Summary
The use of EFV causes decreased concentration of levonorgestrel. Increasing LNG concentrations from 150 mg to 300 mg led to reduced lowering of LNG concentrations in patients on EFV-based ART. However, there is still a reduction in LNG concentrations compared to ART-naive patients. Hence, caution should be exercised by women on LNG based contraceptives receiving EFV-based ART. Moreover, it is recommended that women taking EFV should use second method of contraceptive to prevent pregnancy.
Sources
Efavirenz versus Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
References
Carten ML, Kiser JJ, Kwara A, Mawhinney S, Cu-Uvin S. Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel (plan b), and efavirenz. Infectious Diseases In Obstetrics And Gynecology. 2012; : 1-4.
EFV Vs. Levonorgestrel
^
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 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; : .
Efavirenz versus Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
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 Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
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 Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
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 Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
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. Levonorgestrel
^
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 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; : .
Efavirenz versus Levonorgestrel
^
Study Design
A previous study showed 57% lower levonorgestrel (LNG) exposure in women receiving the LNG subdermal implant (150mg) with efavirenz (EFV)-based antiretroviral therapy (ART) compared to ART-naïve women. In this study, researchers aimed to overcome this interaction by doubling the LNG dose to LNG 300mg over 48 weeks in women receiving EFV-based. Ugandan women (n=28) on EFV-based ART with an undetectable HIV-RNA received LNG implants (300 mg), one in each arm, and a copper intrauterine device were placed at entry. Controls were ART-naive Ugandan women (n=17) who received a standard-dose (150mg) LNG implant at entry. Plasma was collected at 1, 4, 12, 24, 36, and 48 weeks. LNG concentrations were analyzed by a LC-MS/MS, summarized as median (IQR), and compared between groups by geometric mean ratio (GMR) with 90% CI.
Study Results
After 48 weeks, LNG concentrations were GMR 373 (CI 319, 540) pg/mL in the Double LNG group versus 651 (469, 879) pg/mL in the control group [GMR (90% CI) 0.66 (0.61, 0.72)]. During
the study, 18% (n=3) in the control group and 46% (n=13) in the Double LNG group had any LNG value ≤303 pg/mL (p=0.06).
Study Conclusions
Researchers observed 33-44% lower LNG concentrations over 48 weeks
in women receiving EFV-based ART plus LNG 300mg implants compared to ART-naive women on LNG 150mg implants. Relative to the prior study, the magnitude of the interaction with EFV at week 48 was smaller with double-dose LNG (34% lower) vs standard-dose LNG (57% lower). Also, fewer
women receiving EFV-based ART had an LNG ≤ 303 pg/mL in the double- vs standard-dose group (46% vs 90%, respectively; p=0.002). However, doubling the dose of LNG implants does not fully overcome the interaction with EFV, and the contraceptive effectiveness of this approach remains uncertain.
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 Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
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 Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
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. Levonorgestrel
^
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 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; : .
Efavirenz versus Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
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 Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
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. Levonorgestrel
^
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 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; : .
Efavirenz versus Levonorgestrel
^
Study Design
A previous study showed 57% lower levonorgestrel (LNG) exposure in women receiving the LNG subdermal implant (150mg) with efavirenz (EFV)-based antiretroviral therapy (ART) compared to ART-naïve women. In this study, researchers aimed to overcome this interaction by doubling the LNG dose to LNG 300mg over 48 weeks in women receiving EFV-based. Ugandan women (n=28) on EFV-based ART with an undetectable HIV-RNA received LNG implants (300 mg), one in each arm, and a copper intrauterine device were placed at entry. Controls were ART-naive Ugandan women (n=17) who received a standard-dose (150mg) LNG implant at entry. Plasma was collected at 1, 4, 12, 24, 36, and 48 weeks. LNG concentrations were analyzed by a LC-MS/MS, summarized as median (IQR), and compared between groups by geometric mean ratio (GMR) with 90% CI.
Study Results
After 48 weeks, LNG concentrations were GMR 373 (CI 319, 540) pg/mL in the Double LNG group versus 651 (469, 879) pg/mL in the control group [GMR (90% CI) 0.66 (0.61, 0.72)]. During
the study, 18% (n=3) in the control group and 46% (n=13) in the Double LNG group had any LNG value ≤303 pg/mL (p=0.06).
