Random lopinavir concentrations predict resistance on lopinavir-based antiretroviral therapy.

TitleRandom lopinavir concentrations predict resistance on lopinavir-based antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2016
AuthorsCourt R, Gordon M, Cohen K, Stewart A, Gosnell B, Wiesner L, Maartens G
JournalInt J Antimicrob Agents
Volume48
Issue2
Pagination158-62
Date Published2016 Aug
ISSN1872-7913
KeywordsAdolescent, Adult, Anti-HIV Agents, Child, Child, Preschool, Cross-Sectional Studies, Diagnosis, Differential, Drug Resistance, Viral, Female, HIV Infections, Humans, Infant, Lopinavir, Male, Medication Adherence, Middle Aged, Plasma, South Africa, Treatment Failure, Young Adult
Abstract

Considering that most patients who experience virological failure (VF) on lopinavir-based antiretroviral therapy (ART) fail due to poor adherence rather than resistance, an objective adherence measure could limit costs by rationalising the use of genotype antiretroviral resistance testing (GART) in countries with access to third-line ART. A cross-sectional study was conducted in a resource-limited setting at two large clinics in Kwazulu-Natal, South Africa, in patients experiencing VF (HIV-RNA > 1000 copies/mL) on lopinavir-based ART who had undergone GART. Associations between major protease inhibitor (PI) resistance mutations and random plasma lopinavir concentrations were explored. A total of 134 patients, including 31 children, were included in the analysis. The prevalence of patients with major PI resistance mutations was 20.9% (n = 28). A random lopinavir concentration above the recommended minimum trough of 1 µg/mL [adjusted odds ratio (aOR) = 5.81, 95% confidence interval (CI) 2.04-16.50; P = 0.001] and male sex (aOR = 3.19, 95% CI 1.22-8.33; P = 0.018) were predictive of the presence of at least one major PI resistance mutation. Random lopinavir concentrations of <1 µg/mL had a negative predictive value of 91% for major PI resistance mutations. Random lopinavir concentrations are strongly associated with the presence of major PI resistance mutations. Access to costly GART in patients experiencing VF on second-line ART could be restricted to patients with lopinavir concentrations above the recommended minimum trough of 1 µg/mL or, in areas where GART is unavailable, could be used as a criterion to empirically switch to third-line ART.

DOI10.1016/j.ijantimicag.2016.04.030
Alternate JournalInt. J. Antimicrob. Agents
PubMed ID27345268
PubMed Central IDPMC4979317
Grant ListU01 AI068632 / AI / NIAID NIH HHS / United States
UM1 AI068632 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States