Summary
Efavirenz induction of CYP3A4 causes a decrease in concentration of Etonogestrel in women using implanted and vaginal hormonal contraceptives. Larger decreases in Etonogestrel concentrations are noted in patients who are CYP2B6 slow metabolizers given that this is the main metabolizing pathway of Efavirenz. Caution is warranted when administering hormonal vaginal and implanted contraceptives with Efavirenz, especially in patients who are known CYP2B6 slow metabolizers. Alternative contraceptive methods should be considered.
Sources
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
References
Kreitchman, Stek, Best, Capparelli. Interaction between etonogestrel-releasing implant and 3 antiretroviral regimens [abstract]. Conference On Retroviruses And Opportunistic Infections. Seattle, WA, USA. 2017; February 2017.
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
References
Scarsi, K, Cramer, S, Gingrich, D. Vaginal contraceptive hormone exposure profoundly altered by efv- and atv/r-based art. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
References
Scarsi, K, Cramer, S, Gingrich, D. Vaginal contraceptive hormone exposure profoundly altered by efv- and atv/r-based art. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
References
Scarsi, K, Cramer, S, Gingrich, D. Vaginal contraceptive hormone exposure profoundly altered by efv- and atv/r-based art. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
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; : .
EFV Vs. Etonorgestrel
^
Study Design
They 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
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 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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
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; : .
EFV Vs. Etonorgestrel
^
Study Design
They 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
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 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; : .
Efavirenz versus Etonogestrel
^
Study Design
This study enrolled women living with HIV in Africa, Asia, South America
and the US into one of three groups: controls (not on anti-retroviral therapy), Efavirenz (EFV) group (600mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), and Atazanavir (ATV)/Ritonavir (RTV) group (300/100mg daily with NRTIs). On day 0, a vaginal ring (VR) was inserted, releasing Etonogestrel (ENG)/Ethinyl Estradiol (EE) 120/15 mcg/day. On days 0 (pre-VR) and 21 (during VR), Pharmacokinetic sampling for EFV, ATV and RTV was done. On days 7, 14 and 21, single plasma samples for ENG and EE analysis were obtained. 27 single nucleotide polymorphisms (SNPs) were genotyped, including 3 that define CYP2B6 normal, intermediate and slow metabolizers, CYP3A4/5, UGT1A1 and CYP1A1/2 SNPs, and estrogen trait-associated SNPs.
Study Results
In the EFV group, CYP2B6 genotype predicted lower day 21 ENG (p=1.7E-3). Compared to controls, EFV reduced median day 21 ENG concentrations by ~75% in CYP2B6 normal and intermediate metabolizers but by at least 93% in slow metabolizers.
Study Conclusions
CYP2B6 slow metabolizer genotype worsens the PK interaction of EFV with ENG administered by VR, likely due to higher EFV concentrations given that CYP2B6 is the main metabolizing pathway for EFV. Altering EFV dosing based on CYP2B6 genotype may reduce, but likely not eliminate, the impact of EFV on ENG.
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; : .
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
Efavirenz versus Etonogestrel
^
Study Design
This was a non-blinded international study of ARV PK in pregnancy and postpartum. N=12 post-partum women who desired to use etonogestrel (ENG) implant while subsequently taking ARV regimens for at least 2 weeks. PK sampling was taken before 6 to 7 weeks after insertion.
Study Results
Etonogestrel concentrations were determined in two groups of HIV+ women (n=15) using an etonogestrel implant either with efavirenz or with no antiretroviral therapy. Etonogestrel AUC, Cmax and Cmin were decreased by 63%, 54%, and 70%, respectively in the presence of efavirenz, which could impair the etonogestrel implant efficacy.
Study Conclusions
Per the authors, co-administration of efavirenz and ENG greatly decreased ENG levels therefore exhibiting a potential to impair contraceptive efficacy. Although there was no change in EFV exposure the two should not be used concomitantly due to its impact on ENG levels.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
Efavirenz versus Etonogestrel
^
Study Design
A vaginal ring releasing Etonogestrel/Ethinyl Estradiol (ENG/EE 120/15 mcg/day) was inserted at entry in three groups of participants: (1) not yet receiving Antiretroviral Therapy (ART, control group; n=25); (2) ART containing efavirenz (EFV) 600mg daily (EFV group; n=25); (3) ART containing Atazanavir/Ritonavir (ATV/r) 300/100mg daily (ATV/r group; n=24). Participants returned on days 7, 14, and 21 for single measurements of ENG and EE PK, assessed by a validated LC/MS/MS method. Plasma hormone PK exposure was compared between each ART group and the control group at each visit by geometric mean ratio (GMR) with 90% CI, and by Wilcoxon-rank sum at the primary endpoint (day 21).
Study Results
Compared to the control group, participants in the EFV group had 76-79% lower ENG and 53-57% lower EE over 21 days (all p<0.001). In contrast, participants in the ATV/r group had 71-79% higher ENG (all p<0.001), yet 29-35% lower EE (p=0.066, 0.032 and 0.004 for days 7, 14 and 21, respectively) over 21 days compared to the control group. The GMR (90% CI) for ENG and EE concentrations for EFV: Control at Day 21 were 0.24 (0.18-0.32) and 0.43 (0.33-0.57) respectively.
Study Conclusions
Women on EFV-based ART should consider an alternative contraception method or barrier contraception in addition to the vaginal ring until the clinical relevance of these PK changes is better understood.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
EFV Vs. Etonorgestrel
^
Study Design
They 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
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 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
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
Efavirenz versus Etonogestrel
^
Study Design
This study enrolled women living with HIV in Africa, Asia, South America
and the US into one of three groups: controls (not on anti-retroviral therapy), Efavirenz (EFV) group (600mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), and Atazanavir (ATV)/Ritonavir (RTV) group (300/100mg daily with NRTIs). On day 0, a vaginal ring (VR) was inserted, releasing Etonogestrel (ENG)/Ethinyl Estradiol (EE) 120/15 mcg/day. On days 0 (pre-VR) and 21 (during VR), Pharmacokinetic sampling for EFV, ATV and RTV was done. On days 7, 14 and 21, single plasma samples for ENG and EE analysis were obtained. 27 single nucleotide polymorphisms (SNPs) were genotyped, including 3 that define CYP2B6 normal, intermediate and slow metabolizers, CYP3A4/5, UGT1A1 and CYP1A1/2 SNPs, and estrogen trait-associated SNPs.
Study Results
In the EFV group, CYP2B6 genotype predicted lower day 21 ENG (p=1.7E-3). Compared to controls, EFV reduced median day 21 ENG concentrations by ~75% in CYP2B6 normal and intermediate metabolizers but by at least 93% in slow metabolizers.
Study Conclusions
CYP2B6 slow metabolizer genotype worsens the PK interaction of EFV with ENG administered by VR, likely due to higher EFV concentrations given that CYP2B6 is the main metabolizing pathway for EFV. Altering EFV dosing based on CYP2B6 genotype may reduce, but likely not eliminate, the impact of EFV on ENG.
References
Hass, D, Cramer, YS, Godfrey, C, et al.. Pharmacogenetics worsens an adverse antiretroviral hormonal contraceptive interaction. Conference On Retroviruses And Opportunistic Infections. Seattle . ; March 2019.
icon on your home screen.