Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy

Moses R. Kamya, Harriet Mayanja-Kizza, Andrew Kambugu, Sabrina Bakeera-Kitaka, Fred Semitala, Patricia Mwebaze-Songa, Barbara Castelnuovo, Petra Schaefer, Lisa A. Spacek, Anne F. Gasasira, Elly Katabira, Robert Colebunders, Thomas C. Quinn, Allan Ronald, David L. Thomas, Adeodata Kekitiinwa

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Abstract

BACKGROUND: HIV RNA viral load testing is costly and is generally unavailable in resource-limited settings. We identified predictors of viral failure and documented genotypic mutations in a subset of patients with viral failure after 12 months on antiretroviral therapy (ART). METHODS: From April 2004 to June 2005, consecutive treatment-naive patients beginning ART at a university clinic in Uganda were enrolled. Clinical information, CD4 cell count, and HIV RNA level were collected at baseline and every 3 to 6 months. Independent predictors of viral failure were identified using multivariate logistic regression. Genotypic drug resistance for 8 patients with viral failure at 12 months was measured at baseline and at 6 and 12 months. RESULTS: Five hundred twenty-six adults and 250 children (0 to 18 years of age) were started on first-line ART regimens and followed for 12 months. Outcomes could not be assessed in 13% of patients (79 died and 21 were withdrawn). Children were almost twice as likely to have viral failure compared with adults (26% vs. 14%; P = 0.0001). In adults, the sole independent predictor of viral failure was treatment with stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP) versus zidovudine (ZDV)/3TC/efavirenz (EFV) (odds ratio [OR] = 2.59, 95% confidence interval [CI]: 1.20 to 5.59). In children, independent predictors of viral failure included male gender (OR = 2.44, 95% CI: 1.20 to 4.93), baseline CD4% <5 (OR = 2.69, 95% CI: 1.28 to 5.63), and treatment with d4T/3TC/NVP versus ZDV/3TC/EFV (OR = 2.46, 95% CI: 1.23 to 4.90). All 8 patients with viral breakthrough and genotypic drug resistance results had nonnucleoside reverse transcriptase inhibitor (NNRTI)- and 3TC-associated mutations. CONCLUSIONS: These data demonstrate the effectiveness of ART in a low-resource setting. Children and patients of all ages taking the d4T/3TC/NVP regimen were more likely to have viral failure. Our data suggest that viral failure occurring 6 months or more after the start of ART regimens commonly used in Uganda is likely to be associated with NNRTI- and 3TC-resistant virus.

Original languageEnglish (US)
Pages (from-to)187-193
Number of pages7
JournalJournal of acquired immune deficiency syndromes
Volume46
Issue number2
DOIs
StatePublished - Oct 1 2007

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Keywords

  • Antiretroviral therapy
  • Predictors
  • Resource-limited settings
  • Viral failure

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Kamya, M. R., Mayanja-Kizza, H., Kambugu, A., Bakeera-Kitaka, S., Semitala, F., Mwebaze-Songa, P., Castelnuovo, B., Schaefer, P., Spacek, L. A., Gasasira, A. F., Katabira, E., Colebunders, R., Quinn, T. C., Ronald, A., Thomas, D. L., & Kekitiinwa, A. (2007). Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. Journal of acquired immune deficiency syndromes, 46(2), 187-193. https://doi.org/10.1097/QAI.0b013e31814278c0