Combinatorial Therapy to Induce an HIV Remission

Phase 1

Active, not recruiting

Brief Summary: Combination approaches will almost certainly be required to generate durable control of HIV in the absence of antiretroviral therapy (a "remission"). In this study, 20 individuals will receive a combination regimen administered during ART and then undergo an analytic treatment interruption (ATI).

Detailed Description: The investigators will perform a single arm study of twenty individuals with HIV infection on effective ART. All participants will receive a combination regimen administered during ART and then undergo an analytic treatment interruption. Our strategy has five stages

1. IL-12 adjuvanted p24CE DNA prime (p24CE/IL-12) at Weeks 0 and 4

2. IL-12 adjuvanted DNA boost (p24CE plus p55gag) at Week 12

3. MVA/HIV62B (MVA62B) boost at Week 20

4. single dose of two bNAbs (VRC07-523LS and 10-1074, which target CD4 binding site and V3 loop, respectively) at week 24 with a TLR9 agonist (lefitolimod) administered weekly between Weeks 24 and 33 (10 doses)

5. ATI with single dose of VRC07 and 10-1074 at Week 34

Follow-up off ART will occur through at least Week 46 (expected) and on or off ART (depending on outcome) through Week 86.

Should this approach work, viral load would be expected to rebound in all individuals a few weeks after the bNAb levels decrease to sub-therapeutic levels. This acute rebound would be followed by a new lower viral load set-point and perhaps a long-term remission.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Combination intervention arm	Combination Intervention	All volunteers will receive the combination intervention outlined above.

Primary Outcome Measures

Name	Time	Method
Proportion of participants achieving post-treatment control.	Week 34 through 86	This will be defined as: 1. Participants who fail to show any consistent rebound above 400 copies RNA/mL between Week 12 of the ATI (when bNAb levels wane) and Week 36 of the ATI 2. Participants who exhibit a rebound and eventually achieve 24 weeks of virus control will be considered as having achieved post-treatment control
Proportion of participants who experience a new grade 3 or greater adverse event	Week 0 through 86

Secondary Outcome Measures

Name	Time	Method
Frequency of confirmed declines (two consecutive measurements) to below 350 cells/mm3	Week 34 to 86
Proportion experiencing any clinically defined episode of acute retroviral syndrome	Week 34 to 86
Occurrence of any serious adverse events, medically attended adverse event, and potentially immune-mediated medical condition from the time of administration of the first study injection through 12 months after administration of the final study injection	Week 0 through 86
Occurrence of any unsolicited adverse events for 28 days after administration of each study agent	Week 0 through 62
Resumptions of antiretroviral therapy after treatment interruption and the events that trigger them	Week 34 to 86
Frequency of confirmed declines (two consecutive measurements) in CD4+ T cell counts (> 50%)	Week 34 to 86
Magnitude of T cell responses	Week 14
Breadth of T cell responses	Week 14	The proportion of participants with at least one additional epitope response at week 14 (2 weeks after last vaccination) compared to their baseline response
Occurrence of two consecutive measurements HIV RNA >200 copies/mL using conventional assays	Week 34 to 86

Locations (1): Zuckerberg San Francisco General Hospital, University of California San Francisco
🇺🇸
San Francisco, California, United States

Receive instant email notifications about changes in this clinical trial

Receive instant email notifications about changes in this clinical trial