NDLI: Frequent polymorphism at drug resistance sites in HIV-1 protease and reverse transcriptase.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kearney, Mary Palmer, Sarah Maldarelli, Frank Shao, Wei Polis, Michael A. Mican, JoAnn Rock-Kress, Diane Margolick, Joseph B. Coffin, John M. Mellors, John W.
Description	Country affiliation: United States Author Affiliation: Kearney M ( HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702-1201, USA. kearneym@ncifcrf.gov)
Abstract	BACKGROUND: Failure of antiretroviral therapy may result from the selection of pre-existing, drug-resistant HIV-1 variants, but the frequency and type of such variants have not been defined. OBJECTIVE: We used single genome sequencing (SGS) to characterize the frequency of polymorphism at drug resistance sites in protease (PR) and reverse transcriptase (RT) in plasma samples from antiretroviral naive individuals. METHODS: A total of 2229 pro-pol sequences in 79 plasma samples from 30 patients were analyzed by SGS. A mean of 28 single genome sequences was obtained from each sample. The frequency of mutations at all PR and RT sites was compared to those associated with drug resistance. RESULTS: We detected polymorphism at one or more drug resistance sites in 27 of 30 (90%) patients. Polymorphism at positions 179 and 215 of RT was most common, both occurring in 23% of patients. Most (68%) of other drug resistance sites were polymorphic with an average of 3.2% of genomes per sample containing at least one variant from wild type. Seven drug resistance sites were polymorphic in more than 1% of genomes: PR position 33; RT positions 69, 98, 118, 179, 210, and 215. Although frequencies of synonymous polymorphism were similar at resistance and nonresistance sites, nonsynonymous polymorphism were significantly less common at drug resistance sites, implying stronger purifying selection at these positions. CONCLUSIONS: HIV-1 variants that are polymorphic at drug resistance sites pre-exist frequently as minor species in antiretroviral naive individuals. Standard genotype techniques have grossly underestimated their frequency.
File Format	HTM / HTML
ISSN	02699370
e-ISSN	14735571
DOI	10.1097/QAD.0b013e3282f29478
Journal	AIDS
Issue Number	4
Volume Number	22
Language	English
Publisher	Lippincott Williams & Wilkins
Publisher Date	2008-02-19
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Immunology Drug Resistance, Viral Genetics Hiv Infections Hiv Protease Hiv Reverse Transcriptase Hiv-1 Polymorphism, Genetic Genotype Drug Therapy Mutation Multicenter Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Immunology and Allergy Immunology

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