional opportunities will be created to share the highlights with key stakeholders and funders once a full concept note detailing study design, patient characteristics and endpoints is finalized. We anticipate soliciting input on the implementation of the proposed research approach in clinical settings and programmatic contexts from various partners gathered within the clinical research working group of the Global Accelerator for Paediatric Formulations. Alignment among key stakeholders such as researchers, regulators, industry and key funders will be critical to ensure that new strategies for postnatal prophylaxis can be investigated rapidly to deliver at the highest impact and contribute to eliminating vertical transmission globally. 5. CONCLUSIONS AND NEXT STEPS 8Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) is provided by the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the National Institutes of Health (NIH), under Award Number UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), and by NICHD contract number HHSN275201800001l. The content of this report is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. References 1. 2021 UNAIDS global AIDS update: confronting inequalities – lessons for pandemic responses from 40 years of AIDS. Geneva: UNAIDS; 2021 (https://www.unaids.org/en/resources/documents/2021/2021-global-aids-update, accessed 8 June 2022). 2. Global guidance on criteria and processes for validation: elimination of mother-to-child transmission of HIV, syphilis and hepatitis B virus. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/349550, accessed 8 June 2022). 3. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach, 2021 update. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/ handle/10665/342899, accessed 8 June 2022). 4. Joint Virtual Conference on Antiretroviral Drug Optimization (CADO-4), Paediatric Drug Optimization (PADO-5) and HIVResNet Groups, 27 September–15 October 2021: summary meeting report. Geneva: World Health Organization; in press. 9ANNEX AGENDAS AND PARTICIPANTS Meeting 1 – 11 and 13 May 2021: agenda (times provided in CET) Day 1, 11 May: Opening remarks: Meg Doherty (WHO) and Sharon Nachman (IMPAACT) 15:00–15:20 Introductions All 15:20–15:25 Background and objectives of the meeting Martina Penazzato (WHO) 15:25–15:35 Setting the stage: key issues and anticipated outcomes Elaine Abrams (ICAP at Columbia University) 15:35–15:55 Evolving implementation of maternal ART and current status of vertical transmission Mary Mahy (UNAIDS) and George Siberry (USAID) 15:55–16:10 Missed opportunities for preventing vertical transmission Angela Mushavi (Zimbabwe Ministry of Health) 16:10–16:25 Postnatal prophylaxis policy review Ivy Kasirye (WHO) 16:25–16:35 Q&A All 16:35–16:50 Break 16:50–17:20 Country panel: challenges and opportunities to expand access and impact of postnatal prophylaxis interventions • Eswatini • Kenya • Mozambique • Cameroon Facilitated by Morkor Newman (WHO) 17:20–17:30 Community perspectives Betty Mirembe (M2M) 17:30–17:40 Frontline providers’ perspectives Cordelia Kunzekwenyika (PATA) 17:40–17:50 Imagining the future of maternal ART and postnatal prophylaxis Landon Myer (University of Cape Town) 17:50–18:00 Discussion All Day 2, 13 May 15:00–15:05 Review day 1 and overview of day 2 Theodor Ruel (UCSF) 15:05–16:15 Breakout rooms on future scenarios for postnatal prophylaxis (three groups) Facilitated by group leads 16:15–16:30 Break 16:30–17:00 Report back from groups Facilitated by a member of the organizing committee 17:00–17:10 Review postnatal prophylaxis status and emerging issues in high-income countries Pat Flynn (St