Report from the Community HIV Cure Research Workshop

The annual Community HIV Cure Research Workshop took place virtually this year. The workshop, a highlight of CROI, was broken up into two sessions on February 8 and March 1. The Community HIV Cure Workshop sessions aim to foster dialogue between biomedical HIV cure researchers and community members, and to deepen community understanding of the science involving the search for an HIV cure. The CROI meeting itself occurred virtually from February 12–16 and 22–24, 2022. The Community HIV Cure Research Workshop was sponsored by Treatment Action Group (TAG), AIDS Treatment Activists Coalition (ATAC), AVAC, BEAT-HIV Community Advisory Board (CAB), Delaney AIDS Research Enterprise (DARE) CAB, I4C CAB, Enterprise for Research and Advocacy to Stop and Eradicate HIV (ERASE-HIV), HOPE Collaboratory, CRISPR for Cure Collaboratory, PAVE Collaboratory, REACH Collaboratory; University of Washington/Fred Hutch Center for AIDS Research (CFAR) Cure Scientific Working Group, NMAC and European AIDS Treatment Group.

Below are some of the highlights:

Case of HIV “Cure” in Woman of Mixed Race:

• Likely the most significant case report from CROI 2022 was a case of HIV “cure” presented by Ivonne Bryson from UCLA. A middle-aged cisgender woman of mixed race from New York was found free of HIV 14 months after interrupting ART following a haplo-cord transplant from a donor homozygous (inherited from both parents) for the delta-32 gene deletion, making the woman’s cells resistant to HIV. Both her leukemia and HIV are “in remission” and experts are hopeful that the woman will remain without HIV. Following the Berlin patient – Timothy Ray Brown (2009), the London patient – Adam Castillejo (2019), and the Dusseldorf patient (2019), she is referred to as the "New York" patient and is the fourth confirmed case of HIV “cure” following a stem cell transplant (even though most media reported hers as being the third case). Her case provides hope that cord blood cells can be used to achieve cure in people with both HIV and cancer, which would open up this method of curing someone with HIV and a life-threatening cancer to more potential people. Her health will continue to be monitored. For more details, please view the conference session webcast.

Tuesday February 8 Community HIV Cure Research Workshop:

• Nora Jones from the BEAT-HIV Delaney CAB and Danielle Campbell from the BEAT-HIV and DARE CABs opened the workshop with a review of ethical considerations in HIV cure research. There are several guideposts that must be in place for ethical HIV cure research. Besides ensuring autonomy, maximizing benefits, and minimizing risks, presenters emphasized the critical importance of equity and community-based principles including social justice and community involvement, to ensure research remains ethical and acceptable to communities of interest. For more details, please view: https://www.youtube.com/watch?v=o-poD1mvyrs
  
   
• Toni D’orsay from the HIV + Aging Research Project – Palm Springs (HARP-PS) moderated a lively panel discussion on black transgender women and HIV cure-related research. The other panelists were Sydney Rogers, aka Miss Barbie-Q and Brighton “Bee” Meki. The discussion emphasized ensuring inclusion of transgender women at all stages of planning both biomedical and socio-behavioral HIV cure research. The panel noted the importance of incorporating awareness for gender-affirming care and wrap-around services in research study designs, acknowledging the intersectionality of oppression, and ensuring intentional inclusion at all levels – including advocacy, policy, leadership and funding. For more details, please view: https://www.youtube.com/watch?v=kVa88AznuuY
  
   
• Natalia Laufer and Gabriela Turk from the INBIRS Institute in Argentina presented the case of the Esperanza patient, the second woman (after Loreen Willenberg) who has cleared HIV without antiretroviral treatment (ART). The Esperanza patient, a Caucasian woman first diagnosed with HIV at 23 in 2013, was recently, in 2021, found to have no virus capable of replicating itself. Her case gives potential clues to advancing ‘block and lock’ approaches to keep HIV permanently silenced inside the body. For more details, please view: https://www.youtube.com/watch?v=_ikS8_Xwxoo&t=1s
  
   
• Lynda Dee, DARE CAB Community Engagement Coordinator, and Karine Dubé from UNC Chapel Hill led a discussion on HIV cure research terminology – weighing the pros and cons of using various expressions such as ‘sterilizing cure,’ ‘functional cure’ and ‘remission.’ Several members of the community converged on the need for patient/participant-friendly language to describe the science of HIV cure. There was a consensus that the term, ‘sterilizing cure’ should be discouraged and not used because of its association with disinfecting and forced sterilization. Other words that are unacceptable are ‘subjects’ and ‘HIV-infected person’. For more details, please view: https://www.youtube.com/watch?v=UpcpYhkx18g&t=317s

Tuesday March 1 Community HIV Cure Research Workshop:

