Journal Article

Induction Therapy with Protease-Inhibitors Modifies the Effect of Nevirapine Resistance on Virologic Response to Nevirapine-based HAART in Children

Anitha Moorthy, Louise Kuhn, Ashraf Coovadia, Tammy Meyers, Renate Strehlau, Gayle Sherman, Wei-Yann Tsai, Ya Hui Chen, Elaine J. Abrams and Deborah Persaud

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 52, issue 4, pages 514-521
Published in print February 2011 | ISSN: 1058-4838
Published online February 2011 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1093/cid/ciq161
Induction Therapy with Protease-Inhibitors Modifies the Effect of Nevirapine Resistance on Virologic Response to Nevirapine-based HAART in Children

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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.

Journal Article.  4471 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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