Highlights from the HIV Cure Pre-Conference at AIDS 2024

The 2024 HIV Cure Pre-Conference at AIDS 2024, held today, 21 July 2024, in Munich, was a pivotal event that brought together leading experts and researchers from around the globe to discuss the latest advancements, ongoing challenges, and the future direction of HIV cure research. This pre-conference served as a critical platform for sharing insights into the scientific, structural, and global coordination efforts needed to push forward the ambitious goal of achieving a functional or complete cure for HIV.

Keynote Presentation by Deborah Persaud

The event began with a powerful keynote address by Dr. Deborah Persaud, who is recognized for her groundbreaking work in pediatric HIV cure research. Dr Persaud provided a comprehensive overview of the current landscape of HIV cure research, particularly focusing on Latency-Reversing Agents (LRAs) in clinical trials. She presented a detailed systematic review that highlighted the need for meticulously designed studies to determine the precise levels of HIV-1 reactivation necessary to effectively reduce the HIV-1 reservoir—a critical barrier to achieving a cure. Persaud emphasized the significance of pharmacovigilance in these trials, noting that, “Collectively, these investigational clinical studies have provided the foundation for the acceptability, safety, and efficacy of cure interventions and the use of analytic treatment interruption (ATI) for global scale-up.” Her presentation underscored several key advancements:

• Advances in Understanding HIV-1 Reservoirs: Dr. Persaud discussed the significant progress made in understanding the mechanisms that drive the persistence of latent HIV-1 reservoirs. These reservoirs represent the primary obstacle to achieving ART-free remission and a complete cure, making this area of research vital.
• Early ART in Neonates: Dr Persaud also highlighted the impact of initiating ART in neonates with in-utero HIV-1 infection. Early ART has been shown to significantly curtail the establishment of HIV reservoirs in these infants, offering a promising avenue for achieving ART-free remission.
• Cancer Therapies and Stem Cell Transplants: The pre-conference revisited the remarkable cases of HIV-1 cures in adults who were treated for cancers, such as Acute Myeloid Leukemia (AML), with CCR5 homozygous delta 32 stem cell transplants. These cases have shed light on a potential pathway to curing HIV-1, although the approach is not yet broadly applicable.
• Investment in Immunotherapies: Dr. Persaud also discussed the growing investment in immunotherapies, which aim to enhance the body’s immune response to eliminate HIV-infected cells. These therapies represent a critical component of the global strategy to achieve ART-free remission and, ultimately, a cure.

Viral Persistence in Different Populations

Dr. Rose Nabatanzi delivered an insightful presentation on the complexities of viral persistence across different populations. Her talk emphasized the need to understand the biological sex-specific differences in HIV-1 infection, which are often overlooked in research. Dr. Nabatanzi’s powerful slides illustrated why HIV persists differently by age, sex, and among elite controllers, highlighting the critical importance of developing therapies that are efficacious across all demographics. She strongly advocated for the early inclusion of diverse populations in clinical trials, arguing that this approach would save time, reduce costs, and lead to the development of a broadly applicable cure.

Co-Infections and HIV Reservoirs

Dr. Gabriel Duette from the Westmead Institute for Medical Research presented compelling data on the impact of co-infections and co-morbidities on HIV reservoirs. Dr. Duette pointed out that co-infection with pathogens such as Mycobacterium tuberculosis (Mtb) can exacerbate the HIV reservoir, complicating treatment strategies. He emphasized the limited current understanding of the mechanisms driving this increase, marking it as a critical gap in the field that requires further investigation.

Reservoir Timing in Women with Chronic HIV

Dr. Melissa-Rose Abrahams from the University of Cape Town offered new insights into the timing of reservoir establishment in women with chronic HIV. She presented data showing that viruses from the year before ART initiation tend to dominate the long-lived reservoir in these women. This finding suggests a potential window for intervention at the time of ART initiation to restrict the reservoir, particularly as productively infected cells transition to a resting memory state. Dr. Abrahams also discussed findings from the "Baby Cure" project in Zimbabwe, which observed higher rates of vertical HIV transmission in female infants compared to their male counterparts in sex-discordant twins. She hypothesized that this difference might be due to higher immune activation levels and IFN-g immune responses in females, providing a potential explanation for these observations.

Communicating HIV Cure Literacy

A dedicated session on the communication of HIV cure literacy, co-chaired by Jessica from AVAC, emphasized the importance of delivering trial information in a contextually relevant and locally understandable manner. Dr. Krista Dong underscored the necessity of clear and continuous communication, drawing on her experiences with the FRESH cohort. This session highlighted the critical role of effective communication in ensuring that communities are informed and engaged in the research process, which is essential for the success of HIV cure trials.

Stories of HIV Cure and Emerging Research

The pre-conference also celebrated the stories of individuals who have been cured of HIV through stem cell transplants. Mark Franke ("Düsseldorf patient"), Adam Castillejo ("London patient"), and Paul Edmonds ("City of Hope patient") shared their journeys, providing powerful testimonies that highlighted the human aspect of scientific research. These narratives reinforced the importance of integrating lived experiences into both research and policy-making, ensuring that the voices of those affected by HIV are heard and valued.

Innovative Research Highlights

The conference concluded with presentations of several innovative research projects:

• Mauricio Martins showcased a promising macaque model utilizing early treatment interventions combined with adeno-associated virus (AAV) delivery of HIV broadly neutralizing antibodies (bNAbs). This approach has shown positive results in monkeys treated shortly after infection, offering hope for a similar strategy in humans.
• Wadzanai Samaneka discussed the ACTG 5470 study, which explores the use of long-acting bNAbs in conjunction with ART in sub-Saharan Africa. Samaneka summarized the potential of bNAbs as a key component in achieving a cure for HIV.

The 2024 HIV Cure Pre-Conference underscored the necessity of a coordinated, global approach to HIV cure research. The event highlighted the importance of overcoming both scientific and structural challenges to develop effective, widely applicable cure strategies. As the conference concluded, there was a shared sense of urgency and optimism, with attendees leaving more determined than ever to push forward in the quest to eradicate HIV.

 

Kennedy Mupeli

https://x.com/KMupeli