Original research articleInjectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort☆
Introduction
Use of long-acting injectable progestin contraceptives by South African women is widespread: it is estimated that 57% of all women aged 15 to 49 years have used injectable contraceptives at some stage, whilst 30% of all currently sexually active women are using progestin injectables [1]. In recent years, noresthisterone enanthate (NET-EN) has been introduced widely in South Africa as an alternative progestin injectable to depot medroxyprogesterone acetate (DMPA), particularly amongst younger women, including teenagers [2].
It is estimated that about 6 million people are infected with HIV in South Africa [3], making it the country with the largest number of HIV-infected individuals worldwide. The largest ever study investigating the effect of hormonal contraceptive use on HIV acquisition [4] found that there was no overall association, although there was evidence of such an association in the subgroups of women who were herpes simplex virus 2 (HSV-2) negative. Results from other studies have been contradictory [5], [6], [7], [8], [9]. A large cohort study of sexually active women in Uganda found no association between use of hormonal contraception and HIV acquisition after adjusting for confounders [7]. On the other hand, cohort studies of initially HIV-uninfected sex workers in Kenya reported statistically significant increased risks of HIV infection in both users of DMPA as well as users of oral contraceptives (OC) [8], [9]. A systematic review of hormonal contraception and risk of HIV transmission concluded that the relationship remains uncertain [5]. None of the previous studies included young women using the progestin NET-EN for contraception.
The aim of this study was to investigate prospectively whether the incidence of HIV infection is higher among sexually active women using progestin (DMPA or NET-EN) injections for contraception than among women using nonhormonal or no contraception. Due to the increasing use of NET-EN amongst young people, analyses were undertaken of NET-EN and DMPA both combined and separately (post hoc).
The study was a collaborative project between the Reproductive Health and HIV Research Unit (RHRU) of the University of the Witwatersrand, and the Centers for Disease Control and Prevention (CDC), USA, and was approved by the Human Subjects Research Committee of the University of Witwatersrand and the CDC IRB.
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Participants and procedures
From August 1999 through May 2001, HIV-1-negative women were recruited from family planning clinics in Orange Farm, a large settlement 60 km from Johannesburg. Criteria for inclusion included age 18–40 years, sexually active in the past three months (as an indication of likely sexual activity during the study), not pregnant or planning to become pregnant for 12 months, consenting to HIV testing and other study procedures, and not using or planning to use oral contraceptive pills. Progestin
Results
A total of 634 women were enrolled in the study, of whom 8 were excluded from analysis because subsequent testing showed them to have acute primary HIV infection, 72 left the study before their HIV status was determined after enrolment and a further 3 switched to oral contraceptives (OC) by the time of their first follow-up visit. Analysis was carried out on the remaining 551 initially HIV-negative women, of whom 23 sero-converted during the study. Participants were seen for a total of 1942
Discussion
We found no evidence that women using long-acting injectable progestin contraceptives (DMPA or NET-EN) are at increased risk of HIV infection. The unadjusted rate ratio of HIV infection of injectable use relative to nonuse was estimated to be 1.12 (95% CI 0.45 to 2.78) and is therefore consistent with the null hypothesis of no association between HIV infection and progestin contraceptive use. This may have been because no association truly exists or because of the low power in the study.
Point
Acknowledgment
The authors would like to thank Dr. Charles Morrison for valuable comments on an earlier draft of this paper and Dr. Jenni Smit for comments and a literature search on molecular modes of action of synthetic progestins.
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2014, Journal of Biological ChemistryCitation Excerpt :The latter mimic the progestogenic activity of P4 and have been used in a number of therapeutic applications, such as contraception, hormone replacement therapy, and treatment of some gynecological disorders (1–3). Medroxyprogesterone acetate (MPA or Depo-Provera®) is an example of a synthetic progestin extensively used as a progestin-only injectable contraceptive in South Africa (4–7). At the molecular level, MPA elicits its biological effects by binding not only to the progesterone receptor (1, 8) but also to other members of the steroid receptor family such as the glucocorticoid receptor (GR), androgen receptor, and mineralocorticoid receptor (9–13).
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This study was funded by a grant from the Centers for Disease Control and Prevention (CDC), USA.