comparison of two intrauterine devices (iuds) among cape town hiv-positive women

Conditions: HIV

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.

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

Eligibility criteria:
inclusion criteria * willing and able to provide written informed consent (ic) to be screened for and to participate in the trial * interested and willing to use the intrauterine device (iud) as a family planning method. * between 18 to 40 years of age (inclusive): this age range includes women during their years of greatest fertility and 18 is the age of majority for research consent in south africa. * willing to participate in all aspects of the study and to comply with study procedures and visits, for 24 months, including: * be randomized * adhere to follow-up schedule and willing to be contacted by site staff between study visits (by phone and/or in person) * provide contact/locator information * agree for site staff to review clinic chart to confirm hiv status * has documented hiv infection * for pre-antiretroviral therapy (art) entrants: * art-ineligible at screening, based on current south african art guidelines * be at least 6 months post-delivery and not pregnant or desiring pregnancy for the next 30 months. * for art-using entrants: * art-use demonstrated by clinical records reflecting laboratory measures consistent with art use and evidence of viral suppression (plasma viral load (vl)\<1000 copies/ml) at the most recent vl measure. * be at least 6 weeks post-delivery and not pregnant or desiring pregnancy for the next 30 months. * intending residence in cape town area for next 30 months * no documented or known history of infertility or sterilization * no gross evidence of cervical neoplasia on examination * no prior history of ectopic pregnancy * no history of or suspected hormonally-dependent neoplasm or undiagnosed abnormal vaginal bleeding * local language fluency and comprehension * not participating in any other clinical trial with a biomedical intervention * have no condition that, based on the opinion of the site principal investigator (pi), would preclude provision of informed consent, make participation in the study unsafe, or complicate interpretation of data. 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

Keywords: ae adverse event aids acquired immunodeficiency syndrome alt (sgpt) alanine aminotransferase art antiretroviral therapy ast (sgot) aspartate aminotransferase dcf data collection forms dmc data monitoring committee fda (u.s.) food and drug administration gcp good clinical practice guidelines hb sag hepatitis b surface antigen ich international council for harmonization ind investigational new drug application irb institutional review board iu international units mg milligram(s) mm3 cubic millimeter(s) pcr polymerase chain reaction sae serious adverse event µg microgram uln upper limit of the normal range wb western blot