Project: Effect of Pre-Exposure Prophylaxis (PrEP) on immune responses systemically and mucosally in healthy individuals in the CAPRISA 082 study- (PrEP Underlying Mucosal-immunity Before/After PUMBA)

Acronym	PUMBA (Reference Number: TMA2017SF-1960)
Duration	01/02/2019 - 31/01/2024
Project Topic	HIV remains a formidable public health challenge particularly in southern Africa, with young women bearing the highest incident infection rates. Regardless of the advent and proven efficacy of oral pre-exposure prophylaxis (PrEP) in several studies, women remain vulnerable to HIV. As oral PrEP becomes part of the standard of care for HIV prevention, the long-term effects of PrEP in at risk populations is not fully defined. Despite the emerging evidence of the immunological effect of PrEP in animal models, there is a paucity of data regarding the immunological consequences of long-term PrEP usage in healthy human populations. The a priori hypothesis is that PrEP will prevent HIV and HSV-2 infections. The hypothesis being tested is that long-term PrEP modulates the profile of antibody responses, inflammatory cytokine profiles and impacts the microbiome in the female genital tracts of at risk but healthy individuals. With the likely advent of combination HIV prevention strategies that include both vaccines and PrEP, understanding the effect that PrEP may have on the humoral immunity, inflammatory profiles and the microbiome in the genital tract and systemically may have important implications for efficacy of candidate HIV vaccines. Aims of the study: 1. To characterize the antibody isotype profile, the cytokine profile, levels of genital tract Tenofovir (TFV) and Emtricitabine (FTC) and the microbiome (composition, structure, and function) in the genital tracts and blood of healthy women before and after PrEP. 2. To characterize the antibody isotyping profile, the cytokine profile, and the microbiome (composition, structure, and function) in the genital tracts and blood of healthy women who have not taken PrEP- Control Group. Established laboratory methods like customized antibody binding and cytokine multiplexing, 16S rRNA qPCR and mass spectrometry quantify drug levels will be used on the matching mucosal and plasma specimens. Data generated in this study may then enable us to tease apart putative immune correlates of protection in the presence or or absence of oral PrEP that may be highly desirable to elicit or block at the site of exposure. We may then establish whether oral PrEP plays a role in modulating immunity in the genital tract relative to systemic immune profiles. In an era where combination prevention strategies including PrEP and HIV vaccines are being used together to prevent HIV infection, understanding the impact of anti-retroviral PrEP on the immune system is crucial.
Network	EDCTP2
Call	Senior Fellowships 2017

Project partner

Number	Name	Role	Country
1	Centre for the Aids Programme of Research in South Africa	Coordinator	South Africa