Decrease in Single-drug Substitutions in the First 24-months on First-line Treatment amongst HIV-positive Children and Adolescents in South Africa

Abstract

Background: Research has shown that single-drug substitutions have decreased in HIV-positive adults on standard first-line antiretroviral therapy (ART) with the introduction of tenofovir in 2010. We investigated whether the trend was similar in children and adolescents with the phase out of stavudine for abacavir and tenofovir in first-line treatment in South Africa. Methods: We conducted a prospective cohort analysis of HIV-infected children and adolescents 5-19.9 years of age initiating ART between April 2004 and October 2011 at one of eight HIV clinics in Gauteng and Mpumalanga provinces. First-line ART prior to April 2010 for children 5-13.9 years consisted of stavudine/lamivudine/efavirenz, while stavudine or zidovudine with lamivudine and either efavirenz or nevirapine was used for those 14-19.9 years. Abacavir (for ages 5-13.9) and tenofovir (for ages 14-19.9) was substituted for stavudine after April 2010. A single-drug substitution is defined as changing a nucleoside reverse transcriptase inhibitor without switching to second-line therapy. Cox proportional hazards regression was used to identify predictors of single-drug substitutions over 24-months on ART. Results: 1146 (51.7%) children 5-9.9 years of age; 524 (23.6%) 10-13.9 years of age and 548 (24.7%) 14-19.9 years of age were eligible for analysis. Over follow-up, 150 (6.7%; 95%CI:5.7-7.9%) single-drug substitutions occurred: 55 (4.8%), 40 (7.6%) and 55 (10.0%) in children and adolescents 5-9.9, 10-13.9 and 14-19.9 years of age, respectively. From 2007-2009 the frequency of single-drug substitution ranged from 4-9% for 5-9.9 year olds; 5-20% for 10-13.9 year olds and 9-14% in patients 14-19.9 years. In 2011, well after integration of abacavir and tenofovir into first-line ART, there was a substantial drop in substitutions in all three age groups to <1%, 3% and 5%, respectively. Patients 5-9.9 and 10-13.9 years of age initiating an abacavir-based regimen had fewer substitutions (1%; 95%CI:0.3-3.4% and 0.7%; 95%CI:0.1-4.0, respectively) than those on stavudine-based (5.3%; 95%CI:4.0-6.9% and 9.6%; 95%CI:7.1-13.0, respectively) regimen over follow-up. We also observed fewer substitutions amongst patients 14-19.9 years of age on a tenofovir-based regimen (0.8%; 95%CI:0.1-4.2%) than zidovudine- (15.0%; 95%CI:5.2-36.0%) and stavudine-based (13.3%; 95%CI:10.3-17.0%). Adjusted models showed that children ages 5-9.9 and 10-13.9 on a stavudine-based compared to abacavir-based regimen had roughly a 5- and 12-fold increase, respectively, in the hazards of single-drugs substitutions over the first 24 months on treatment; while adolescents 14-19.9 years of age on stavudine- or zidovudine- had over a 17-fold increase over the period of follow-up when compared to those on a tenofovir-based regimen. Conclusions: Introduction of abacavir and tenofovir in to standard first-line ART for treatment of HIV in children and adolescents is associated with a marked decrease in single-drug substitution in the first 24-months on ART, demonstrating improvement in the durability of first-line treatment regimens. These findings are consistent with those previously published in adults.

Conference: IWHOD 2014, Sitges, Spain