HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention

Deborah Donnell, Jared M. Baeten, Namandjé N. Bumpus, Justin Brantley, David Bangsberg, Jessica E. Haberer, Andrew Mujugira, Nelly Mugo, Patrick Ndase, Craig Hendrix, Connie Celum

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Background: Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. Methods: In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. Results: Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P < 0.001) for individuals receiving TDF and 91% (95% confidence interval: 47 to 98, P = 0.008) for individuals receiving FTC/TDF. Controls had consistent patterns of PrEP concentrations during follow-up; among the 81% with concentrations >40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations #40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Conclusions: Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence.

Original languageEnglish (US)
Pages (from-to)340-348
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume66
Issue number3
StatePublished - Jul 1 2014
Externally publishedYes

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Tenofovir
Clinical Trials
HIV
Pre-Exposure Prophylaxis

Keywords

  • Adherence
  • Africa
  • Drug concentrations
  • HIV prevention
  • Pre-exposure prophylaxis
  • Serodiscordant couples

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases

Cite this

HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. / Donnell, Deborah; Baeten, Jared M.; Bumpus, Namandjé N.; Brantley, Justin; Bangsberg, David; Haberer, Jessica E.; Mujugira, Andrew; Mugo, Nelly; Ndase, Patrick; Hendrix, Craig; Celum, Connie.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 66, No. 3, 01.07.2014, p. 340-348.

Research output: Contribution to journalArticle

Donnell, D, Baeten, JM, Bumpus, NN, Brantley, J, Bangsberg, D, Haberer, JE, Mujugira, A, Mugo, N, Ndase, P, Hendrix, C & Celum, C 2014, 'HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention', Journal of Acquired Immune Deficiency Syndromes, vol. 66, no. 3, pp. 340-348.
Donnell, Deborah ; Baeten, Jared M. ; Bumpus, Namandjé N. ; Brantley, Justin ; Bangsberg, David ; Haberer, Jessica E. ; Mujugira, Andrew ; Mugo, Nelly ; Ndase, Patrick ; Hendrix, Craig ; Celum, Connie. / HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention. In: Journal of Acquired Immune Deficiency Syndromes. 2014 ; Vol. 66, No. 3. pp. 340-348.
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abstract = "Background: Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. Methods: In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. Results: Among controls, 71{\%} of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21{\%} of cases at the visit HIV was first detected. Pill count data indicated that 96{\%} of controls and 66{\%} of cases had >80{\%} adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88{\%} (95{\%} confidence interval: 60 to 96, P < 0.001) for individuals receiving TDF and 91{\%} (95{\%} confidence interval: 47 to 98, P = 0.008) for individuals receiving FTC/TDF. Controls had consistent patterns of PrEP concentrations during follow-up; among the 81{\%} with concentrations >40 ng/mL at month 1, 75{\%} maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations #40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Conclusions: Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence.",
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AU - Donnell, Deborah

AU - Baeten, Jared M.

AU - Bumpus, Namandjé N.

AU - Brantley, Justin

AU - Bangsberg, David

AU - Haberer, Jessica E.

AU - Mujugira, Andrew

AU - Mugo, Nelly

AU - Ndase, Patrick

AU - Hendrix, Craig

AU - Celum, Connie

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N2 - Background: Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. Methods: In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. Results: Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P < 0.001) for individuals receiving TDF and 91% (95% confidence interval: 47 to 98, P = 0.008) for individuals receiving FTC/TDF. Controls had consistent patterns of PrEP concentrations during follow-up; among the 81% with concentrations >40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations #40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Conclusions: Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence.

AB - Background: Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. Methods: In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. Results: Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P < 0.001) for individuals receiving TDF and 91% (95% confidence interval: 47 to 98, P = 0.008) for individuals receiving FTC/TDF. Controls had consistent patterns of PrEP concentrations during follow-up; among the 81% with concentrations >40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations #40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Conclusions: Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence.

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