Introduction Treatment failure is a key challenge in the management of HIV-1 infection. We examined the association of nevirapine blood levels with virologic treatment outcome and adherence among Kenyan patients on antiretroviral therapy (ART).
Methods A cross-sectional study involving 58 subjects receiving nevirapine as part of ART regimen. Clinical, demographic and adherence data were captured using structured questionnaires. Five millilitres of EDTA blood was collected at 1, 4 and 24 h post-dosing and used for quantification of nevirapine levels using High-Performance Liquid Chromatography (HPLC). Plasma viral load was determined on m2000 Abbott RealTime HIV-1 assay platform and used to determine virologic treatment failure (VF).
Results Median duration of ART was 42 months and 43.1% of the patients had VF with a mean viral load of 4.24 log10 copies. Measured at 1 hr (log 2.93, p = 0.003) and at 4 hrs (log 3.07, p < 0.001) post dosing, Nevirapine levels were significantly lower for VF than non-VF patients and were significantly associated with virologic response (c2 p < 0.001). These nevirapine levels at 1 hr (R2 = 0.218, p = 0.002) and at 4 hrs (R2 = 0.156, p = 0.001) were significantly and inversely correlated with same day VL in a Spearman’s rho model. Up to 53.4%, 24.1% and 22.4% of the patients had good, fair and poor adherence respectively, with adherence being significantly associated with plasma nevirapine levels at 1 hr (c2p = 0.001) and at 4 hr (c2p = 0.021). No significant associations were found at 24 hrs post nevirapine dosing.
Conclusion Majority of VF patients attained nevirapine levels in plasma that were significantly lower than non-VF patients. These patients were also more likely to have poor adherence than virologic responders with higher nevirapine levels. Suboptimal exposures to nevirapine may be mitigated partly by improving adherence support mechanisms. Additional investigations should focus on pharmacogenetics and other factors influencing optimal drug uptake in blood.
Disclosure of interest statement ISSTDR and IUSTI recognise the considerable contribution that industry partners make to professional and research activities. We also recognise the need for transparency of disclosure of potential conflicts of interest by acknowledging these relationships in publications and presentations.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.