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J Acquir Immune Defic Syndr. Author manuscript; available in PMC 2017 January 01. Published in final edited form as: J Acquir Immune Defic Syndr. 2016 January 1; 71(1): 31–37. doi:10.1097/QAI.0000000000000811.
Treatment failure, drug resistance, and CD4 T-cell count decline among postpartum women on antiretroviral therapy in South Africa
Author Manuscript
Christopher J Hoffmann1, Silvia Cohn1, Fildah Mashabela2, Jennifer D Hoffmann1, Helen McIlleron3, Paolo Denti3, David Haas4, Kelly E Dooley1, Neil A Martinson1,2, and Richard E Chaisson1 Christopher J Hoffmann: [email protected]; Silvia Cohn: [email protected]; Fildah Mashabela: [email protected]; Jennifer D Hoffmann: [email protected]; Helen McIlleron: [email protected]; Paolo Denti: [email protected]; David Haas: [email protected]; Kelly E Dooley: [email protected]; Neil A Martinson: [email protected]; Richard E Chaisson: [email protected] 1Johns
Hopkins University School of Medicine, Baltimore, MD, USA
2Perinatal
HIV Research Unit (PHRU), University of the Witwatersrand, Soweto, South Africa
3Division
of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
4Vanderbilt
University School of Medicine, Nashville, TN, USA
Abstract Author Manuscript
Background—We assessed HIV RNA suppression, resistance, and CD4 T-cell count 12 months post-partum among pregnant women retained in care in an observational cohort study. Methods—We prospectively followed two groups of HIV-infected pregnant women - with or without tuberculosis - recruited from pre-natal clinics in South Africa. Women who received antiretroviral therapy during pregnancy and reported being on therapy 12 months post-partum were included. Serum samples from women with HIV viremia 12 months post-partum were tested for drug resistance.
Author Manuscript
Results—Of 103 women in the study, median age and CD4 T-cell count at enrollment were 29 years [interquartile range (IQR): 26, 32] and 317 cells/mm3 (IQR: 218, 385), respectively; 43 (42%) had tuberculosis at baseline. During pregnancy, 87% of the women achieved an HIV RNA 0.2). Of the 103 women in the study population, median age was 29 years (interquartile range [IQR]: 26, 32), gestational age at enrollment was 29 weeks (IQR: 25, 34), and enrollment CD4 T-cell count was 317 cells/mm3 (IQR: 218, 385; Table 1). Forty-three (42%) women were either receiving TB treatment at the time of enrollment or were diagnosed with TB during
J Acquir Immune Defic Syndr. Author manuscript; available in PMC 2017 January 01.
Hoffmann et al.
Page 5
Author Manuscript
enrollment screening. Twenty-three (22%) women were already on ART prior to pregnancy and 80 (78%) were started during pregnancy. ART was started later in pregnancy in participants with TB co-infection (median 22 weeks before delivery; IQR: 18, 26) than among women with HIV alone (median 28 weeks before delivery; IQR: 22, 94; Fisher's exact p=0.007) and the CD4 count at enrollment was lower among woman with TB coinfection, 278 cells/mm3 (IQR: 144, 385) and 348 cells/mm3 (IQR: 263, 394), respectively (Fisher's exact p=0.01). There were no differences in terms of age, parity, or ART regimen (all p>0.2). At 12 months post-partum, most women were receiving a nucleoside backbone of tenofovir and lamivudine (95, 92%). The remaining women were receiving zidovudine (3, 2.9%) or stavudine (5, 4.8%). The additional agent was efavirenz for 86 (83%), nevirapine for 10 (9%), or lopinavir/ritonavir for 7 (7%). Edinburgh Depression scale scores ranged from 0 to 16 with a median of 3 (IQR: 0, 7); 12 women (12%) met criteria for depression at one or more study visits.
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Efavirenz pharmacokinetics and pharmacogenetics
Author Manuscript
Genotype data for CYP2B6 were available for 80 women. Of these women, 2 (2.5%) were very slow metabolizers of efavirenz, 17 (21%) were slow, 42 (52%) were intermediate, and 19 (24%) were extensive metabolizers. Estimated efavirenz trough concentrations were available for 75 of 86 women dispensed EFV post-partum and ranged from undetectable (
J Acquir Immune Defic Syndr. Author manuscript; available in PMC 2017 January 01. Published in final edited form as: J Acquir Immune Defic Syndr. 2016 January 1; 71(1): 31–37. doi:10.1097/QAI.0000000000000811.