Jude’s Children Research Hospital) 17:10–17:45 Discussion All 17:45–18:00 Wrap-up and closing Elaine Abrams (ICAP at Columbia University) Martina Penazzato (WHO) 10 Meeting 1 – Participants Surname Name Affiliation Abrams Elaine IMPAACT Archary Mo IMPAACT Bekker Adrie IMPAACT Bigirigama Francoise WHO Buck Chris UCLA Chi Ben IMPAACT Cressey Tim PHPT De Vos Marieta NACOSA, South Africa Dungerdorj Ider UNICEF Essajee Shaffiq UNICEF Fanny Epie Nkwen Baptist Health Center, Cameroon Flynn Pat IMPAACT Goga Ameena South African Medical Research Council Harwell Herb Clinton Health Access Initiative Ismail Shabir Elizabeth Glaser Pediatric AIDS Foundation Jacobs Tom Radboud University Medical Center Kasirye-Kiddu Ivy WHO Kiruthi Faith Sunshine Smiles Clinic, Kenya Kose Judith Elizabeth Glaser Pediatric AIDS Foundation Lain Maria Grazia Ariel Foundation Lallemant Marc PENTA/GAP-f Magongo Eleanor Uganda Ministry of Health Mahy Mary UNAIDS Mbori-Nghaca Dorothy UNICEF Mirembe Betty M2M Mofenson Lynne Elizabeth Glaser Pediatric AIDS Foundation Montadon Michelle CDC Mukui Irene DNDi Mushavi Angela Ministry of Health, Zimbabwe Musoke Phillipa IMPAACT Myer Landon University of Cape Town Nachman Sharon IMPAACT Nairimo Lilian Kilgoris Subcounty Hospital, Kenya Newman Morkor WHO Nyanya Winnie Ministry of Health, Kenya Obimbo Elisabeth University of Nairobi Penazzato Martina WHO Ruel Ted IMPAACT Shapiro Roger Harvard University Siberry George USAID Simione Beatrice Mozambique Ministry of Health Simnoue Nem Danielle WHO, Ministry of Health Cameroon Stranix-Chibanda Lynda IMPAACT Wolf Hilary US State Department, Office of the Global AIDS Coordinator Zech Jennifer ICAP at Columbia University 11 Meeting 2 – Participants Surname Name Affiliation Abrams Elaine IMPAACT Archary Mo IMPAACT Bekker Adrie IMPAACT Belew Yodit U.S. FDA Capparelli Ed IMPAACT Clarke Diana IMPAACT Colbers Angela Radboudumc Cressey Tim PHPT Essajee Shaffiq UNICEF Flynn Pat IMPAACT Goga Ameena South African Medical Research Council Harwell Herb Clinton Health Access Initiative Jacobs Tom Radboudumc Lain Maria Grazia Ariel Foundation Lallemant Marc PENTA/GAP-f Lewis Linda Clinton Health Access Initiative Lyall Hermione PENTA Magongo Eleanor Uganda Ministry of Health McFarland Betsy University of Colorado Meeting 2 – 8 and 10 June 2021: agenda (times provided in CET) Day 1, Tuesday, 8 June 16:00–16:20 Introductions All 16:20–16:25 Background and objectives of the meeting Elaine Abrams 16:25–16:35 Summary of the key findings from meeting 1 Martina Penazzato 16:35–16:55 Review of current postnatal prophylaxis drugs and approaches Tim Cressey and Roger Shapiro 16:55–17:05 Approaches and agents for prevention among adults Raphael Landovitz 17:05–17:15 Similarities and differences between sexual and postnatal transmission: implications for prevention Sallie Permar 17:15–17:25 Q&A All 17:25–17:35 Break 17:35–17:50 Future possibilities: novel delivery systems and long-acting agents Ted Ruel 17:50–18:20 Debate: risk-based perinatal prophylaxis is essential to achieve the elimination of perinatal transmission Facilitated by Lynda Stranix-Chibanda For: Irene Njahira Mukui Against: Mo Archary 18:20–18:50 Debate: all infants should receive postnatal prophylaxis throughout breastfeeding Facilitated by Landon Myer For: Maria Grazia Lain Against: Herb Harwell 18:50–19:00 Summary and orientation for day 2 Ted Ruel 12 Meeting 2 – Participants (continued) Surname Name Affiliation Mirembe Betty M2M Mirochnick Mark IMPAACT Mofenson Lynne Elizabeth Glaser Pediatric AIDS Foundation Mukui Irene DNDi Musoke Phillipa IMPAACT Muturi-Kioi Vincent IAVI Myer Landon University of Cape Town Nachman Sharon IMPAACT Newman Morkor WHO Obimbo Elisabeth University of Nairobi Penazzato Martina WHO Prendergast Andrew Zvitambo Ruel Ted IMPAACT Shapiro Roger Harvard University Siberry George USAID Stranix-Chibanda Lynda IMPAACT Van de Perre Philippe Université Montpellier Zech Jennifer ICAP at Columbia University Meeting 3 – 1 October 2021: agenda (times provided in CET) Day 3: Friday, 1 October 2021 14:00–14:15 Introduction Martina Penazzato (WHO) 14:15-14:30 Overview talk on neonates to cover treatment and prevention Mo Archary (University of Kwazulu–Natal) 14:30–14:45 Pharmacokinetics and dosing for neonates and infants for treatment and prevention Tim Cressey (PHPT) 14:45–15:00 Q&A and discussion All (facilitated by Hilary Wolf, USAID) 15:00–15:15 HIV drug resistance considerations to treat and prevent HIV among neonates and infants Roger Paredes (Institut de Recerca de la SIDA) 15:15–15:30 WHO-IMPAACT postnatal prophylaxis outcomes Ted Ruel (IMPAACT/UCSF) 15:30–16:00 Q&A and discussion All (facilitated by WHO) 16:00–16:15 Break 16:15–16:30 Broadly neutralizing HIV antibodies for babies Edmund Capparelli (UCSD) 16:30–16:45 Q&A and discussion All (facilitated by Natella Rakhmanina, Elizabeth Glaser Pediatric AIDS Foundation) 16:45–17:00 Technologies landscape Andrew Owen (Liverpool University) 17:00–17:15 Microneedle patches Manjari Quintanar-Solares (PATH) 17:15–17:45 Q&A and discussion All (facilitated by WHO) 17:45–18:00 Wrap-up and next steps Martina Penazzato and Asma Hafiz (WHO) 13 Meeting 3 – Participants – PADO-5 Surname Name Affiliation Abrams Elaine IMPAACT Archary Mo IMPAACT Bekker Adrie IMPAACT Belew Yodit U.S. FDA Capparelli Ed IMPAACT Clarke Diana IMPAACT Colbers Angela Radboudumc Capparelli Ed IMPAACT Casas Esther MSF Ciaranello Andrea Massachusetts General Hospital Clarke Diana Boston Medical Center Clayden Polly i-Base Colbers Angela Radboud University Medical Center Cressey Tim PHPT De Lisa Roberto European Medicines Agency Denti Paolo University of Cape Town Domanico Paul Clinton Health Access Initiative Essajee Shaffiq UNICEF Frigati Lisa Stellenbosch University Gibb Diana MRC Clinical Trials Unit at UCL Hackett Stephanie CDC Hazra Rohan NICHD Jacobs Tom Radboud University Medical Center Lallemant Marc PENTA/GAP-f Lewis Linda Clinton Health Access Initiative Lockman Shahin Harvard University Magongo Eleanor Uganda Ministry of Health Malati Christine USAID McFarland Betsy University of Colorado Mir Fatima Agha Khan University Mirochnick Mark IMPAACT Mofenson Lynne Elizabeth Glaser Pediatric AIDS Foundation Mukui Irene DNDi 14 Meeting 3 – Participants – PADO-5 (continued) Surname Name Affiliation Mushavi Angela Ministry of Health, Zimbabwe Musiime Victor Joint Clinical Research Center Nawaggi Pamela Unitaid Obimbo Elisabeth University of Nairobi Ojoo Mary Atieno UNICEF Perez-Casas Carmen Unitaid Piccolis Manuele MPP Pinto Jorge Federal University of Minas Gerais, Brazil Puthanakit Thanyawee Chulalongkorn University, Bangkok Rakhmanina Natella Elizabeth Glaser Pediatric AIDS Foundation Reinisch Annette Global Fund to Fight AIDS, Tuberculosis and Malaria Rojo Pablo Hospital de 12 Octubre Ruel Ted IMPAACT Sam-Agudu Nadia University of Maryland Siberry George USAID Simione Beatrice Ministry of Health, Mozambique Simon Kate Tingathe, Malawi Singh Vindi Global Fund to Fight AIDS; Tuberculosis and Malaria Sugandhi Nandita ICAP at Columbia University Sylla Mariam EVA Network, Mali Thior Ibou PATH Turkova Anna UCL Vicari Marissa IAS Wahaca Imelda Pangea Zimbabwe Watkins Melynda Clinton Health Access Initiative Wolf Hilary CDC Zech Jennifer ICAP at Columbia University 15 Meeting 