Poor Early Virologic Performance and Durability of Abacavir-based First-line Regimens for HIV-infected Children

Abstract

Concerns about stavudine (d4T) toxicity have led to increased use of abacavir (ABC) in first-line pediatric antiretroviral treatment (ART) regimens. Field experience with ABC in ART-naïve children is limited. Deidentified demographic, clinical and laboratory data on HIV-infected children initiating ART between 2004 and 2011 in a large pediatric HIV treatment program in Johannesburg, South Africa, were used to compare viral suppression at 6 and 12 months by initial treatment regimen, time to suppression (<400 copies/mL) and rebound (>1000 copies/mL after initial suppression). Adjusted logistic regression was used to investigate confounders and calendar effects. Two thousand thirty-six children initiated either d4T/3TC- or ABC/3TC-based first-line regimens in combination with either boosted lopinavir (LPV/r) or efavirenz (EFV). 1634 received d4T regimens (LPV/r n = 672; EFV n = 962) and 402 ABC regimens (LPV/r n = 192; EFV n = 210). At 6 and 12 months on ART, viral suppression rate was poorer in ABC versus d4T groups within both the LPV/r and EFV groups (P < 0.0001 for all points). In ABC groups, time to suppression was significantly slower (log-rank P < 0.0001 and P = 0.0092 for LPV/r- and EFV-based, respectively) and time to rebound after suppression significantly faster (log-rank P = 0.014 and P = 0.0001 for LPV/r- and EFV-based, respectively). Logistic regression confirmed the worse outcomes in the ABC groups even after adjustment for confounders. Data from this urban pediatric ART service program show significantly poorer virological performance of ABC compared with d4T-based regimens, a signal that urgently warrants further investigation.