Therapeutic drug levels and treatment responsiveness among Kenyan patients infected with HIV type 1.

Abstract

Treatment failure is a key challenge in the management of HIV-1 infection, with multiple viral and host dependent variables as well as socio-demographic factors variously influencing treatment outcome. A mixed-model survey of plasma Nevirapine (NVP) concentrations (cNVP) and viral load was conducted to examine associations of cNVP, with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therapy (ART). Blood plasma was collected at 1, 4 and 24 hours post-ART dosing from 58 patients receiving NVP-containing ART and used to determine cNVP and viral load (VL). The median duration of treatment was 42 (range, 12-156) months, and 25 (43.1%) of the patients had virologic failure. cNVP was significantly lower for virologic failure than nonvirologic failure at 1hr (mean, 2,111ng/ml vs. 3,432ng/ml, p=0.003) and at 4hr (mean 1,625ng/ml vs. 3,999ng/ml, p=0.001) but not at 24hr post-ART dosing. Up to 53.4%, 24.1% and 22.4% of the patients had good, fair and poor adherence respectively. cNVP peaked and was >= 3g.ml at 4 hours in a majority of patients with good adherence and those with virologic success. Using a threshold of 3g/ml for optimal therapeutic drug level of NVP, 74% (43/58), 65.5% (38/58) and 86% (50/58) of all patients had sub-therapeutic cNVP at 1, 4 and 24 hours respectively. cNVP at 4 hours was associated with adherence (p=0.05) and virologic response outcome (p=0.002) in a chi-square test. Mean cNVP differed significantly in non-parametric tests between adherence categories at 1hr (p=0.005) and 4hrs (p=0.01) and between ART regimen categories at 1hr (p=0.004) and 4hrs (p<0.0001), as well as correlated inversely with VL (p=<0.002). Nevirapine plasma levels correlated inversely with VL and positively with adherence behavior. Hence, the concentrations of NVP and other ART drugs should be considered for structured monitoring in a clinical setting, particularly in patients not suppressing VL after months of initiating HAART.