Effect of Dolutegravir on Etonogestrel Levels in HIV-infected Women in Botswana

NCT ID: NCT03336346

Last Updated: 2020-02-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 148 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-11-15
• Study Completion Date: 2019-12-11

Brief Summary

The primary aim is to assess if etonogestrel (ENG) implant users taking dolutegravir (DTG) have a 20% or greater change in their ENG plasma levels, compared to women taking no antiretroviral therapy (ART). A secondary aim is to assess whether ENG implant users taking dolutegravir have significantly higher ENG plasma levels than ENG implant users taking efavirenz.

This is a cross-sectional, non-randomized evaluation to compare ENG levels between 3 and 12 months post-implant insertion in three groups of women: 1) women using DTG-based ART (n=90), 2) women using EFV-based ART (n=90), and 3) women using no ART (not HIV infected) (n=90). This study will be conducted in Botswana in Southern Africa among women using the ENG implant, and involves a one-time collection of blood and questionnaire.

Detailed Description

Efavirenz-based antiretroviral therapy is effective in treating HIV and had become standard in the World Health Organization (WHO) guidelines. However, despite its effectiveness in lowering viral load, there is also solid evidence that it decreases the effectiveness of etonogestrel-releasing implants. This presents a difficult clinical scenario in countries where the HIV burden is significant in reproductive age women.

Following the SINGLE trial, dolutegravir has replaced efavirenz in many settings as first-line ART. In 2016, Botswana became the first country in Africa to adopt this as a guideline, however, the effect that dolutegravir has on hormonal contraceptives has not been widely studied. This project seeks to understand the interaction between etonogestrel levels in HIV-infected women who are using dolutegravir-based ART by directly measuring etonogestrel blood levels using liquid chromatography-mass spectrometry in HIV-negative and HIV-infected women using contraceptive implants.

Because the implant is fairly new in Botswana, most participants will have had implants inserted 3-12 months prior to study. An HIV-infected, non-ART, comparison group is no longer permissible, practically or ethically, as countries across Africa, including Botswana, are moving to HIV "Test and Treat." This means that ART initiation is now occurring at time of HIV-diagnosis regardless of cluster of differentiation 4 (CD4) count or disease stage; therefore, in this study, the comparison group will be HIV-uninfected implant users. This comparison will answer the key question of whether the ENG implant when used simultaneously with DTG provides plasma ENG levels comparable to a group in which it has established contraceptive efficacy (i.e. HIV-uninfected, healthy women of reproductive age).

Conditions

Contraceptive Usage; HIV Infections; Drug Interaction

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

DTG group

Reproductive-aged HIV-infected women taking dolutegravir-based ART and using single-rod, etonogestrel-releasing, subdermal implant (ENG implant)

dolutegravir

Intervention Type: DRUG

HIV integrase strand transfer inhibitor used in combination ART

ENG implant

Intervention Type: DEVICE

Reversible contraception implant

No ART group

Reproductive-aged HIV-uninfected women using single-rod, etonogestrel-releasing, subdermal implant (ENG implant)

ENG implant

Intervention Type: DEVICE

Reversible contraception implant

EFV group

Reproductive-aged HIV-infected women taking efavirenz-based ART and using single-rod, etonogestrel-releasing, subdermal implant (ENG implant)

ENG implant

Intervention Type: DEVICE

Reversible contraception implant

Efavirenz

Intervention Type: DRUG

non-nucleoside reverse transcriptase inhibitor used in combination ART

Interventions

dolutegravir

HIV integrase strand transfer inhibitor used in combination ART

Intervention Type: DRUG

ENG implant

Reversible contraception implant

Intervention Type: DEVICE

Efavirenz

non-nucleoside reverse transcriptase inhibitor used in combination ART

Intervention Type: DRUG

Other Intervention Names

Tivicay; DTG; Nexplanon ®; Implanon NXT ®; single-rod, etonogestrel-releasing, subdermal implant; Sustiva; EFV

Eligibility Criteria

Inclusion Criteria

• Etonogestrel implant as their sole method of hormonal contraception
• Etonogestrel implant in-situ for three to twelve months.
• Dolutegravir (DTG) use for at least 60 days (Using DTG-based ART-regimen if applicable)
• Efavirenz (EFV) use for at least 60 days (Using EFV-based ART-regimen if applicable)

Exclusion Criteria

• Exclude women using concomitant enzyme-inducing drugs, including rifampicin for tuberculosis treatment and anti-convulsant medications (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Carolyn Westhoff

Professor of Population and Family Health; Chief, Division of Family Planning & Preventive Services

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carolyn L Westhoff, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Botswana-UPenn Partnership

Gaborone, , Botswana

Countries

Botswana

Other Identifiers

AAAQ8556

Identifier Type: -

Identifier Source: org_study_id