Study Conclusions
Researchers observed 33-44% lower LNG concentrations over 48 weeks
in women receiving EFV-based ART plus LNG 300mg implants compared to ART-naive women on LNG 150mg implants. Relative to the prior study, the magnitude of the interaction with EFV at week 48 was smaller with double-dose LNG (34% lower) vs standard-dose LNG (57% lower). Also, fewer
women receiving EFV-based ART had an LNG ≤ 303 pg/mL in the double- vs standard-dose group (46% vs 90%, respectively; p=0.002). However, doubling the dose of LNG implants does not fully overcome the interaction with EFV, and the contraceptive effectiveness of this approach remains uncertain.
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 vs Double Dose Levonorgestrel
^
Study Design
This was a pharmacokinetic evaluation of double-dose (300mg) LNG
implants in Ugandan women receiving EFV-based ART with an undetectable
HIV-RNA (DoubLNG group; n=28). LNG implants, one in each arm, and a copper
intrauterine device were placed at entry. Historical controls were ART-naïve
Ugandan women (n=17) who received a standard-dose (150mg) LNG implant at
entry. Plasma was collected at 1, 4, 12, 24, 36, and 48 weeks. LNG concentrations
were analyzed by a validated LC-MS/MS method (range 50-1500 pg/mL),
summarized as median (IQR), and compared between groups by geometric
mean ratio (GMR) with 90% CI. The proportion with LNG ≤303 pg/mL were
compared by Fisher’s Exact test.
Study Results
All women were Black African. The DoubLNG group had a median age
of 33 years and median weight of 58 kg; the control group was 29 years and 69
kg, respectively. The Table summarizes LNG results by visit. After 48 weeks, LNG
concentrations were 373 (319, 540) pg/mL in the DoubLNG group versus 651
(469, 879) pg/mL in the control group [GMR (90% CI) 0.66 (0.61, 0.72)]. During
the study, 18% (n=3) in the control group and 46% (n=13) in the DoubLNG
group had any LNG value ≤303 pg/mL (p=0.
Study Conclusions
We observed 33-44% lower LNG concentrations over 48 weeks
in women receiving EFV-based ART plus LNG 300mg implants compared
to ART-naïve women on LNG 150mg implants. Relative to our prior study,
the magnitude of the interaction with EFV at week 48 was smaller with
double-dose LNG (34% lower) vs standard-dose LNG (57% lower). Also, fewer
women receiving EFV-based ART had an LNG ≤303 pg/mL in the double- vs
standard-dose group (46% vs 90%, respectively; p=0.002). Doubling the dose
of LNG implants does not fully overcome the interaction with EFV, and the
contraceptive effectiveness of this approach remains uncertain.
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 Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
References
Scarsi, SS, Cirrincione, L, Nakalema, S, et al.. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections. Seattle. ; March 2019.
Efavirenz versus Levonorgestrel
^
Study Design
A previous study showed 57% lower levonorgestrel (LNG) exposure in women receiving the LNG subdermal implant (150mg) with efavirenz (EFV)-based antiretroviral therapy (ART) compared to ART-naïve women. In this study, researchers aimed to overcome this interaction by doubling the LNG dose to LNG 300mg over 48 weeks in women receiving EFV-based. Ugandan women (n=28) on EFV-based ART with an undetectable HIV-RNA received LNG implants (300 mg), one in each arm, and a copper intrauterine device were placed at entry. Controls were ART-naive Ugandan women (n=17) who received a standard-dose (150mg) LNG implant at entry. Plasma was collected at 1, 4, 12, 24, 36, and 48 weeks. LNG concentrations were analyzed by a LC-MS/MS, summarized as median (IQR), and compared between groups by geometric mean ratio (GMR) with 90% CI.
Study Results
After 48 weeks, LNG concentrations were GMR 373 (CI 319, 540) pg/mL in the Double LNG group versus 651 (469, 879) pg/mL in the control group [GMR (90% CI) 0.66 (0.61, 0.72)]. During
the study, 18% (n=3) in the control group and 46% (n=13) in the Double LNG group had any LNG value ≤303 pg/mL (p=0.06).
