Investigating the Interaction Between Two Long-acting Reversible Methods of Contraception and Dolutegravir, a Treatment for HIV — CODA  

Contraception Clinical Trial

Official title: Contraceptives and Dolutegravir-based ART

Status Active, not recruiting

Clinical Trial Summary

It is important to make sure that women have access to effective methods of contraception to prevent pregnancy so that they can make choices about when and if they will have their first or next child. Some of the most effective methods of contraception are the long-acting, reversible methods of contraception (LARCS), including the contraceptive implant and the contraceptive injection. In areas of the world where there are high numbers of people living with HIV, providing contraception to women is sometimes complicated, as there are known to be interactions between some of the medications that treat HIV and some hormonal methods of contraception. One medication to treat HIV, dolutegravir, is now one of the first-line treatments for HIV in Botswana, and more and more women of childbearing age are taking dolutegravir to treat HIV. At the moment, there is limited information on whether or not there are interactions between dolutegravir (the HIV medication) and the contraceptive implant or the contraceptive injection, two commonly used methods of contraception in Botswana. The main purpose of this study is to find out if women using contraception and also taking dolutegravir have lower levels of contraceptive hormone in their blood compared to women taking no HIV treatment. The study hypothesis is that there is no interaction between dolutegravir and the contraceptive implant or injection.

In this study, levels of hormone from the injection or the implant will be measured in women living with HIV who take dolutegravir and compared to hormone levels in women who do not have HIV and who have never taken any medications to treat HIV. Women will be counselled about all of the possible methods of contraception (including the pill, the injection, the implant and the copper intrauterine device (or coil/loop)) that are available and will be empowered to make their own decision about the method of contraception they feel will be best for them. Women who choose the implant or the injection will be invited to enrol in the study; and will be categorised into one of four groups, based on whether or not they are living with HIV and taking dolutegravir. At several time points, women will have blood tests to check the level of hormone from the implant or the injection, over a course of 12 weeks for women starting the injection and 24 weeks for women starting the implant. Women will also be asked to complete a short questionnaire about any side effects from the contraception including changes to bleeding patterns. At the end of the 12 weeks (for women starting the injection) or 24 weeks (for women starting the implant), the results from these blood samples will be analysed to see how the levels of the hormone in their blood changed over time. The study will also look at whether the levels of dolutegravir (the HIV medication) changed over time. These results will be compared between women living with HIV taking dolutegravir and women without HIV who have never taken dolutegravir to see whether there is any interaction between dolutegravir and the hormonal contraceptive implant or contraceptive injection.

Clinical Trial Description

This study will evaluate whether dolutegravir (DTG)-based antiretroviral therapy (ART) given with two widely used hormonal contraceptives avoid pharmacokinetic drug-drug interactions that lead to reduced levels of hormonal concentrations and could, thus, reduce contraceptive effectiveness. Two highly effective and commonly used methods of hormonal contraception in African settings will be studied: the levonorgestrel (LNG) sub-dermal contraceptive implant and the depot medroxyprogesterone acetate (DMPA) injectable contraceptive.

Overall, the investigators hypothesise that the plasma concentrations of the studied hormonal contraceptives in women living with HIV-1 and taking DTG-based ART will be equivalent to concentrations in HIV-negative, ART naïve women.

Specific Aims:

Specific Aim 1: To compare plasma LNG concentrations among (a) levonorgestrel contraceptive implant-users in Botswana receiving DTG-based ART and (b) HIV-negative, ART naïve levonorgestrel contraceptive implant users.

Specific Aim 2: To compare plasma medroxyprogesterone acetate (MPA) concentrations among (a) DMPA injectable-users in Botswana receiving DTG-based ART and (b) HIV-negative, ART naïve DMPA injectable users.

Specific Aim 3: To compare the trough plasma concentrations of DTG before and after contraceptive use to understand how LNG and DMPA may affect DTG exposure.

Specific Aim 4: To determine if the LNG implant and DMPA injectable inhibit ovulation in the presence of DTG.

Specific Aim 5: To evaluate safety, tolerability, bleeding patterns and contraceptive method continuation with concomitant LNG implant or DMPA injectable, compared to controls (HIV negative, ART naïve women). ;

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• ART
• Contraception
• HIV Infections
• Human Immunodeficiency Virus

• NCT number: NCT04910711
• Study type: Interventional
• Source: Botswana Harvard AIDS Institute Partnership
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 21, 2021
• Completion date: October 31, 2024