Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated

Jim Aizire, Mary Glenn Fowler, Jing Wang, Avinash K. Shetty, Lynda Stranix-Chibanda, Moreen Kamateeka, Elizabeth R. Brown, Steve G. Bolton, Philippa M. Musoke, Hoosen Coovadia

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective: Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed. Design: Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1. Methods: Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole+nevirapine and the cotrimoxazole+placebo groups were compared using negative-binomial regression. Results: Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole+nevirapine and cotrimoxazole+placebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole+nevirapine versus cotrimoxazole+placebo. Conclusion: Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.

Original languageEnglish
Pages (from-to)325-333
Number of pages9
JournalAIDS
Volume26
Issue number3
DOIs
Publication statusPublished - 28-01-2012
Externally publishedYes

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Nevirapine
Sulfamethoxazole Drug Combination Trimethoprim
HIV
Exanthema
Neutropenia
Anemia
Placebos
Peripartum Period
Safety
Zidovudine
Human Milk
Standard of Care
Breast Feeding
HIV-1
Acquired Immunodeficiency Syndrome
Randomized Controlled Trials
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Aizire, J., Fowler, M. G., Wang, J., Shetty, A. K., Stranix-Chibanda, L., Kamateeka, M., ... Coovadia, H. (2012). Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated. AIDS, 26(3), 325-333. https://doi.org/10.1097/QAD.0b013e32834e892c
Aizire, Jim ; Fowler, Mary Glenn ; Wang, Jing ; Shetty, Avinash K. ; Stranix-Chibanda, Lynda ; Kamateeka, Moreen ; Brown, Elizabeth R. ; Bolton, Steve G. ; Musoke, Philippa M. ; Coovadia, Hoosen. / Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated. In: AIDS. 2012 ; Vol. 26, No. 3. pp. 325-333.
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abstract = "Objective: Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed. Design: Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1. Methods: Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole+nevirapine and the cotrimoxazole+placebo groups were compared using negative-binomial regression. Results: Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole+nevirapine and cotrimoxazole+placebo groups: hazard ratio (95{\%} confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole+nevirapine versus cotrimoxazole+placebo. Conclusion: Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.",
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Aizire, J, Fowler, MG, Wang, J, Shetty, AK, Stranix-Chibanda, L, Kamateeka, M, Brown, ER, Bolton, SG, Musoke, PM & Coovadia, H 2012, 'Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated', AIDS, vol. 26, no. 3, pp. 325-333. https://doi.org/10.1097/QAD.0b013e32834e892c

Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated. / Aizire, Jim; Fowler, Mary Glenn; Wang, Jing; Shetty, Avinash K.; Stranix-Chibanda, Lynda; Kamateeka, Moreen; Brown, Elizabeth R.; Bolton, Steve G.; Musoke, Philippa M.; Coovadia, Hoosen.

In: AIDS, Vol. 26, No. 3, 28.01.2012, p. 325-333.

Research output: Contribution to journalArticle

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T1 - Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated

AU - Aizire, Jim

AU - Fowler, Mary Glenn

AU - Wang, Jing

AU - Shetty, Avinash K.

AU - Stranix-Chibanda, Lynda

AU - Kamateeka, Moreen

AU - Brown, Elizabeth R.

AU - Bolton, Steve G.

AU - Musoke, Philippa M.

AU - Coovadia, Hoosen

PY - 2012/1/28

Y1 - 2012/1/28

N2 - Objective: Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed. Design: Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1. Methods: Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole+nevirapine and the cotrimoxazole+placebo groups were compared using negative-binomial regression. Results: Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole+nevirapine and cotrimoxazole+placebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole+nevirapine versus cotrimoxazole+placebo. Conclusion: Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.

AB - Objective: Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed. Design: Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1. Methods: Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazole+nevirapine and the cotrimoxazole+placebo groups were compared using negative-binomial regression. Results: Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazole+nevirapine and cotrimoxazole+placebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazole+nevirapine versus cotrimoxazole+placebo. Conclusion: Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.

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Aizire J, Fowler MG, Wang J, Shetty AK, Stranix-Chibanda L, Kamateeka M et al. Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated. AIDS. 2012 Jan 28;26(3):325-333. https://doi.org/10.1097/QAD.0b013e32834e892c