| Autor: |
Dabee S; Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa., Mkhize NN; National Institute for Communicable Diseases (NICD), Johannesburg, South Africa., Jaspan HB; Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa.; Seattle Childrens Hospital, Seattle, Washington, USA., Lewis D; Western Sydney Sexual Health Centre, Parramatta, Australia.; Westmead Clinical School and Centre for Infectious Diseases and Microbiology & Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia., Gumbi PP; Department of Biochemistry, University of KwaZulu Natal, Pietermaritzburg, South Africa., Passmore JS; Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa.; NRF-DST Centre of Excellence in HIV Prevention, Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa.; National Health Laboratory Service, Cape Town, South Africa. |
| Abstrakt: |
Antiretroviral therapy (ART) has significantly improved the quality of life of HIV-infected individuals: reducing plasma viremia, restoring CD4 + T cell numbers, and correcting imbalances in blood memory T cell subsets. While ART improves immune correlates at mucosal sites, including the lower female genital tract (FGT), ART initiation has been associated with reactivation of common FGT infections. We investigated the effect of ART on immune activation and inflammation in the genital tract. We measured blood and genital T cell activation, proliferation, and immunosenescence (CD38, HLADR, Ki67, CD127, and CD57), and cytokine levels in women on ART for ∼7 years (cross-sectional analysis) or initiating ART (immediately before and 1 month after). Effector memory T cells predominated in blood and FGT during chronic infection, irrespective of ART status. In women initiating ART, 1 month was insufficient for T cell reconstitution, or alterations in T cell subset distribution, despite both plasma and genital viral loads decreasing to undetectable levels in most participants. Initiating ART was accompanied by a decline in plasma IP-10 that correlated with decreased blood CD38 expression in blood ( p = .0204) but not in the FGT. The reduction in plasma (but not genital) cytokine levels due to ART initiation was dependent on their concentrations before treatment. While T cell activation decreased significantly in blood (CD4: p = .032; CD8: p = .0137), activation levels remained similar in the genital tract despite 1 month of treatment. Overall, the decrease in cellular activation and inflammation seen in blood with ART initiation was not evident in the FGT. |
