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Impact of Anti-PD-1 and Anti-CTLA-4 on the Human Immunodeficiency Virus (HIV) Reservoir in People Living With HIV With Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium 095 Study
- Source :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol 73, iss 7
- Publication Year :
- 2021
- Publisher :
- eScholarship, University of California, 2021.
-
Abstract
- BackgroundAntibodies to programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated 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-PD-1 alone or in combination with anti-CTLA-4 in people living with HIV (PLWH) and cancer.MethodsThis was a substudy of the AIDS Malignancy Consortium 095 Study. ART-suppressed PLWH with advanced malignancies were assigned to nivolumab (anti-PD-1) with or without ipilimumab (anti-CTLA-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.ResultsOf 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, 1.16-1.89) 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.ConclusionsAnti-PD-1 alone showed no effect on HIV latency or the latent HIV reservoir, but the combination of anti-PD-1 and anti-CTL-4 induced a modest increase in CA-US HIV RNA and may potentially eliminate cells containing replication-competent HIV.Clinical trials registrationNCT02408861.
- Subjects :
- Acquired Immunodeficiency Syndrome
anti–PD-1
Programmed Cell Death 1 Receptor
HIV
HIV Infections
Biological Sciences
Medical and Health Sciences
Microbiology
Virus Latency
Infectious Diseases
Clinical Research
Neoplasms
anti–CTLA-4
anti-CTLA-4
HIV-1
Genetics
Humans
HIV/AIDS
anti-PD-1
CTLA-4 Antigen
HIV latency
Infection
Cancer
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol 73, iss 7
- Accession number :
- edsair.od.......325..6b029e7fd09429c188adbb33fe460988