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

NCT ID: NCT00592124

Last Updated: 2021-10-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

168 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2010-07-31

Brief Summary

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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.

Detailed Description

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It is necessary to monitor both the adherence and blood levels of microbicides in order to gauge its efficacy in a study population. Utilizing an experimental microbicide (tenofovir gel) and an anti-HIV drug (TDF), this study will measure the adherence and acceptability to and blood levels of the two interventions in three separate regimens given to HIV-uninfected women.

The expected duration of participation for each participant is 21 weeks. Study participants will be randomly assigned into one of six study groups, each with a different regimen sequence. Each sequence will consist of three study periods and three wash-out periods. Each study period lasts 6 weeks, followed by a 1 week wash-out period. The regimen assigned for a given study period will include either oral TDF, tenofovir vaginal gel, or both. All participants will be prescribed all three regimens in the order designated by their randomized assignment.

Study visits will occur at Weeks 1, 3, 6, 7, 10, 13, 14, 17, 20, and 21. Medical history, a physical exam, behavioral assessment, and urine, blood, pelvic sample collection, and counseling will occur at all visits. At some study sites rectal swabs may be performed. Counseling will include information regarding contraception, protocol adherence, HIV, HIV/Sexually Transmitted Infection risk reduction, and male condom use. Pharmacokinetic (PK) studies, to be determined by the study site, will occur during all three study periods. These studies may involve additional procedures.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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1

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

Group Type EXPERIMENTAL

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg tablet daily

Tenofovir gel

Intervention Type DRUG

1 gm/100 ml of 1% gel vaginally daily

2

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

Group Type EXPERIMENTAL

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg tablet daily

Tenofovir gel

Intervention Type DRUG

1 gm/100 ml of 1% gel vaginally daily

3

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

Group Type EXPERIMENTAL

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg tablet daily

Tenofovir gel

Intervention Type DRUG

1 gm/100 ml of 1% gel vaginally daily

4

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

Group Type EXPERIMENTAL

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg tablet daily

Tenofovir gel

Intervention Type DRUG

1 gm/100 ml of 1% gel vaginally daily

5

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

Group Type EXPERIMENTAL

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg tablet daily

Tenofovir gel

Intervention Type DRUG

1 gm/100 ml of 1% gel vaginally daily

6

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

Group Type EXPERIMENTAL

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg tablet daily

Tenofovir gel

Intervention Type DRUG

1 gm/100 ml of 1% gel vaginally daily

Interventions

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Tenofovir disoproxil fumarate

300 mg tablet daily

Intervention Type DRUG

Tenofovir gel

1 gm/100 ml of 1% gel vaginally daily

Intervention Type DRUG

Other Intervention Names

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TDF TFV 9-[2-(Phosphonomethoxy)propyl]adenine

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
* Per participant report, use of the following at enrollment, and/or anticipated use during the period of study participation - use of a diaphragm, vaginal ring, and/or spermicide for contraception, acyclovir or valacyclovir, post-exposure prophylaxis for HIV exposure, TDF/emtricitabine, non-study vaginal products
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Microbicide Trials Network

NETWORK

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Craig W. Hendrix, MD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

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Alabama Microbicide CRS

Birmingham, Alabama, United States

Site Status

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

The Bronx, New York, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

Pitt CRS

Pittsburgh, Pennsylvania, United States

Site Status

Botha's Hill CRS

Durban, KwaZulu-Natal, South Africa

Site Status

Umkomaas CRS

Durban, KwaZulu-Natal, South Africa

Site Status

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

Kampala, , Uganda

Site Status

Countries

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United States South Africa Uganda

References

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

Reference Type BACKGROUND
PMID: 17805450 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16470118 (View on PubMed)

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.

Reference Type RESULT
PMID: 23383037 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25969178 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23065145 (View on PubMed)

Other Identifiers

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10617

Identifier Type: REGISTRY

Identifier Source: secondary_id

1U01AI068633-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MTN-001

Identifier Type: -

Identifier Source: org_study_id