Elsevier

Contraception

Volume 75, Issue 6, June 2007, Pages 461-467
Contraception

Original research article
Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort

https://doi.org/10.1016/j.contraception.2007.02.002Get rights and content

Abstract

Objective

To investigate whether the incidence of HIV infection is higher among sexually active women using depot medroxyprogesterone acetate (DMPA) or noresthisterone enanthate (NET-EN) injections for contraception than among women using nonhormonal or no contraception.

Methods

Five hundred and fifty-one initially HIV-negative women were followed up for a total of 491 person-years. Participants were interviewed, counselled, examined, tested for HIV and other STIs, and treated, at three monthly intervals for 1 year.

Results

There was no significant association between progestin contraceptive use and HIV infection (rate ratio 1.1, 95% CI 0.5 to 2.8; log-rank test, p=.73). In proportional hazards regression, the only significant hazard ratios for HIV acquisition were prevalent Neisseria gonorrhoea (5.2; 95% CI 1.1 to 23.7, p=.035) and Trichomonas vaginalis (4.8; 95% CI 1.0 to 22.8, p=.049); bacterial vaginosis was marginally significant (2.8; 95% CI 1.0 to 8.3, p=.057). The adjusted hazard ratios for NET-EN and DMPA were 1.76 (95% CI 0.64 to 4.84) and 0.46 (95% CI 0.06 to 3.79), respectively, relative to nonuse. Five hundred and twelve of 551 women had one or more confirmed STIs during the study.

Conclusions

There is no evidence of an association between HIV infection and injectable contraceptives. Due to the limited power of this study and because similar studies have not included young women using NET-EN, we recommend that further research be carried out to focus on the use of NET-EN and HIV acquisition in high risk groups.

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.

Section snippets

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.

References (24)

  • L. Govender et al.

    Bacterial vaginosis and associated infections in pregnancy

    Int J Gynaecol Obstet

    (1996)
  • J.P. Hapgood et al.

    Not all progestins are the same: implications for usage

    Trends Pharmacol Sci

    (2004)
  • South Africa demographic and health survey 1998

  • J. Smit et al.

    Counting the costs: comparing depot medroxyprogesterone acetate and norethisterone enanthate utilization patterns in South Africa

    BMC Health Serv Rese

    (2001)
  • National Department of Health, South Africa

    National HIV and syphilis antenatal sero-prevalence survey in South Africa 2005. Pretoria 2006

  • C.S. Morrison et al.

    Hormonal contraception and the risk of HIV acquisition

    AIDS

    (2007)
  • J.M. Stephenson

    Systematic review of hormonal contraception and risk of HIV transmission: when to resist meta-analysis

    AIDS

    (1998)
  • C.C. Wang et al.

    Risk of HIV infection in oral contraceptive pill users: a meta-analysis

    J Acquir Immune Defic Syndr

    (1999)
  • M. Kiddugavu et al.

    Hormonal contraceptive use and HIV-1 infection in a population-based cohort in Rakai, Uganda

    AIDS

    (2003)
  • H.L. Martin et al.

    Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1

    J Infect Dis

    (1998)
  • L. Lavreys et al.

    Hormonal contraception and risk of HIV-1 acquisition: results of a 10-year prospective study

    AIDS

    (2004)
  • D. Schoenfeld

    Sample size formula for the proportional hazards regression model

    Biometrics

    (1983)
  • Cited by (69)

    • Medroxyprogesterone acetate differentially regulates interleukin (IL)-12 and IL-10 in a human ectocervical epithelial cell line in a glucocorticoid receptor (GR)-dependent manner

      2014, Journal of Biological Chemistry
      Citation 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).

    View all citing articles on Scopus

    This study was funded by a grant from the Centers for Disease Control and Prevention (CDC), USA.

    View full text