Reversal of Viral Latency and Induction of Gag-Specific T-Cell Responses in HIV-1-Infected Adults Through Cyclic Treatment Interruption of Rosuvastatin: A Proof-of-Concept Study

Background: HIV-1 infection remains incurable through combination antiretroviral therapy. Previous studies have shown statins have immunomodulatory effects, and interruption of statins may cause an immune rebound. Methods: In this proof-of-concept study, we longitudinally assessed the impact of immune rebound by cyclic treatment-interruption (CTI) of rosuvastatin on the reversal of HIV latency. The HIV-1-infected persons with stable viral control were considered to be enrolled for CTI of rosuvastatin with a fixed 12-week interval for 72 weeks (3 treatment-interruption cycles). HIV-1 Gag-specific T-cell responses, cell-associated RNA, and proviral DNA were determined. Results: From Feb 2017 to Dec 2019, 10 subjects were enrolled. During the 72-week follow-up, their CD4(+) T-cell counts did not significantly change, and plasma HIV RNA remained undetectable. Transient but remarkable increases in levels of cell-associated RNA, Gag-specific interferon-gamma production from CD4(+) T cells and Gag-specific CD8(+) cytotoxic capacity were detected shortly after stopping rosuvastatin in every cycle of CTI of rosuvastatin. Furthermore, there was a 2.63-fold reduction (range, 1.41-4.82) in proviral DNA levels (P = 0.005) during the 72-week follow-up. A significant linear association was demonstrated between their nadir CD4(+) T-cell counts and the fold decrease in proviral DNA levels (R = 0.81, P = 0.004). Conclusion: It may be possible to reverse viral latency in CD4(+) T cells, activate Gag-specific T cells, and reduce viral reservoir size through CTI of rosuvastatin in HIV-1-infected subjects with stable combination antiretroviral therapy, especially in those with nadir CD4(+) T-cell counts > 350 cells/mu L.