Dataset Information

Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch.

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.

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.

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.

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.

SUBMITTER: Johnston V

PROVIDER: S-EPMC3923537 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch.

Johnston Victoria V Cohen Karen K Wiesner Lubbe L Morris Lynn L Ledwaba Johanna J Fielding Katherine L KL Charalambous Salome S Churchyard Gavin G Phillips Andrew A Grant Alison D AD

The Journal of infectious diseases 20130813 5

<h4>Background</h4>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.<h4>Methods</h4>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 pr ...[more]

PMID: 23943851

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Dataset Information

Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch.

Background

Methods

Results

Conclusions

Publications

Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch.

Similar Datasets

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