Hormonal contraception and HIV acquisition among women: an updated systematic review

Abstract

Objective: To update a 2016 systematic review on hormonal contraception use and HIV acquisition.

Methods: We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses.

Results: In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk.

Conclusions: High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.

Keywords: epidemiology; hormonal contraception; human immunodeficiency virus; intrauterine devices.

Figure 1

Use of depot medroxyprogesterone acetate (DMPA) (or unspecified injectable) versus non-hormonal or no contraception and HIV acquisition, among 14 studies considered “informative but with important limitations” or “informative with few limitations”. Error bars show 95% confidence intervals (CIs), with the exception of the ECHO trial which uses 96% CI. Observational studies arranged in order of decreasing magnitude of risk estimate. Graph does not display estimates from marginal structural models, except where use of such models resulted in a different conclusions regarding statistical significance; in such cases, estimates from both models are displayed on a single line (also identified by bracket signs). Note: restricted to all data on DMPA or unspecified injectables, as estimates of unspecified injectables are likely comprised largely of DMPA. *Analysis showed significant findings at p=0.05. †Estimate for Cox model taken from slightly updated analysis that controlled for total number of unprotected sex acts. ^¶Updated estimate from Baeten et al, 2007. ˆUnpublished estimates from a sub-analysis of Morrison 2015 meta-analysis, restricted to pooled analysis using databases not previously used to publish estimates on hormonal contraceptive methods and HIV acquisition risk. ¥Different statistical models adjusted for slightly different confounders. §Unpublished estimates disaggregated by injectable type. adjHR, adjusted HR; adjIRR, adjusted incidence risk ratio; CI, confidence interval; DMPA, depot medroxyprogesterone acetate; ECHO, Evidence for Contraceptive Options and HIV Outcomes Trial; HR, hazard ratio; ITT, intention-to-treat; MSM, marginal structural models.

Figure 2

Use of norethisterone enanthate versus non-hormonal or no contraception and HIV acquisition, among seven studies considered informative but with important limitations. Error bars show 95% confidence intervals. Studies arranged in order of decreasing magnitude of risk estimate. Graph does not display estimates from marginal structural models. ˆUnpublished estimates from a sub-analysis of Morrison et al. 2015 meta-analysis, restricted to pooled analysis using databases not previously used to publish estimates on hormonal contraceptive methods and HIV acquisition risk. §Unpublished estimates disaggregated by injectable type. adjHR, adjusted HR; adjIRR, adjusted incidence risk ratio; CI, confidence interval; HR, hazard ratio; NET-EN, norethisterone enanthate.

Figure 3

Use of implants* (versus non-hormonal or no contraception) and HIV acquisition, among four studies considered “informative but with important limitations” or “informative with few limitations”. Error bars show 95% confidence intervals (CIs), with the exception of the ECHO trial which uses 96% CI. Studies arranged in order of decreasing magnitude of risk estimate. *Sabo et al, Wall et al and the ECHO trial included levonorgestrel implants; Palanee-Phillips et al did not specify implant type. **The ECHO trial reported an adjHR 1.18 (96% CI 0.91 to 1.53) for the comparison of copper intrauterine devices (Cu-IUDs) versus levonorgestrel (LNG) implant. The inverse association is represented on this figure for LNG implant versus Cu-IUD. adjHR, adjusted HR; CI, confidence interval; ECHO, Evidence for Contraceptive Options and HIV Outcomes Trial; HR, hazard ratio; ITT, intention-to-treat.

Figure 4

Hormonal contraceptive methods and HIV acquisition in head-to-head studies, among four studies considered “informative but with important limitations” or “informative with few limitations”. Error bars show 95% confidence intervals (CIs), with the exception of the ECHO trial which uses 96% CI. Within each comparison group, studies are arranged in order of decreasing magnitude of risk estimate. *Analysis showed significant findings at p=0.05. **Results from randomised clinical trial; all other results from observational studies. adjHR, adjusted HR; CI, confidence interval; COC, combined oral contraception; ECHO, Evidence for Contraceptive Options and HIV Outcomes Trial; DMPA, depot medroxyprogesterone acetate; HR, hazard ratio; LNG, levonorgestrel; NET-EN, norethisterone enanthate.