Long acting reversible contraceptives are highly efficacious and used to prevent unplanned pregnancies in HIV infected women worldwide. There are limited data on pharmacokinetic (PK) interactions between the etonogestrel releasing implant (ENG) and antiretroviral therapy. We evaluated both the effect of ENG on the PK parameters of 3 highly active antiretroviral (ARV) regimens including: ritonavir boosted atazanavir (ATV/r), ritonavir boosted lopinavir (LPV/r) or efavirenz (EFV) and the effect of these antiretrovirals on ENG levels in HIV infected postpartum women.
IMPAACT P1026s is an ongoing, non-blinded international study of ARV PK in pregnancy and postpartum. We enrolled postpartum women who desired to use ENG implants and were taking ATV/r, LPV/r, or EFV-based regimens for at least 2 weeks. ENG implant was inserted between 2 and 12 weeks postpartum. PK sampling was performed before and 6 to 7 weeks after insertion. ARV and ENG concentrations (conc) were measured using liquid chromatography-mass spectrometry. The P1026s target minimum AUC for ATV, LPV and EFV were 29.4, 52 and 40 μg*hr/mL (10th percentile in non-pregnant historical controls), respectively. Median (range) ENG conc within the first few weeks of use in women not receiving ARV’s is 400 pg/mL (250-500 pg/mL). ENG conc >90 pg/mL is believed to reliably suppress ovulation.
PK data are available for 62 postpartum women (6 Black, 49 Hispanic, 7 Asian). Median (range) age at enrollment was 26.9 (15.8-41.1) yr, weight 62.7 (38.7-157.9) kg, median duration of LPV/r, ATV/r and EFV use before implant insertion was 30.0, 32.1 and 4.4 weeks, respectively. Median CD4 was 584/mm3 (79-1578) in 61 women and VL was <400 in 40/54 women (74.1%) before ENG initiation. Table 1 presents ENG concentrations and ARV AUCs among these three arms. Median ENG conc of EFV arm was <10% of the other two arms. ARV AUCs before and after ENG insertion did not differ significantly. Proportions of women meeting ARV PK targets before and after ENG insertion were: 77% and 66% for ATV/r, 84% and 84% for LPV/r and 90% and 81% for EFV (p=0.73).
No significant change in ATV/r, LPV/r and EFV exposure was seen after ENG insertion. EFV use was associated with greatly decreased ENG conc to levels that may impair contraceptive efficacy. Co-administration of LPV/r and ATV/r with ENG resulted in adequate ENG conc, suggesting that these combinations should have no impact on implant efficacy.