Effects of Contraceptive Ring on Vaginal Microbiota, HIV Shedding and Local Immunity

HIV Clinical Trial

Official title:

Effects of Contraceptive Ring on Vaginal Microbiota, HIV Shedding and Local Immunity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02445989
• Other study ID #: 48663
• Secondary ID: R01HD077872
• Status: Completed
• Phase: Phase 4
• Start date: May 2016
• Est. completion date: December 2018

Study information

• Verified date: December 2018
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators propose to explore the hypothesis—supported by limited data—that a contraceptive vaginal ring (CVR) that is commonly used in the United States, the NuvaRing, will enhance women's genital and reproductive health. The investigators propose that this CVR will increase the bacteria that help the vaginal environment protect against infection by HIV and other STIs, and that in women who already have HIV, use of the CVR will lower the quantity of HIV that is shed in the female genital tract.

Description:

The investigators objective is to study effects of a contraceptive vaginal ring (CVR) containing estrogen and progesterone (NuvaRing) on vaginal bacteria, HIV shedding, and local immunity in women. The investigators will build on data that support a favorable effect of CVR on vaginal bacteria. Bacterial vaginosis (BV) is found in >50% of women in sub-Saharan Africa. BV significantly increases risk of HIV acquisition in, and HIV transmission to male partners from, HIV-infected women, genital HIV shedding, and viral set point in infected male partners. Pregnancy is also an independent risk for HIV acquisition and transmission. Contraception comprises critical biomedical prevention for women with or at risk for HIV. Systemic depot progesterone—commonly used throughout Africa—may independently increase risk of HIV acquisition and transmission. Hormonal interventions preventing unintended pregnancy and promoting a protective vaginal microenvironment could synergistically reduce HIV risk especially combined with topical antiretrovirals (ARV). The investigators propose NuvaRing use may contribute to reduction in BV, pregnancy prevention, and decreased rates of HIV shedding in HIV-infected women. Sustained vaginal delivery of contraceptive and ARV PrEP as "multicomponent prevention" is a major focus for scientists but effects on the vaginal environment need careful definition before broad implementation.

Total duration of follow up is no more than 8 months, with 5 months of CVR usage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• BV+ by Amsel Criteria

• Not intending to become pregnant over the course of the study

• If HIV infected, not taking ART

• Capable of providing written informed consent

Exclusion Criteria:

• Current pregnancy

• Desire/intent to become pregnant over the course of the study

• Contraindications to hormonal contraceptive use

• Current cigarette smoking if age is older than 35 years

• Unable to comprehend consent material because of language barrier or psychological difficulty

Related Conditions & MeSH terms

• Bacterial Vaginosis
• HIV
• Vaginal Diseases
• Vaginosis, Bacterial

Intervention

Drug:
• NuvaRing
Provide NuvaRing to women seeking contraception

Locations

Country	Name	City	State
Kenya	Thika Clinic	Thika

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

Kenya, 

References & Publications (14)

Ahrendt HJ, Nisand I, Bastianelli C, Gómez MA, Gemzell-Danielsson K, Urdl W, Karskov B, Oeyen L, Bitzer J, Page G, Milsom I. Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. Contraception. 2006 Dec;74(6):451-7. Epub 2006 Sep 27. — View Citation

Atashili J, Poole C, Ndumbe PM, Adimora AA, Smith JS. Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS. 2008 Jul 31;22(12):1493-501. doi: 10.1097/QAD.0b013e3283021a37. Review. — View Citation

Baeten JM, Kahle E, Lingappa JR, Coombs RW, Delany-Moretlwe S, Nakku-Joloba E, Mugo NR, Wald A, Corey L, Donnell D, Campbell MS, Mullins JI, Celum C; Partners in Prevention HSV/HIV Transmission Study Team. Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Sci Transl Med. 2011 Apr 6;3(77):77ra29. doi: 10.1126/scitranslmed.3001888. — View Citation

Cohen CR, Lingappa JR, Baeten JM, Ngayo MO, Spiegel CA, Hong T, Donnell D, Celum C, Kapiga S, Delany S, Bukusi EA. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PLoS Med. 2012;9(6):e1001251. doi: 10.1371/journal.pmed.1001251. Epub 2012 Jun 26. — View Citation

Heffron R, Donnell D, Rees H, Celum C, Mugo N, Were E, de Bruyn G, Nakku-Joloba E, Ngure K, Kiarie J, Coombs RW, Baeten JM; Partners in Prevention HSV/HIV Transmission Study Team. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. Lancet Infect Dis. 2012 Jan;12(1):19-26. doi: 10.1016/S1473-3099(11)70247-X. Epub 2011 Oct 3. Erratum in: Lancet Infect Dis. 2012 Feb;12(2):98. — View Citation

Kiser PF, Johnson TJ, Clark JT. State of the art in intravaginal ring technology for topical prophylaxis of HIV infection. AIDS Rev. 2012 Jan-Mar;14(1):62-77. Review. — View Citation

Marrazzo JM, Martin DH, Watts DH, Schulte J, Sobel JD, Hillier SL, Deal C, Fredricks DN. Bacterial vaginosis: identifying research gaps proceedings of a workshop sponsored by DHHS/NIH/NIAID. Sex Transm Dis. 2010 Dec;37(12):732-44. doi: 10.1097/OLQ.0b013e3181fbbc95. — View Citation

Marrazzo JM, Thomas KK, Fiedler TL, Ringwood K, Fredricks DN. Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann Intern Med. 2008 Jul 1;149(1):20-8. — View Citation

Mugo NR, Heffron R, Donnell D, Wald A, Were EO, Rees H, Celum C, Kiarie JN, Cohen CR, Kayintekore K, Baeten JM; Partners in Prevention HSV/HIV Transmission Study Team. Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples. AIDS. 2011 Sep 24;25(15):1887-95. doi: 10.1097/QAD.0b013e32834a9338. — View Citation

Mugwanya K, Baeten JM, Mugo NR, Irungu E, Ngure K, Celum C. High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial. J Infect Dis. 2011 Dec 15;204(12):1912-7. doi: 10.1093/infdis/jir649. Epub 2011 Oct 12. — View Citation

Polis CB, Curtis KM. Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence. Lancet Infect Dis. 2013 Sep;13(9):797-808. doi: 10.1016/S1473-3099(13)70155-5. Epub 2013 Jul 19. Review. — View Citation

Taha TE, James MM, Hoover DR, Sun J, Laeyendecker O, Mullis CE, Kumwenda JJ, Lingappa JR, Auvert B, Morrison CS, Mofensen LM, Taylor A, Fowler MG, Kumenda NI, Eshleman SH. Association of recent HIV infection and in-utero HIV-1 transmission. AIDS. 2011 Jul 17;25(11):1357-64. doi: 10.1097/QAD.0b013e3283489d45. — View Citation

van der Straten A, Montgomery ET, Cheng H, Wegner L, Masenga G, von Mollendorf C, Bekker L, Ganesh S, Young K, Romano J, Nel A, Woodsong C. High acceptability of a vaginal ring intended as a microbicide delivery method for HIV prevention in African women. AIDS Behav. 2012 Oct;16(7):1775-86. — View Citation

Veres S, Miller L, Burington B. A comparison between the vaginal ring and oral contraceptives. Obstet Gynecol. 2004 Sep;104(3):555-63. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantity of L. crispatus determined by species-specific qPCR assay		Up to 8 months
Secondary	Rates of bacterial vaginosis during contraceptive ring uses		Up to 8 months
Secondary	Number of adverse events with CVR use		Up to 8 months
Secondary	Acceptability of CVR to male sex partners of study participants assessed by questionnaire		Up to 1 month

External Links

•   Medical Eligibility Criteria for contraceptive use - Executive Summary
•   WHO Hormonal contraceptive eligibility for women at high risk of HIV