A Pilot Study of Pre-Exposure Prophylaxis (PrEP) to Evaluate Safety, Acceptability, and Adherence in At-risk Populations in Uganda, Africa

NCT ID: NCT00931346

Last Updated: 2011-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2010-10-31

Brief Summary

This study will evaluate the safety and acceptability of intermittent and daily pre-exposure prophylaxis (PrEP) regimens with FTC/TDF (emtricitabine/tenofovir disoproxil fumarate) in HIV discordant couples, and it will directly compare adherence and intracellular drug levels in daily and intermittent PrEP recipients. It will also evaluate the relationship between drug adherence, sexual behavior and intracellular drug levels with an intermittent PrEP regimen. In addition it will evaluate the relationship between adherence to an intermittent PrEP regimen and timing of sexual activity in relation to PrEP dosing. The pilot will use objective medication event monitoring (MEMS) adherence measurement and evaluate the feasibility of newer adherence measurements such as hair sampling and plasma drug levels. This study will also evaluate the feasibility of using text messaging (SMS) to collect sexual activity data in an African setting. It will allow study teams and communities to prepare for potential subsequent larger trials of intermittent PrEP. The study is not sized to evaluate efficacy. If the intermittent PrEP regimen is safe, feasible in terms of adherence, and achieves intracellular drug levels similar to daily PrEP, the data could be used to design a larger phase 2 study with one or more intermittent PrEP regimens. The goal of such a larger trial would be to provide bridging data if daily PrEP regimens are found to be effective or to prepare for efficacy or non-inferiority trials of intermittent versus daily PrEP.

Investigation of immune responses associated with FTC/TDF will also be evaluated in the pilot study. The proportion of volunteers on FTC/TDF with HIV-specific immune responses, due to exposures that did not lead to established HIV infection, will be assessed at 2-3 time points and compared to responses in volunteers assigned to placebo. Immune responses may be correlated with risk behavior and host factors, such as human leukocyte antigen (HLA) type. As noted above, very few HIV infections are expected to occur during the study, so correlation of HIV-specific immune responses and protection from infection or attenuation of disease progression will not be possible until a larger study is conducted.

Conditions

HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

FTC/TDF Daily

Daily dosing

Group Type: EXPERIMENTAL

FTC/TDF

Intervention Type: DRUG

emtricitabine/tenofovir disoproxil fumarate

FTC/TDF Intermittent

Dosed intermittently

Group Type: EXPERIMENTAL

FTC/TDF

Intervention Type: DRUG

emtricitabine/tenofovir disoproxil fumarate

Placebo Daily

Placebo dosed daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Placebo Intermittent

Placebo dosed intermittently, orally.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

FTC/TDF

emtricitabine/tenofovir disoproxil fumarate

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Willing to comply with the protocol and available for follow-up for the study duration
• Has understood the information provided and has provided written informed consent before any study-related procedures are performed
• Willing to undergo couple HIV testing, sexually transmitted infection (STI) screening, HIV counseling and receive test results, and share results with partner
• At risk for HIV infection as defined by: has an HIV-infected partner not using ART in the past 3 months and had episodes of unprotected sex with partner in the past 3 months
• If a female of childbearing potential:

• using an effective method of non-barrier contraception (hormonal contraceptive
• intrauterine device (IUD)
• surgical sterility) from 7 days prior to randomization until the end of the study
• all female volunteers must be willing to undergo urine pregnancy tests
• HIV-infected partner is willing and eligible to enroll in the study

• HIV-1 infected partner of an HIV-uninfected volunteer who meets study eligibility
• Plan to remain in the relationship for the duration of the study period
• Willing and able to provide written informed consent & locator information

Exclusion Criteria

• Confirmed HIV-1 or HIV-2 infection
• Any clinically significant acute or chronic medical condition that is considered progressive, including severe infections requiring treatment such as tuberculosis, and alcohol or drug abuse
• Any of the following abnormal lab parameters:

• Haemoglobin < 9.0 g/dL
• Creatinine clearance <80mL/min, as calculated by Cockcroft-Gault equation
• AST: > 2.5 x ULN
• ALT: > 2.5 x ULN
• Total bilirubin > 1.5 x ULN
• Serum amylase > 1.5 x ULN
• Serum phosphorus < 2.4 mg/dL
• Urinalysis: Two abnormal dipsticks showing any of the following:

• blood = 2+ or more (not due to menses);
• protein = 1+ or more
• leucocytes = 2+ or more
• glucose= 1+ or more
• Confirmed diagnosis of chronic hepatitis B infection (HBsAg positive)
• If female, pregnant or planning a pregnancy within 4 months after enrolment or lactating
• Participation in another clinical study of a product currently, or within the 3 mo. prior to enrolment

• Current use of antiretroviral therapy
• Concurrent enrollment in another HIV treatment trial

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

International AIDS Vaccine Initiative

NETWORK

Sponsor Role: lead

Responsible Party

International AIDS Vaccine Initiative

Principal Investigators

Heiner Grosskurth, MD

Role: STUDY_CHAIR

MRC Entebbe

Anatoli Kamali, MD

Role: PRINCIPAL_INVESTIGATOR

MRC Entebbe

Locations

MRC-Entebbe

Entebbe, Entebbe, Uganda

Countries

Uganda

References

Baxi SM, Liu A, Bacchetti P, Mutua G, Sanders EJ, Kibengo FM, Haberer JE, Rooney J, Hendrix CW, Anderson PL, Huang Y, Priddy F, Gandhi M. Comparing the novel method of assessing PrEP adherence/exposure using hair samples to other pharmacologic and traditional measures. J Acquir Immune Defic Syndr. 2015 Jan 1;68(1):13-20. doi: 10.1097/QAI.0000000000000386.

Reference Type: DERIVED

PMID: 25296098 (View on PubMed)

Kibengo FM, Ruzagira E, Katende D, Bwanika AN, Bahemuka U, Haberer JE, Bangsberg DR, Barin B, Rooney JF, Mark D, Chetty P, Fast P, Kamali A, Priddy FH. 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. PLoS One. 2013 Sep 26;8(9):e74314. doi: 10.1371/journal.pone.0074314. eCollection 2013.

Reference Type: DERIVED

PMID: 24086333 (View on PubMed)

Related Links

http://www.iavi.org

International AIDS Vaccine Initiative

Other Identifiers

IAVI E002

Identifier Type: -

Identifier Source: org_study_id