Comparison of Two Intrauterine Devices (IUDs) Among Cape Town HIV-positive Women

Not Applicable

Completed

Conditions: HIV

Interventions: Device: Copper T-380a IUD
Device: Mirena levonorgestrel IUD

Registration Number: NCT01721798

Lead Sponsor: FHI 360

Brief Summary: This study will inform international medical guidelines as to whether the Levonorgestrel intrauterine device (LNG IUD), a highly effective long-acting reversible contraceptive method, is safe and acceptable as compared to the copper intrauterine device (C-IUD) for HIV-positive women in Cape Town, South Africa. If the LNG IUD is found to be safe and acceptable, the introduction of this method to HIV positive women in developing countries could significantly reduce unplanned pregnancy and mother-to-child transmission of HIV, and confer non-contraceptive benefits to HIV-positive women in Sub-Saharan Africa.

Detailed Description: Design: Single site, double-blind, randomized controlled trial

Population: HIV-positive South African women between the ages of 18 and 40 years

Study size: At least 166 women

Study intervention: Levonorgestrel intrauterine device (LNG IUD) or the copper T-380 intrauterine device (C-IUD)

Duration \& Follow-up: Approximately 48 months in total. Recruitment will take approximately 24 months. After enrollment, each participant will be followed for 24 months.

Primary Objectives: To compare LNG IUD safety to the safety of the C-IUD with respect to genital HIV shedding, a surrogate for potential for HIV transmission, overall and in the presence and absence of antiretroviral therapy (ART).

Secondary Objectives: 1) To compare LNG IUD safety to the safety of the C-IUD with respect to HIV progression as measured by changes in plasma viral load (VL) at 6 months between the two pre-ART study arms. 2) To explore LNG IUD safety with respect to non-HIV related outcomes, including hemoglobin change, incidence of sexually-transmitted infections (STIs) and pelvic inflammatory disease (PID). 3) To measure LNG IUD acceptability through device continuation and other measures for the LNG IUD as compared to the C-IUD. 4) To compare three genital tract sampling methods to determine which provides optimal recovery of HIV RNA and immune mediators over a series of three visits.

Primary Endpoints: Change in detection and quantity of HIV ribonucleic acid (RNA) genital VL measures between study arms at baseline and 6 months, and over 24 months following IUD insertion.

Secondary Endpoints: 1) Measures of HIV disease progression, including CD4 change, time to ART initiation, and mean plasma VL change from baseline to 6 and through 24 months among pre-ART women. 2) Hemoglobin change and incidence of STIs and PID for all participants through 24 months. 3) IUD continuation and expulsion rates between study arms comparing different IUDs over a 24-month period and acceptability measures through quantitative and qualitative methods. 4) Comparison of female genital tract sampling methods for recovery of HIV RNA as measured by VL and immune mediators (e.g. cytokines).

Study Site: Gugulethu Community Health Centre (GCHC), Cape Town, South Africa

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 199

Inclusion Criteria

Not provided

Exclusion Criteria

Known congenital or acquired uterine anomaly including fibroids distorting the uterine cavity;
Known acute liver disease or hepatic neoplasm;
Known copper storage disease;
Known hypersensitivity to any component of the levonorgestrel IUD (LNG IUD) or copper IUD (C-IUD) or latex allergy
Pregnant or desiring pregnancy in next 24 months
Gross cervical lesion concerning for neoplasia
CD4 lymphocyte count<350 cells/mm3 if not using ART
Less than 6 weeks postpartum

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Copper T-380a Intrauterine Device (C-IUD)	Copper T-380a IUD	Copper T-380A Intrauterine Device with approximately 380 mm2 exposed copper. Devices used were those included as part of the South African public sector health formulary.
Levonorgestrel IUD (LNG-IUD)	Mirena levonorgestrel IUD	Levonorgestrel IUD containing 52 mg levonorgestrel registered for contraceptive use in South Africa at the time of the trial.

Primary Outcome Measures

Name	Time	Method
Participants With Detectable Genital Tract HIV Ribonucleic Acid (RNA) Viral Load (VL)	Enrollment to 24 months	Number of women with detectable genital tract HIV RNA as measured with menstrual cup sampling at each scheduled visit. Level of detection was 20-40 copies/mL depending on assay; outcome was dichotomous with copies above level of detection coded as detectable and those below level of detection considered undetectable.

Secondary Outcome Measures

Name	Time	Method
Mean Hemoglobin Concentration as Part of Intrauterine Contraceptive Safety	Enrollment to 24 months	Participant hemoglobin measured at baseline, 6, 12, 18, and 24 months with blood sample with mean hemoglobin calculated and trends over time assessed. Other safety measures were included with this secondary outcome, such as adverse events, summarized with descriptive statistics.
HIV Ribonucleic Acid (RNA) Concentration by Lower Female Genital Tract Sampling Method	6 months	Proportion of specimens with quantifiable genital viral load compared by specific sampling method (menstrual cup, endocervical swab, and swab-enriched lavage) at enrollment, 3 months and 6 months among women not using antiretroviral therapy (ART). Allocated intrauterine device (IUD) was not considered in this analysis.
Participants With Detectable Plasma HIV Ribonucleic Acid (RNA) Viral Load Among Those Using Antiretroviral Therapy (ART)	Enrollment to 24 months	The proportion of women using ART at enrollment with detectable plasma HIV RNA viral load. Viral load assays detected HIV RNA levels at 20-40 copies/mL as the lower limit of detection. The outcome measure coded values above that limit as detectable and those below as undetectable for women using ART and in mean viral load for women not using ART.
Participants Continuing Use of the Allocated Intrauterine Device (IUD)	Enrollment to 24 months	Measure of the number of women continuing to use the allocated intrauterine device (IUD) across all visits as a measure of acceptability. Proportion of women using the allocated IUD measured at each scheduled visit with time using the IUD adjusted for discontinuation at unscheduled visits. Continuation rate analyzed longitudinally with Kaplan-Meier survival analysis.