24-month treatment outcomes amongst HIV-positive children and adolescent patients prescribed stavudine vs. abacavir

Background: In April 2010 the South African government replaced stavudine with abacavir in first-line antiretroviral therapy (ART) for children and young adolescents 5-14 years old. It was hoped that this change would improve treatment outcomes, partly through reduced toxicity and improved adherence. We examined treatment outcomes among HIV-positive children and adolescents initiated on abacavir-based versus stavudine-based first-line regimens. Methods: Prospective cohort analysis among HIV-positive children (5-9.9 years) and adolescents (10-13.9 years) initiating lamivudine/efavirenz with either stavudine (between April 2009- March 2010) or abacavir (between April 2010- March 2011) at one of eight HIV clinics in Gauteng and Mpumalanga provinces in South Africa. Modified Poisson regression was used to evaluate the association of regimen with all-cause mortality, loss to follow-up and detectable viral load over 24-months on ART. Linear regression was used to evaluate the relationship between regimen and immunologic response. Results: 371 (56.9%) patients initiating stavudine and 240 (43.1%) initiating abacavir were included in our analysis. A total of 12 (3.8%) stavudine and 5 (2.1%) abacavir patients died, while 43 (13.6%) stavudine and 34 (14.2%) abacavir patients were lost to follow-up over the first 24-months on ART. A total of 97 (30.6%) stavudine and 72 (30.0%) abacavir had a detectable viral load at 24-months on treatment. While estimates lacked precision, our regression analysis showed that patients on stavudine may be at increased risk of death (RR 2.0; 95%CI:0.6-6.3) compared to abacavir. However, results showed that regimens were comparable in regards to loss to follow-up (RR 0.8; 95%CI:0.5-1.4), viral load status (RR 1.1; 95%CI:0.8-1.7) and mean change in CD4 count from ART initiation (-22 cells/mm3; 95%CI:-94.5-50.6 cells/mm3). Adjusted models also showed that adolescents (10-13.9 years) compared to children (5-9.9 years) and those with CD4 count < 200 vs. >200 cell/smm3 were also at increased risk of death and loss from care. Conclusions: Although comparable in regards to loss to follow-up, viral load status and immunological response by 24-months on treatment, patients initiated on stavudine may have a higher risk of death versus those initiated on abacavir. The use of abacavir could help improve long-term treatment outcomes in HIV-positive children and adolescents.