Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia

Allison Navis; Ifunanya Dallah; Charles Mabeta; Kalo Musukuma; Omar K. Siddiqi; Christopher M. Bositis; Igor J. Koralnik; Harris A. Gelbard; William H. Theodore; Jason F. Okulicz; Brent A. Johnson; Izukanji Sikazwe; David R. Bearden; Gretchen L. Birbeck

doi:10.1111/epi.16723

Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia

Allison Navis^*, Ifunanya Dallah, Charles Mabeta, Kalo Musukuma, Omar K. Siddiqi, Christopher M. Bositis, Igor J. Koralnik, Harris A. Gelbard, William H. Theodore, Jason F. Okulicz, Brent A. Johnson, Izukanji Sikazwe, David R. Bearden, Gretchen L. Birbeck

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Objective: Interactions between enzyme-inducing anti-seizure medications (EI-ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co-usage of ARVs and EI-ASMs is associated with ARV-resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. Methods: Eligible participants were ≥18 years of age and concurrently taking ASMs and ARVs for at least 1 month of the prior 6-month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000 copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI-ASM was associated with pVL >1000/mL copies. Results: Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6 months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6 months. Median CD4 nadir was 205 cells/mm³ (interquartile range [IQR] 88-389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464 cells/mm³ (SD 226.3). Seven participants (14%) had a CD4 count <200 cells/mm³. Four (8%) had a pVL >1000 copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200 cells/mm³. None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P =.58). Significance: EI-ASMs are commonly used in sub-Saharan Africa. Despite concurrent use of EI-ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm³ and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV-resistant HIV.

Original language	English
Pages (from-to)	2705-2711
Number of pages	7
Journal	Epilepsia
Volume	61
Issue number	12
DOIs	https://doi.org/10.1111/epi.16723
State	Published - Dec 2020
Externally published	Yes

Keywords

HIV resistance
carbamazepine
enzyme-inducing anti-seizure medications
virological failure

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10.1111/epi.16723

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Navis, A., Dallah, I., Mabeta, C., Musukuma, K., Siddiqi, O. K., Bositis, C. M., Koralnik, I. J., Gelbard, H. A., Theodore, W. H., Okulicz, J. F., Johnson, B. A., Sikazwe, I., Bearden, D. R., & Birbeck, G. L. (2020). Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia. Epilepsia, 61(12), 2705-2711. https://doi.org/10.1111/epi.16723

@article{3c74e941815f4e869998815c21c63eec,

title = "Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia",

abstract = "Objective: Interactions between enzyme-inducing anti-seizure medications (EI-ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co-usage of ARVs and EI-ASMs is associated with ARV-resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. Methods: Eligible participants were ≥18 years of age and concurrently taking ASMs and ARVs for at least 1 month of the prior 6-month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000 copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI-ASM was associated with pVL >1000/mL copies. Results: Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6 months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6 months. Median CD4 nadir was 205 cells/mm3 (interquartile range [IQR] 88-389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464 cells/mm3 (SD 226.3). Seven participants (14%) had a CD4 count <200 cells/mm3. Four (8%) had a pVL >1000 copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200 cells/mm3. None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P =.58). Significance: EI-ASMs are commonly used in sub-Saharan Africa. Despite concurrent use of EI-ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm3 and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV-resistant HIV.",

keywords = "HIV resistance, carbamazepine, enzyme-inducing anti-seizure medications, virological failure",

author = "Allison Navis and Ifunanya Dallah and Charles Mabeta and Kalo Musukuma and Siddiqi, {Omar K.} and Bositis, {Christopher M.} and Koralnik, {Igor J.} and Gelbard, {Harris A.} and Theodore, {William H.} and Okulicz, {Jason F.} and Johnson, {Brent A.} and Izukanji Sikazwe and Bearden, {David R.} and Birbeck, {Gretchen L.}",

note = "Publisher Copyright: {\textcopyright} 2020 International League Against Epilepsy",

year = "2020",

month = dec,

doi = "10.1111/epi.16723",

language = "English",

volume = "61",

pages = "2705--2711",

journal = "Epilepsia",

issn = "0013-9580",

number = "12",

}

Navis, A, Dallah, I, Mabeta, C, Musukuma, K, Siddiqi, OK, Bositis, CM, Koralnik, IJ, Gelbard, HA, Theodore, WH, Okulicz, JF, Johnson, BA, Sikazwe, I, Bearden, DR & Birbeck, GL 2020, 'Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia', Epilepsia, vol. 61, no. 12, pp. 2705-2711. https://doi.org/10.1111/epi.16723

TY - JOUR

T1 - Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia

AU - Navis, Allison

AU - Dallah, Ifunanya

AU - Mabeta, Charles

AU - Musukuma, Kalo

AU - Siddiqi, Omar K.

AU - Bositis, Christopher M.

AU - Koralnik, Igor J.

AU - Gelbard, Harris A.

AU - Theodore, William H.

AU - Okulicz, Jason F.

AU - Johnson, Brent A.

AU - Sikazwe, Izukanji

AU - Bearden, David R.

AU - Birbeck, Gretchen L.

PY - 2020/12

Y1 - 2020/12

N2 - Objective: Interactions between enzyme-inducing anti-seizure medications (EI-ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co-usage of ARVs and EI-ASMs is associated with ARV-resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. Methods: Eligible participants were ≥18 years of age and concurrently taking ASMs and ARVs for at least 1 month of the prior 6-month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000 copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI-ASM was associated with pVL >1000/mL copies. Results: Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6 months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6 months. Median CD4 nadir was 205 cells/mm3 (interquartile range [IQR] 88-389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464 cells/mm3 (SD 226.3). Seven participants (14%) had a CD4 count <200 cells/mm3. Four (8%) had a pVL >1000 copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200 cells/mm3. None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P =.58). Significance: EI-ASMs are commonly used in sub-Saharan Africa. Despite concurrent use of EI-ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm3 and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV-resistant HIV.

AB - Objective: Interactions between enzyme-inducing anti-seizure medications (EI-ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co-usage of ARVs and EI-ASMs is associated with ARV-resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. Methods: Eligible participants were ≥18 years of age and concurrently taking ASMs and ARVs for at least 1 month of the prior 6-month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000 copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI-ASM was associated with pVL >1000/mL copies. Results: Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6 months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6 months. Median CD4 nadir was 205 cells/mm3 (interquartile range [IQR] 88-389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464 cells/mm3 (SD 226.3). Seven participants (14%) had a CD4 count <200 cells/mm3. Four (8%) had a pVL >1000 copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200 cells/mm3. None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P =.58). Significance: EI-ASMs are commonly used in sub-Saharan Africa. Despite concurrent use of EI-ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm3 and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV-resistant HIV.

KW - HIV resistance

KW - carbamazepine

KW - enzyme-inducing anti-seizure medications

KW - virological failure

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U2 - 10.1111/epi.16723

DO - 10.1111/epi.16723

M3 - Article

C2 - 33084053

AN - SCOPUS:85092926398

SN - 0013-9580

VL - 61

SP - 2705

EP - 2711

JO - Epilepsia

JF - Epilepsia

IS - 12

ER -

Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia

Abstract

Keywords

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