Trial Outcomes & Findings for Combinatorial Therapy to Induce an HIV Remission (NCT NCT04357821)

The final study included ten individuals who had initiated ART during the acute, early, or chronic phase of HIV infection (defined as \<30 days, between 1-6 months, or ≥6 months following estimated date of acquisition; n = 3, 4, and 3 participants, respectively). Participants were recruited from local clinics.

The study enrolled 11 individuals. The study was terminated early for one participant as one of the investigational products was set to expire before planned dosing. Ten individuals received the complete set of interventions.

Combinatorial Therapy to Induce an HIV Remission

Number of participants who experience a new grade 3 or greater adverse event

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

Occurrence of any unsolicited adverse events for 28 days after administration of each study agent

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

We measured the magnitude of the CD8+ T cells to gag conserved elements (CE) 2 weeks after MVA boost (Week 22). We measured new or boosted pre-existing interferon (IFN)ɣ+ Gag/CE-specific CD8+ T cell responses. The magnitude was determined based on intracellular cytokine staining (ICS) by measuring the frequency of interferon (IFN)ɣ+ Gag/CE-specific CD8+ T cell responses after 6 hour stimulation with peptide pools matching the CE immunogen.

We measured the breadth of the vaccine-induced T cell response after DNA/MVA vaccination (two weeks after the MVA boost; Week 22). We defined breadth based on the number of conserved epitope (CE) pools with a positive CD8+ T cell responses, as defined by measuring the frequency of interferon (IFN)ɣ+ Gag/CE-specific CD8+ T cell responses after 6 hour stimulation with peptide pools matching the CE immunogen (using intracellular cytokine staining, ICS). Seven smaller CE pools were tested on each sample. Positive responses were determined based on a magnitude of IFNg+ cells greater than 0.001% of CD8+ T cells after peptide stimulation and after subtraction of background responses.

The HIV-1 DNA reservoir was estimated using digital droplet PCR (Intact Proviral DNA Assay; IPDA). The frequency of intact proviruses (per million CD4+ T cells) was estimated at baseline and prior to the antiretroviral treatment interruption (Week 34). The change from baseline to Week 34 was calculated. A decrease (negative number) is a better outcome. The units are intact genomes/million CD4+ T cells.

Number of participants who exhibit two consecutive measurements HIV RNA \>200 copies/mL during the analytic treatment interruption

Number of participants who resumed antiretroviral therapy after treatment interruption due to protocol-defined events, including virologic failure as defined in the protocol, CD4+ T cell declines as defined in the protocol, or clinical progression

Proportion experiencing any clinically defined episode of acute retroviral syndrome

Number of participants experiencing confirmed declines (two consecutive measurements) in CD4+ T cell counts (\> 50% from baseline)