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CompletedNCT03336346Updated Feb 5, 2020

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

An observational study in Contraceptive Usage, HIV Infections and Drug Interaction, sponsored by Columbia University. Completed at 1 site in Botswana. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-02-05.

Sponsored by Columbia University · Observational

Study type
Observational
Model
Other
Time perspective
Cross-sectional
Enrollment
148
Ages
18 Years to 45 Years
Sex
Female
01

Study 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.

Read the 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).

02

Conditions studied

  • Contraceptive Usage
  • HIV Infections
  • Drug Interaction

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Keywords

  • DTG
  • Dolutegravir
  • Efavirenz
  • Etonogestrel
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Reproductive-aged HIV-infected women using dolutegravir and using single-rod, etonogestrel-releasing subdermal implant.

Reproductive-aged HIV-infected women using efavirenz and using single-rod, etonogestrel-releasing subdermal implant.

Reproductive-aged HIV-unifected women using single-rod, etonogestrel-releasing subdermal implant.

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

Exclusion Criteria:

  • Exclude women using concomitant enzyme-inducing drugs, including rifampicin for tuberculosis treatment and anti-convulsant medications (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine)
04

Study design

Observational model
Other
Time perspective
Cross-sectional
Enrollment
148 participants (actual)
Patient registry
No
Biospecimen retention
Samples without dna

Groups and cohorts

  • DTG group

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

    Drug: dolutegravir · Device: ENG implant

  • No ART group

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

    Device: ENG implant

  • EFV group

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

    Device: ENG implant · Drug: Efavirenz

Interventions

  • Drugdolutegravir

    HIV integrase strand transfer inhibitor used in combination ART

    Also known as: Tivicay, DTG

  • DeviceENG implant

    Reversible contraception implant

    Also known as: Nexplanon ®, Implanon NXT ®, single-rod, etonogestrel-releasing, subdermal implant

  • DrugEfavirenz

    non-nucleoside reverse transcriptase inhibitor used in combination ART

    Also known as: Sustiva, EFV

05

What researchers measure

Primary outcomes

  1. Difference (percentage) in ENG plasma levels in the DTG group compared to no ART group

    Difference between the DTG group and no ART group

    Time frame: Up to 12 months after implant

Secondary outcomes

  1. Difference (percentage) in ENG plasma levels in the DTG group compared to EFV group

    Difference between the DTG group and EFV group

    Time frame: Up to 12 months after implant

06

Study locations

1 site
  • Botswana-UPenn Partnership
    Gaborone, Botswana
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03336346
Lead sponsor
Columbia University
Responsible party
Carolyn Westhoff (Professor of Population and Family Health; Chief, Division of Family Planning & Preventive Services, Columbia University) — Principal investigator
First posted
Nov 8, 2017
Start date
Nov 15, 2017
Primary completion
Oct 30, 2019
Completion
Dec 11, 2019
Last update
Feb 5, 2020

Study contacts

Carolyn L Westhoff, MD
principal investigator · Columbia University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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