Byrne Elizabeth H, Anahtar Melis N, Cohen Kathleen E, Moodley Amber, Padavattan Nikita, Ismail Nasreen, Bowman Brittany A, Olson Gregory S, Mabhula Amanda, Leslie Alasdair, Ndung'u Thumbi, Walker Bruce D, Ghebremichael Musie S, Dong Krista L, Kwon Douglas S
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Cambridge, MA, USA.
Females Rising through Education, Support, and Health, Durban, KwaZulu-Natal, South Africa.
Lancet Infect Dis. 2016 Apr;16(4):441-8. doi: 10.1016/S1473-3099(15)00429-6. Epub 2015 Dec 24.
The use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies, but the biological mechanisms of this risk remain poorly understood. We aimed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract.
In this prospective cohort, we enrolled HIV-negative South African women aged 18-23 years who were not pregnant and were living in Umlazi, South Africa from the Females Rising through Education, Support, and Health (FRESH) study. We tested for HIV-1 twice per week to monitor incident infection. Every 3 months, we collected demographic and behavioural data in addition to blood and cervical samples. The study objective was to characterise host immune determinants of HIV acquisition risk, including those associated with injectable progestin-only contraceptive use. Hazard ratios (HRs) were estimated using Cox proportional hazards methods.
Between Nov 19, 2012, and May 31, 2015, we characterised 432 HIV-uninfected South African women from the FRESH study. In this cohort, 152 women used injectable progestin-only contraceptives, 43 used other forms of contraception, and 222 women used no method of long-term contraception. Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV (12·06 per 100 person-years, 95% CI 6·41-20·63) than women using no long-term contraception (3·71 per 100 person-years, 1·36-8·07; adjusted hazard ratio [aHR] 2·93, 95% CI 1·09-7·868, p=0·0326). HIV-negative injectable progestin-only contraceptive users had 3·92 times the frequency of cervical HIV target cells (CCR5+ CD4 T cells) compared with women using no long-term contraceptive (p=0·0241). Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3·25 times higher frequency of cervical target cells compared with those in the follicular phase (p=0·0488), suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives.
Injectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix, the site of initial HIV entry in most women, providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure.
The Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases.
在观察性研究中，仅使用注射用孕激素避孕药与感染艾滋病毒的风险增加有关，但这种风险的生物学机制仍知之甚少。我们旨在评估孕激素对艾滋病毒感染风险和女性生殖道免疫环境的影响。
在这项前瞻性队列研究中，我们从“通过教育、支持和健康实现女性崛起”（FRESH）研究中招募了年龄在18 - 23岁、未怀孕且居住在南非乌姆拉齐的艾滋病毒阴性南非女性。我们每周对她们进行两次艾滋病毒-1检测以监测新发感染情况。每3个月，我们除了采集血液和宫颈样本外，还收集人口统计学和行为数据。研究目的是确定艾滋病毒感染风险的宿主免疫决定因素，包括与仅使用注射用孕激素避孕药相关的因素。使用Cox比例风险方法估计风险比（HRs）。
在2012年11月19日至2015年5月31日期间，我们对FRESH研究中的432名未感染艾滋病毒的南非女性进行了特征描述。在这个队列中，152名女性使用仅注射用孕激素避孕药，43名使用其他形式的避孕方法，222名女性未采用任何长期避孕方法。与未采用任何长期避孕方法的女性（每100人年3.71例，95%置信区间1.36 - 8.07；调整后风险比[aHR]2.93，95%置信区间1.09 - 7.868，p = 0.0326）相比，仅使用注射用孕激素避孕药的女性感染艾滋病毒的风险显著更高（每100人年12.06例，95%置信区间6.41 - 20.63）。与未采用任何长期避孕方法的女性相比，艾滋病毒阴性的仅使用注射用孕激素避孕药的使用者宫颈艾滋病毒靶细胞（CCR5 + CD4 T细胞）的频率高出3.92倍（p = 0.0241）。月经周期黄体期未采用任何长期避孕方法的女性与卵泡期相比，宫颈靶细胞频率也高出3.25倍（p = 0.0488），这表明自然的高孕激素状态与仅注射用孕激素避孕药具有相似的免疫效应。
仅使用注射用孕激素避孕药和高内源性孕酮均与宫颈处活化的艾滋病毒靶细胞频率增加有关，宫颈是大多数女性艾滋病毒最初进入的部位，这为孕激素暴露高的女性艾滋病毒感染增加提供了一种可能的生物学机制。
比尔及梅琳达·盖茨基金会和美国国立过敏与传染病研究所。