• Marina Caskey  from the Rockefeller University provided an overview of broadly neutralizing antibodies (bNAbs) being investigated in several HIV cure-related trials—some of which will be initiated in 2022. Antibodies find specific targets on the virus and have numerous properties that make them attractive. For example, bNAbs are specific, diverse and have a memory. Antibodies can either block free HIV or help clear infected cells. There is emerging evidence that a combination of bNAbs will be necessary to maintain viral suppression after ART interruption. Some challenges remain, such as diversity of the HIV reservoir, and pre-existing resistance to bNAb-based approaches. For more details, please view: https://www.youtube.com/watch?v=m0s08rxDM5o
  
   
• Thumbi Ndung’u from the Africa Health Research Institute (AHRI) provided an overview of HIV cure research in low- and middle-income countries (LMICs). Dr. Ndung’u discussed some of the approaches that may be more appropriate for LMICs, such as early ART, bNAbs and immune-based approaches. The Female Rising through Education, Support and Health (FRESH) research team in Durban, South Africa will soon initiate a trial to study post-treatment control of HIV in young women diagnosed during acute HIV. Dr. Ndung’u said that HIV cure studies need to prioritize LMICs with the highest burden of HIV in those settings. For more details, please view: https://www.youtube.com/watch?v=Rz_YqMfMGN8&t=43s
  
   
• Philister Adhiambo Madiega, a community member from Kenya, spoke about what motivates her to advance HIV cure research. Philister discussed important considerations for HIV cure research in LMICs, including ongoing cure research education, acknowledging how HIV cure is interpreted in different communities, the need for careful language to manage expectations, avoiding myth and misconceptions, discussing safety of interventions, and challenging issues around accessibility, affordability, acceptability, and appropriateness of interventions for all populations, including hard to reach groups and women of all ages. For more details, please view: https://www.youtube.com/watch?v=coWPL-WDG4o&t=94s
  
   
• Drs. Deborah Persaud, Lishomwa (Lish) Ndhvolu, Katie Bar and Luis Montaner provided a report back on HIV cure-related science presented at CROI 2022, including a question-and-answer session. For more details, please view: https://www.youtube.com/watch?v=vhP38HkRdlo&t=147s

Additional select CROI 2022 highlights:

• Peter Hunt from the University of California San Francisco (UCSF) provided an overview of advances in HIV cure with clinical perspectives. Regarding latency-reversing agents, novel agents are being identified in animal models, also explaining that more research will be needed to make them safer before research in humans is undertaken. He said we will also need to focus on effective strategies towards HIV clearance, and that combination approaches will be needed for immunotherapy strategies. For gene therapy, there are many promising approaches in development, and again the focus will need to be on both safety and scalability. Dr. Hunt also urged that more research should be directed towards ‘block and lock’ approaches which will hopefully keep latent reservoirs in a deep state of latency. The ‘block’ agent might also help reduce persistent inflammation.
  
   
• Ole Søgaard from Aarhus University presented the results of a study that used 3BNC117, a bNAb, and romidepsin, a latency-reversing agent, when ART was initiated. The trial enrolled 60 participants in Denmark and England and found that starting the 3BNC117 at ART initiation led to faster reduction of viral load and helped eliminate HIV-infected cells. There was also improved immunity and delayed time to virus rebound in the groups of participants that were sensitive to the 3BNC117. One participant remained with undetectable viral load in the group that used both 3BNC117 and romidepsin.
  
   
• Jim Riley from the University of Pennsylvania discussed the attractiveness of chimeric antigen receptor (CAR) T-cells for HIV cure-related studies. His team presented the results of a pilot study utilizing T-cells modified by CCR5-specific zinc finger nucleases, a form of gene therapy, and CD4 CAR receptor. Of the eight participants that were able to be evaluated, one maintained very low viral loads and has remained off ART for approximately 65 weeks. This person also participated in two previous gene therapy studies and will continue to be closely monitored.
  
   
• “River Deep, Mountain High: Pathways Towards a Cure for HIV”: At the Margarita Breakfast Club, a CROI-related community session free to everyone, scientists and advocates from across the globe held a passionate discussion via Zoom about the big news of  the ‘possible cure’ of HIV in a woman of mixed race, in addition to some more subtle news from CROI 2022. Moderators Danielle M. Campbell and Michael Louella stirred up conversation with Dr. Katherine Bar and Moses Supercharger that inspired much comment and reflection about the issues raised by the news. The end result is a conversation informed by global perspectives and an example of why we ought to always include a variety of voices if we wish to understand the global impact and implications of HIV cure research.

Additional Resources on HIV Cure-Related Research:

There is a community resource related to HIV cure research that is free to all. It is called the CUREiculum. It consists of six modules about various topics related to HIV cure research. They are free for all to download and use and edit. All modules are available for use by individuals or groups interested in spreading the word about HIV cure research!

CUREiculum 2.0: https://www.treatmentactiongroup.org/cure/cureiculum-2-0/

For more information about CROI 2022 Community Events: