Project Details

Description


The HIV epidemic has a tremendous impact on global health as 38 million people live with and more than a million die from HIV every year. Although antiretroviral therapy (ART) is very effective and resulted in suppression of viral replication and substantially reduced AIDS-related morbidity and mortality, it does not eliminate HIV that persists in a latent state. In many people with HIV (PHIV) treatment interruption results in a rapid viral rebound from these latently infected cellular reservoirs. Consequently, PHIV must commit to expensive, lifelong therapies, continuous clinical and laboratory monitoring, and face drug toxicities and chronic immune activation. So, there is an urgent need to develop safe, affordable, and globally accessible curative strategies that reduce these latently infected viral reservoirs and boost the host immune system to control the infection. Such an integrated intervention would eliminate the need for lifelong therapy while improving health, reducing HIV-related stigma and discrimination.
The dominant HIV-1 subtype in Western Europe, Americas, and Australasia, representing only 12% of global HIV-1 infection, is subtype B. As a result, thus far, fundamental, translational, and clinical HIV research has been conducted and driven almost exclusively by HIV-1 subtype B and in populations where subtype B predominates, mostly men who have sex with men (MSM), although women account for 52% of HIV-1 infections globally. This project will shift the focus entirely to describing, characterizing, and targeting the HIV-1 reservoir in women and men infected with HIV-1 subtype C (47% of global infections), A (10% of global infections) and D (5 % of global HIV-1 infections). A comparative analysis of HIV-1 subtypes A, C, D and B would account for 75% of global HIV-1 infections. A prospective approach comparing the HIV reservoir ATLAS of these subtypes in women and men, in blood and tissue, and generating models to identify and evaluate specific cure approaches in these different HIV reservoir contexts significantly closes the gap in knowledge and would inform the design of more equitable cure interventions.
It is unclear what integrated interventions are required to achieve durable HIV control globally. Additionally, we do not know the contextual barriers, facilitators, and perspectives of stakeholders required to successfully implement a cure. In this interdisciplinary proposal, biomedical researchers, clinicians, social scientists, modelers, health economists, PHIV, health care professionals, industry partners, and communication specialists, from both the Global North and the Global South, join forces to achieve a durable control of HIV for all. We will identify crucial correlates of immune control and develop innovative combinatorial immune-based and genetic therapies to reduce the HIV reservoir and control HIV. Novel exciting ex-vivo models will be developed to identify and select the most powerful interventions. Studies will include (trans-)gender, minorities, and age diverse populations globally. We will provide health economics and population level assessment of the impact of developed strategies and incorporate perspectives of unrepresented global stakeholders in HIV cure in an equitable way. Implementation and development of cure strategies will be informed by analyzing decision-making processes, dynamics, and experiences of the involved collaborators. Our unique expertise is instrumental in achieving biomedical breakthroughs and gaining fundamental insights into social and economic challenges to succeed in developing and implementing an HIV cure for all.
AcronymSpiral
StatusActive
Effective start/end date1/06/20241/06/2030