Use of hormonal contraceptives and risk of HIV-1 transmission

Abstract

Coital frequency could be the real reason for Heffron and colleagues' findings1Heffron R Donnell D Rees H et al.Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study.Lancet Infect Dis. 2012; 12: 19-26Summary Full Text Full Text PDF PubMed Scopus (342) Google Scholar that hormonal contraception increases risk of HIV acquisition. Although the investigators examined and dismissed the possibility that more sexual activity in hormonal contraceptive users than non-users was to blame, the veracity of self-reports about sex has always been questionable. Could women not using contraception or using only condoms have the same level of sexual activity as those using hormonal contraception? Women are probably likely to choose effective birth control, such as hormonal contraception, when the risks of unintended pregnancy are high. When sexual activity is sporadic or absent, risk of HIV acquisition is low, as is motivation to use hormonal contraception. Nevertheless, non-users might have overstated their sexual activity because of study requirements for participation. However, in the final relative risk analysis, hormonal contraception could be falsely implicated for the noted increase in risk of HIV acquisition. Misreported condom use is the other possible confounder. The investigators concluded that condom use did not skew the findings; however, self-reports of this topic are notoriously inaccurate2Minnis AM Steiner MJ Gallo MF et al.Biomarker validation of reports of recent sexual activity: results of a randomized controlled study in Zimbabwe.Am J Epidemiol. 2009; 170: 918-924Crossref PubMed Scopus (133) Google Scholar and can substantially affect research. Reported condom use was balanced at roughly 91%. If those using hormonal contraception overstated condom use to avoid a lecture about safe sex, non-use of condoms combined with high sexual activity would put them at significant risk of HIV acquisition. Consequently, the raw data show that the comparison groups were equally protected by condoms, which could falsely leave hormonal contraception as the risk factor for HIV acquisition. Marginal structural models cannot salvage the truth from potentially biased data. In summary, the results of this and similar studies are built on shaky ground; far more evidence exists that self-reported coital frequency and condom use are poor scientific variables. However, at the margins these factors can be easily obscured, thus distorting the risk estimates for a primary exposure. In the published report, only 13 women on hormonal contraception seroconverted. Epidemiology often fails to prove causation. New approaches are needed to answer the important question of whether hormonal contraception increases risk of HIV acquisition.3Morrison CN Nanda K Hormonal contraception and HIV: an unanswered question.Lancet Infect Dis. 2012; 12: 2-3Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar I have served on a scientific advisory board for Bayer HealthCare. Use of hormonal contraceptives and risk of HIV-1 transmission – Authors' replyWe acknowledge the limitations of self-reported sexual behaviour; however, findings from several supplementary analyses suggest that incomplete statistical control for sexual behaviour does not explain our findings. First, self-reported unprotected sex was strongly associated with HIV-1 risk in our multivariate models (adjusted hazard ratio [HR] 2·82, 95% CI 1·62–4·92; p=0·0002 for HIV-1 acquisition in women and 2·57, 1·38–4·77; p=0·003 for HIV-1 transmission from women to men). Second, unprotected sex strongly correlated with increased pregnancy incidence1 and self-reported condom use was associated with an 80% reduction in per-contact risk,2 which is consistent with widely accepted estimates of condom effectiveness. Full-Text PDF