AVAC convened three important conversations in the last month on new data that delivered the analysis and evidence that choice and equity in access to PrEP products can make the difference between real-world population-level impact or an epidemic marching on for many years to come.
More and More Evidence that Choice is the Key
Will the Pandemic Accord Fail to Learn the Lessons of the HIV Response?
The Office of the United Nations High Commissioner for Human Rights (OHCHR) highlighted that from the HIV experience we know that if public health measures do not take human rights into account, we will leave marginalised populations behind, fail to address structural barriers to access to quality healthcare, and miss essential interventions altogether.
Biomedical HIV Prevention Summit and PrEP in Black America Summit
AVAC Highlights
1,000+ community advocates, researchers, policy experts, federal public health leadership, medical and service providers attended the NMAC annual Biomedical HIV Prevention Summit in Seattle. The discussion and debate on PrEP access, especially for racial and ethnic minorities and key populations, PrEP research, care, policy and community-based programs are ones to follow.
Jeanne Marrazzo and Community Leaders Amplify Their Voices for Choice
Recently, NIAID Director Jeanne Marrazzo joined our Choice Agenda webinar, The More We Know: Evolving our understanding of PrEP for cisgender women, to present a re-assessment of the safety and effectiveness of PrEP options for women—including oral, vaginal ring, and injectable options.
Announcing the 2024/25 AVAC Advocacy Fellows
We are pleased to announce our 13th class of the flagship AVAC Advocacy Fellows Program for 2024-2025! This group of seven advocates will participate in an 18-month program that supports their advocacy efforts, invests in the further development of their skills, shapes the agenda for HIV prevention research, and influences how quickly new interventions move into policy and programs in their communities and countries.
AVAC Response to Uganda’s Constitutional Court Ruling on the Anti-Homosexuality Act
AVAC is gravely concerned with the Constitutional Court of Uganda’s recent decision to uphold the core provisions of the Anti-Homosexuality Act of 2023 (AHA) that was signed into law nearly one year ago. AVAC stands in solidarity with the LGBTQIA+ community in Uganda, and globally, in calling out this dangerous law.
AVAC Responds to the Pandemic Accord Negotiations
AVAC’s Sam Rick responds to the latest in Pandemic Accord negotiations—member states have engaged in text-based negotiations throughout the end of March. She offered the following position on the state of negotiations as of March 28, 2024 to Politico Pro.
“The draft puts us in serious jeopardy: We are so close to having a sorely needed agreement on how countries will operate in the wake of the next pandemic, yet Global North countries are risking this all to satisfy the interests of pharmaceutical companies. There are places in the draft where it seems countries are finally coming to some baseline consensus, but the textual edits made by Member States this week in the Article on Pathogen Access and Benefits, which is the lynchpin of the entire agreement, show that we are very far from reaching consensus. Without a shift in the US delegation’s position, we’ll have no agreement at all. The US seems to have taken a knife to the text, rendering it toothless. It seems that if the US has its way in this Article, there will be no system to compel benefits sharing, which is the whole point of the Article. The US delegation must compromise and permit an opt-in.”
The Coalition of Advocates for Global Health and Pandemic Preparedness, a group of organizations advocating for an integrated and holistic approach to preparedness that emphasizes equity, inclusion, and synergies of multiple global health programs in advancing preparedness, published their considerations and asks in these negotiations.
African Leadership and Global Health Advocacy
A Journey of growth, change, sustainability and success for the COMPASS Coalition
The Coalition to build Momentum, Power, Activism, Strategy & Solidarity in Africa (COMPASS) has finalized a transformative and power-sharing approach to the governance and leadership of South-North coalitions. This new approach represents innovation that harnesses the power of the coalition. It is redefining and strengthening South-North relationships, and it offers a model for a field seeking to decolonize global health. The effort was built on a founding principle of power-sharing, and a commitment that COMPASS would ultimately be led by an African-based organization. Pursuing this vision has involved a multi-year, member-led process for creating a participatory governance framework. And it has resulted in reimagining COMPASS leadership, with African organizations in control.
This case study explores the COMPASS approach that made these changes possible, the growing pains that informed the process for instituting change, and what others can learn from this experience.
Tune in for a podcast from AVAC!
Hear from COMPASS partners on the pioneering approach to power sharing, and from Dr. Madhukar Pai on the global context.
What is COMPASS?
