Rohwer Christa, McCaul Michael, Hofmeyr G Justus, Rohwer Anke C
Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Centre for Evidence-based Health Care, Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Cochrane Database Syst Rev. 2025 Jun 6;6(6):CD015701. doi: 10.1002/14651858.CD015701.pub2.
There is controversy about a possible link between hormonal contraception, specifically injectable depot medroxyprogesterone acetate (DMPA) and HIV acquisition. Following the results of a large randomised controlled trial, there is a need to update the previous version of this Cochrane review.
To determine the effects of hormonal contraception on HIV acquisition in women who live in settings with high HIV prevalence.
We searched CENTRAL, MEDLINE, Embase, SCOPUS, Global Index Medicus and trial registries (together with reference checking, citation searching and contacting study authors), to identify studies up to 13 September 2023.
We included randomised controlled trials (RCTs) comparing hormonal contraception with non-hormonal or other methods of contraception for women at high risk of HIV.
Outcomes of interest were HIV acquisition, pregnancy, discontinuation of method, amenorrhoea, adverse events and condomless sexual activity.
We used the Cochrane risk of bias 2 tool to assess bias in the RCTs.
We synthesised results for each outcome using random-effects meta-analysis where possible and meaningful. We assessed the certainty of evidence with GRADE.
We included four trials with 9726 participants, conducted across four countries.
DMPA injection compared to copper intrauterine device (IUD) DMPA compared to copper IUD likely results in little to no difference in HIV acquisition (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.82 to 1.26; 2 RCTs, n = 6417; moderate-certainty evidence), resulting in one more woman per 1000 acquiring HIV (from 9 fewer to 13 more). DMPA compared to copper IUD results in a slight reduction in pregnancy (RR 0.53, 95% CI 0.39 to 0.71; 1 RCT, n = 5216; high-certainty evidence), resulting in 21 fewer women per 1000 becoming pregnant (from 27 to 13 fewer). DMPA compared to copper IUD results in a reduction in discontinuation of method (RR 0.50, 95% CI 0.40 to 0.62; 1 RCT, n = 5216; high-certainty evidence) and in adverse events (RR 0.53, 95% CI 0.38 to 0.75; 1 RCT, n = 5216; high-certainty evidence). In the DMPA group 'any unprotected sex' was reported at 66.4% of follow-up visits, compared to 70.9% in the copper IUD group. Levonorgestrel (LNG) implant compared to copper IUD LNG compared to copper IUD likely results in little to no difference in HIV acquisition (RR 0.84, 95% CI 0.66 to 1.06; 1 RCT, n = 5159; moderate-certainty evidence), resulting in nine fewer women per 1000 acquiring HIV (from 18 fewer to 3 more). LNG compared to copper IUD likely results in a slight reduction in pregnancy (RR 0.67, 95% CI 0.51 to 0.89; 1 RCT, n = 5220; moderate-certainty evidence), resulting in 15 fewer women per 1000 becoming pregnant (from 22 to 5 fewer). LNG compared to copper IUD likely results in little to no difference in adverse events (RR 0.85, 95% CI 0.63 to 1.14; 1 RCT, n = 5220; moderate-certainty evidence) and discontinuation of method (RR 1.03, 95% CI 0.87 to 1.24; P = 0.71; 1 RCT, n = 5220; moderate-certainty evidence). DMPA injection compared to LNG implant DMPA compared to LNG probably slightly increases HIV acquisition (RR 1.25, 95% CI 0.98 to 1.58; 1 RCT, n = 5144; moderate-certainty evidence), resulting in 11 more women per 1000 acquiring HIV (from 1 fewer to 26 more). DMPA compared to LNG probably results in little to no difference in pregnancy (RR 0.78, 95% CI 0.56 to 1.09; 1 RCT, n = 5222; moderate-certainty evidence), resulting in seven fewer women per 1000 becoming pregnant (from 13 fewer to 3 more). DMPA compared to LNG reduces adverse events (RR 0.63, 95% CI 0.44 to 0.90; 1 RCT, n = 5222; high-certainty evidence), and discontinuation of methods (RR 0.48, 95% CI 0.39 to 0.60; P < 0.00001; 1 RCT, n = 5222; high-certainty evidence). No included studies in the above comparisons measured amenorrhoea. In the DMPA group 'any unprotected sex' was reported at 66.4% of follow-up visits, compared to 69.4% in the LNG implant group. DMPA injection compared to NET-EN injection The evidence is very uncertain about the effect of DMPA compared to NET-EN on HIV acquisition (RR 0.67, 95% CI 0.19 to 2.35; 1 RCT, n = 450; very low-certainty evidence) resulting in nine fewer women per 1000 acquiring HIV (from 22 fewer to 36 more); and pregnancy (RR 2.03, 95% CI 0.19 to 22.19; 1 RCT, n = 449; very low-certainty evidence), resulting in five more women per 1000 becoming pregnant (from 4 fewer to 94 more). DMPA compared to NET-EN probably increases amenorrhoea (RR 1.12, 95% CI 0.89 to 1.41; P = 0.33; 1 RCT, n = 449; moderate-certainty evidence). Discontinuation of methods was not measured.
