Pharmacokinetics and predicted neutralization coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials

The phase 2b AMP trials are testing whether the broadly neutralizing antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modeling of longitudinal serum VRC01 concentrations to characterize pharmacokinetics and predict HIV-1 neutralization coverage. We found that body weight significantly influenced clearance, and that the mean peripheral volume of distribution, steady state volume of distribution, elimination half-life, and accumulation ratio were significantly higher in MSM/TG than in women. Neutralization coverage was predicted to be higher in the first (versus second) half of a given 8-week infusion interval, and appeared to be higher in MSM/TG than in women overall. Study cohort differences in pharmacokinetics and neutralization coverage provide insights for interpreting the AMP results and for investigating how VRC01 concentration and neutralization correlate with HIV incidence. ### Competing Interest Statement The authors of this manuscript have read the journal's policy and have the following competing interests: LC and PBG are recipients of funding from The National Institute of Allergy and Infectious Diseases of the National Institutes of Health, and this publication is a result of activities funded by the NIAID. ### Clinical Trial NCT02568215, [NCT02716675][1] ### Funding Statement This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) U.S. Public Health Service Grants UM1 AI068614 [LOC: HIV Vaccine Trials Network] and UM1AI068619 [LOC: HIV Prevention Trials Network], UM1 AI068635 [HVTN SDMC FHCRC] and UM1AI068617 [HPTN SDMC], UM1 AI068618 [HVTN Laboratory Center FHCRC] and UM1AI068613 [HPTN Laboratory Center]. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: SITESIRB/EC BR-Rio de JaneiroInstituto de Pesquisa ClÃnica Evandro Chagas Ethics Committee CH-LausanneCentre Hospitalier Universitaire Saudois Institutional Review Board PE-IquitosImpacta Ethics Committee PE-Lima-BarrancoImpacta Ethics Committee PE-Lima-San MarcosVia Libre Ethics Committee PE-Lima-San MiguelImpacta Ethics Committee PE-Lima-Via LibreVia Libre Ethics Committee US-Atlanta-Hope ClinicFred Hutch Institutional Review Board US-Atlanta-Ponce de LeonFred Hutch Institutional Review Board US-BirminghamFred Hutch Institutional Review Board US-Boston-BrighamPartners Institutional Review Board US-Boston-FenwayFenway Institutional Review Board US-Chapel HillFred Hutch Institutional Review Board US-ClevelandFred Hutch Institutional Review Board US-Los Angeles-Vine StreetUCLA Office for Human Research Participant Protection US-NashvilleVanderbilit Institutional Review Board US-New York-Bronx PreventionFred Hutch Institutional Review Board US-New York-Harlem PreventionFred Hutch Institutional Review Board US-New York-NYBCFred Hutch Institutional Review Board US-New York-Physicians & SurgeonsFred Hutch Institutional Review Board US-NewarkFred Hutch Institutional Review Board US-PhiladelphiaFred Hutch Institutional Review Board US-RochesterFred Hutch Institutional Review Board US-San FranciscoFred Hutch Institutional Review Board US-SeattleFred Hutch Institutional Review Board US-Washington, DCGeorge Washington University Institutional Review Board All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Upon acceptance, the data underlying the findings of this manuscript will be made publicly available at the public-facing HVTN website (https://atlas.scharp.org/). [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02716675&atom=%2Fmedrxiv%2Fearly%2F2020%2F09%2F03%2F2020.09.02.20182881.atom