Long-Acting Progestin Contraception and the Vaginal Microbiome
Condition: Sexually Transmitted Infection
MeSH terms: Sexually Transmitted Diseases
Study type: Observational

Summary: 
      Despite many years of research, controversy persists as to whether hormonal contraception
      promotes HIV acquisition. A number of observational studies on depot medroxyprogesterone
      acetate (DMPA) injection showed an increase in HIV risk and no evidence of increased risk
      with oral contraceptive pills. There are no human studies currently published on the impact
      of the levonorgestrel intrauterine device (LNG IUD) on HIV transmission risk and minimal data
      on the effects of the etonogestrel subdermal implant (ESI) on risk of HIV acquisition.
      Establishing whether any of these highly effective contraceptives increases the risk of HIV
      infection would have far-reaching public health implications, particularly in areas of high
      HIV prevalence such as sub-Saharan Africa, where injectable contraception accounts for nearly
      half of contraceptive use.

      Perturbations in the normal vaginal microbiota, or community of microorganisms inhabiting the
      vaginal body niche, have long been known to affect the risk of transmission of HIV. Studies
      have shown altered vaginal microbiota with DMPA injection and preserved vaginal microbiota
      with the LNG IUD, but no studies have compared these methods head-to-head or used
      culture-independent sequencing methodology. The investigators propose a prospective pilot
      study to evaluate the impact of different long-acting progestin contraceptive formulations on
      the vaginal microbiome. Specifically, the investigators aim to identify and compare
      metagenomics profiles associated with DMPA, LNG IUD, and ESI contraceptive use by community
      analysis of vaginal swab samples from women collected longitudinally after contraceptive
      method initiation. The investigators hypothesize that DMPA will increase community diversity
      in the vaginal microbiota, whereas the LNG IUD and ESI will not affect the balance of
      microorganisms in the vagina. Women who are planning to initiate DMPA, LNG IUD, and ESI
      contraception as well as controls not seeking contraception will be recruited for the study
      from Boston Medical Center (BMC), a tertiary care center with a racially and
      socioeconomically diverse patient population. Women will have longitudinal follow-up with
      self-sampling of the vagina for sexually transmitted infection testing and metagenomics
      analysis at method initiation, 2-3 months, and 6 months. Establishing the safest long-acting
      progestin contraceptive alternative will promote effective contraception use and lower rates
      of HIV acquisition worldwide.
    

Detailed description: 
      Women between the ages of 18-45 initiating long-acting progestin contraception will be
      enrolled at a routine office visit at the family planning clinics of each institution.
      Enrollment will begin in April 2016 and will stop after 6 months to allow for longitudinal
      follow-up and analyses. For this pilot study, a total of 30 long-acting progestin
      contraceptive initiators with 10 subjects in each method group (DMPA, LNG IUD, ESI) and 5
      age-matched, controls seeking tubal sterilization will be selected for longitudinal STI
      screening and vaginal sampling for microbiome analysis.

      After consent is obtained, trained staff will interview subjects using a brief
      sociodemographic/habits questionnaire that includes questions on age, race, body mass index,
      smoking status, history of sexually transmitted infections and yeast vaginitis, weekly
      frequency of coitus, and number of lifetime sexual partners. Subjects will be instructed to
      self-sample the vagina at three timepoints: 1) at method initiation, 2) 2-3 months later, and
      3) 6 months later. Self-collected vaginal swab specimens will be assayed for Trichomonas
      vaginalis, Chlamydia trachomatis, and Neisseria gonorrhoeae using DNA amplification in the
      clinical lab. Microbiome samples collected at each timepoint will be analyzed and compared to
      the initiation sample to detect longitudinal differences.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Women between the ages of 18-40 initiating long-acting progestin contraception or who are
        seeking tubal sterilization will be enrolled at a routine office visit at the ambulatory
        practice/family planning clinic.
      
Biospecimen description: 
      Vaginal swabs for microbiome analysis and sexually transmitted infection testing.
    
Keywords: Microbiome; Progestin; Long-acting contraception