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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Induction therapy with protease-inhibitors modifies the effect of nevirapine resistance on virologic response to nevirapine-based HAART in children
Clinical Infectious Diseases, Volume 52, No. 4, Year 2011
Notification
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Description
Background: Nevirapine resistance after failed prophylaxis to prevent mother-to-child human immunodeficiency virus (HIV) transmission can compromise subsequent nevirapine-based highly active antiretroviral therapy (HAART). Methods: Nevirapine-exposed children who achieved virologic suppression with lopinavir/ritonavir-based induction HAART before switch to nevirapine-based HAART or who continued the lopinavir/ritonavir regimen were studied. Nevirapine-resistant HIV was quantified (≥1% frequency) in plasma before therapy and archived in peripheral blood mononuclear cells after induction HAART with ultradeep pyrosequencing. The primary endpoint was virologic failure (confirmed viremia ≥1000 copies/mL by 52 weeks) on nevirapine-based HAART, and Receiver operating characteristic analysis identified threshold levels of resistance associated with failure. Results: Nevirapine resistance mutations were detected in plasma at a median frequency of 25.6% in 41 (33%) of 124 children starting HAART at median 9 months of age. After a median nine months of induction HAART, nevirapine-resistant HIV remained archived in cells in 59 (61%) of 96 children (median 13.6% of cells). The threshold frequency of nevirapine resistance in plasma most predictive of virologic failure on nevirapine-based HAART was 25%. Children maintaining resistance before therapy at or above this threshold frequency had a 3.5 fold higher risk of failure (95% confidence interval, 1.1-10.8) than children without detectable plasma resistance. In contrast, virologic failure was not independently associated with age, resistance in plasma below 25% frequencies, or archived in cells. Conclusions: Virologic suppression with lopinavir/ritonavir-based HAART in nevirapine-exposed children raises the threshold level of resistance at which reuse of nevirapine-based therapy is compromised. Standard genotyping may allow identification of children likely to benefit from an induction-switch approach. © The Author 2011.
Authors & Co-Authors
Moorthy, Anitha
United States, Baltimore
Johns Hopkins Bloomberg School of Public Health
Kuhn, Louise
United States, New York
Mailman School of Public Health
Coovadia, Ashraf Hassen
South Africa, Johannesburg
Rahima Moosa Mother and Child Hospital
Meyers, Tammy M.M.
South Africa, Johannesburg
Rahima Moosa Mother and Child Hospital
Strehlau, Renate
South Africa, Johannesburg
Rahima Moosa Mother and Child Hospital
Sherman, Gayle Gillian
South Africa, Johannesburg
University of the Witwatersrand
Tsai, Wei Yann
United States, New York
Mailman School of Public Health
Chen, Y. H.
United States, Baltimore
School of Medicine
Abrams, Elaine J.
United States, New York
Mailman School of Public Health
Persaud, Deborah
United States, Baltimore
School of Medicine
Statistics
Citations: 22
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.1093/cid/ciq161
ISSN:
10584838
e-ISSN:
15376591
Research Areas
Infectious Diseases
Maternal And Child Health