Treatment failure, drug resistance, and CD4 T-cell count decline among postpartum women on antiretroviral therapy in South Africa
Author Manuscript
Christopher J Hoffmann1, Silvia Cohn1, Fildah Mashabela2, Jennifer D Hoffmann1, Helen McIlleron3, Paolo Denti3, David Haas4, Kelly E Dooley1, Neil A Martinson1,2, and Richard E Chaisson1 Christopher J Hoffmann: [email protected]; Silvia Cohn: [email protected]; Fildah Mashabela: [email protected]; Jennifer D Hoffmann: [email protected]; Helen McIlleron: [email protected]; Paolo Denti: [email protected]; David Haas: [email protected]; Kelly E Dooley: [email protected]; Neil A Martinson: [email protected]; Richard E Chaisson: [email protected] 1Johns
Hopkins University School of Medicine, Baltimore, MD, USA
2Perinatal
HIV Research Unit (PHRU), University of the Witwatersrand, Soweto, South Africa
3Division
of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
4Vanderbilt
University School of Medicine, Nashville, TN, USA
Abstract Author Manuscript
Background—We assessed HIV RNA suppression, resistance, and CD4 T-cell count 12 months post-partum among pregnant women retained in care in an observational cohort study. Methods—We prospectively followed two groups of HIV-infected pregnant women - with or without tuberculosis - recruited from pre-natal clinics in South Africa. Women who received antiretroviral therapy during pregnancy and reported being on therapy 12 months post-partum were included. Serum samples from women with HIV viremia 12 months post-partum were tested for drug resistance.
Author Manuscript
Results—Of 103 women in the study, median age and CD4 T-cell count at enrollment were 29 years [interquartile range (IQR): 26, 32] and 317 cells/mm3 (IQR: 218, 385), respectively; 43 (42%) had tuberculosis at baseline. During pregnancy, 87% of the women achieved an HIV RNA 0.2). Of the 103 women in the study population, median age was 29 years (interquartile range [IQR]: 26, 32), gestational age at enrollment was 29 weeks (IQR: 25, 34), and enrollment CD4 T-cell count was 317 cells/mm3 (IQR: 218, 385; Table 1). Forty-three (42%) women were either receiving TB treatment at the time of enrollment or were diagnosed with TB during
J Acquir Immune Defic Syndr. Author manuscript; available in PMC 2017 January 01.
Hoffmann et al.
Page 5
Author Manuscript
enrollment screening. Twenty-three (22%) women were already on ART prior to pregnancy and 80 (78%) were started during pregnancy. ART was started later in pregnancy in participants with TB co-infection (median 22 weeks before delivery; IQR: 18, 26) than among women with HIV alone (median 28 weeks before delivery; IQR: 22, 94; Fisher's exact p=0.007) and the CD4 count at enrollment was lower among woman with TB coinfection, 278 cells/mm3 (IQR: 144, 385) and 348 cells/mm3 (IQR: 263, 394), respectively (Fisher's exact p=0.01). There were no differences in terms of age, parity, or ART regimen (all p>0.2). At 12 months post-partum, most women were receiving a nucleoside backbone of tenofovir and lamivudine (95, 92%). The remaining women were receiving zidovudine (3, 2.9%) or stavudine (5, 4.8%). The additional agent was efavirenz for 86 (83%), nevirapine for 10 (9%), or lopinavir/ritonavir for 7 (7%). Edinburgh Depression scale scores ranged from 0 to 16 with a median of 3 (IQR: 0, 7); 12 women (12%) met criteria for depression at one or more study visits.
Author Manuscript
Efavirenz pharmacokinetics and pharmacogenetics
Author Manuscript
Genotype data for CYP2B6 were available for 80 women. Of these women, 2 (2.5%) were very slow metabolizers of efavirenz, 17 (21%) were slow, 42 (52%) were intermediate, and 19 (24%) were extensive metabolizers. Estimated efavirenz trough concentrations were available for 75 of 86 women dispensed EFV post-partum and ranged from undetectable (
