Impact of Anti PD-1 Immunotherapy on HIV Reservoir and Anti-Viral Immune Responses in People Living with HIV and Cancer.
Marine BaronCathia SouliéArmelle LavoléLambert AssoumouBaptiste AbbarBaptiste FouquetAlice RousseauMarianne VeyriAssia SamriAlain MakinsonSylvain ChoquetJulien MazièresSolenn BrosseauBrigitte AutranDominique CostagliolaChristine KatlamaJacques CadranelAnne Geneviève MarcelinOlivier LambotteJean-Philippe SpanoAmélie Guihotnull The French Cooperative Thoracic Intergroup Ifct Chiva-Investigatorsnull The Anrs Co OncoVIHAC Study GroupPublished in: Cells (2022)
The role of immune checkpoints (ICPs) in both anti-HIV T cell exhaustion and HIV reservoir persistence, has suggested that an HIV cure therapeutic strategy could involve ICP blockade. We studied the impact of anti-PD-1 therapy on HIV reservoirs and anti-viral immune responses in people living with HIV and treated for cancer. At several timepoints, we monitored CD4 cell counts, plasma HIV-RNA, cell associated (CA) HIV-DNA, EBV, CMV, HBV, HCV, and HHV-8 viral loads, activation markers, ICP expression and virus-specific T cells. Thirty-two patients were included, with median follow-up of 5 months. The CA HIV-DNA tended to decrease before cycle 2 ( p = 0.049). Six patients exhibited a ≥0.5 log 10 HIV-DNA decrease at least once. Among those, HIV-DNA became undetectable for 10 months in one patient. Overall, no significant increase in HIV-specific immunity was observed. In contrast, we detected an early increase in CTLA-4 + CD4+ T cells in all patients ( p = 0.004) and a greater increase in CTLA-4+ and TIM-3 + CD8+ T cells in patients without HIV-DNA reduction compared to the others ( p ≤ 0.03). Our results suggest that ICP replacement compensatory mechanisms might limit the impact of anti-PD-1 monotherapy on HIV reservoirs, and pave the way for combination ICP blockade in HIV cure strategies.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- ejection fraction
- immune response
- end stage renal disease
- newly diagnosed
- south africa
- single molecule
- magnetic resonance imaging
- poor prognosis
- clinical trial
- prognostic factors
- peritoneal dialysis
- patient reported outcomes
- randomized controlled trial
- toll like receptor
- hepatitis b virus
- diffuse large b cell lymphoma