Durability of First Line Antiretroviral Therapy: Reasons and Predictive Factors for Modifications in a Swaziland Cohort

Abstract

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/mm 3 (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.

Has the phasing out of stavudine in accordance with changes in WHO guidelines led to a decrease in single-drug substitutions in first-line antiretroviral therapy for HIV in sub-Saharan Africa?

“…This is consistent with previous studies conducted in sub-Saharan Africa[13-21], however, it is important to note that time to substitution is partly a function of the frequency of monitoring, which differs for each NRTI. Laboratory monitoring for tenofovir and zidovudine is often conducted early on after treatment initiation, while for stavudine monitoring begins more often when the patient begins to develop clinical symptoms of toxicity diagnosed at a medical visit[2,3].…”

“…Our approach to Bayesian analysis[33] is essentially a weighted average incorporating the prior distribution (previous literature) and our data. To do this, point estimates and corresponding 95% confidence intervals (CI) for priors were obtained from previous publications assessing predictors of SDS[13-21]. Ratio measures for each potential predictor of SDS (age, sex, clinic, CD4 count, weight, hemoglobin levels, WHO stage, NRTI and NNRTI used in first-line regimen) were extracted from the existing literature.…”

“…All studies found that patients on tenofovir had about an 82% decrease in the risk of SDS(summary risk ratio (RR):0.18; 95% confidence interval (CI):0.15-0.20) compared to patients on stavudine[13-21], while patients on zidovudine, although at higher risk of SDS compared to tenofovir, remained at lower risk of substitution compared to patients on stavudine(summary RR:0.41; 95%CI:0.37-0.45)[13-18]. …”

“…While previous observational studies do suggest tenofovir and zidovudine are associated with fewer SDS compared to stavudine[13-21], many had important limitations. Two studies[13,14] had patient populations that initiated tenofovir prior to implementation of the 2010 WHO policy change.…”

Low body mass index increases risk of anemia in patients with HIV-AIDS receiving antiretroviral therapy

“…The increased risk in anemia among patients with immunosuppresion is in agreement with previous published reports. (18) Our study found that low CD4+ cell count was not a risk factor for anemia in HIV subjects. Another study in Mexico found different results, i.e.…”