A Randomized Clinical Trial on the Effects of Progestin-based Contraception in the Genital Tract of HIV-infected and Uninfected Women
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 131
- 试验地点
- 1
- 主要终点
- HIV viral load in the genital tract of HIV-infected women before and after initiation of progestin-containing contraception
研究概览
简要总结
The purpose of this study is to determine the acceptability of randomization to contraceptive options and estimate the effect of progestin contraception on HIV genital shedding and inflammatory/immune perturbations in women who may or may not be on antiretroviral therapy, as well as in HIV-uninfected women controls. It is hypothesized that progestin-containing contraception will lead to inflammatory changes that may affect the local immune activity, influencing HIV acquisition or transmissibility risk.
详细描述
Hormonal contraception is a central component in the prevention of unintended pregnancy; however there are concerns that certain methods may increase the risk of heterosexual HIV acquisition and transmission. Some studies, but not others, have suggested a link between hormonal contraceptive use and enhanced HIV-susceptibility, more rapid HIV disease progression, and increased transmissibility to partners. Hormonal contraception modifies the genital mucosa in several ways, and the interactions of the endocrine and immune system are complex but incompletely understood. In some cross-sectional studies, hormonal contraceptives appear to be associated with increased shedding of HIV DNA, but not RNA, in the genital tract, and the significance of these findings for HIV transmissibility are unclear. Very few studies have examined genital HIV shedding prospectively before and after initiation of contraception. The effects of hormonal contraception in the setting of antiretroviral therapy (ART) are also unknown.
Hormonal contraception, particularly injectable DMPA, is widely used in many parts of the world, including settings with high HIV prevalence. It is important that the effects of hormonal contraception on HIV acquisition and HIV shedding and subsequent transmissibility be determined. The effect of progestin contraceptive implants, such as the levonorgestrel rod implant (LNG implant), on HIV shedding is unknown, and it will be of interest to evaluate it compared with the injectable progestin (DMPA), given their different kinetics of hormone release, differences in progestin type, and the high efficacy of both methods.
We propose a pilot study among 100 HIV-infected women and 30 uninfected women in Lilongwe, Malawi randomized to either DMPA or LNG implant to: 1) assess the effect and compare the impact of type of progestin-containing contraception (injectable versus implant) on HIV viral shedding in the genital tract of HIV+ women, 2) assess the effect and compare the impact of type of progestin-containing contraception (injectable versus implant) on inflammatory/immune markers in the genital tract of both HIV+ and HIV- women, and 3) assess the interaction of progestin-based hormonal contraception and ART by examining: i. contraceptive efficacy (measured by systemic hormone levels and pregnancy rate during follow-up), and ii. ART efficacy (by drug concentrations in blood and genital tract and HIV viral load response in the plasma in women on ART).
An overall study aim is to determine the feasibility and need for a larger study of determinants of HIV transmissibility and acquisition in this population.
The study would take place at Bwaila Maternity Hospital, which was the site of the CDC-sponsored Breastfeeding, Antiretrovirals, and Nutrition (BAN) clinical trial, a partner project with this study. Women attending the clinics at Bwaila (a large proportion of whom participated in the BAN study) who desire to start hormonal contraception will be informed of the new study and counseled on the progestin-based contraceptives that are available within the study. BAN women will be specifically targeted for recruitment through radio messages. Eligible women who provide informed consent and agree to randomization to either DMPA or the LNG implant will be enrolled. HIV-infected women may be on ART or they may be pre-ART.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
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
- •Known HIV status, as documented by at least 2 concordant rapid tests (Determine and Uni-Gold, respectively). If the 2 rapid tests are discordant, then a confirmatory test will be done via Western blot.
- •Female, pre-menopausal, age 18 to 45 years
- •At least 2 regular, monthly cycles (~21-35 days) in the 3 months preceding study enrollment.
- •If on hormonal or intrauterine contraception in the past, they must have been off for at least 6 months. If they were previously using DMPA, their last -injection must have been ≥6 months ago.
- •If recently pregnant, they must be at least 6 months postpartum
- •Able and willing to provide informed consent
- •Be otherwise a good candidate for study participation based on assessment by investigator or designee
- •Interested in initiating a family planning method, specifically depot medroxyprogesterone acetate (DMPA) or the LNG implant (Jadelle)
- •Willing to be randomized to receive either DMPA or LNG implant (Jadelle)
- •Willing to wait 4-6 weeks after enrollment to receive this method and to use non-hormonal and non-intrauterine methods (such as abstinence or condoms) consistently during this period
排除标准
- •Pregnancy (by clinical history or a positive urine pregnancy test at screening)
- •Women currently using any hormonal contraceptive method
- •Desire pregnancy within next 12 months
- •Untreated visible genital ulcers or lesions on initial pelvic examination
- •Known or suspected genital tract cancer (by clinical history or noted during initial pelvic examination).
- •Contraindications to DMPA or LNG implant per the WHO medical eligibility114 criteria or judgment of clinician (contraindications include lactation within first 6 weeks postpartum, acute deep venous thrombosis or pulmonary embolism, lupus, migraine with aura, unexplained vaginal bleeding, current or history of breast cancer, severe cirrhosis, liver tumors, history of stroke, current or history of ischemic heart disease).
- •Acute HIV infection (as documented by a known negative HIV test 6 months or less prior to screening).
研究组 & 干预措施
Depo-Medroxyprogesterone Acetate
Half of women will be randomized to receive Depo-Medroxyprogesterone Acetate injections every 13 weeks
干预措施: Depo-Medroxyprogesterone Acetate (Drug)
Progestin Implant (Jadelle)
Half of women will be randomized to receive progestin implant.
干预措施: Progestin Contraceptive (Jadelle) (Drug)
结局指标
主要结局
HIV viral load in the genital tract of HIV-infected women before and after initiation of progestin-containing contraception
时间窗: 6 months post randomization; 24 months to 33 months post randomization
Genital HIV viral load at each study visit will be modeled longitudinally as a continuous outcome using a generalized estimating equation (GEE) model. The model will include a covariate indicating whether the measurement was taken before or after receiving the contraceptive method, and the null hypothesis will be tested using a z-test on this covariate.
HIV viral load in the genital tract of HIV-infected women by contraceptive type
时间窗: 6 months post randomization;24 months to 33 months post randomization
Genital HIV viral load at each study visit will be modeled longitudinally as a continuous outcome using a generalized estimating equation (GEE) model. The model will include a covariate for contraception arm, and the null hypothesis will be tested using a z-test on this covariate.
次要结局
- Interaction of progestin-based hormonal contraception and antiretroviral therapy(6 months post randomization;24 months to 33 months post randomization)
- Impact of the type of progestin-containing contraception (injectable versus implant) on inflammatory/immune markers in the genital tract women.(6 months post randomization)
- Contraceptive efficacy in HIV-infected women(6 months post randomization; 24 months to 33 months post randomization)