Characterization of HIV seroconverters in a TDF/FTC PrEP study: HPTN 067/ADAPT

Mariya V. Sivay, Maoji Li, Estelle Piwowar-Manning, Yinfeng Zhang, Sarah E. Hudelson, Mark A Marzinke, Rivet K. Amico, Andrew Redd, Craig Hendrix, Peter L. Anderson, Kevin Bokoch, Linda Gail-Bekker, Frits van Griensven, Sharon Mannheimer, James P. Hughes, Robert Grant, Susan Eshleman

Research output: Contribution to journalArticle

Abstract

BACKGROUND:: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. METHODS:: HIV rapid testing was performed at study sites. Retrospective testing included: 4 generation assays; HIV RNA testing; Western blot; an HIV-1/2 discriminatory assay; resistance testing; and antiretroviral (ARV) drug testing. RESULTS:: Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; one was not randomized due to pregnancy). One of the six randomized participants had acute infection at randomization but was not diagnosed for 3-4 months because HIV rapid tests were non-reactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The five participants infected after randomization included four with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing prior to infection. Three participants had TDF/FTC resistance (M184I, K65R), including two who received only four once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. CONCLUSIONS:: In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Original languageEnglish (US)
JournalJournal of Acquired Immune Deficiency Syndromes
DOIs
StateAccepted/In press - Mar 22 2017

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HIV
Tenofovir
Random Allocation
Drug Resistance
HIV Infections
RNA
HIV Seropositivity
HIV-2
Thailand
Licensure
South Africa
Infection
Pre-Exposure Prophylaxis
HIV-1
Western Blotting
Pregnancy
Mutation
Antibodies
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Characterization of HIV seroconverters in a TDF/FTC PrEP study : HPTN 067/ADAPT. / Sivay, Mariya V.; Li, Maoji; Piwowar-Manning, Estelle; Zhang, Yinfeng; Hudelson, Sarah E.; Marzinke, Mark A; Amico, Rivet K.; Redd, Andrew; Hendrix, Craig; Anderson, Peter L.; Bokoch, Kevin; Gail-Bekker, Linda; van Griensven, Frits; Mannheimer, Sharon; Hughes, James P.; Grant, Robert; Eshleman, Susan.

In: Journal of Acquired Immune Deficiency Syndromes, 22.03.2017.

Research output: Contribution to journalArticle

Sivay, MV, Li, M, Piwowar-Manning, E, Zhang, Y, Hudelson, SE, Marzinke, MA, Amico, RK, Redd, A, Hendrix, C, Anderson, PL, Bokoch, K, Gail-Bekker, L, van Griensven, F, Mannheimer, S, Hughes, JP, Grant, R & Eshleman, S 2017, 'Characterization of HIV seroconverters in a TDF/FTC PrEP study: HPTN 067/ADAPT', Journal of Acquired Immune Deficiency Syndromes. https://doi.org/10.1097/QAI.0000000000001374
Sivay, Mariya V. ; Li, Maoji ; Piwowar-Manning, Estelle ; Zhang, Yinfeng ; Hudelson, Sarah E. ; Marzinke, Mark A ; Amico, Rivet K. ; Redd, Andrew ; Hendrix, Craig ; Anderson, Peter L. ; Bokoch, Kevin ; Gail-Bekker, Linda ; van Griensven, Frits ; Mannheimer, Sharon ; Hughes, James P. ; Grant, Robert ; Eshleman, Susan. / Characterization of HIV seroconverters in a TDF/FTC PrEP study : HPTN 067/ADAPT. In: Journal of Acquired Immune Deficiency Syndromes. 2017.
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abstract = "BACKGROUND:: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. METHODS:: HIV rapid testing was performed at study sites. Retrospective testing included: 4 generation assays; HIV RNA testing; Western blot; an HIV-1/2 discriminatory assay; resistance testing; and antiretroviral (ARV) drug testing. RESULTS:: Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; one was not randomized due to pregnancy). One of the six randomized participants had acute infection at randomization but was not diagnosed for 3-4 months because HIV rapid tests were non-reactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The five participants infected after randomization included four with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing prior to infection. Three participants had TDF/FTC resistance (M184I, K65R), including two who received only four once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. CONCLUSIONS:: In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.",
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T1 - Characterization of HIV seroconverters in a TDF/FTC PrEP study

T2 - HPTN 067/ADAPT

AU - Sivay, Mariya V.

AU - Li, Maoji

AU - Piwowar-Manning, Estelle

AU - Zhang, Yinfeng

AU - Hudelson, Sarah E.

AU - Marzinke, Mark A

AU - Amico, Rivet K.

AU - Redd, Andrew

AU - Hendrix, Craig

AU - Anderson, Peter L.

AU - Bokoch, Kevin

AU - Gail-Bekker, Linda

AU - van Griensven, Frits

AU - Mannheimer, Sharon

AU - Hughes, James P.

AU - Grant, Robert

AU - Eshleman, Susan

PY - 2017/3/22

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N2 - BACKGROUND:: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. METHODS:: HIV rapid testing was performed at study sites. Retrospective testing included: 4 generation assays; HIV RNA testing; Western blot; an HIV-1/2 discriminatory assay; resistance testing; and antiretroviral (ARV) drug testing. RESULTS:: Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; one was not randomized due to pregnancy). One of the six randomized participants had acute infection at randomization but was not diagnosed for 3-4 months because HIV rapid tests were non-reactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The five participants infected after randomization included four with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing prior to infection. Three participants had TDF/FTC resistance (M184I, K65R), including two who received only four once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. CONCLUSIONS:: In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

AB - BACKGROUND:: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. METHODS:: HIV rapid testing was performed at study sites. Retrospective testing included: 4 generation assays; HIV RNA testing; Western blot; an HIV-1/2 discriminatory assay; resistance testing; and antiretroviral (ARV) drug testing. RESULTS:: Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; one was not randomized due to pregnancy). One of the six randomized participants had acute infection at randomization but was not diagnosed for 3-4 months because HIV rapid tests were non-reactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The five participants infected after randomization included four with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing prior to infection. Three participants had TDF/FTC resistance (M184I, K65R), including two who received only four once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. CONCLUSIONS:: In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

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