Adherence and Acceptability to and Blood Levels of Tenofovir Gel and Tablets in HIV Uninfected Women

NCT00592124 | Completed Phase 2 Results DMC

• 3 other identifiers: MTN-001106171U01AI068633-01
• Study Type: interventional
• Target: 168
• Locations: 3 countries
• Sites: 7

Brief Summary

A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) is an oral, FDA-approved, anti-HIV drug, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the adherence and acceptability to and blood levels of three daily regimens of tenofovir in both oral and gel form.

Conditions

HIV Infections

Keywords

Microbicide; HIV Seronegativity

Outcome Measures

Primary Outcomes (3)

• Self-reported Adherence to Each Regimen

  Participant self-reported product use. For each woman, adherence to each regimen was computed by dividing the number of daily doses she reported having taken by the number of doses expect if she were fully adherent.

  Measured through Week 21

• Proportion of Participants Who Indicate They Would be "Unlikely" Use Study Product in the Future

  Measured through Week 21

• Systemic and Local PK Among Three Regimens of Tenofovir (Oral, Vaignal, and Dual Use)

  PK measures, including maximum concentrations (Cmax) in serum, tissue, and cervicovaginal lavage.

  Measured through Week 21

Secondary Outcomes (15)

• Frequency of Product Use

  Measured through Week 21

• Number of Days Product Missed

  Measured through Week 21

• Proportion of Women Who Report Taking at Least 90% of Expected Daily Doses

  Measured through Week 21

• Frequency of Sexual Activity

  Measured through Week 21

• Frequency of Male Condom Use

  Measured through Week 21

Study Arms (6)

1

EXPERIMENTAL

Oral tenofovir disoproxil fumarate (TDF) for Weeks 1 through 6, vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF and vaginal tenofovir gel application for Weeks 15 through 20

Drug: Tenofovir disoproxil fumarate; Drug: Tenofovir gel

2

EXPERIMENTAL

Vaginal tenofovir gel application for Weeks 1 through 6, oral TDF for Weeks 8 through 13, and oral TDF and vaginal tenofovir gel application for Weeks 15 through 20

Drug: Tenofovir disoproxil fumarate; Drug: Tenofovir gel

3

EXPERIMENTAL

Oral TDF and vaginal tenofovir gel application for Weeks 1 through 6, oral TDF for Weeks 8 through 13, and vaginal tenofovir gel application for Weeks 15 through 20

Drug: Tenofovir disoproxil fumarate; Drug: Tenofovir gel

4

EXPERIMENTAL

Oral TDF and vaginal tenofovir gel application for Weeks 1 through 6, vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF for Weeks 15 through 20

Drug: Tenofovir disoproxil fumarate; Drug: Tenofovir gel

5

EXPERIMENTAL

Oral TDF for Weeks 1 through 6, oral TDF and vaginal tenofovir gel application for Weeks 8 through 13, and vaginal tenofovir gel application for Weeks 15 through 20

Drug: Tenofovir disoproxil fumarate; Drug: Tenofovir gel

6

EXPERIMENTAL

Vaginal tenofovir gel application for Weeks 1 through 6, oral TDF and vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF for Weeks 15 through 20

Drug: Tenofovir disoproxil fumarate; Drug: Tenofovir gel

Interventions

Tenofovir disoproxil fumarate DRUG

300 mg tablet daily

Also known as: TDF

1; 2; 3; 4; 5; 6

Tenofovir gel DRUG

1 gm/100 ml of 1% gel vaginally daily

Also known as: TFV, 9-[2-(Phosphonomethoxy)propyl]adenine

1; 2; 3; 4; 5; 6

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General good health
• HIV-uninfected
• Normal menstrual cycle. More information can be found in the protocol.
• Creatinine clearance greater than 70 ml/min
• Sexually active. More information can be found in the protocol.
• Normal Pap smear result within 12 months prior to study entry
• Agrees to not participate in other investigational studies
• Willing to use effective forms of contraception. More information can be found in the protocol.

