Clinical trial NCT03301480: Contraceptive/HIV Affecting Risk in Adolescents
Official title: Contraceptive/HIV Affecting Risk in Adolescents
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Contraception
Hiv
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2017-10-04
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: non-pregnant, HIV negative, healthy 18-19 year old women and 25-45 year old women

Brief summary: This study will evaluate the impact of hormonal contraceptives on HIV risk associated with changes to the innate immunity in the female genital tract in a cross-sectional study. HIV risk will be evaluated by the capacity of cervical tissue to replicate HIV when challenged ex vivo and correlated to the number of CD4 T cells, DCs, and macrophages; the capacity of cervicovaginal fluid to inhibit HIV will be correlated to soluble mucosal mediators, and the vaginal microbiota. The lower genital tract samples will be collected from 120 adolescents aged 18-19 (40 using no hormonal contraception, 40 using ENG-I, 40 using LNG-IUS). For comparison, 90 adult women aged 25-45 will be equally distributed between the same groupings.


Eligibility criteria: Inclusion Criteria:

1. Meets one of the following age groups (at the time of sample collection):

   1. Adolescent aged 18-19
   2. Adult aged 25-45
2. Meets one of the following contraception groups:

   1. Regular menstrual cycles by participant history (if not using hormonal contraception)
   2. Use of ENG-I (i.e. Implanon/Nexplanon) for at least 30 days by participant history
   3. Use of LNG-IUS (Mirena or Skyla) for at least 30 days by participant history
3. HIV uninfected Note: HIV testing will be done as part of screening. However, if a woman participated in a recent research study and has an HIV test result available from that study, this will suffice provided the date of the test is within 6 months of the study visit.
4. Willing to undergo pelvic exam and collection of cervical biopsies
5. Willing to provided written informed consent
6. Agree to be sexually abstinent for 48 hours prior to the cervical biopsies and for one week after the biopsies.

Exclusion Criteria:

1. Use of any other hormonal contraception other than ENG-I or LNG-IUS
2. Use of a diaphragm or spermicide for contraception
3. Pregnant or pregnancy within 90 days
4. Currently breastfeeding
5. Currently menstruating/bleeding (at time of specimen collection) Note: participant can return after cessation of bleeding for specimen collection
6. Past participation in more than one study involving cervical biopsies per participant report
7. Cervical biopsies within one month of specimen collection visit
8. Abnormal vaginal discharge or other genital tract symptoms at the time of specimen collection
9. Pelvic findings on the day of specimen collection consistent with cervicitis (i.e. MPC, erythema, edema) or anatomy making cervical biopsies difficult
10. Menopausal
11. Hysterectomy
12. History of malignancy of the genital tract (including cervix, uterus, vagina, and vulva)
13. History of immunosuppression (including HIV infection, diabetes, and chronic steroid use)
14. Known history of a platelet/bleeding/clotting disorder
15. Use of a systemic or vaginal antimicrobial agent within 7 days of specimen collection
16. Use of any vaginal product (i.e. douching, spermicide, lubricant) or device within 7 days of specimen collection Note: tampon use is acceptable
17. Any other condition that in the opinion of the Study Investigator would preclude provision of informed consent or make study participation unsafe, complicate the interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Primary outcomes:
measure: HIV replication in cervical tissue as measured by levels of HIV p24/viral transcripts
timeFrame: baseline
measure: number of immune cells in cervical tissue, including CD45, CD3, CD4, and CD8 and their expression of CCR5, CCR6 and CD69, and CD11c+ DCs and CD14+ macrophages
timeFrame: baseline
Secondary outcomes:
measure: Prevalence of bacterial vaginosis defined as a Nugent score ≥7 on a vaginal smear
timeFrame: baseline
measure: prevalence and quantity of lactobacillus species and bacterial vaginosis associated bacteria as measured by traditional culture methods and quantitative PCR
timeFrame: baseline
measure: HIV inhibitory activity in mucosal fluid; and soluble mucosal factors identified through pathway analyses and confirmed by targeted ELISA/multiplexing technology (proteases/ anti-proteases, keratin, IFNε, and other molecules)
timeFrame: baseline
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Katherine Bunge, MD
role: PRINCIPAL_INVESTIGATOR
References: