Botswana TDF/FTC Oral HIV Prophylaxis Trial

HIV Infections Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00448669
• Other study ID #: CDC-NCHHSTP-4940
• Secondary ID: BOTUSA MB06
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 2007
• Est. completion date: March 2011

Study information

• Verified date: February 2016
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1219
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infection

Intervention

Drug:
• Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg

• Placebo Oral Tablet

Locations

Country	Name	City	State
Botswana	BOTUSA HIV Prevention Research Unit	Gaborone
United States	Centers for Disease Control and Prevention	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	Botswana Ministry of Health, Gilead Sciences

Countries where clinical trial is conducted

United States,  Botswana, 

References & Publications (7)

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. — View 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 Acq — View 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. — View 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. — View 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. — View 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, Hend — View 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. Epub 2015 Feb 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Monthly, for up to 3 years
Primary	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).	Monthly, for up to 3 years
Secondary	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.	12 months
Secondary	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.	36 months
Secondary	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.	At time HIV infection diagnosed,1 month post-time of HIV infection diagnosis, and 6 months post-time of HIV infection diagnosis
Secondary	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.	1-year post seroconversion