{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:37:36Z","timestamp":1791571056477,"version":"4.3.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100001117","name":"American Foundation for AIDS Research","doi-asserted-by":"crossref","award":["109226-58-RGRL"],"award-info":[{"award-number":["109226-58-RGRL"]}],"id":[{"id":"10.13039\/100001117","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Australian National Health and Medical Research Council","award":["GNT1149990"],"award-info":[{"award-number":["GNT1149990"]}]},{"name":"Australian Centre for HIV and Hepatitis Research"},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AIDS Malignancy Consortium","award":["UM1 CA121947"],"award-info":[{"award-number":["UM1 CA121947"]}]},{"name":"AIDS Malignancy Consortium","award":["CA239583"],"award-info":[{"award-number":["CA239583"]}]},{"name":"AIDS Malignancy Consortium","award":["DE018304"],"award-info":[{"award-number":["DE018304"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Antibodies to programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte\u2013associated protein 4 (CTLA-4) may perturb human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) by reversing HIV latency and\/or boosting HIV-specific immunity, leading to clearance of infected cells. We tested this hypothesis in a clinical trial of anti\u2013PD-1 alone or in combination with anti\u2013CTLA-4 in people living with HIV (PLWH) and cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a substudy of the AIDS Malignancy Consortium 095 Study. ART-suppressed PLWH with advanced malignancies were assigned to nivolumab (anti\u2013PD-1) with or without ipilimumab (anti\u2013CTLA-4). In samples obtained preinfusion and 1 and 7 days after the first and fourth doses of immune checkpoint blockade (ICB), we quantified cell-associated unspliced (CA-US) HIV RNA and HIV DNA. Plasma HIV RNA was quantified during the first treatment cycle. Quantitative viral outgrowth assay (QVOA) to estimate the frequency of replication-competent HIV was performed before and after ICB for participants with samples available.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 40 participants, 33 received nivolumab and 7 nivolumab plus ipilimumab. Whereas CA-US HIV RNA did not change with nivolumab monotherapy, we detected a median 1.44-fold increase (interquartile range, 1.16\u20131.89) after the first dose of nivolumab and ipilimumab combination therapy (P = .031). There was no decrease in the frequency of cells containing replication-competent HIV, but in the 2 individuals on combination ICB for whom we had longitudinal QVOA, we detected decreases of 97% and 64% compared to baseline.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Anti\u2013PD-1 alone showed no effect on HIV latency or the latent HIV reservoir, but the combination of anti\u2013PD-1 and anti\u2013CTL-4 induced a modest increase in CA-US HIV RNA and may potentially eliminate cells containing replication-competent HIV.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT02408861.<\/jats:p>\n               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