AUTHORS' CONCLUSIONS: HIV incidence was high in all groups, regardless of contraceptive used, as would be expected in a setting with high HIV prevalence. All contraceptives used in the included studies are widely used and known to prevent pregnancy. When comparing different contraceptive methods, DMPA injections compared to copper IUD may result in little to no difference in HIV acquisition and result in a slight reduction in pregnancy. LNG implants compared to copper IUDs likely result in little to no difference in HIV acquisition and in a slight reduction in pregnancy. DMPA injections compared to LNG implants likely result in a slight increase in HIV acquisition and likely result in little to no difference in pregnancy. The evidence is very uncertain about the effect of DMPA compared to NET-EN on HIV acquisition and pregnancy. HIV acquisition and pregnancy are important outcomes that have a long-lasting impact. Access to safe, effective contraception is important for women wanting to prevent unplanned pregnancies, as pregnancies have long-lasting physical, social and economic ramifications. Evidence from included studies shows that across groups, many participants report engaging in condomless sexual activity, even when living in high HIV prevalence settings. HIV prevention methods such as pre-exposure prophylaxis and HIV education remain crucial in the fight against HIV.
This Cochrane review had no dedicated funding.
Protocol available via (DOI: 10.1002/14651858.CD015701).
激素避孕，尤其是注射用醋酸甲羟孕酮长效避孕针（DMPA）与HIV感染之间是否存在潜在联系存在争议。在一项大型随机对照试验得出结果后，有必要更新本Cochrane系统评价的上一版。
确定激素避孕对生活在HIV高流行地区女性HIV感染的影响。
我们检索了Cochrane系统评价数据库、MEDLINE、Embase、SCOPUS、全球医学索引以及试验注册库（同时进行参考文献核对、引文检索并联系研究作者），以识别截至2023年9月13日的研究。
我们纳入了比较激素避孕与非激素或其他避孕方法对HIV高风险女性影响的随机对照试验（RCT）。
感兴趣的结局包括HIV感染、妊娠、方法停用、闭经、不良事件以及无保护性行为。
我们使用Cochrane偏倚风险2工具评估RCT中的偏倚。
我们尽可能且有意义地使用随机效应荟萃分析对每个结局的结果进行综合。我们使用GRADE评估证据的确定性。
我们纳入了四项试验，共9726名参与者，这些试验在四个国家进行。
