Analytical treatment interruption among women with HIV in southern Africa who received VRC01 or placebo in the Antibody Mediated Prevention Study: ATI stakeholder engagement, implementation and early clinical data

Abstract

Introduction: Antiretroviral therapy (ART) prevents and treats, but does not eradicate, HIV. Early ART initiation is associated with post-ART virologic control, particularly among African women, and anti-HIV-1 broadly neutralizing antibodies (bnAbs) may modulate immune responses to HIV. We evaluate whether early ART with or without anti-HIV-1 bnAb VRC01, present at HIV acquisition, is associated with later ART-free control in African women and we assess potential associations with observed control.

Methods: Stakeholder engagement informed analytical treatment interruption (ATI) study design and implementation. Participants who received placebo or VRC01 and acquired HIV in the Antibody Mediated Prevention efficacy trial were assessed for ATI eligibility, including HIV acquisition within 8 weeks of receiving VRC01 or placebo, followed by early ART initiation and ≥1 year of viral suppression. Participation facilitators and barriers were assessed. From May 2021 to February 2024, participants enrolled, stopped ART and received frequent viral load and CD4+ T-cell count monitoring for safety and assessment of meeting ART reinitiation criteria.

Results: Thirteen women enrolled from southern Africa. No ATI-related serious adverse events (AEs), HIV transmissions, pregnancies or ≥Grade 2 AEs were observed. Eight sexually transmitted infections were diagnosed in seven women during ATI. Two participants had tenofovir levels consistent with use during ATI; 2/11 (18%) who completed ATI without antiretroviral use exhibited ART-free control for ≥32 weeks. The median time to confirmed VL≥200 was 5.4 weeks (range 2.7-112). The most common ART reinitiation criterion met was virologic (n = 7). VRC01 receipt proximate to HIV acquisition was not associated with control. Controllers versus non-controllers did not differ by early post-acquisition viral load kinetics, acquired virus characteristics, or time from estimated acquisition to closest infusion or to ART initiation.

Conclusions: In a safe, well-tolerated ATI, 18% of 11 African women exhibited post-intervention control. Design and implementation lessons inform future ATIs in Africa. Analyses of peri-acquisition and post-ATI host and viral characteristics can inform the development of interventions for HIV cure, prevention and treatment.

Clinical trial registration: NCT04860323.

Keywords: ATI; Africa; HIV cure; HIV remission; broadly neutralizing antibodies; stakeholder engagement.

Figure 1

AMP ATI stakeholder engagement. (A) Clinical research sites, countries and roles of AMP ATI stakeholder meeting participants. (B) Themes and recommendations raised in AMP ATI stakeholder engagement prior to AMP ATI Study launch. (C) Quotes excerpted from post‐meeting surveys completed by AMP ATI stakeholder meeting attendees regarding the stakeholder meetings and the AMP ATI Study and HIV remission research that was discussed there.

Figure 2

Trial schema. (A) HVTN 805/HPTN 093/A5393 AMP ATI‐Africa design schematic. (B) CONSORT and ART reinitiation criteria. (C) Graph of exclusion reasons after pre‐screening (dark grey) and screening (light grey).

Figure 3

Individual participant viral load and CD4+ T‐cell counts over time during ATI among African women. Viral load shown in red circles, T‐cell counts in blue squares. The treatment each participant received in the parent AMP Study is indicated above each panel. Time of first viremia (i.e. confirmed VL ≥ 200 copies/ml) is indicated by the grey dashed line. Time of meeting ART reinitiation criteria is indicated by the beginning of the grey shaded areas. Two participants with DBS ARV levels consistent with ongoing ARV use during ATI were excluded from this analysis and are not shown here.

Figure 4

Virologic control by receipt of VRC01 or placebo in the AMP Study. (A) Survival plot of time to viral load ≥ 200 copies/ml. (B) Cumulative incidence of time to meet ART reinitiation criteria. Estimated survival or cumulative incidence is reflected in the solid line and 95% confidence intervals are reflected by the dashed line. Two participants with DBS ARV levels consistent with ongoing ARV use during ATI are excluded from this analysis.

Figure 5

Estimated time of HIV acquisition relative to closest infusion and ART initiation relative to estimated time of HIV acquisition. The vertical dashed line reflects the time of the AMP infusion received closest to the estimated date of HIV acquisition. Two participants with DBS ARV levels consistent with ongoing ARV use during ATI are excluded from this analysis.

Figure 6

Scatter plot of time to ART initiation and predicted serum neutralization 80% inhibitory dilution titre (PT80) for the most sensitive (to VRC01) viral isolate. Five VRC01 recipients who completed ATI without ARV use are included, while placebo recipients (i.e. those who did not receive VRC01 in the AMP trial) are not included. Some participants acquired multiple viral isolates with varying degrees of VRC01 neutralization sensitivity. The PT80 of the most VRC01‐sensitive acquired isolate is reflected here.