Hormonal Contraceptive Methods on Immunologic Changes in the Female Genital Tract (FGT) and Systemically

Emerging data suggests that certain hormonal contraceptives may induce mucosal and systemic
immune changes that could increase the risk of infection with HIV. While several studies have
aimed to characterize immunologic changes in women using hormonal contraceptives, the nature
and the magnitude of these immune changes have not been adequately defined due to limitations
in study design rigor, and small and statistically underpowered sample sizes.

The study will prospectively recruit cohorts of HIV-uninfected women initiating hormonal
contraception to characterize systemic and lower genital tract innate and adaptive
immunologic changes that occur over the course of 1 year. This study will test the
overarching hypothesis that hormonal contraceptives induce systemic and mucosal immune
changes capable of altering susceptibilities and/or responses to diseases including HIV
infection, and that these effects vary markedly in nature and magnitude by contraceptive type
and will be modified by the vaginal microenvironment. The main aim is to determine the
immunologic alterations in female genital and systemic immune profile associated with depot
medroxyprogesterone acetate (DMPA), Etonogestrel implant (Eng-Implant) and Levonorgestrel IUD
(Lng-IUD).

Inclusion Criteria:

- Female sex, defined by sex at birth

- Age ≤ 45 years. If < 18 years of age, participant must be capable of providing assent,
understanding and complying with all study procedures, and have written informed
consent from a parent or legal guardian.

- Normal menses (occurring within 22-35 day intervals) for > 2 cycles. Women who are
postpartum or post-abortion who have resumed menses are eligible.

- Intact uterus and cervix, (e) Interested in initiating HC and willing to accept DMPA,
Eng-Implant or Lng-IUD

- Willing to delay initiation of HC for up to 1 month

- Interested in initiating HC and willing to accept DMPA, Eng-Implant or Lng-IUD

- Able and willing to provide informed consent, and undergo study procedures. See
criterion (b) for participants <18 years of age.

- Negative HIV test by Ora-Quick© method at Screening Visit.

- Agree to abstain from vaginal intercourse or using intra-vaginal products for 1 day
prior to each study visit

Exclusion Criteria:

- Pregnant or planning to become pregnant within the next year

- Breastfeeding, if not having active menstrual cycles. Breastfeeding is not
exclusionary if the participant is actively cycling.

- History of loop electrosurgical excision procedure (LEEP), conization, or cryosurgery
within the past year

- Current use of systemic HC or IUD, based on self-report and/or hormonal testing

- Taking concurrent medications that interact with selected HC

- Contraindications to selected contraceptive per the Center for Disease Control medical
eligibility criteria or judgment of clinician.

- Allergy to lidocaine for cervical biopsies (if consenting to optional biopsies).