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Original article

HIV type-1 drug resistance in treatment-naive patients monitored using minority species assays: a systematic review and meta-analysis

Andrew J Buckton, Ross J Harris, Deenan Pillay, Patricia A Cane

Corresponding author name: Andrew JBuckton
Corresponding author e-mail: andrew.buckton@hpa.org.uk

Citation: Antiviral Therapy 2011; 16:9-16
doi: 10.3851/IMP1687

Date accepted: 27 May 2010
Date published online: 04 November 2010

Abstract

Background: The detection of mutations associated with drug resistance in HIV type-1 might be increased by applying minority species assays capable of identifying low frequency mutations in comparison with the use of population sequencing alone. Because minority species assays are mutation-specific, the benefit of this approach differs depending on the mutation being detected.

Methods: We performed a systematic review of published data reporting detection of genotypic drug resistance using allele-specific (AS)-PCR minority assays and by standard DNA sequencing in drug-naive populations. We calculated the fold increase of mutation detection for each study and pooled these via meta-analysis, displaying results using Forest plots.

Results: Our studies revealed an increase in detection of 1.9-fold (95% confidence interval [CI] 1.3–2.7; P<0.0005) for K103N, 4.4-fold (95% CI 1.2–16.6; P=0.026) for Y181C, 4.8-fold (95% CI 1.5–15.1; P=0.008) for L90M and 8.7-fold (95% CI 4.0–18.6; P<0.0005) for M184V. We found no relationship between AS-PCR assay sensitivity and frequency of additional mutation detection.

Conclusions: Additional detection of drug resistance mutations using AS-PCR minority mutation assays vary significantly depending on the mutation examined; however, the most marked increase in detection of resistance mutations was observed for M184V, a mutation seldom detected by standard techniques in drug-naive patients. We suggest that the presence of drug resistance mutations can be more accurately estimated using a combination of AS-PCR and standard genotyping.

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