Abstract 514LB: PK Study of Depot Medroxyprogesterone Acetate in HIV+ Women On Lopinavir/Ritonavir: ACTG 5283
Background: Little is known about use of depot medroxyprogesterone acetate (MPA) with boosted-protease inhibitors (PIs), a commonly used antiretroviral treatment regimen. Interactions with boosted PIs could lead to changes in efficacy or toxicity of any of these drugs. Methodology: We prospectively determined the effect of twice daily lopinavir (LPV) 400mg/ritonavir (RTV) 100 mg along with 2 or more nucleoside reverse transcriptase inhibitors (NRTIs) on the PK exposure of MPA through every 2 week sampling from baseline (day 0) to week 12 (AUC 0 to 12wk) (Wilcoxon rank-sum test). We also determined the effect of MPA on the PK of LPV and RTV using AUC for LPV and RTV at baseline and after 4 weeks of depot MPA using intensive PK sampling at pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hours post-LPV/r dosing (Wilcoxon signed-rank test). Safety and toxicity of depot MPA and ovulation suppression (using progesterone levels of <5ng/mL) were assessed biweekly during the 12-week study, and were compared with 14 HIV+ control subjects not on HIV meds or only NRTIs, previously enrolled in A5093, who received depot MPA with identical assessments. All MPA assays were performed by PPD, Inc. Results: 24 evaluable women on LVP/RTV were enrolled; 58% were black, 25% Hispanic and 13% white; median age 32 years; median CD4 622 cells/ mm3; all had HIV RNA<400 copies/mL and negative pregnancy tests. Of the 14 historical controls, 79% were black, 14% Hispanic, and 7% white; median age 33 years. No women appeared to ovulate during the study and there were no pregnancies. MPA concentrations (median AUC0-12wk 18.08 ng*week/mL) were higher than the 14 A5093 controls (median AUC0-12wk 12.38 ng*week/mL) (p<0.001). There were no changes in the LPV/RTV levels after depot MPA (see table below). In this study, possible treatment-related toxicities occurred in 8 (33%) subjects, the most frequent being vaginal bleeding (8), and irritability (2). These side effects are similar to those described with use of DMPA (http://www.accessdata.fda.gov/drugsatfda_docs/ label/2010/020246s036lbl.pdf). Conclusions: MPA levels were significantly higher in HIV-infected women taking ritonavir-boosted lopinavir compared to HIV-infected women on no HIV medications or NRTIs alone. Levels of LPV and RTV were not altered by depot MPA and there was no evidence of ovulation through week 12. Depot MPA was well-tolerated despite having AUC levels 46% higher compared to historical controls, and side effects were similar to those reported in women on depot MPA.
Cohn, SE; Luque, AE; Park, JG; Cramer, Y; Aweeka, F; Weinberg, A; Livingston, E; Klingman, KL; Bastow, B; Watts, H
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