A5338 P. G . MARIMBE-NYATSAMBO ANNUAL RESEARCH DAY 8 APRIL 2016

A5338 A Study of the Pharmacokinetic Interactions Among DMPA, Rifampicin , and Efavirenz in Women Co-Infected with HIV and TB

BACKGROUND TB remains the most common cause of morbidity in HIV infected patients in RLS A large percentage of patients on TB treatment also require cART Women are disproportionately burdened with HIV : globally (PLWHIV) 52% ; SSA 57% ; Zim 59.3% SSA, >50% of women who are on reversible contraception, opt for DMPA

BACKGROUND Unfortunately there is limited data regarding interactions of TB tmt, cART and DMPA Yet reliable contraception is crucial in HIV/TB coinfected women to avoid the increased risks of treating them if they fall pregnant

PRIMARY OBJECTIVES To estimate the optimal dosing frequency of DMPA for HIV and TB coinfected women taking EFV-based cART and RIF-containing TB treatment To determine whether a 150 mg DMPA IM injection will be adequate to suppress ovulation through 12 weeks in women taking EFV-based cART and RIF- containing TB treatment 1st objective being achieved by measuring MPA concentration which needs to be >0.1ng/ml. 2nd: measuring serial progesterone concentrations,which should remain< 5ng/ml

SECONDARY OBJECTIVES To estimate the area under the concentration-time curve (AUC), trough concentration (Cmin), maximum concentration (Cmax), apparent clearance (CL/F), and half-life (t1/2) of MPA To estimate the proportion of participants who maintain MPA levels above the minimum level thought to suppress ovulation through 12 weeks after DMPA administration. To evaluate the toxicity and safety of concurrent RIF, EFV, and DMPA use

EXPLORATORY OBJECTIVES To explore whether pharmacokinetic (PK) interactions between EFV, RIF, and/or DMPA are affected by human genetic polymorphisms that have been reported to affect metabolism of these drugs.   To explore whether there is a relationship between DMPA , body mass index (BMI) and body fat content over time. To explore relationship between DMPA and bone metabolism in the HIV and TB coinfected women. DMPA suppresses the pituitary-ovarian-uterine axis and consequently may result in a hypoestrogen state leading to bone resorption>bone formation resulting in low BMD

STUDY POPULATION Premenopausal women 18 to 46 years of age who are co-infected with HIV and TB. 46 evaluable participants ( 15 for Harare site)

PK SAMPLING DMPA will be given im as a single dose of 150mg at study entry PK blood samples will be collected pre-dose,then every 2 weeks thereafter All participants will be followed for 12 weeks.

WHO CAN BE ENROLLED? HIV infected on EFV-based cART for at least 28 days Active TB and currently receiving RIF + INH based TB therapy Regular menstrual cycles Reliable non-hormonal contraceptive method Meet laboratory requirements within 30 days prior to study entry NB: Should be enrolled within the 1st 4 weeks on continuation phase to allow adequate time to complete the required 12 weeks on study.

IMPORTANT EXCLUSION CRITERIA Receipt of DMPA OR any other injectable contraceptive within 180 days prior to entry Receipt of other hormonal contraceptives within 30 days prior to study entry Use of any drugs other than RIF/EFV known to either induce or inhibit the CYP3A4 system within 30 days prior to study entry

STUDY STATUS All IRB approvals received DAIDS registration done Study product on site Staff protocol training done Awaiting protocol activation

ACKNOWLEGEMENTS -ALL OUR STUDY PARTICIPANTS -COMMUNITY ADVISORY BOARD.