Clinical trial NCT03336346: Effect of Dolutegravir on Etonogestrel Levels in HIV-infected Women in Botswana
Official title: The Effect of Dolutegravir-based ART on Plasma Etonogestrel Levels in HIV-infected Women Using Contraceptive Implants in Botswana
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Contraceptive Usage
HIV Infections
Drug Interaction
Keywords: DTG
Dolutegravir
Efavirenz
Etonogestrel
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2017-11-08
Enrollment: 148
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
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.

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).

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)

Primary outcomes:
measure: Difference (percentage) in ENG plasma levels in the DTG group compared to no ART group
timeFrame: Up to 12 months after implant
Secondary outcomes:
measure: Difference (percentage) in ENG plasma levels in the DTG group compared to EFV group
timeFrame: Up to 12 months after implant
Other outcomes:
Locations:
city: Gaborone
country: Botswana
facility: Botswana-UPenn Partnership
Study officials:
affiliation: Columbia University
name: Carolyn L Westhoff, MD
role: PRINCIPAL_INVESTIGATOR
References: