Contraceptives and Dolutegravir-based ART
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- 12-week medroxyprogesterone acetate AUC
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
- •Willing to undergo questionnaires, examinations and phlebotomy per schedule for the duration of the study period
- •Able to consent for study participation in English or Setswana
- •For HIV-positive participants:
- •Documented HIV-1 infection
- •Using DTG-based ART (DTG 50mg once daily co-administered with 2 NRTIs (emtricitabine/tenofovir or lamivudine/tenofovir)
- •DTG-based ART use (for at least 30 days prior to contraceptive method initiation). On stable regimen containing DTG and 2 NRTIs for ≥ 30 days without gaps in adherence in the last 30 days prior to study entry, and no known plans to change ART regimen for the duration of the study
- •Most recent HIV plasma RNA below lower limit of quantitation of the assay used per standard of care
排除标准
- •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
- •The study puts the participant at unacceptable risk based on the judgment of the study staff
- •Known allergy/sensitivity or any hypersensitivity to components of study medication(s) or their formulation
- •Active drug or alcohol use or dependence that would interfere with adherence to study requirements
- •Concomitant use of drugs known to be contraindicated with LNG or MPA
- •Use of any drugs known to: 1) induce CYP3A4 system within 30 days or 2) inhibit the CYP3A4 system with one week prior to enrolment visit
- •Use or anticipated use of concomitant enzyme-inducing drugs, including but not limited to rifampicin for tuberculosis treatment and anti-convulsant medications (e.g., phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, felbamate)
- •Unwilling to attend study visits or adhere to study visit procedures
- •Unable to consent
- •For HIV-positive participants:
- •Self-reported non-adherence to ART
- •Concomitant use of drugs known to be contraindicated with DTG or medicinal products that reduce DTG exposure (e.g. magnesium/ aluminium-containing antacid, iron and calcium supplements, multivitamins and inducing agents, rifampicin, St. John's wort and anti-epileptic medicinal products carbamazepine, oxcarbazepine, phenytoin and phenobarbital)
研究组 & 干预措施
DTG/LNG
Receiving dolutegravir-based antiretroviral therapy and initiating the levonorgestrel implant
干预措施: Levonorgestrel implant (Drug)
DTG/LNG
Receiving dolutegravir-based antiretroviral therapy and initiating the levonorgestrel implant
干预措施: Dolutegravir (Drug)
NEG/LNG
HIV negative, not receiving antiretroviral therapy and initiating the levonorgestrel implant
干预措施: Levonorgestrel implant (Drug)
DTG/MPA
Receiving dolutegravir-based antiretroviral therapy and the depot medroxyprogesterone acetate injection
干预措施: Dolutegravir (Drug)
DTG/MPA
Receiving dolutegravir-based antiretroviral therapy and the depot medroxyprogesterone acetate injection
干预措施: Depo medroxyprogesterone acetate injection (Drug)
NEG/MPA
HIV negative, not receiving antiretroviral therapy and receiving the depot medroxyprogesterone acetate injection
干预措施: Depo medroxyprogesterone acetate injection (Drug)
结局指标
主要结局
12-week medroxyprogesterone acetate AUC
时间窗: 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.
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.
24-week levonorgestrel area under the concentration-time curve (AUC)
时间窗: 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.
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.
次要结局
- 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))
- Contraception method continuation(24 weeks (LNG) or 12 weeks (MPA))
- 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))
研究者
Chelsea Morroni
Principal Investigator
Botswana Harvard AIDS Institute Partnership