Study Conclusions
Researchers observed 33-44% lower LNG concentrations over 48 weeks
in women receiving EFV-based ART plus LNG 300mg implants compared to ART-naive women on LNG 150mg implants. Relative to the prior study, the magnitude of the interaction with EFV at week 48 was smaller with double-dose LNG (34% lower) vs standard-dose LNG (57% lower). Also, fewer
women receiving EFV-based ART had an LNG ≤ 303 pg/mL in the double- vs standard-dose group (46% vs 90%, respectively; p=0.002). However, doubling the dose of LNG implants does not fully overcome the interaction with EFV, and the contraceptive effectiveness of this approach remains uncertain.
References
Scarsi, SS, Cirrincione, L, Nakalema, S, et al.. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections. Seattle. ; March 2019.
EFV Vs. Levonorgestrel
^
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 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
Scarsi, SS, Cirrincione, L, Nakalema, S, et al.. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections. Seattle. ; March 2019.
Efavirenz versus Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
References
Scarsi, SS, Cirrincione, L, Nakalema, S, et al.. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections. Seattle. ; March 2019.
Efavirenz versus Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
References
Scarsi KK, Cirrincione L, Nakalema S, Darin K, Musinguzi I. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections . Seattle, WA. 2019; March 2019.
Efavirenz versus Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
References
Scarsi KK, Cirrincione L, Nakalema S, Darin K, Musinguzi I. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections . Seattle, WA. 2019; March 2019.
Efavirenz versus Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
References
Scarsi KK, Cirrincione L, Nakalema S, Darin K, Musinguzi I. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections . Seattle, WA. 2019; March 2019.
EFV Vs. Levonorgestrel
^
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 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
Scarsi KK, Cirrincione L, Nakalema S, Darin K, Musinguzi I. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections . Seattle, WA. 2019; March 2019.
EFV Vs. Levonorgestrel
^
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 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
Scarsi KK, Cirrincione L, Nakalema S, Darin K, Musinguzi I. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections . Seattle, WA. 2019; March 2019.
Efavirenz versus Levonorgestrel
^
Study Design
A pharmacokinetic (PK) evaluation of the interaction between efavirenz (EFV) and levonorgestrel (LNG) was evaluated in a longitudinal, parallel group study among HIV-infected Ugandan women. A standard dose LNG subdermal implant was inserted at entry into two groups: the control group, comprised of participants not yet eligible to start antiretroviral therapy (ART; n=17), and a second group whose partipants had an undetectable viral load and were taking efavirenz/emtricitabine/tenofovir (n=20).
All participants were counseled on condom use and a pregnancy test was performed at each visit. Blood was collected at 1, 4, 12, 24, 36 and 48 weeks after entry for analysis of plasma LNG concentrations.
Study Results
Subjects in the EFV group were on EFV for a median of 10 (range 5-66) months prior to entry. Results revealed a 45-57% reduction in LNG concentrations, beginning at week 1 and persisting through week 48. Three women in the EFV group became pregnant between weeks 36 and 48, versus none in the control group. The EFV study arm was halted for subject safety.The effect on EFV was not formally studied.
Study Conclusions
In a separate prospective, open-label, single arm study, the PK interaction between LNG (emergency contraception, Plan B) and EFV was evaluated. Among the 21 women who completed the study, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) and Cmax was reduced 41% (95% CI: 33%, 50%).
The authors state that alternative contraception should be offered to women on EFV-based ART. Alternatively, the ART regimen could be switched.
References
Scarsi KK, Cirrincione L, Nakalema S, Darin K, Musinguzi I. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections . Seattle, WA. 2019; March 2019.