COMPASS was founded in 2017 as a data and evidence-based South-North civil society coalition. The coalition from its beginnings has been dedicated to advancing strategic advocacy campaigns to influence policies, programs and funding for the HIV response in East and Southern Africa, with a particular focus in Malawi, Tanzania, and Zimbabwe, and at the global level. In December 2023, Pangaea Zimbabwe signed a new two-year, $4.9 million grant agreement with the Bill & Melinda Gates Foundation as the new secretariat of COMPASS Africa, a role previously served by AVAC. In recent years, AVAC was part of a coalition-wide effort to develop a clear transition plan for COMPASS to be led by African civil society organizations.
Since 2017, with a grant from the Bill & Melinda Gates Foundation, 29 COMPASS partner organizations have launched dozens of campaigns and logged 31 significant advocacy wins, with many multi-year campaigns still in progress. To name just a few of the wins from COMPASS campaigns:
- Tanzania has changed the legal age of consent to access HIV services from age 18 to 15 and uptake has since seen a marked increase in testing, and increased awareness of HIV status among people 15 and older from approximately 60% to 82%.
- Zimbabwe and Tanzania piloted community-led monitoring (CLM), which funds communities to track data on HIV services and report back on progress toward country targets, and whether services are meeting community needs. CLM was so successful, PEPFAR expanded the program in Zimbabwe and rolled it out globally.
- Malawi’s once marginalized civil society now serves on technical working groups, influences the allocation of PEPFAR dollars and has become an essential partner to the national government in planning for HIV policies and programs. All three countries have secured funds for key population programs.
In the initial three years, results like these were delivered from a coalition with centralized leadership. Africa-based partners identified priorities, activated strategic relationships, navigated in-country challenges and executed co-created campaigns. US-based COMPASS partner organizations shared expertise on data and other technical assistance and leveraged access to global-level decision makers, with AVAC holding the primary grant and coordinating the coalition Secretariat. Coalition guidelines, partnership agreements and a robust process for co-developing strategy kept the coalition on track, but with success came challenges.
Partners wanted more opportunities to share lessons learned from each other’s campaigns and to lend capacity to one another. Roles and responsibilities needed more clarity. Partners sought broader participation and transparency in coalition decision-making, in selecting new members, and having a more formalized governance. Partners also sought to improve the existing channels for sharing feedback and resolving conflicts transparently and equitably.
Coalition members were ready to see power structures rearranged, redistributed, formalized and documented.
Ulanda Mtamba, a COMPASS member based in Malawi, put it this way: “For us partners in the South, it could feel like someone else is driving the vehicle from afar, while all the work is happening here.”
These sentiments reinforced the founding plan to shift management of the primary grant to an African-based partner. Just as important, these considerations informed an effort to re-shape the coalition and create structures to support an African partner-led, multi-country, multi-continent coalition.
Coalition Governance: Transparency, Participation and Trust
To create the needed structures and support for greater transparency and power-sharing among all partners in the coalition, COMPASS spent one year developing a governance manual that increases accountability and consistency, formulates the coalition structure, clarifies roles and responsibilities, and establishes a process for determining who holds the Secretariat.
Thirty-six volunteers from across the COMPASS Africa responded to an open call to develop a comprehensive, participatory governance framework. The volunteers selected a two-chair leadership team and a steering committee to run the development process.
“Partners were given a chance to select the leaders of the process. It was important that the process was community-led and participatory, so coalition members truly felt ownership of COMPASS. That itself was something very important,” said Francis Luwole, COMPASS country coordinator in Tanzania.
As four working groups tackled issues such as sub-granting protocols, new membership and definition of roles and responsibilities, the steering committee focused on overall goals to be reflected in the governance manual: prioritize transparency; ensure accountability to COMPASS values; maximize opportunities for members to participate in decision-making; and ensure the country coalitions had ample opportunity to review, provide feedback and validate the manual. Through regular in-person and remote meetings, anonymous surveys and country visits, the co-chairs fostered a shared ownership of the coalition’s structure, purpose and future.
“Before now… there were no guidelines to answer questions such as ‘who we are, why we’re here, or who are we doing this for—there was no clarity in some of the roles and responsibilities of members in the coalition, especially for new members. The expectation now is for the governance manual to provide an outline of what the structure of the coalition is and the roles and responsibilities of all coalition members,” said Ulanda Mtamba.
The case study found that the participatory nature of the process ensured that diversity and inclusivity were at the forefront of the new COMPASS governance structure by allowing the opportunity for as many voices as possible to have their opinions and inputs considered. It also fostered a shared sense of ownership that empowered many coalition members to invest and believe in the change to create an African-led coalition.
The 63-page governance manual now covers, among other things: member obligations and benefits; a protocol for conflict resolution; a selection process for new members; guidelines for meetings; sub-grant management; an M&E framework; a process for ending coalition membership and terminating the secretariat; and defined principles and core values. It also establishes a governance committee to serve as a decision-making and strategy-setting body with representatives from every COMPASS country, global partners, and key constituencies such as adolescent girls and young women, key populations and people living with HIV. The governance committee will be the primary leadership structure of COMPASS going forward, with coordination support from Pangaea Zimbabwe as the coalition secretariat.
“It speaks to inclusion. It speaks to equity. Our core values and principles have been reflected in the way we have structured the coalition. I’m very optimistic that, once we fully operationalize the governance manual, we are going to come up with something really beautiful, something that other partners or other coalitions may want to adapt,” said Maureen Luba, Malawi-based COMPASS member.
For more on the colonial legacy of global health, The Choice Agenda held a discussion examining the historical legacies and power dynamics that continue shaping global health. Watch the recording.
Shifting the Secretariat
As of December 2023, coalition member Pangaea Zimbabwe became the primary grant-holder and COMPASS Secretariat. In this role, Pangaea Zimbabwe will make sub-grants, convene the coalition, and be the primary point of contact for the coalition with its donors, support campaign tracking & evaluation, and administer the process that selects coalition leadership and new members. Dedicated teams comprised of in-country partners with expertise on data analysis and monitoring & evaluation will provide technical assistance across the coalition. AVAC is now a sub-grantee partner of COMPASS, continuing to coordinate the team that provides strategic and technical support to partner campaigns, provide status updates and background on the R&D pipeline for HIV prevention, support COMPASS partners in their engagement with PEPFAR and the Global Fund, and link the coalition to global platforms and advocacy initiatives.
“From our earliest conception, we outlined a vision of collective power and shared decision-making that has been central to COMPASS’s success. For that success to be sustainable, AVAC and the COMPASS coalition at large pursued a future in which governance would be centered among African-based partners,” said Mitchell Warren.
“Since 2017, we’ve been breaking new ground under COMPASS. We’ve expanded our networks and brought together the superpowers of seasoned advocates with diverse strengths to develop and share technical expertise and winning strategies,” said Imelda Mahaka, Executive Director of Pangaea Zimbabwe. “COMPASS has built a strong foundation based on collaboration, knowledge-exchange and trust that can and will accelerate innovative advocacy under African leadership.”
Putting in the Time: Sustaining the partnerships
The development of the manual and Pangaea Zimbabwe’s assumption of the Secretariat involved a phased, transparent multi-year transition plan to guide the handover of the secretariat and sub-grants management. AVAC and Pangaea Zimbabwe held weekly calls on the process, COMPASS partners contributed feedback to the plan, and the entire coalition was able to track milestones defined for the transition process.
“Partners stressed to us repeatedly the importance of not rushing the process. All coalition partners needed time and opportunity to meaningfully participate in designing the new governance framework. Integrating this input into the governance manual was more important than finding quick solutions. We found the same was true in the process of transitioning the secretariat. Pangaea Zimbabwe wanted an appropriate on-ramp to get comfortable in their new role, with plenty of support and other partners also wanted to know how AVAC was supporting the relationship between Pangaea Zimbabwe and the project’s donor. We all invested time in building trust and confidence. For those in power who are now looking for a sustainable way to shift that power to others, my message to you is that you can’t just throw the bag and run,” said Justine MacWilliam, AVAC’s senior program manager.
“This process has showed how to share power and take away the dominance of power. The desire for social justice has underpinned these values, the desire to equalize power, and the desire to contribute to something that is a legacy,” said David Kamkwamba of the Network of Journalists living with HIV (JONEHA) in Malawi.
As COMPASS campaigns continue apace with a freshly inked grant from the Gates Foundation, coalition members, and Pangaea Zimbabwe are referencing the manual, testing its strength, making changes and sharing their insights. It is bold, careful and imperative work to build and use structures for collective power and effective action.
