Olivia D Council1, Susan Ruone, Philip A Mock, George Khalil, Amy Martin, Marcel E Curlin, Janet M McNicholl, Walid Heneine, Wanna Leelawiwat, Kachit Choopanya, Suphak Vanichseni, Thitima Cherdtrakulkiat, Rapeepan Anekvorapong, Michael Martin, José Gerardo García-Lerma. 1. aLaboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA bThailand Ministry of Public Health - U.S. Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand cQuantitative Sciences and Data Management Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia dDepartment of Medicine, Division of Infectious Diseases, Oregon Health and Sciences University, Portland, Oregon, USA eBangkok Tenofovir Study Group, Bangkok, Thailand.
Abstract
OBJECTIVE: To estimate time of HIV infection in participants from the Bangkok Tenofovir Study (BTS) withdaily oral tenofovir disoproxil fumarate (TDF) for preexposure prophylaxis (PrEP) and relate infection with adherence patterns. DESIGN: We used the diversity structure of the virus population at the first HIV RNA-positive sample to estimate the date of infection, and mapped these estimates to medication diaries obtained under daily directly observed therapy (DOT). METHODS:HIV genetic diversity was investigated in all 17 PrEP breakthrough infections and in 16 placebo recipients. We generated 10-25 HIV env sequences from each participant by single genome amplification, and calculated time since infection (and 95% confidence interval) using Poisson models of early virus evolution. Study medication diaries obtained under daily DOT were then used to compute the number of missed TDF doses at the approximate date of infection. RESULTS: Fifteen of the 17 PrEP breakthrough infections were successfully amplified. Of these, 13 were initiated by a single genetic variant and generated reliable estimates of time since infection (median = 47 [IQR = 35] days). Eleven of these 13 were under daily DOT at the estimated time of infection. Analysis of medication diaries in these 11 participants showed 100% adherence in five, 90-95% adherence in two, 55% adherence in one, and nonadherence in three. CONCLUSION: We estimated time of infection in participants from BTS and found several infections when high levels of adherence to TDF were reported. Our results suggest that the biological efficacy of daily TDF against parenteral HIV exposure is not 100%.
RCT Entities:
OBJECTIVE: To estimate time of HIV infection in participants from the Bangkok Tenofovir Study (BTS) with daily oral tenofovir disoproxil fumarate (TDF) for preexposure prophylaxis (PrEP) and relate infection with adherence patterns. DESIGN: We used the diversity structure of the virus population at the first HIV RNA-positive sample to estimate the date of infection, and mapped these estimates to medication diaries obtained under daily directly observed therapy (DOT). METHODS: HIV genetic diversity was investigated in all 17 PrEP breakthrough infections and in 16 placebo recipients. We generated 10-25 HIV env sequences from each participant by single genome amplification, and calculated time since infection (and 95% confidence interval) using Poisson models of early virus evolution. Study medication diaries obtained under daily DOT were then used to compute the number of missed TDF doses at the approximate date of infection. RESULTS: Fifteen of the 17 PrEP breakthrough infections were successfully amplified. Of these, 13 were initiated by a single genetic variant and generated reliable estimates of time since infection (median = 47 [IQR = 35] days). Eleven of these 13 were under daily DOT at the estimated time of infection. Analysis of medication diaries in these 11 participants showed 100% adherence in five, 90-95% adherence in two, 55% adherence in one, and nonadherence in three. CONCLUSION: We estimated time of infection in participants from BTS and found several infections when high levels of adherence to TDF were reported. Our results suggest that the biological efficacy of daily TDF against parenteral HIV exposure is not 100%.
Authors: Ivana Parker; George Khalil; Amy Martin; Michael Martin; Suphak Vanichseni; Wanna Leelawiwat; Janet McNicholl; Andrew Hickey; J Gerardo García-Lerma; Kachit Choopanya; Kelly A Curtis Journal: AIDS Res Hum Retroviruses Date: 2020-12-09 Impact factor: 2.205