title: Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure.
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.
authors.affiliation: Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya.|ITROMID, Jomo Kenyatta University of Science and Technology, Nairobi, Kenya.
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Kimulwo
authors.affiliation: Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya.
authors.forename: Javan
authors.initials: J
authors.lastname: Okendo
authors.affiliation: Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya.|Institute of Healthcare Management, Strathmore University, Nairobi, Kenya.|African Centre for Clinical Trials, Nairobi, Kenya.
authors.forename: Rashid A
authors.initials: RA
authors.lastname: Aman
authors.affiliation: Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya.|Institute of Healthcare Management, Strathmore University, Nairobi, Kenya.|Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Bernhards R
authors.initials: BR
authors.lastname: Ogutu
authors.affiliation: Institute of Healthcare Management, Strathmore University, Nairobi, Kenya.
authors.forename: Gilbert O
authors.initials: GO
authors.lastname: Kokwaro
authors.affiliation: School of Pharmacy, MCPHS University, Worcester, Massachusetts, United States of America.
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Ochieng
authors.affiliation: ITROMID, Jomo Kenyatta University of Science and Technology, Nairobi, Kenya.
authors.forename: Anne W T
authors.initials: AW
authors.lastname: Muigai
authors.affiliation: Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya.|Department of Chemical Science and Technology, Technical University of Kenya, Nairobi, Kenya.
authors.forename: Florence A
authors.initials: FA
authors.lastname: Oloo
authors.affiliation: Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya.|Institute of Healthcare Management, Strathmore University, Nairobi, Kenya.|Kenya Medical Research Institute, Nairobi, Kenya.|Immunology and Infectious Diseases Department, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Washingtone
authors.identifier: http://orcid.org/0000-0002-9035-4405
authors.initials: W
authors.lastname: Ochieng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007630:Kenya; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D019829:Nevirapine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine