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Botswana TDF/FTC Oral HIV Prophylaxis Trial (TDF2)

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
Placebo Oral Tablet
Sponsored by
Centers for Disease Control and Prevention
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring HIV incidence, HIV prevention, Tenofovir, Emtricitabine, Botswana, HIV seronegativity

Eligibility Criteria

18 Years - 39 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • citizen of Botswana 18-39 years old
  • sexually active
  • HIV uninfected
  • Hepatitis B and C uninfected
  • Calculated creatinine clearance >= 60 mL/min
  • hemoglobin >= 8 gm/dL
  • ALT and AST <= 2x ULN
  • total bilirubin <= 1.5 mg/dL
  • total serum amylase <= 1.5x ULN
  • Serum phosphorus >= 2.2 mg/dL
  • willing to use hormonal contraception (females)
  • living within 1 hours travel of study clinic
  • pass comprehension test
  • willing and able to give informed consent

Exclusion Criteria:

  • 18-20 without parent/guardian consent
  • history of significant renal or bone disease
  • any chronic illness requiring ongoing prescription medication
  • pregnant or breastfeeding
  • planning to move away from site in the next year
  • participating in another HIV prevention or vaccine safety trial
  • any other clinical condition or prior therapy that, in the opinion of the study physician, would make the volunteer unsuitable for the study or unable to comply with the dosing requirements

Sites / Locations

  • Centers for Disease Control and Prevention
  • BOTUSA HIV Prevention Research Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

TDF-FTC,condoms,adh/risk counseling

Placebo,condoms,adh/risk counseling

Arm Description

Eligible participants were randomized to oral Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg (TDF-FTC) once daily in the form of a single tablet. The ratio of randomization was 1:1. Participants randomized to the active arm received male and female condoms, risk reduction counseling, adherence counseling, and routine monitoring for HIV infection, laboratory abnormalities, and adverse events.

Eligible participants were randomized to the placebo arm and received placebo oral tablets that were visually identical to the TDF-FTC tablet and taken once daily. The placebo tablets contained no active ingredients. The ratio of randomization was 1:1. Participants randomized to the placebo arm received male and female condoms, personalized risk reduction counseling, adherence counseling, and routine monitoring for HIV infection, laboratory abnormalities, and adverse events.

Outcomes

Primary Outcome Measures

Percentage of Participants With Adverse Drug Reactions in the Tenofovir/Emtricitabine and Placebo Arms
Study visits were scheduled every 30 days until completion of the study, and participants were instructed to return to the clinic for evaluation in the event of an illness. Participants reported any adverse effects at monthly visits and interim visits.
HIV Incidence in the Tenofovir/Emtricitabine and Placebo Arms
Study visits were scheduled every 30 days until completion of the study and during monthly study visits, we performed testing for HIV infection. At completion of the study, we tested all participants for HIV infection, using an enzyme-linked immunosorbent assay (ELISA).The primary efficacy end point was the difference in the rates of HIV infection between participants assigned to receive TDF-FTC and those assigned to receive placebo. The initial efficacy analysis included all study participants who were randomly assigned to receive a study medication (intention-to-treat cohort).

Secondary Outcome Measures

Changes in Condom Use During Study: Number of Participants With >=1 Condomless Sex Acts
We assessed condom use of the enrolled participants by face-to-face interviews (at baseline and monthly thereafter) and provided a comprehensive package of HIV prevention services, including individualized counseling on risk reduction, free male and female condoms, and screening for sexually transmitted infections followed, if applicable, by partner notification and treatment.
Rates of Adherence to Study Medication
The rates of adherence to study medication by treatment arm was assessed over the entire course of the study. This comparison was done by assessing the percentage of pills taken by participants within each study arm. The difference between the 2 arms was compared with a Fisher' exact test.
Antiretroviral (ARV) Resistance Patterns in Seroconverters
Participants who seroconverted had blood samples taken at the time of infection and at one month and six months post seroconversion to detect any HIV resistance mutations.
CD4 Evaluation After HIV Seroconversion
Study medication was stopped when HIV infected was diagnosed. Seroconvertors were referred for clinical care and followed an additional year with scheduled quarterly CD4+ cell count assessments. A model-estimated geometric mean of the CD4+ cell counts by each treatment group was evaluated.

