The purpose of this study is to evaluate whether a single dose of Nivolumab in people living with HIV can reduce the latent reservoir. The latent HIV reservoir is a group of immune system cells in the body that are infected with HIV but are not actively producing new virus. This is the reason why people living with HIV are unable to stop their antiretroviral treatment.
This study consists of 2 Parts. Part 1 is a dose escalation phase. This phase is open-label, single dose titration study in adult people living with HIV. There are 3 stages: a screening stage of up to 14 days; on study study treatment stage, where Nivolumab will be administered on Day 7 and a follow-up stage of up to 168 days (6 months), depending on the dose level. The maximum total duration on study for each participant enrolled in this phase is 140 days (6.3 months). Part 2 is a double-blind, randomized, placebo controlled clinical trial of a single fixed dose of 1.0mg/kg Nivolumab administered intravenous (IV) infusion compared with placebo in adult people living with HIV. This part of the study will consist of 3 stages: a screening stage of up to 21 days; on study study treatment stage, where Nivolumab/placebo will be administered on Day 0, followed by a maximum of 6months of an analytical treatment interruption (where antiretroviral therapy (ART) is ceased), before the participant re-commences ART. The maximum total duration on study for each participant enrolled in this phase is 241 days (approximately 8 months).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
42
Cohort A: Dose escalation phase: Nivolumab will be administered intravenously as a single dose in the dose escalation phase.
Cohort B: Randomization phase: Nivolumab will be administered intravenously as a fixed single dose (1.0 mg/kg) in the randomization phase.
Cohort B: Randomisation phase: Saline will be administered intravenously as a single dose in the randomisation arm.
Alfred Hospital - Department of Infecious Diseases
Melbourne, Victoria, Australia
RECRUITINGTan Tock Seng Hospital
Singapore, Singapore
RECRUITINGNumber of participants with treatment-emergent adverse events enrolled in Cohort A
Incidence and severity of Adverse Events (defined as Common Terminology Criteria (CTC) grade 3 or higher according to the Division of AIDS (DAIDS) grading table) that are definitely, probably or possibly related to study treatment during the study period
Time frame: 23 weeks
Number of participants with treatment-emergent adverse events enrolled in Cohort B
Incidence and severity of Adverse Events (defined as CTC grade 3 or higher according to the DAIDS grading table) that are definitely, probably or possibly related to study treatment during the study period
Time frame: 31 weeks
Change in PD-1 receptor occupancy in peripheral blood following a single low dose of nivolumab in participants enrolled in Cohort A
Time course change in the percentage PD-1 receptor occupancy on T-cells in peripheral blood determined by flow cytometry. Nivolumab infusion occurs on Day 7 study visit. Day 168 timepoint only applicable to 1.0mg/kg cohort
Time frame: Day 7, Day 14, Day 21, Day 35, Day 63, Day 91, Day 126, Day 168
Change in PD-1 receptor occupancy in lymph node T-cells following a single low dose of nivolumab in participants enrolled in Cohort A.
Time course change in the percentage PD-1 receptor occupancy on T-cells in inguinal lymph node T-cells determined by flow cytometry
Time frame: Day 0, Day 21
Cohort A: T-cell responses to Gag peptides
Number of cluster of differentiation 4 (CD4) and/or cluster of differentiation 8 (CD8) T-cells responses to Gag peptides by intracellular cytokine staining both in peripheral blood and lymph nodes
Time frame: Day 0, Day 126
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Cohort A: T-cell responses to Pol/Env/Nef peptides
Number of CD4 and/or CD8 T-cells responses to Pol/Env/Nef peptides by intracellular cytokine staining in both peripheral blood and lymph nodes
Time frame: Day 0, Day 126
Change in PD-1 receptor occupancy in peripheral blood following a single low dose of nivolumab in participants enrolled in Cohort B
Time course change in the percentage PD-1 receptor occupancy on T-cells in peripheral blood determined by flow cytometry. Nivolumab/placebo infusion occurs on Day 0 (baseline) visit
Time frame: Day 0, Day 7, Day 28, Day 168
Cohort B: HIV RNA
Proportion of participants with a viral load (HIV RNA) \> 50 and \> 1000c/ml measured weekly during an ART interruption, which starts on Day 7 and ends at a maximum of week 24 (earlier if ART re-start criteria are met)
Time frame: 24 weeks
Cohort B: viral rebound
Number of participants who experience a viral rebound (defined as first viral load \> 50 copies/mL) during an ATI period which starts on Day 7 and ends at a maximum of week 24 (earlier if ART re-start criteria are met).
Time frame: 24 weeks
Cohort B: T-cell responses to Gag peptides
Number of CD4 and/or CD8 T-cells responses to Gag peptides by intracellular cytokine staining both in peripheral blood and lymph nodes
Time frame: Day 7, Day 168
Cohort B: T-cell responses to Pol/Env/Nef peptides
Number of CD4 and/or CD8 T-cells responses to Pol/Env/Nef peptides by intracellular cytokine staining in both peripheral blood and lymph nodes
Time frame: Day 7, Day 168