Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships: A Randomized, Clinical Trial

Freddie M. Kibengo, Eugene Ruzagira, David Katende, Agnes N. Bwanika, Ubaldo Bahemuka, Jessica E. Haberer, David Bangsberg, Burc Barin, James F. Rooney, David Mark, Paramesh Chetty, Patricia Fast, Anatoli Kamali, Frances H. Priddy

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Abstract

Background:Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens.Design:Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment.Methods:Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT.Results:Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen.Conclusions:Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing.Registration:Clinicaltrials.gov number NCT00931346.

Original languageEnglish (US)
Article numbere74314
JournalPLoS One
Volume8
Issue number9
DOIs
StatePublished - Sep 26 2013
Externally publishedYes

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Tenofovir
randomized clinical trials
volunteers
Volunteers
disease control
Randomized Controlled Trials
HIV
mouth
Safety
Monitoring
Outages
Pharmaceutical Preparations
Text Messaging
drug therapy
Animals
Servers
Self Report
placebos
Placebos
Enzyme-Linked Immunospot Assay

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships : A Randomized, Clinical Trial. / Kibengo, Freddie M.; Ruzagira, Eugene; Katende, David; Bwanika, Agnes N.; Bahemuka, Ubaldo; Haberer, Jessica E.; Bangsberg, David; Barin, Burc; Rooney, James F.; Mark, David; Chetty, Paramesh; Fast, Patricia; Kamali, Anatoli; Priddy, Frances H.

In: PLoS One, Vol. 8, No. 9, e74314, 26.09.2013.

Research output: Contribution to journalArticle

Kibengo, Freddie M. ; Ruzagira, Eugene ; Katende, David ; Bwanika, Agnes N. ; Bahemuka, Ubaldo ; Haberer, Jessica E. ; Bangsberg, David ; Barin, Burc ; Rooney, James F. ; Mark, David ; Chetty, Paramesh ; Fast, Patricia ; Kamali, Anatoli ; Priddy, Frances H. / Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships : A Randomized, Clinical Trial. In: PLoS One. 2013 ; Vol. 8, No. 9.
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abstract = "Background:Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens.Design:Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment.Methods:Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT.Results:Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98{\%} (IQR: 93-100) for daily PrEP regimen, 91{\%} (IQR: 73-97) for fixed intermittent dosing and 45{\%} (IQR: 20-63) for post-coital dosing. SMS response rate was 74{\%}, but increased to 80{\%} after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen.Conclusions:Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing.Registration:Clinicaltrials.gov number NCT00931346.",
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T2 - A Randomized, Clinical Trial

AU - Kibengo, Freddie M.

AU - Ruzagira, Eugene

AU - Katende, David

AU - Bwanika, Agnes N.

AU - Bahemuka, Ubaldo

AU - Haberer, Jessica E.

AU - Bangsberg, David

AU - Barin, Burc

AU - Rooney, James F.

AU - Mark, David

AU - Chetty, Paramesh

AU - Fast, Patricia

AU - Kamali, Anatoli

AU - Priddy, Frances H.

PY - 2013/9/26

Y1 - 2013/9/26

N2 - Background:Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens.Design:Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment.Methods:Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT.Results:Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen.Conclusions:Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing.Registration:Clinicaltrials.gov number NCT00931346.

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