biostudies-literatureTalla AU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)505-517https://www.ebi.ac.uk/biostudies/studies/S-EPMC12920136biostudies-literatureUnknown32(2)Antiretroviral therapy (ART) suppresses HIV but does not eliminate the latent viral reservoir, which persists in programmed cell death protein 1 (PD-1)-expressing CD4⁺ T cells. Anti-PD-1 therapies have reduced the HIV reservoir in people living with HIV (PLWH) and cancer; however, the individuals who benefit and the mechanisms driving reservoir reduction remain unclear. We performed a prespecified exploratory, longitudinal multiomic profiling of 30 PLWH (29 males and one female) with cancer in the phase 1 CITN-12 clinical trial, in which pembrolizumab was evaluated for safety and preliminary antitumor activity. The therapy was generally well tolerated, with most adverse events graded 1-2 and objective antitumor response observed in five participants (one complete response and foNature medicineInnate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy.PMC12920136P01AI178376UM1AI164561Azevedo JLLCBal SKMaldarelli FLewin SRCheever MAPelletier ANLurain KD'Amico LRamaswami RSekaly RPFling SPSharma AAEnriquez ABTalla ASharon EMartinez-Picado JLatif MBChomont NSanchez GPKumari SGhneim KYarchoan RSchuch VRhodes AHess BWUldrick TSDeeks SGfalseInnate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy.Antiretroviral therapy (ART) suppresses HIV but does not eliminate the latent viral reservoir, which persists in programmed cell death protein 1 (PD-1)-expressing CD4⁺ T cells. Anti-PD-1 therapies have reduced the HIV reservoir in people living with HIV (PLWH) and cancer; however, the individuals who benefit and the mechanisms driving reservoir reduction remain unclear. We performed a prespecified exploratory, longitudinal multiomic profiling of 30 PLWH (29 males and one female) with cancer in the phase 1 CITN-12 clinical trial, in which pembrolizumab was evaluated for safety and preliminary antitumor activity. The therapy was generally well tolerated, with most adverse events graded 1-2 and objective antitumor response observed in five participants (one complete response and fo2026-01-01T00:00:00Z2026 Feb2026-07-16T12:38:02.896Z2026-07-09T10:55:01.389ZS-EPMC129201364168048210.1038/s41591-025-04139-y