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 >= 3g.ml at 4 hours in a majority of patients with good adherence and those with
virologic success. Using a threshold of 3g/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.
