Concomitant use of LNG (150 mg) and NVP-based ART (NVP 200 mg twice daily plus 2 NRTIs) resulted in increased LNG plasma concentrations. However, investigators indicated that this difference was potentially due to different baseline weights (69.0 (90% CI 58.5-86.5) in ART-naïve group vs 59.5 (90% CI 54.3 - 69.8) in NVP-based ART group).
Nevirapine vs levonorgestrel
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Study Design
This was a non-randomized, parallel group, pharmacokinetic (PK) study in HIV-infected female in Uganda. Levonorgestrel (LNG) implants (2 rods; 75 mg/rod) were inserted at baseline in both ART-naïve group (n=17) and nevirapine (NVP) -based ART group (NVP 200 mg twice daily plus two NRTIs; n=20). Blood samples for PK analysis were collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was LNG concentrations at week 24.
Study Results
The geometric mean ratios (GMRs; NVP+LNG / LNG) [90% CIs] of LNG were 1.35 [1.29, 1.43] for AUC.
References
Kimberly K Scarsi, Kristin M Darin, Shadia Nakalema, David J Back, Pauline Byakika-Kibwika, Laura J Else, Sujan Dilly Penchala, et al. Unintended pregnancies observed with combined use of the levonorgestrel contraceptive implant and efavirenz-based antiretroviral therapy: a three-arm pharmacokinetic evaluation over 48 weeks. Clinical Infectious Diseases. 2016; 6: 675-682.
NVP Vs. levonorgestrel
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Study Design
The authors included 60 HIV-positive implant users enrolled in the Partners PrEP Study in Kenya and Uganda. Blood samples were collected at 6-month intervals and antiretroviral therapy (ART) initiation was self-reported. We measured serum LNG and ENG concentrations using liquid chromatography- tandem mass spectrometry and genotyped 18 variants in CYP2B6, CYP2A6, CYP3A4, CYP3A5, NR1I2 and ABCB1. We used linear mixed models to calculate geometric mean ratios (GMRs) comparing post-ART to pre-ART progestin concentrations, and to assess for interactions between ART group and allele variants. Multivariable models adjusted for age, nationality, body mass index, closest HIV viral load, days from ART initiation, and implant type
Study Results
They found that EFV- and nevirapine (NVP)-containing regimens were initiated by 11 and 13 women during the study, respectively; 36 women did not initiate ART and therefore contributed only pre-ART initiation data. In multivariable models, geometric mean serum LNG and ENG concentrations were 61% and 49% lower with EFV use compared to pre-ART initiation, respectively (LNG GMR=0.39,
95% CI: 0.31-0.49; ENG GMR=0.51, 95% CI: 0.34-0.76). GMRs of EFV use vs. pre-ART initiation progestin concentrations were lower with CYP3A5 rs776746 (p=0.009), CYP3A5 rs41303343 (p=0.002), CYP2B6 rs28399499 (p=0.001), and ABCB1 rs1045642 (p<0.001) allele variants relative to the wildtype (Table 1). They found no significant differences in LNG or ENG concentrations, or interactions between ART group and allele variants, with NVP use.
Study Conclusions
The authors concluded that the use of EFV but not NVP resulted in lower LNG and ENG concentrations among implant users, and polymorphisms in CYP450 enzyme (CYP3A5 and CYP2B6) and ATP-binding cassette transporter (ABCB1) genes resulted in greater decreases, suggesting a modulating role of genetics
References
Baeten, J, Scarsi, K, Tamraz, B, Thomas, K, Erikson, D, Lingappa, J, etc.. Pharmacokinetic and pharmacogenetic assessment of art and contraceptive implants. Conference On Retroviruses And Opportunistic Infections. 2019; : .
Nevirapine vs levonorgestrel
^
Study Design
This was a non-randomized, parallel group, pharmacokinetic (PK) study in HIV-infected female in Uganda. Levonorgestrel (LNG) implants (2 rods; 75 mg/rod) were inserted at baseline in both ART-naïve group (n=17) and nevirapine (NVP) -based ART group (NVP 200 mg twice daily plus two NRTIs; n=20). Blood samples for PK analysis were collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was LNG concentrations at week 24.
Study Results
The geometric mean ratios (GMRs; NVP+LNG / LNG) [90% CIs] of LNG were 1.35 [1.29, 1.43] for AUC.
References
Baeten, J, Scarsi, K, Tamraz, B, Thomas, K, Erikson, D, Lingappa, J, etc.. Pharmacokinetic and pharmacogenetic assessment of art and contraceptive implants. Conference On Retroviruses And Opportunistic Infections. 2019; : .
Nevirapine vs levonorgestrel
^
Study Design
This was a non-randomized, parallel group, pharmacokinetic (PK) study in HIV-infected female in Uganda. Levonorgestrel (LNG) implants (2 rods; 75 mg/rod) were inserted at baseline in both ART-naïve group (n=17) and nevirapine (NVP) -based ART group (NVP 200 mg twice daily plus two NRTIs; n=20). Blood samples for PK analysis were collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was LNG concentrations at week 24.
Study Results
The geometric mean ratios (GMRs; NVP+LNG / LNG) [90% CIs] of LNG were 1.35 [1.29, 1.43] for AUC.
References
Baeten, J, Scarsi, K, Tamraz, B, Thomas, K, Erikson, D, Lingappa, J, etc.. Pharmacokinetic and pharmacogenetic assessment of art and contraceptive implants. Conference On Retroviruses And Opportunistic Infections. 2019; : .
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