Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy.
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 Outcomes could not be assessed in 13% of patients (79 died and 21 were withdrawn).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.
Kamya
Moses R
MR
Department of Medicine, Makerere University, Kampala, Uganda. mkamya@infocom.co.ug
Mayanja-Kizza
Harriet
H
Kambugu
Andrew
A
Bakeera-Kitaka
Sabrina
S
Semitala
Fred
F
Mwebaze-Songa
Patricia
P
Castelnuovo
Barbara
B
Schaefer
Petra
P
Spacek
Lisa A
LA
Gasasira
Anne F
AF
Katabira
Elly
E
Colebunders
Robert
R
Quinn
Thomas C
TC
Ronald
Allan
A
Thomas
David L
DL
Kekitiinwa
Adeodata
A
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003906:Developing Countries; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019259:Lamivudine / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D012737:Sex Factors; D018119:Stavudine / Q000627:therapeutic use; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine