Assessment of automated genotyping protocols as tools for surveillance of HIV-1 genetic diversity

Publication

Title: Assessment of automated genotyping protocols as tools for surveillance of HIV-1 genetic diversity
Authors: Gifford R, de Oliveira T, Rambaut A, Myers RE, Gale CV, Dunn D, Shafer R, Vandamme AM, Kellam P, Pillay D; UK Collaborative Group on HIV Drug Resistance.
Journal: AIDS,20(11):1521-9 (2006)

Abstract

BACKGROUND: The routine use of drug resistance testing provides an abundant source of HIV-1 sequence data. However, it is not clear how reliable standard genotyping of these sequences is for describing HIV-1 genetic variation and for detecting novel genetic variants and epidemiological trends.

OBJECTIVES: To compare assignment of HIV-1 resistance test sequences to reference strains across commonly used genotyping protocols.

METHODS: Subtype assignments were compared across three standard genotyping protocols for 10 537 resistance test sequences, representing approximately one-fifth of all reported infections in the United Kingdom. Sequences that were inconsistently genotyped across methods, or that were unassigned by at least one method, were examined for evidence of recombination using sliding-window-based approaches.

RESULTS: Although agreement across methods was high for subtypes B, C and H, it was generally much lower (< 50%) for other subtypes. Disagreement between methods typically involved closely related, but epidemiologically distinct, groups or involved a significant proportion ( approximately 12%) of divergent sequences in which analysis revealed widespread evidence of recombination and a remarkable diversity of unusual recombinant forms.

CONCLUSIONS: With frequent long-distance transfer of viral strains and widespread recombination between them, genetic and epidemiological relationships within HIV-1 are becoming increasingly complex. Current methods of subtype assignment vary in their ability to identify novel genetic variants and to distinguish epidemiologically distinct strains. Capturing meaningful epidemiological information from resistance test data will require a critical understanding of the methodologies used in order to appreciate the possible sources of error and misclassification.

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Citation: Gifford R, de Oliveira T, Rambaut A, Myers RE, Gale CV, Dunn D, Shafer R, Vandamme AM, Kellam P, Pillay D; UK Collaborative Group on HIV Drug Resistance. Assessment of automated genotyping protocols as tools for surveillance of HIV-1 genetic diversity AIDS,20(11):1521-9 (2006).

Media Coverage of this Publication:

Drug Resistance Increasing in Children - AIDSmap - 2011-06-27

Indeed, drug resistance is emerging in children on ART in South Africa.

High noon in Libya - Nature - 2007-07-19

This week sees yet another crisis point in the Libyan case of six foreign health professionals sentenced to death on charges of injecting hundreds of children with HIV. Declan Butler traces the efforts of scientists to help establish the truth.

Genetic Analysis Clears Accused Medics - Science - 2006-12-20

A new molecular study provides the strongest scientific evidence yet that six foreign medics held in Libya are innocent of charges that they deliberately infected more than 400 children with HIV. Accumulated mutations in the virus genomes reveal that the outbreak began well before the medics arrived in the country. The Libyan supreme court is set to decide on 19 December whether to execute the medics. It is unclear whether the new study will influence its verdict.

New evidence in Libyan HIV trial - New Scientist - 2006-12-20

New and compelling scientific evidence has emerged in support of five Bulgarian nurses and a Palestinian doctor accused of deliberately spreading HIV to 426 Libyan children in 1998.

Libya sentences medics to death - BBC - 2006-12-19

A Libyan court has sentenced five Bulgarian nurses and a Palestinian doctor to death for knowingly infecting hundreds of Libyan children with HIV.

Medics face death while Libya uses HIV children as diplomatic pawns - The Guardian - 2006-12-17

Alex Duval Smith The Observer, Sunday 17 December 2006 13.12 GMT - The death in Libya six weeks ago of nine-year-old Marwa Annouiji from Aids was much more than just another developing world statistic. In her short, life, dominated by illness, the frail child was a pawn in a high-level game of international relations. Marwa, from al-Bayda on the Mediterranean coast, was the 52nd Libyan child to die as a result, Libya claims, of a deliberate operation by foreign medical workers to pump HIV-infected blood into 426 girls and boys at the al-Fatah Hospital in Benghazi.

New scientific evidence in Libya HIV death penalty case - University of Oxford - BluePrint News - 2006-12-07

OXFORD - New molecular evidence from Oxford Zoology Department casts significant doubt on charges against six medical workers who are facing execution in Libya. The medical workers are charged with deliberately contaminating more than 400 children with HIV in 1998.However, new evidence published online in Nature from the Evolutionary Biology Group at Oxford, in collaboration with several European universities, shows that the subtype of HIV involved began infecting patients well before the medical workers arrived in Libya.

New Evidence Disputes Libya Case in H.I.V. Trial - NY Times - 2006-12-07

LONDON, Dec. 6 (Reuters) - Scientists have produced new evidence that casts doubt on charges against five Bulgarian nurses and a Palestinian doctor accused by Libya of deliberately infecting 426 children with the virus that causes AIDS in 1998.

Study backs Libya HIV case medics - BBC - 2006-12-06

LONDON - Scientists have cast doubt on charges that five Bulgarian nurses and a Palestinian doctor deliberately infected Libyan children with HIV. The medics could face the death penalty if found guilty by a court in Tripoli later this month.

Molecular HIV evidence backs accused medics - Nature - 2006-12-06

International experts in DNA forensics say that a paper published online by Nature this week provides a firm alibi for the six medical workers facing the death penalty in Libya. The workers have been charged with deliberately infecting more than 400 children with HIV in 1998.