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AIDS. 2018 Dec 21. doi: 10.1097/QAD.0000000000002105. [Epub ahead of print]

Caution is needed in interpreting HIV transmission chains by ultra-deep sequencing.

Author information

1
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, F-75013 Paris, France.
2
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Department of Infectious Diseases, F-75013 Paris, France.
3
Department of Internal Medicine, Hôpital Pitié-Salpêtrière, AP-HP, F75013, Paris, France.
4
Centre National de Référence du VIH, laboratoire de Virologie, CHRU de Tours, Inserm U1259, Université François Rabelais, Tours, France.
5
Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

Abstract

OBJECTIVES:

Molecular epidemiology is applied to various aspects of HIV transmission analyses. With ultra-deep sequencing (UDS), in-depth characterisation of transmission episodes involving minority variants are permitted. We explored HIV-1 epidemiological linkage and evaluated characteristics of transmission dynamics and transmitted drug resistance (TDR) detection through the added value of UDS.

DESIGN:

HIV pol gene fragments were sequenced by UDS and Sanger sequencing (SS) on samples of 70 HIV-1 infected, treatment-naïve recently diagnosed men having sex with men (MSM).

METHODS:

Pairwise genetic distances and maximum likelihood phylogenies were computed. Transmission events were identified as clades with branch support ≥70% and intra-clade genetic difference <4.5%. TDR mutations were recognised from the TDR consensus list. Transmission directionality, directness and inoculum size were inferred from tree topologies.

RESULTS:

Both datasets concurred in the identification of 7 transmission pairs and 1 cluster of 3 patients. With UDS, direction of transmission was inferred in 4/8 chains. Evidence for multiple founder viruses was found in 2/8 chains. No transmission of minority resistant variants was evidenced. TDR mutations prevalence in protease and reverse transcriptase fragments was 4.3% with SS and 18.6% with UDS.

CONCLUSIONS:

While SS and UDS identified the same transmission chains, UDS provided additional information on founder viruses, direction of transmission and levels of TDR. Nevertheless, topology of clusters was not always consistent across gene fragments, calling for a cautious interpretation of the data. Moreover, unobserved intermediary links cannot be excluded. Phylogenetic analysis use as a forensic technique for HIV transmission investigations is risky.

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