Efavirenz decreases exposure to hormonal contraceptive implant

Polly Clayden, HIV i-Base

Efavirenz (EFV) significantly decreases exposure to levonorgestrol – the active progesterone component of one commonly used contraceptive implant – according to findings from a study conducted in Uganda, presented at the HIV Drug Therapy Glasgow Congress 2014.

The study showed levonorgestral concentrations in women receiving EFV-based antiretroviral treatment (ART) that were approximately half of those in women not receiving ART, despite the EFV group having significantly lower body weight. But concentrations of levonorgestral in women receiving nevirapine (NVP)-based ART were approximately one third higher than the control group.

Kimberly Scarsi presented these findings on behalf of investigators from University of Nebraska Medical Center, Makerere University, Uganda, and Liverpool University.

Both EFV and NVP induce cytochrome P450 3A, giving the potential for drug-drug interactions with concomitant medications.

The aim of the study is to characterise the pharmacokinetics (PK) of levonorgestrol released from a sub-dermal implant over six months in HIV positive Ugandan women receiving EFV- or NVP-based ART. Interim 24-week data were presented at the conference.

The study is a non-randomised, parallel group study that compares levonorgestrol PK in Ugandan women not yet eligible for ART (control group, n=17) and on stable EFV- (n=20) or NVP- (n=20) based ART.

The women had a two-rod (75 mg/rod) levonorgestrol sub-dermal implant inserted at enrolment. Sampling for PK was performed before the implant and at weeks 1, 4, 12 and 24 after insertion. The investigators used a validated LC-MS/MS method, with an assay calibration range of 50-1500 pg/mL to analyse levonorgestrol concentrations.

At baseline, participants were a mean age of 31 years; CD4 counts were similar between the control, EFV and NVP groups. All women receiving ART were virologically suppressed. Women in the control group had a higher baseline body weight (73 kg) compared to those in the EFV group (59 kg), p<0.01, or NVP (63 kg), p=0.03, groups.

At week 24 the EFV:control and NVP:control AUC 0-24 ng*wk/mL geometric mean ratios were respectively: 0.56 (90% CI 0.55 – 0.58) and 1.23 (90% CI 1.18-1.31), both p<0.01.

Adjusted for weight these values were: 0.47 (90% CI 0.45 – 0.50) and 1.09 (90% CI 1.02 -1.20).

Dr Scarsi noted that in the EFV group, three participants had levonorgestrol concentrations below the proposed level for contraceptive efficacy at two time points. All participants receiving NVP had concentrations above the proposed level for efficacy and no adverse events were observed in this group.

She concluded that levonorgestrol concentrations were reduced by 40-54% over 24 weeks in women receiving EFV-based ART. Conversely women receiving NVP-based ART had consistently higher concentrations by 32-39%, although the increase was less pronounced after controlling for body weight, which gave a 16-21% increase.

“Identifying an effective strategy to provide hormonal contraception options for women receiving EFV-based ART remains a critical public health priority”, she said.


Scarsi K et al. Efavirenz- but not nevirapine-based antiretroviral therapy decreases exposure to the levonorgestrel released from a sub-dermal contraceptive implant. HIV Drug Therapy Glasgow Congress, 2-6 November 2014. Oral abstract 0131. Journal of the International AIDS Society 2014, 17(Suppl 3):19484.

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