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

NCT04910711 | Unknown Phase 4

• 1 other identifier: UBR/RES/IRB//BIO/236
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Human Immunodeficiency Virus; Contraception; ART

Keywords

Contraception; HIV; Antiretroviral Therapy; Dolutegravir; Drug interactions; Etonogestrel implant; Contraceptive implant; DMPA injection; Contraceptive injection

Outcome Measures

Primary Outcomes (2)

• 24-week levonorgestrel area under the concentration-time curve (AUC)

  The AUC of levonorgestrel over 0-24 weeks will be estimated in women initiating the levonorgestrel implant. The levonorgestrel AUC0-24 weeks will be compared between women living with HIV receiving dolutegravir-based antiretroviral therapy and HIV-negative women who have never taken antiretroviral therapy.

  The AUC0-24 weeks will be calculated at 24 weeks from participant enrolment, using levonorgestrel concentrations measured at 0, 2, 4, 8, 12, 16 and 24 weeks post-levonorgestrel implant initiation.

• 12-week medroxyprogesterone acetate AUC

  The AUC of medroxyprogesterone acetate over 0-12 weeks will be estimated in women initiating the depot medroxyprogesterone acetate injection. The medroxyprogesterone acetate AUC0-12 weeks will be compared between women living with HIV receiving dolutegravir-based antiretroviral therapy and HIV-negative women who have never taken antiretroviral therapy.

  The AUC0-12 weeks will be calculated at 12 weeks from participant enrolment, using medroxyprogesterone acetate concentrations measured at 0, 2, 4, 8, 10 and 12 weeks post-DMPA injection initiation.

Secondary Outcomes (6)

• Cmin for levonorgestrel, medroxyprogesterone acetate and dolutegravir

  24 weeks (LNG) or 12 weeks (MPA)

• Cmax for levonorgestrel, medroxyprogesterone acetate and dolutegravir

  24 weeks (LNG) or 12 weeks (MPA)

• CL/F of levonorgestrel, medroxyprogesterone acetate and dolutegravir

  24 weeks (LNG) or 12 weeks (MPA)

• Ovulation

  24 weeks (LNG) or 12 weeks (MPA)

• Safety, tolerability, side effects and bleeding patterns

  24 weeks (LNG) or 12 weeks (MPA)

Study Arms (4)

DTG/LNG

ACTIVE COMPARATOR

Receiving dolutegravir-based antiretroviral therapy and initiating the levonorgestrel implant

Drug: Dolutegravir; Drug: Levonorgestrel implant

NEG/LNG

OTHER

HIV negative, not receiving antiretroviral therapy and initiating the levonorgestrel implant

Drug: Levonorgestrel implant

DTG/MPA

ACTIVE COMPARATOR

Receiving dolutegravir-based antiretroviral therapy and the depot medroxyprogesterone acetate injection

Drug: Dolutegravir; Drug: Depo medroxyprogesterone acetate injection

NEG/MPA

OTHER

HIV negative, not receiving antiretroviral therapy and receiving the depot medroxyprogesterone acetate injection

Drug: Depo medroxyprogesterone acetate injection

Interventions

Dolutegravir DRUG

Dolutegravir-based antiretroviral therapy

DTG/LNG; DTG/MPA

Levonorgestrel implant DRUG

Women initiating the levonorgestrel implant

DTG/LNG; NEG/LNG

Depo medroxyprogesterone acetate injection DRUG

Women initiating the depo medroxyprogesterone acetate injection

DTG/MPA; NEG/MPA

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sex female
• Age 18-45 years
• Desire to use LNG implant (for at least 6 months) or for at least one cycle of use of DMPA injectable (3 months), following comprehensive client-centered contraceptive counselling
• Willing and able to initiate the LNG implant or the DMPA injectable at enrolment visit or soon thereafter
• Participants who are engaging in sexual activity that could lead to pregnancy must agree to use a non-hormonal method of contraception, in addition to the LNG implant or DMPA injectable, while participating in the study. Acceptable contraceptives include: condoms (male or female); diaphragm or cervical cap with spermicide; non-hormonal intrauterine device; bilateral tubal ligation; and male partner vasectomy
• No acute infections or other opportunistic diseases requiring systemic medication of hospitalisation within 14 days prior to study entry
• The following laboratory values:
• Haemoglobin ≥8.0 g/dL
• Creatinine clearance \>60 mL/min/1.73m2
• Aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) \<2.5 x upper limit of normal ULN
• Alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) \<2.5 x ULN
• Platelet count ≥50,000 platelets/mm3
• Last menstrual period ≤35 days prior to study entry
• No sexual activity that could lead to pregnancy since last menstrual period without contraception (condoms, male or female); diaphragm or cervical cap with spermicide; non-hormonal intrauterine device; bilateral tubal ligation; and male partner vasectomy), as reported by study participant and assessed by study clinician
• Negative serum or urine pregnancy test at screening and study enrolment

You may not qualify if:

• Sex male
• Women \<18 years
• Any contraindication (WHO Medical Eligibility Criteria for Contraceptive Use Category 3 or 4) to receiving the selected contraceptive method, based on WHO Medical Eligibility Criteria for Contraceptive Use (24)
• Postpartum less than 6 weeks
• Currently breastfeeding
• Currently pregnant or intends to become pregnant during the study
• The following laboratory values:
• Hemoglobin \<8.0 g/dL
• Creatinine clearance ≤60 mL/min/1.73m2
• Aspartate transaminase (AST; SGOT) ≥2.5 x ULN
• Alanine transaminase (ALT; SGPT) ≥2.5 x ULN
• Platelet count \<50,000 platelets/mm3
• Receipt of DMPA during the 120 days or norethisterone enanthate (NET-EN) during the 60 days prior to study entry
• Initiated the LNG implant prior to study entry
• Receipt of other hormonal treatments (e.g., oral contraceptives, contraceptive vaginal ring, contraceptive patch, or oral hormone replacement therapy) within the 30 days prior to study entry

Sponsors & Collaborators

• Botswana Harvard AIDS Institute Partnership: lead
• University of Liverpool: collaborator

Study Sites (1)

Princess Marina Hospital

Gaborone, Botswana

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

dolutegravir; Levonorgestrel; Medroxyprogesterone Acetate

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes

Study Officials

• Chelsea Morroni, PhD MBChB

  Botswana Harvard AIDS Institute Partnership

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 2, 2021
• Study Start: October 21, 2021
• Primary Completion: August 31, 2023
• Study Completion: October 31, 2024
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

BO (1)