| dc.description.abstract | Background
Limited combined antiretroviral therapy (cART) regimens in resource constrained settings call for the need to optimize the available options in order to improve the durability of potent and well-tolerated first line regimen, subsequently ensuring good patient prognosis.
Objective: To evaluate the incidence rates, reasons and factors associated with first time antiretroviral treatment modification in a resource-constrained setting.
Methods
The study involved a retrospective cohort analysis of records from HIV infected patients attending routine health care in New Nyanza Provincial General Hospital in western Kenya. Patients in this study were aged ≥ 15 years, treatment naïve who initiated cART between 1st January 2009 and 31st January 2011 and had at least one follow-up visit. In addition the patients had at least one follow-up visit and complete records of important clinical (either CD4 or WHO staging) and regimen information. The primary endpoint was time to first antiretroviral treatment modification, defined as either drug substitutions or regimen switch. Multivariate piecewise Cox regression models were used to identify independent predictors of cART modification.
Results
A total of 969 patients were eligible for the analysis and contributed 935.8 years over a median follow-up period of 10.7 months. During this period, 210 (21.7%) participants modified regimens resulting with an incidence rate of 22.4 per 100 person years [95% CI 19.6-25.7]. The rate of cART modification was highest in patients initiating an Efavirenz containing regimen (28.7 per 100py 95% CI 20.1-41.1) followed by those initiating d4T-based regimen (24.2 per 100py 95% CI 20.7-28.0). 90.5% of the modifications were single drug substitutions while 4.8% were 2nd line switch. Drug toxicity was the most common cited reason for cART modifications (39%). In the adjusted multivariate Cox piecewise regression model, low baseline CD4 (<=100 compared to >200 cells/mm3, adjusted hazard ratio (AHR) 1.88, 95%CI 1.08-3.25), advanced WHO disease stage (I/II vs. III/IV, AHR 1.62, 95%CI 1.11-2.35), and a yearly increase in age (AHR 1.02, 95%CI 1.0-1.04), were significantly associated with increased risk for cART modification by 10 months of cART initiation. Tenofovir drug in regimen on the other hand led to a 44% reduction in hazard for cART modification. Factors associated with risk of modification beyond 10 months post cART were presence of stavudine in regimen (AHR 2.75 95% CI 1.38-5.48), a yearly increase in age (AHR 1.04 95%CI 1.02-1.06) and higher baseline weight (>60kg vs. <= 60kg AHR 1.98 95% CI 1.29-3.03).
Conclusion and Recommendation
Our findings indicated a relatively moderate rate of cART modification in a clinical set-up in resource-limited setting, which occurred primarily due to drug toxicity. cART initiation at higher CD4 counts and at less-advanced disease stage as well as the avoidance of drugs with poor safety profile such as stavudine are likely to reduce treatment modification and subsequently improve the durability of 1st line regimens. | en_US |
