Research

Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338)

Susan A Fiscus^1,2 , Andrea Kovacs³ , Leslie A Petch² , Chengcheng Hu⁴ , Andrew A Wiznia⁵ , Lynne M Mofenson⁶ , Ram Yogev⁷ , Kenneth McIntosh⁸ , Stephen I Pelton⁹ , Sonia Napravnik² , Kenneth Stanley⁴ and Sharon A Nachman¹⁰

¹  Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

²  Center for AIDS Research, University of North Carolina, Chapel Hill, NC, USA

³  Maternal, Child and Adolescent Program, University of Southern California Medical Center, Los Angeles, CA, USA

⁴  Center for Biostatistics in AIDS Research and Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

⁵  Department of Pediatrics, Jacobi Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA

⁶  Pediatric, Adolescent and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, USA

⁷  Division of Infectious Diseases, Children's Memorial Hospital and Northwestern University School of Medicine, Chicago, IL, USA

⁸  Division of Infectious Diseases, Children's Hospital and Harvard Medical School, Boston, MA, USA

⁹  Department of Pediatrics, Boston Medical Center, Boston, MA, USA

¹⁰  Department of Pediatrics, SUNY Health Science Center at Stony Brook, Stony Brook, NY, USA

author email corresponding author email

AIDS Research and Therapy 2007, 4:2doi:10.1186/1742-6405-4-2

Published:	6 February 2007

Abstract

Background

The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied.

Results

There were few primary PI associated mutations in this PI-naïve population, but 84% had NRTI mutations – codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017).

Conclusion

No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.