Full Information

First Posted
March 16, 2007
Last Updated
January 24, 2020
Sponsor
Centers for Disease Control and Prevention
Collaborators
Botswana Ministry of Health, Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT00448669
Brief Title
Botswana TDF/FTC Oral HIV Prophylaxis Trial
Acronym
TDF2
Official Title
Study of the Safety and Efficacy of Daily Oral Antiretroviral Use for the Prevention of HIV Infection in Heterosexually Active Young Adults in Botswana
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centers for Disease Control and Prevention
Collaborators
Botswana Ministry of Health, Gilead Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study tested whether taking a pill of tenofovir and emtricitabine (two antiretroviral medicines) was safe for sexually-active young adults in Botswana without HIV infection and whether it reduced their risk of getting an HIV infection.
Detailed Description
Twelve hundred and nineteen healthy, sexually active women and men, 18-39 years old, without HIV infection were enrolled in Francistown and Gaborone, Botswana. They were provided with free male and female condoms, repeated individualized risk-reduction counseling, diagnosis and treatment of sexually transmitted diseases, and women will be provided with a choice of effective family planning methods. In addition, volunteers were randomized to receive either Tenofovir and emtricitabine (in a single pill) or a placebo pill to take once a day. Volunteers were seen monthly for at least 12 months to monitor for side effects and toxicities and to test their HIV status. Persons who become HIV infected during the trial received ongoing supportive counseling, CD4 and viral load monitoring, education about HIV infection/disease, and access to HIV care including free antiretrovirals when clinically indicated. Volunteer safety was monitored by a local ethics committee, Centers for Disease Control Institutional Review Board (CDC IRB) and an independent data safety and monitoring board

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV incidence, HIV prevention, Tenofovir, Emtricitabine, Botswana, HIV seronegativity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1219 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TDF-FTC,condoms,adh/risk counseling
Arm Type
Active Comparator
Arm Description
Eligible participants were randomized to oral Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg (TDF-FTC) once daily in the form of a single tablet. The ratio of randomization was 1:1. Participants randomized to the active arm received male and female condoms, risk reduction counseling, adherence counseling, and routine monitoring for HIV infection, laboratory abnormalities, and adverse events.
Arm Title
Placebo,condoms,adh/risk counseling
Arm Type
Placebo Comparator
Arm Description
Eligible participants were randomized to the placebo arm and received placebo oral tablets that were visually identical to the TDF-FTC tablet and taken once daily. The placebo tablets contained no active ingredients. The ratio of randomization was 1:1. Participants randomized to the placebo arm received male and female condoms, personalized risk reduction counseling, adherence counseling, and routine monitoring for HIV infection, laboratory abnormalities, and adverse events.
Intervention Type
Drug
Intervention Name(s)
Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg
Other Intervention Name(s)
Truvada
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Other Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Drug Reactions in the Tenofovir/Emtricitabine and Placebo Arms
Description
Study visits were scheduled every 30 days until completion of the study, and participants were instructed to return to the clinic for evaluation in the event of an illness. Participants reported any adverse effects at monthly visits and interim visits.
Time Frame
Monthly, for up to 3 years
Title
HIV Incidence in the Tenofovir/Emtricitabine and Placebo Arms
Description
Study visits were scheduled every 30 days until completion of the study and during monthly study visits, we performed testing for HIV infection. At completion of the study, we tested all participants for HIV infection, using an enzyme-linked immunosorbent assay (ELISA).The primary efficacy end point was the difference in the rates of HIV infection between participants assigned to receive TDF-FTC and those assigned to receive placebo. The initial efficacy analysis included all study participants who were randomly assigned to receive a study medication (intention-to-treat cohort).
Time Frame
Monthly, for up to 3 years
Secondary Outcome Measure Information:
Title
Changes in Condom Use During Study: Number of Participants With >=1 Condomless Sex Acts
Description
We assessed condom use of the enrolled participants by face-to-face interviews (at baseline and monthly thereafter) and provided a comprehensive package of HIV prevention services, including individualized counseling on risk reduction, free male and female condoms, and screening for sexually transmitted infections followed, if applicable, by partner notification and treatment.
Time Frame
12 months
Title
Rates of Adherence to Study Medication
Description
The rates of adherence to study medication by treatment arm was assessed over the entire course of the study. This comparison was done by assessing the percentage of pills taken by participants within each study arm. The difference between the 2 arms was compared with a Fisher' exact test.
Time Frame
36 months
Title
Antiretroviral (ARV) Resistance Patterns in Seroconverters
Description
Participants who seroconverted had blood samples taken at the time of infection and at one month and six months post seroconversion to detect any HIV resistance mutations.
Time Frame
At time HIV infection diagnosed,1 month post-time of HIV infection diagnosis, and 6 months post-time of HIV infection diagnosis
Title
CD4 Evaluation After HIV Seroconversion
Description
Study medication was stopped when HIV infected was diagnosed. Seroconvertors were referred for clinical care and followed an additional year with scheduled quarterly CD4+ cell count assessments. A model-estimated geometric mean of the CD4+ cell counts by each treatment group was evaluated.
Time Frame
1-year post seroconversion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: citizen of Botswana 18-39 years old sexually active HIV uninfected Hepatitis B and C uninfected Calculated creatinine clearance >= 60 mL/min hemoglobin >= 8 gm/dL ALT and AST <= 2x ULN total bilirubin <= 1.5 mg/dL total serum amylase <= 1.5x ULN Serum phosphorus >= 2.2 mg/dL willing to use hormonal contraception (females) living within 1 hours travel of study clinic pass comprehension test willing and able to give informed consent Exclusion Criteria: 18-20 without parent/guardian consent history of significant renal or bone disease any chronic illness requiring ongoing prescription medication pregnant or breastfeeding planning to move away from site in the next year participating in another HIV prevention or vaccine safety trial any other clinical condition or prior therapy that, in the opinion of the study physician, would make the volunteer unsuitable for the study or unable to comply with the dosing requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Thigpen, MD MPH
Organizational Affiliation
National Institutes of Health (NIH)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lynn Paxton, MD MPH
Organizational Affiliation
Centers for Disease Control and Prevention
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centers for Disease Control and Prevention
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30333
Country
United States
Facility Name
BOTUSA HIV Prevention Research Unit
City
Gaborone
Country
Botswana

