Abstract
Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations 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 subjects receiving NVP-containing ART and used to determine cNVP and viral load (VL). Median duration of treatment was 42 (range, 12–156) months, and 25 (43.1%) of the patients had virologic failure (VF). cNVP was significantly lower for VF than non- VF 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 subjects had good, fair and poor adherence respectively. cNVP levels peaked and were > = 3μg.ml at 4 hours in a majority of patients with good adherence and those without VF. Using a threshold of 3μg/ml for optimal therapeutic nevirapine level, 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 VF (p = 0.002) in a chi-square test. These mean cNVP levels 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). Moreover, cNVP levels correlated inversely with VL (p< = 0.006) and positively with adherence behavior. In multivariate tests, increased early peak NVP (cNVP4) was independently predictive of lower VL (p = 0.002), while delayed high NVP peak (cNVP24) was consistent with increased VL (p = 0.033). These data strongly assert the need to integrate plasma concentrations of NVP and that of other ART drugs into routine ART management of HIV-1 patients.
Highlights
Scaling of antiretroviral treatment (ART) has significantly reduced deaths and morbidity for HIV patients
A few studies have suggested that plasma NVP concentrations may affect virologic outcome [3,4,5], therapeutic drug level (TDL) measurements is excluded from highly active antiretroviral therapy (HAART) management of patients in many countries, including Kenya
Two subjects (3.4%) were on NVP+TDF and 3TC+NVP regimens and one (1.7%) on NVP alone. These 3 subjects not receiving the optimal triple antiretroviral therapy (ART) regimen had the highest baseline viral load (VL1) of 3.51 log10 HIV RNA copies compared to the other regimen groups
Summary
Scaling of antiretroviral treatment (ART) has significantly reduced deaths and morbidity for HIV patients. A few studies have suggested that plasma NVP concentrations (cNVP) may affect virologic outcome [3,4,5], therapeutic drug level (TDL) measurements is excluded from HAART management of patients in many countries, including Kenya. Even in patients reporting good adherence, some demonstrate subtherapeutic concentrations of drug that confounds interpretation and application of adherence data, often largely due to high interpatient variability [19, 20] Such variability can be partly due to differences in host genetics and drug metabolism [21], supporting the need for TDL monitoring to bolster clinical management of HIV [22]. We aimed to assess if cNVP would accurately predict virologic treatment outcome and if that predictive value was a proxy measure of adherence in these long-term HAART patients receiving nevirapine as part of a 3-drug regimen
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