You may not qualify if:

• Adverse reaction to either of the study products
• Adverse reaction to latex
• Currently sexually active with a partner with history of adverse reaction to latex
• More than three sexual partners in the month prior to screening
• Pathologic bone fracture not related to trauma
• Last pregnancy outcome within 90 days or less prior to enrollment
• Gynecologic or genital procedure within 90 days of study entry
• Enrollment in other investigational study within 30 days of study entry
• Nontherapeutic injection drug use within 12 months of screening
• Any social or medical condition that, in the opinion of the investigator, would interfere with the study
• Abnormal laboratory values
• Grade 2 or higher genital lesions, erythema, and/or edema or has any other abnormal physical or pelvic exam finding that, in the opinion of the investigator, would interfere with the study
• Kidney, reproductive, or urinary tract infection requiring treatment. More information on this criterion can be found in the protocol.
• Pregnant, breastfeeding, or intend to become pregnant
• Unwilling to comply with study participation requirements, including attendance at all scheduled study visits

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Microbicide Trials Network: collaborator

Study Sites (7)

Alabama Microbicide CRS

Birmingham, Alabama, 35294, United States

Location

Bronx- Lebanon Hospital Center Clinical Research Site (BLHC CRS)

The Bronx, New York, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

Pitt CRS

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

Botha's Hill CRS

Durban, KwaZulu-Natal, South Africa

Location

Umkomaas CRS

Durban, KwaZulu-Natal, South Africa

Location

Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS

Kampala, Uganda

Location

Related Publications (5)

• Bateman C. Tenofovir gel--the new HIV prevention 'banker'? S Afr Med J. 2007 Jul;97(7):496, 498. No abstract available.

  PMID: 17805450 BACKGROUND

• Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006 Feb 28;20(4):543-51. doi: 10.1097/01.aids.0000210608.70762.c3.

  PMID: 16470118 BACKGROUND

• Hendrix CW, Chen BA, Guddera V, Hoesley C, Justman J, Nakabiito C, Salata R, Soto-Torres L, Patterson K, Minnis AM, Gandham S, Gomez K, Richardson BA, Bumpus NN. MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. PLoS One. 2013;8(1):e55013. doi: 10.1371/journal.pone.0055013. Epub 2013 Jan 30.

  PMID: 23383037 RESULT

• Minnis AM, van der Straten A, Salee P, Hendrix CW. Pre-exposure Prophylaxis Adherence Measured by Plasma Drug Level in MTN-001: Comparison Between Vaginal Gel and Oral Tablets in Two Geographic Regions. AIDS Behav. 2016 Jul;20(7):1541-8. doi: 10.1007/s10461-015-1081-3.

  PMID: 25969178 DERIVED

• Minnis AM, Gandham S, Richardson BA, Guddera V, Chen BA, Salata R, Nakabiito C, Hoesley C, Justman J, Soto-Torres L, Patterson K, Gomez K, Hendrix CW. Adherence and acceptability in MTN 001: a randomized cross-over trial of daily oral and topical tenofovir for HIV prevention in women. AIDS Behav. 2013 Feb;17(2):737-47. doi: 10.1007/s10461-012-0333-8.

  PMID: 23065145 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir; hexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenine

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

Limitations and Caveats

For a full discussion of the difficulties of sampling and comparing findings in the varied and complex anatomic spaces in this study, please see the primary results publication, listed in the References section (PLoS One 2013;8(1):e55013.)

Results Point of Contact

• Title: Craig W. Hendrix, MD
• Organization: Johns Hopkins University

chendrix@jhmi.edu

1 410 955-9707

Study Officials

• Craig W. Hendrix, MD

  Johns Hopkins University

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2007
• First Posted: January 11, 2008
• Study Start: June 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: October 19, 2021
• Results First Posted: February 27, 2017

Record last verified: 2017-01

Locations

US (4); UG (1); ZA (2)