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Data sharing will be governed by prevailing CDC data sharing policies.
Citations:
PubMed Identifier
26767149
Citation
Toledo L, McLellan-Lemal E, Henderson FL, Kebaabetswe PM. Knowledge, Attitudes, and Experiences of HIV Pre-Exposure Prophylaxis (PrEP) Trial Participants in Botswana. World J AIDS. 2015 Mar;5(2):10-20. doi: 10.4236/wja.2015.51002. Epub 2015 Feb 12.
Results Reference
background
PubMed Identifier
24625530
Citation
Kasonde M, Niska RW, Rose C, Henderson FL, Segolodi TM, Turner K, Smith DK, Thigpen MC, Paxton LA. Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana. PLoS One. 2014 Mar 13;9(3):e90111. doi: 10.1371/journal.pone.0090111. eCollection 2014.
Results Reference
background
PubMed Identifier
24361682
Citation
Chirwa LI, Johnson JA, Niska RW, Segolodi TM, Henderson FL, Rose CE, Li JF, Thigpen MC, Matlhaba O, Paxton LA, Brooks JT. CD4(+) cell count, viral load, and drug resistance patterns among heterosexual breakthrough HIV infections in a study of oral preexposure prophylaxis. AIDS. 2014 Jan 14;28(2):223-6. doi: 10.1097/QAD.0000000000000102.
Results Reference
background
PubMed Identifier
25186785
Citation
Kebaabetswe PM, Stirratt MJ, McLellan-Lemal E, Henderson FL, Gray SC, Rose CE, Williams T, Paxton LA. Factors Associated with Adherence and Concordance Between Measurement Strategies in an HIV Daily Oral Tenofovir/Emtricitibine as Pre-exposure Prophylaxis (Prep) Clinical Trial, Botswana, 2007-2010. AIDS Behav. 2015 May;19(5):758-69. doi: 10.1007/s10461-014-0891-z.
Results Reference
background
PubMed Identifier
24714095
Citation
Segolodi TM, Henderson FL, Rose CE, Turner KT, Zeh C, Fonjungo PN, Niska R, Hart C, Paxton LA. Normal laboratory reference intervals among healthy adults screened for a HIV pre-exposure prophylaxis clinical trial in Botswana. PLoS One. 2014 Apr 8;9(4):e93034. doi: 10.1371/journal.pone.0093034. eCollection 2014.
Results Reference
background
PubMed Identifier
22784038
Citation
Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, Henderson FL, Pathak SR, Soud FA, Chillag KL, Mutanhaurwa R, Chirwa LI, Kasonde M, Abebe D, Buliva E, Gvetadze RJ, Johnson S, Sukalac T, Thomas VT, Hart C, Johnson JA, Malotte CK, Hendrix CW, Brooks JT; TDF2 Study Group. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012 Aug 2;367(5):423-34. doi: 10.1056/NEJMoa1110711. Epub 2012 Jul 11.
Results Reference
result
PubMed Identifier
27509251
Citation
Gust DA, Soud F, Hardnett FP, Malotte CK, Rose C, Kebaabetswe P, Makgekgenene L, Henderson F, Paxton L, Segolodi T, Kilmarx PH. Evaluation of Sexual Risk Behavior Among Study Participants in the TDF2 PrEP Study Among Heterosexual Adults in Botswana. J Acquir Immune Defic Syndr. 2016 Dec 15;73(5):556-563. doi: 10.1097/QAI.0000000000001143.
Results Reference
result

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Botswana TDF/FTC Oral HIV Prophylaxis Trial

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