Efavirenz vs Double Dose Levonorgestrel
^
Study Design
This was a pharmacokinetic evaluation of double-dose (300mg) LNG
implants in Ugandan women receiving EFV-based ART with an undetectable
HIV-RNA (DoubLNG group; n=28). LNG implants, one in each arm, and a copper
intrauterine device were placed at entry. Historical controls were ART-naïve
Ugandan women (n=17) who received a standard-dose (150mg) LNG implant at
entry. Plasma was collected at 1, 4, 12, 24, 36, and 48 weeks. LNG concentrations
were analyzed by a validated LC-MS/MS method (range 50-1500 pg/mL),
summarized as median (IQR), and compared between groups by geometric
mean ratio (GMR) with 90% CI. The proportion with LNG ≤303 pg/mL were
compared by Fisher’s Exact test.
Study Results
All women were Black African. The DoubLNG group had a median age
of 33 years and median weight of 58 kg; the control group was 29 years and 69
kg, respectively. The Table summarizes LNG results by visit. After 48 weeks, LNG
concentrations were 373 (319, 540) pg/mL in the DoubLNG group versus 651
(469, 879) pg/mL in the control group [GMR (90% CI) 0.66 (0.61, 0.72)]. During
the study, 18% (n=3) in the control group and 46% (n=13) in the DoubLNG
group had any LNG value ≤303 pg/mL (p=0.
Study Conclusions
We observed 33-44% lower LNG concentrations over 48 weeks
in women receiving EFV-based ART plus LNG 300mg implants compared
to ART-naïve women on LNG 150mg implants. Relative to our prior study,
the magnitude of the interaction with EFV at week 48 was smaller with
double-dose LNG (34% lower) vs standard-dose LNG (57% lower). Also, fewer
women receiving EFV-based ART had an LNG ≤303 pg/mL in the double- vs
standard-dose group (46% vs 90%, respectively; p=0.002). Doubling the dose
of LNG implants does not fully overcome the interaction with EFV, and the
contraceptive effectiveness of this approach remains uncertain.
References
Scarsi KK, Cirrincione L, Nakalema S, Darin K, Musinguzi I. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections . Seattle, WA. 2019; March 2019.
Efavirenz versus Levonorgestrel
^
Study Design
A previous study showed 57% lower levonorgestrel (LNG) exposure in women receiving the LNG subdermal implant (150mg) with efavirenz (EFV)-based antiretroviral therapy (ART) compared to ART-naïve women. In this study, researchers aimed to overcome this interaction by doubling the LNG dose to LNG 300mg over 48 weeks in women receiving EFV-based. Ugandan women (n=28) on EFV-based ART with an undetectable HIV-RNA received LNG implants (300 mg), one in each arm, and a copper intrauterine device were placed at entry. Controls were ART-naive Ugandan women (n=17) who received a standard-dose (150mg) LNG implant at entry. Plasma was collected at 1, 4, 12, 24, 36, and 48 weeks. LNG concentrations were analyzed by a LC-MS/MS, summarized as median (IQR), and compared between groups by geometric mean ratio (GMR) with 90% CI.
Study Results
After 48 weeks, LNG concentrations were GMR 373 (CI 319, 540) pg/mL in the Double LNG group versus 651 (469, 879) pg/mL in the control group [GMR (90% CI) 0.66 (0.61, 0.72)]. During
the study, 18% (n=3) in the control group and 46% (n=13) in the Double LNG group had any LNG value ≤303 pg/mL (p=0.06).
Study Conclusions
Researchers observed 33-44% lower LNG concentrations over 48 weeks
in women receiving EFV-based ART plus LNG 300mg implants compared to ART-naive women on LNG 150mg implants. Relative to the prior study, the magnitude of the interaction with EFV at week 48 was smaller with double-dose LNG (34% lower) vs standard-dose LNG (57% lower). Also, fewer
women receiving EFV-based ART had an LNG ≤ 303 pg/mL in the double- vs standard-dose group (46% vs 90%, respectively; p=0.002). However, doubling the dose of LNG implants does not fully overcome the interaction with EFV, and the contraceptive effectiveness of this approach remains uncertain.
References
Scarsi KK, Cirrincione L, Nakalema S, Darin K, Musinguzi I. Double-dose levonorgestrel implant does not fully overcome interaction with efavirenz. Conference On Retroviruses And Opportunistic Infections . Seattle, WA. 2019; March 2019.
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