Botswana TDF/FTC Oral HIV Prophylaxis Trial

NCT00448669 | Completed Phase 2 Results DMC

• 2 other identifiers: CDC-NCHHSTP-4940BOTUSA MB06
• Study Type: interventional
• Target: 1,219
• Locations: 2 countries
• Sites: 2

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.

Conditions

HIV Infections

Keywords

HIV incidence; HIV prevention; Tenofovir; Emtricitabine; Botswana; HIV seronegativity

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• Changes in Condom Use During Study: Number of Participants With >=1 Condomless Sex Acts

  12 months

• Rates of Adherence to Study Medication

  36 months

• Antiretroviral (ARV) Resistance Patterns in Seroconverters

  At time HIV infection diagnosed,1 month post-time of HIV infection diagnosis, and 6 months post-time of HIV infection diagnosis

• CD4 Evaluation After HIV Seroconversion

  1-year post seroconversion

Study Arms (2)

TDF-FTC,condoms,adh/risk counseling

ACTIVE COMPARATOR

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.

Drug: Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg

Placebo,condoms,adh/risk counseling

PLACEBO COMPARATOR

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.

Drug: Placebo Oral Tablet

Interventions

Tenofovir Disoproxil Fumarate 300 mg + Emtricitabine 200 mg DRUG

Also known as: Truvada

TDF-FTC,condoms,adh/risk counseling

Placebo Oral Tablet DRUG

Also known as: Placebo

Placebo,condoms,adh/risk counseling

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Botswana Ministry of Health: collaborator
• Gilead Sciences: collaborator

Study Sites (2)

Centers for Disease Control and Prevention

Atlanta, Georgia, 30333, United States

Location

BOTUSA HIV Prevention Research Unit

Gaborone, Botswana

Location

Related Publications (7)

• 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.

  PMID: 26767149 BACKGROUND

• 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.

  PMID: 24625530 BACKGROUND

• 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.

  PMID: 24361682 BACKGROUND

• 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.

  PMID: 25186785 BACKGROUND

• 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.

  PMID: 24714095 BACKGROUND

• 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.

  PMID: 22784038 RESULT

• 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.

  PMID: 27509251 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

The rates of study completion were lower than predicted because more participants withdrew from the study, mostly due to relocation or conflicting obligations.Findings may not be generalizable to other populations.

Results Point of Contact

• Title: Dr. Michael Thigpen
• Organization: National Institutes of Health

michael.thigpen@nih.gov

1-240-669-2877

Study Officials

• Michael Thigpen, MD MPH

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

• Lynn Paxton, MD MPH

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2007
• First Posted: March 19, 2007
• Study Start: March 1, 2007
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: February 5, 2020
• Results First Posted: February 5, 2020

Record last verified: 2016-02

Locations

BO (1); US (1)