Durability of first line antiretroviral therapy: reasons and predictive factors for modifications in a Swaziland cohort

Background: Optimizing initial antiretroviral therapy (ART) regimens is critical in improving the durability of treatment efficacy and patient prognosis. Reasons for and risk factors relating to the need for ART modifications were evaluated in an outpatient cohort in Mbabane, Swaziland. Methods: We examined routine clinical data for 782 patients initiating first-line ART between 1 March 2006 and 31 March 2008. Treatment modification was defined as either a first time single drug substitution or first time regimen switch. Multivariate piecewise Cox regression models were used to identify risk factors for ART modification. Results: Over a median follow-up period of 21 months, 17.5% of patients modified their regimen. Drug toxicity (incidence rate of 6.3 per 100 person years (95% CI 5.2-7.7)) accounted for 76.6% of the reasons for modification. Drug contra-indications (incidence rate 9.5 per 100 person years (95% CI 6.5-13.9)), namely tuberculosis (13.1%) and pregnancy (6.6%), accounted for 19.7% of modifications. In the adjusted multivariate Cox piecewise regression model, beyond 11 months on ART, a baseline CD4 cell count <200 cells/mm3 (HR 4.42; 95% CI: 1.62 -12.1), having stavudine (d4T) in the initial regimen (HR 2.64; 95% CI: 1.56- 4.46), baseline weight > 60kg (HR 2.40; 95% CI: 1.43-4.04) and increase in age (HR 1.03; 95% CI: 1.00- 1.05) increased the risk of modification. Conclusions: Initiating ART earlier, at higher CD4 counts, avoiding drugs with poor safety profiles, such as d4T, and identifying individuals who may require tuberculosis treatment or may become pregnant could reduce modification rates. This would improve regimen tolerability, while preserving future treatment options.