Header

UZH-Logo

Maintenance Infos

Emergence of Minor Populations of Human Immunodeficiency Virus Type 1 Carrying the M184V and L90M Mutations in Subjects Undergoing Structured Treatment Interruptions


Metzner, Karin J; Bonhoeffer, Sebastian; Fischer, Marek; Karanicolas, Rose; Allers, Kristina; Joos, Beda; Weber, Rainer; et al (2003). Emergence of Minor Populations of Human Immunodeficiency Virus Type 1 Carrying the M184V and L90M Mutations in Subjects Undergoing Structured Treatment Interruptions. Journal of Infectious Diseases, 188(10):1433-1443.

Abstract

The use of structured treatment interruption (STI) in human immunodeficiency virus (HIV)-infected subjects is currently being studied as an alternative therapeutic strategy for HIV-1. The potential risk for selection of drug-resistant HIV-1 variants during STI is unknown and remains a concern. Therefore, the emergence of drug resistance in sequential plasma samples obtained from 28 subjects with chronic HIV infection was studied. They underwent 4 cycles of 2-week STI, followed by 8-week retreatment with highly active antiretroviral therapy identical to that used before STI, and they had never failed treatment before undergoing STI. At week 40, treatment was stopped for a longer period. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction, by use of allele-discriminating oligonucleotides for 2 key resistance mutations: L90M (protease) and M184V (reverse transcriptase). The approximate discriminative power was 0.1%. In 14 of 25 and in 3 of 25 subjects, the M184V and the L90M mutations, respectively, were detected as minor populations, at different times during STI. Overall, these results indicate that, in subjects undergoing multiple STIs, HIV-1 variants carrying drug-resistance mutations can emerge during periods of increased HIV-1 replication

Abstract

The use of structured treatment interruption (STI) in human immunodeficiency virus (HIV)-infected subjects is currently being studied as an alternative therapeutic strategy for HIV-1. The potential risk for selection of drug-resistant HIV-1 variants during STI is unknown and remains a concern. Therefore, the emergence of drug resistance in sequential plasma samples obtained from 28 subjects with chronic HIV infection was studied. They underwent 4 cycles of 2-week STI, followed by 8-week retreatment with highly active antiretroviral therapy identical to that used before STI, and they had never failed treatment before undergoing STI. At week 40, treatment was stopped for a longer period. Minor populations of drug-resistant variants were detected by quantitative real-time polymerase chain reaction, by use of allele-discriminating oligonucleotides for 2 key resistance mutations: L90M (protease) and M184V (reverse transcriptase). The approximate discriminative power was 0.1%. In 14 of 25 and in 3 of 25 subjects, the M184V and the L90M mutations, respectively, were detected as minor populations, at different times during STI. Overall, these results indicate that, in subjects undergoing multiple STIs, HIV-1 variants carrying drug-resistance mutations can emerge during periods of increased HIV-1 replication

Statistics

Citations

Dimensions.ai Metrics
108 citations in Web of Science®
113 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

5 downloads since deposited on 20 Sep 2018
5 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:15 November 2003
Deposited On:20 Sep 2018 13:23
Last Modified:24 Nov 2018 02:52
Publisher:Oxford University Press
ISSN:0022-1899
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1086/379215
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101086379215 (Library Catalogue)

Download

Download PDF  'Emergence of Minor Populations of Human Immunodeficiency Virus Type 1 Carrying the M184V and L90M Mutations in Subjects Undergoing Structured Treatment Interruptions'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 343kB
View at publisher