Viral suppression following switch to second-line antiretroviral therapy: associations with NRTI resistance and 'sub-therapeutic' drug concentrations prior to switch.


Johnston, V; Cohen, K; Wiesner, L; Morris, L; Ledwaba, J; Fielding, KL; Charalambous, S; Churchyard, G; Phillips, A; Grant, AD; (2014) Viral suppression following switch to second-line antiretroviral therapy: associations with NRTI resistance and 'sub-therapeutic' drug concentrations prior to switch. The Journal of infectious diseases, 209 (5). pp. 711-20. ISSN 0022-1899 DOI: 10.1093/infdis/jit411

[img]
Preview
Text - Published Version
License:

Download (277Kb) | Preview

Abstract

BACKGROUND: High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification.<br/> METHODS: Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression.<br/> RESULTS: One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77-263) and 4.3 log10 copies/mL (IQR, 3.8-4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥ 1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL.<br/> CONCLUSIONS: Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Antimicrobial Resistance Centre (AMR)
Tropical Epidemiology Group
PubMed ID: 23943851
Web of Science ID: 331873700011
URI: http://researchonline.lshtm.ac.uk/id/eprint/1247713

Statistics


Download activity - last 12 months
Downloads since deposit
497Downloads
304Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item