“AVAC and COMPASS have set new benchmarks in effective civil society mobilization, advocacy and collaboration between global North and South. AVAC’s commitment to empowering African leadership within the coalition reflects a profound dedication to ensuring sustainability and maximizing impact. Coalition members are beginning a new chapter, founded on their inspired, tireless commitment to deepening the impact of COMPASS under African leadership,” said Uganda-based COMPASS member, Kenneth Mwehonge.
“This is giving hope, especially to global south partners, especially in these times when we are talking about decolonizing global health. It’s timely and strategic. It’s proving to each other our readiness to say ‘This is possible. We can have leadership in the Global South where the work is happening, where the epidemic is being fought,” said Luba.
The COMPASS Coalition understands that doing business as usual will not advance HIV prevention or global health equity. And this new power-sharing model cannot turn the tide all by itself. But COMPASS partners hope fellow travelers who see the necessity of decolonizing global health will be interested in this model and will follow its progress. The work will certainly change and evolve based on what is learned in the months and years ahead, but there’s no going back.
Unpacking Cure at CROI: A Q&A with Jessica Salzwedel
This year’s Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, Colorado, was the setting for important updates on the HIV reservoir lending to new insights into potential cure strategies. AVAC’s Senior Program Manager for Research Engagement, Jessica Salzwedel, leads AVAC’s advocacy for HIV cure research and serves as the community engagement coordinator for three of ten NIH-funded international collaboratories: the Research Enterprise to Advance a Cure for HIV (REACH), Immunotherapy for Cure (I4C), and Pediatric Adolescent Virus Elimination (PAVE). These are aimed at developing therapeutic interventions to cure HIV infection. Jessica shares her highlights from the research and what it means for advocacy.
There was so much on HIV cure presented at CROI. What stood out to you as most important for advocates to follow?
I was really excited to see advances in both basic science and clinical research. Four results in preclinical and clinical research stood out because they advanced how researchers might tailor cure strategies to optimize the impact for people with HIV. We heard more about the potential role of sex hormones in directing the immune system in a study looking at fetus acquisition of HIV by Gabriela Cromhout. Another study by Toong Seng Tan of the Ragon Institute showed that women may be better candidates for the so-called “block and lock” strategy. We also heard results from IMPAACT P1115 trial by Deborah Persaud, which showed that early HIV treatment can lead to control of the virus in children. Finally Maurico Martin’s nonhuman primate study of adeno-associated virus, which delivered broadly neutralizing antibodies (bNAbs) and may offer a pathway to a scalable, durable control option for pediatric cure. In basic science, Katherine Bar presented data that suggests researchers, and by default advocates, should be looking at autologous neutralizing antibodies in some people to delay rebound. And finally, I’m excited about early-career investigator Louise Leyre’s research out of Weill-Cornell, which is looking at rare T-cells that seem to resist killing, which could be important in developing strategies that could lead to durable control and eradication of HIV.
Can you break down the research on sex hormones? Will biological sex play a role in cure strategies?
We’ve got more evidence now that biological sex plays a role. Cromhout showed differences in HIV acquisition between male and female fetuses in utero, building off data she presented at IAS 2023. This data analyzes the virus from a cohort of 281 mother-infant pairs. Her team found that male fetuses tend to acquire a “high fitness” virus sensitive to IFN-1, a first-line immune defense, while female fetuses acquire a “low fitness” virus resistant to IFN-1. Viral fitness refers to the ability of the virus to replicate. Cromhout showed that the acquisition of HIV in utero is driven by the immune system of the fetus and not differences in the virus of the mothers. Understanding the host-virus relationship, and how the immune system puts pressure on the virus to change in the early stages of infection is important for directing future cure strategies.
In the study of people with HIV who have long-term suppression via ART, presented by Toong Seng Tan from the Ragon Institute, biological sex is a factor in determining reservoir composition over time. Tan looked at intact versus defective proviruses (the pieces of HIV that have integrated into DNA) as well as where HIV had integrated into a person’s DNA. He did not find any significant difference between the amount of intact virus (which can cause harm) and defective virus between men and women. But women had a higher portion of HIV integrated into areas of their DNA that were “transcriptionally silent”, meaning HIV could not rebound, after long-term suppression on ART. The women in the study were all post-menopausal at the time of enrollment, so more work is needed to understand how hormones shape reservoir characteristics in women, both cis and trans, at younger ages. The results suggest that women may be better candidates for a cure strategy under investigation known as “block and lock”. The strategy is trying to drive HIV deeper into latency so it cannot rebound.