4 – 7, 8 and 10 December: agenda (times provided in CET) Day 1, Tuesday, 8 June 16:00–16:20 Introductions All 16:20–16:25 Background and objectives of the meeting Elaine Abrams 16:25–16:40 Summary of key findings from previous infant optimization meetings Martina Penazzato 16:40–17:20 Panel 1: Pitfalls and lessons learned from large-scale prevention trials Facilitated by Ted Ruel Lynda Stranix–Chibanda (PROMISE) Nicholas Nagot (PROMISE PEP) Marc Lallemant (PTPT5) Laura Balzer (SEARCH) 17:20–18:00 Panel 2: Real-world data challenges and opportunities Facilitated by Elaine Abrams Ben Chi (Kafue PMTCT) Suzue Saito (ICAP) Mary-Ann Davies (IeDEA) Roger Shapiro (TSEPAMO) 18:00–18:10 Break 18:10–18:50 Panel 3: What evidence do we need to adopt new strategies for postnatal prophylaxis? Facilitated by Martina Penazzato Yodit Belew (Regulatory Bodies) Landon Myer (Global Guidelines) Eleanor Magongo (National Guidelines) 18:50–19:00 Wrap-up and introduction to day 2 Ted Ruel Day 2, Wednesday, 8 December (16:00–19:00 CET) 16:00–16:15 Review day 1 and overview of day 2 Ted Ruel 16:15–17:15 Outcomes and endpoints Objective: Reach consensus on the primary endpoints and secondary outcomes for studies of postnatal prophylaxis, considering that different endpoints might be required for drugs we have now (near future) and new agents and platforms (far future) Facilitated by Elaine Abrams Group discussion 17:15–17:30 Break 17:30–18:50 Potential study designs Objective: to explore different study designs that could be used to study new postnatal prophylaxis approaches and outcomes Facilitated by Martina Penazzato Laura Balzer (Cluster RCT) Matt Sydes (Adaptive Design) Billy Amzal (Bayesian) Ellie Caniglia (Target Trial) 18:50–19:00 Wrap-up and closing Martina Penazzato Day 3, Friday, 10 December (15:00–18:00 CET) 15:00–15:15 Review day 2 and overview of day 3 Ted Ruel 15:15–16:15 Working groups for study design selection Louise Kuhn (near) Tim Cressey (far) Roger Shapiro (both) 16:15–16:30 Break 16:30–17:00 Report back Working groups 17:00–17:45 Discussion All 17:45–18:00 Wrap-up and closing Martina Penazzato and Elaine Abrams 16 Meeting 4 – Participants Surname Name Affiliation Abrams Elaine IMPAACT Amzal Billy Quinten Health Archary Mo IMPAACT Balzer Laura UMass Amherst Bekker Adrie IMPAACT Belew Yodit U.S. FDA Berry Donald Bayesian Bwakura-Dangarembizi Mutsa IMPAACT Caniglia Ellie UPenn Capparelli Ed IMPAACT Chi Ben UNC Cressey Tim PHPT Davies Mary-Anne University of Cape Town Flynn Pat IMPAACT Ford Debbie UCL Fox Matt Boston University Kuhn Louise Columbia Lain Maria Grazia Ariel Foundation Lallemant Marc PENTA/GAP-f Lee Sonia NIH Lewis Linda Clinton Health Access Initiative Lyall Hermione PENTA Magongo Eleanor Uganda Ministry of Health McFarland Betsy University of Colorado Mofenson Lynne Elizabeth Glaser Pediatric AIDS Foundation Montoya Lina UNC Musoke Phillipa IMPAACT Myer Landon University of Cape Town Nachman Sharon IMPAACT Nagot Nicholas Université Montpellier Obimbo Elisabeth University of Nairobi Penazzato Martina WHO Perez Carmen UNITAID Peterson Maya UC Berkeley Prendergast Andrew Zvitambo Ruel Ted IMPAACT Saito Suzue ICAP-PHIA Shapiro Roger Harvard University Shapiro David IMPAACT Siberry George USAID Stranix-Chibanda Lynda IMPAACT Sydes Matthew UCL Jean-Philippe Patrick NIAID DeLisa Roberto European Medicines Agency Tierney Camlin IMPAACT Van de Perre Philippe Université Montpellier Yin Dwight NIAID Zech Jennifer ICAP at Columbia University
For more information, contact: World Health Organization Department of HIV/AIDS 20, Avenue Appia 1211 Geneva 27 Switzerland E-mail: hiv-aids@who.int www.who.int/hiv