Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms: data from seroconverters in the CASCADE collaboration from 1987 to 2003


Masquelier, B; Bhaskaran, K; Pillay, D; Gifford, R; Balestre, E; Jorgensen, LB; Pedersen, C; van der Hoek, L; Prins, M; Balotta, C; Longo, B; Kucherer, C; Poggensee, G; Ortiz, M; de Mendoza, C; Gill, J; Fleury, H; Porter, K; (2005) Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms: data from seroconverters in the CASCADE collaboration from 1987 to 2003. Journal of acquired immune deficiency syndromes (1999), 40 (5). pp. 505-11. ISSN 1525-4135 DOI: https://doi.org/10.1097/01.qai.0000186361.42834.61

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Abstract

OBJECTIVES: To examine factors influencing the rate of transmitted drug resistance (TDR) among seroconverters, with particular emphasis on 3 widely used genotypic drug resistance algorithms. METHODS: The study used data from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration of seroconverter cohorts in Europe and Canada. Genotypic resistance data were derived within 18 months of the last seronegative test or date of laboratory evidence of acute infection and before the initiation of antiretroviral therapy. The Stanford algorithm was used to analyze each individual's nucleotide sequence. A multivariate logistic model was used to assess independent relationships between the presence of TDR and exposure category, sex, age at seroconversion, and year of seroconversion. The paper also describes 3 alternative definitions of resistance: the Stanford algorithm, the key resistance mutations defined by the International AIDS Society, and the Agence Nationale de Recherches sur le Sida (ANRS) algorithm. RESULTS: Forty-five of 438 patients (10.3%) seroconverting between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty patients (9.1%) showed resistance mutations to only 1 class of antiretroviral drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral therapy. It was suggested that individuals seroconverting later in calendar time were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003, respectively, compared with pre-1996; P trend = 0.08). This trend was apparent regardless of the definition of TDR used. The total estimated proportion of individuals with TDR varied between 10.3% and 15.5% according to which definition was used. CONCLUSIONS: Evidence was found for the rise of TDR over time. A specific definition of what constitutes TDR rather than a simple list of mutations is needed.

Item Type: Article
Keywords: Adolescent, Adult, Aged, Algorithms, Anti-HIV Agents/pharmacology, Canada/epidemiology, Cohort Studies, Drug Resistance, Viral/ genetics, Europe/epidemiology, Female, Genotype, HIV Seropositivity/ epidemiology/ transmission/virology, HIV-1/classification/ drug effects/genetics, Humans, International Cooperation, Male, Middle Aged, Mutation, Phylogeny, Reverse Transcriptase Inhibitors/pharmacology, Adolescent, Adult, Aged, Algorithms, Anti-HIV Agents, pharmacology, Canada, epidemiology, Cohort Studies, Drug Resistance, Viral, genetics, Europe, epidemiology, Female, Genotype, HIV Seropositivity, epidemiology, transmission, virology, HIV-1, classification, drug effects, genetics, Humans, International Cooperation, Male, Middle Aged, Mutation, Phylogeny, Reverse Transcriptase Inhibitors, pharmacology
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 16284524
Web of Science ID: 233694600001
URI: http://researchonline.lshtm.ac.uk/id/eprint/7352

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