与铜宫内节育器（IUD）相比，DMPA注射剂与铜IUD相比，HIV感染率可能几乎没有差异（风险比（RR）1.02，95%置信区间（CI）0.82至1.26；2项RCT，n = 6417；中等确定性证据），每1000名女性中感染HIV的人数增加1人（从少9人到多13人）。与铜IUD相比，DMPA导致妊娠略有减少（RR 0.53，95%CI 0.39至0.71；1项RCT，n = 5216；高确定性证据），每1000名女性中怀孕的人数减少21人（从27人减少到13人）。与铜IUD相比，DMPA导致方法停用减少（RR 0.50，95%CI 0.40至0.62；1项RCT，n = 5216；高确定性证据）以及不良事件减少（RR 0.53，95%CI 0.38至0.75；1项RCT，n = 5216；高确定性证据）。在DMPA组中，66.4%的随访就诊报告有“任何无保护性行为”，而铜IUD组为70.9%。与铜IUD相比，左炔诺孕酮（LNG）植入剂与铜IUD相比，HIV感染率可能几乎没有差异（RR 0.84，95%CI 0.66至1.06；1项RCT，n = 5159；中等确定性证据），每1000名女性中感染HIV的人数减少9人（从少18人到多3人）。与铜IUD相比，LNG可能导致妊娠略有减少（RR 0.67，95%CI 0.51至0.89；1项RCT，n = 5220；中等确定性证据），每1000名女性中怀孕的人数减少15人（从22人减少到5人）。与铜IUD相比，LNG在不良事件（RR 0.85，95%CI 0.63至1.14；1项RCT，n = 5220；中等确定性证据）和方法停用方面可能几乎没有差异（RR 1.03，95%CI 0.87至1.24；P = 0.71；1项RCT，n = 5220；中等确定性证据）。与LNG植入剂相比，DMPA注射剂与LNG相比可能会使HIV感染率略有增加（RR 1.25，95%CI 0.98至1.58；1项RCT，n = 5144；中等确定性证据），每1000名女性中感染HIV的人数增加11人（从少1人到多26人）。与LNG相比，DMPA在妊娠方面可能几乎没有差异（RR 0.78，95%CI 0.56至1.09；1项RCT，n = 5222；中等确定性证据），每1000名女性中怀孕的人数减少7人（从少13人到多3人）。与LNG相比，DMPA减少了不良事件（RR 0.63，95%CI 0.44至0.90；1项RCT，n = 5222；高确定性证据）以及方法停用（RR 0.48，95%CI 0.39至0.60；P < 0.00001；1项RCT，n = 5222；高确定性证据）。上述比较中纳入的研究均未测量闭经情况。在DMPA组中，66.4%的随访就诊报告有“任何无保护性行为”，而LNG植入剂组为69.4%。与炔诺酮庚酸酯（NET-EN）注射剂相比，DMPA注射剂与NET-EN相比，关于DMPA对HIV感染影响的证据非常不确定（RR 0.67，95%CI 0.19至2.35；1项RCT，n = 450；极低确定性证据），每1000名女性中感染HIV的人数减少9人（从少22人到多36人）；以及妊娠（RR 2.03，95%CI 0.19至22.19；1项RCT，n = 449；极低确定性证据），每1000名女性中怀孕的人数增加5人（从少4人到多94人）。与NET-EN相比，DMPA可能会增加闭经（RR 1.12，95%CI 0.89至1.41；P = 0.33；1项RCT，n = 449；中等确定性证据）。未测量方法停用情况。
正如在HIV高流行地区所预期的那样，无论使用何种避孕方法，所有组的HIV发病率都很高。纳入研究中使用的所有避孕方法都被广泛使用且已知可预防妊娠。在比较不同避孕方法时，与铜IUD相比，DMPA注射剂在HIV感染方面可能几乎没有差异，且会使妊娠略有减少。与铜IUD相比，LNG植入剂在HIV感染方面可能几乎没有差异，且会使妊娠略有减少。与LNG植入剂相比，DMPA注射剂可能会使HIV感染率略有增加，且在妊娠方面可能几乎没有差异。关于DMPA与NET-EN相比对HIV感染和妊娠影响的证据非常不确定。HIV感染和妊娠是具有长期影响的重要结局。获得安全、有效的避孕措施对于想要预防意外怀孕的女性很重要，因为怀孕会产生长期的身体、社会和经济影响。纳入研究的证据表明，在所有组中，许多参与者报告有未采取保护措施的性行为，即使生活在HIV高流行地区。暴露前预防和HIV教育等HIV预防方法在抗击HIV的斗争中仍然至关重要。
本Cochrane系统评价没有专门的资助。
方案可通过（DOI：10.1002/14651858.CD015701）获取。
