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

Primary Purpose

HIV Infection

Status

Completed

Phase

Phase 1

Locations

Uganda

Study Type

Interventional

Intervention

FTC/TDF

Placebo

About this trial

This is an interventional prevention trial for HIV Infection focused on measuring HIV, Human Immunodeficiency Virus

Eligibility Criteria

18 Years - 49 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria (for HIV-uninfected volunteers):

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

Inclusion Criteria (for HIV-1 infected partner):

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 (for HIV-uninfected volunteer):

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

Exclusion Criteria (for HIV-1 infected partner):

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

Sites / Locations

MRC-Entebbe

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

FTC/TDF Daily

FTC/TDF Intermittent

Placebo Daily

Placebo Intermittent

Arm Description

Daily dosing

Dosed intermittently

Placebo dosed daily

Placebo dosed intermittently, orally.

Outcomes

Primary Outcome Measures

Safety and tolerability: volunteers with moderate and greater severity clinical adverse events, renal toxicities, and other moderate and severe laboratory abnormalities.

Acceptability: proportion of volunteers who report willingness to use the study regimen; the acceptability to the HIV-infected partner of their partner using the investigational product

Intracellular drug concentrations: the mean intracellular drug concentration for each group assigned to FTC/TDF

Adherence: proportion of vol. who took, by MEMS data, at least 80% of doses; vol. assigned to FTC/TDF with detectable drug plasma levels within 48 hrs of use; relationship between intracellular drug levels and adherence in vol. assigned to FTC/TDF

Behavioral: reported number of steady and casual sex partners; frequency of unprotected vaginal intercourse; substance use prior to or during sex

Secondary Outcome Measures

The proportion of volunteers who report somewhat high or high levels of burden in using electronic medication monitoring to measure adherence, and using cell phone communication to measure sexual activity

The proportion of study days with missing SMS sexual activity data

The proportion of volunteers assigned to placebo who have detectable intracellular drug levels

The proportion of HIV-infected partners in discordant couples not on ART with detectable drug levels

The proportion of volunteers with HIV-specific immune responses as measured by analysis of cellular or humoral immune response, or changes in gene regulation as measured by microarray or proteomic techniques

The proportion of volunteers who report sharing medications

Full Information

NCT ID

NCT00931346

First Posted

June 29, 2009

Last Updated

August 24, 2011

Sponsor

International AIDS Vaccine Initiative

1. Study Identification

Unique Protocol Identification Number

NCT00931346

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2011

Overall Recruitment Status

Completed

Study Start Date

October 2009 (undefined)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

October 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

International AIDS Vaccine Initiative

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infection

Keywords

HIV, Human Immunodeficiency Virus

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

FTC/TDF Daily

Arm Type

Experimental

Arm Description

Daily dosing

Arm Title

FTC/TDF Intermittent

Arm Type

Experimental

Arm Description

Dosed intermittently

Arm Title

Placebo Daily

Arm Type

Placebo Comparator

Arm Description

Placebo dosed daily

Arm Title

Placebo Intermittent

Arm Type

Placebo Comparator

Arm Description

Placebo dosed intermittently, orally.

Intervention Type

Drug

Intervention Name(s)

FTC/TDF

Intervention Description

emtricitabine/tenofovir disoproxil fumarate

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Safety and tolerability: volunteers with moderate and greater severity clinical adverse events, renal toxicities, and other moderate and severe laboratory abnormalities.

Time Frame

6 months

Title

Acceptability: proportion of volunteers who report willingness to use the study regimen; the acceptability to the HIV-infected partner of their partner using the investigational product

Time Frame

6 months

Title

Intracellular drug concentrations: the mean intracellular drug concentration for each group assigned to FTC/TDF

Time Frame

6 months

Title

Time Frame

6 months

Title

Behavioral: reported number of steady and casual sex partners; frequency of unprotected vaginal intercourse; substance use prior to or during sex

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Time Frame

6 months

Title

The proportion of study days with missing SMS sexual activity data

Time Frame

6 months

Title

The proportion of volunteers assigned to placebo who have detectable intracellular drug levels

Time Frame

6 months

Title

The proportion of HIV-infected partners in discordant couples not on ART with detectable drug levels

Time Frame

6 months

Title

Time Frame

6 months

Title

The proportion of volunteers who report sharing medications

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

49 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria (for HIV-uninfected volunteers): 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 Inclusion Criteria (for HIV-1 infected partner): 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 (for HIV-uninfected volunteer): 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 Exclusion Criteria (for HIV-1 infected partner): Current use of antiretroviral therapy Concurrent enrollment in another HIV treatment trial

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Heiner Grosskurth, MD

Organizational Affiliation

MRC Entebbe

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Anatoli Kamali, MD

Organizational Affiliation

MRC Entebbe

Official's Role

Principal Investigator

Facility Information:

Facility Name

MRC-Entebbe

City

Entebbe

Country

Uganda

12. IPD Sharing Statement

Citations:

PubMed Identifier

25296098

Citation

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.

Results Reference

derived

PubMed Identifier

24086333

Citation

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.

Results Reference

derived

Links:

URL

http://www.iavi.org

Description

International AIDS Vaccine Initiative

Learn more about this trial

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

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