We’re seeing more results on children’s ability to control HIV off treatment, how significant is this?
This is significant, but we know early treatment is not for everyone. Deborah Persaud of Johns Hopkins University presented the results of IMPAACT P1115, which enrolled 54 infants who acquired HIV in utero and received combination therapy within 48 hours of birth. Six children met the criteria for an analytic treatment interruption (ATI). These criteria were sustained viral suppression from 48 weeks onward, normal CD4 count, negative HIV serostatus using a highly sensitive assay, and no detectable virus. Of the six children who underwent an ATI, four achieved durable control, defined by the study as remaining undetectable over 44 weeks. One of the four controllers rebounded at 80 weeks while the other three remain on an ATI. Two of the six children who met the criteria for ATI rebounded at eight and ten weeks respectively. The study confirms that early treatment can lead to control of the virus in some children; however, it is not a strategy for all. Even with the vastly reduced reservoir size caused by almost immediate treatment, the virus is not completely eradicated and may rebound in some children off therapy.
Another study, this one in nonhuman primates, presented by Maurico Martins of the University of Florida, showed promising progress toward a 4-dose single injection regimen that led to durable control in all animals treated with the investigational product. This study evaluated the adeno-associated virus (AAV) vector delivering antibodies. AAV is a unique platform because it has been shown to last for the duration of the cell. This study is targeting muscle cells, some of the longest-lived cells in the body, to deliver the AAV vector. The next step is to move this strategy into human clinical trials. This approach could offer a durable, scalable and cost-effective way to control or cure pediatric HIV.
For advocates new to cure, why is the reservoir important and what can you tell us about these rare T-cells and their role?
The “reservoir” is the collection of cells that have HIV integrated into the DNA but are not replicating. They are important because once cell replication begins, so does virus production. In the absence of ART, this is the cause of rebound. At CROI, we saw several advances in basic understanding, targeting and reactivating the reservoir. Early-career investigator Louise Leyre of Weill-Cornell presented research on a potential mechanism for why a small subset of HIV-infected T-cells resist being killed by natural killer cells. These rare HIV-infected T-cells are “slippery and squishy” and avoid being killed due to weak adhesion proteins on the cell surface. This prevents the killer cell from attaching properly. This is important for cure research because a small subset of cells can lead to viral rebound off therapy. Identifying why some cells resist killing is important to develop strategies that can lead to durable control and eradication of HIV.
Lastly, I wanted to highlight Katherine Bar’s presentation on the potential of autologous neutralizing antibodies. Autologous neutralizing antibodies are the antibodies the body makes against the virus. In natural infection the virus is always one step ahead. When treatment is started, virus evolution pauses. To see what role autologous antibodies play, Bar tested the sensitivity of the reservoir and rebound virus of trial participants in the BEAT-2 trial, which evaluated the impact of a combination of bNAbs (3BNC117 and 10-1074) and type 1 interferon (IFN-1) with an ATI against the autologous antibodies. When a researcher says “testing sensitivity” they are looking at whether a virus is neutralized by an antibody or not. Bar and her team found that the two participants who experienced delayed rebound in the trial had reservoir virus sensitive, meaning it could be neutralized, by autologous antibodies. This may have delayed rebound after the broadly neutralizing antibodies waned from their system. It is important for cure research because autologous antibodies may be another approach to increase the duration of control off therapy. Researchers may look at approaches to enhance these antibodies before a treatment interruption in future combination approaches.
So, what are our key points for advocacy coming out of CROI?
- Diversity matters. It is critical clinical research includes participants from all geographic locations, age, and sex.
- Cure will not bring a one-size-fits-all strategy, and it is important to learn the combination strategies currently being pursued in clinical research as well as the future strategies that basic science discovery is generating.
- There are still basic questions that need to be answered for researchers to find a safe, scalable, durable and affordable cure. Advocates should follow the science and encourage funders to continue to invest, build community and research infrastructures to translate knowledge, and prepare for future clinical research.
Wednesday’s CROI Update
The presentations on the last day of CROI 2024 highlighted yet again that research conducted in ethical partnership with communities is about developing products and delivering them with speed, scale, equity and impact.