PDF(Pubmed)
Abstract：
Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1β, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1β) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p<0.01), MIP-3α (0.02), Elafin (p = 0.03) and RANTES (p<0.01) differed significantly by race whereas IL-6 was significantly different by age (p = 0.03). We conclude that 3-month use of LNG-IUD, ETNG and DMPA have minimal effects on adolescent vaginal immune microenvironment, and therefore unlikely to impact HIV risk. Future studies with larger sample size and longer follow-up are recommended to continue to evaluate effects of contraceptives on the lower genital tract immunity and susceptibility to sexually transmitted infections.
摘要：
少女在艾滋病毒流行和意外怀孕中承担着不成比例的负担；然而，关于激素避孕药对阴道免疫微环境的影响，重要的问题仍未得到回答。这可能会影响这个群体的艾滋病毒易感性。多项研究报告了与基于孕激素的避孕药Depot醋酸甲羟孕酮（DMPA）相关的生殖器免疫改变，但是青少年的可用数据很少。这项纵向队列研究的目的是评估短期使用三种孕激素避孕药的效果。左炔诺孕酮宫内节育器（LNG-IUD），皮下依托孕烯（ETNG），和可注射的DMPA，青春期女孩中与HIV相关的阴道免疫生物标志物和微生物组。五十九个性活跃，15-19岁的未感染艾滋病毒的女孩从华盛顿特区都会区招募，并自我选择进入控制（仅限避孕套），联合口服避孕药，液化天然气宫内节育器，ETNG和DMPA组。在使用避孕药之前的基线和3个月的随访时收集阴道拭子。阴道分泌物进行促炎测试(IL-1α，IL-1β,TNF-α,IL-6，IL-8，MIP-3α，IP-10,RANTES,MIP-1α,MIP-1β）和抗炎/抗HIV（Serpin-A1，Elafin，β-防御素-2，SLPI）使用ELISA的免疫生物标志物和使用TZM-bl测定的抗HIV活性。使用16SrRNA基因测序评估阴道微生物组。使用SAS版本9分析数据。在完成两次访问的34名参与者中，中值生物标志物浓度没有显著变化，在基线和随访之间观察到任何避孕组的HIV抑制和微生物组组成。IL-8（p<0.01），MIP-3α(0.02),Elafin（p=0.03）和RANTES（p<0.01）因种族而异，而IL-6因年龄而异（p=0.03）。我们得出的结论是，使用液化天然气宫内节育器3个月，ETNG和DMPA对青少年阴道免疫微环境的影响很小，因此不太可能影响艾滋病毒的风险。建议进行更大样本量和更长随访时间的未来研究，以继续评估避孕药对下生殖道免疫和性传播感染易感性的影响。
