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The impact of transmission clusters on primary drug resistance in newly diagnosed HIV-1 infection

von Wyl, Viktor
Günthard, Huldrych F.
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Published in AIDS. 2009, vol. 23, no. 11, p. 1415-23
Abstract OBJECTIVES: To monitor HIV-1 transmitted drug resistance (TDR) in a well defined urban area with large access to antiretroviral therapy and to assess the potential source of infection of newly diagnosed HIV individuals. METHODS: All individuals resident in Geneva, Switzerland, with a newly diagnosed HIV infection between 2000 and 2008 were screened for HIV resistance. An infection was considered as recent when the positive test followed a negative screening test within less than 1 year. Phylogenetic analyses were performed by using the maximum likelihood method on pol sequences including 1058 individuals with chronic infection living in Geneva. RESULTS: Of 637 individuals with newly diagnosed HIV infection, 20% had a recent infection. Mutations associated with resistance to at least one drug class were detected in 8.5% [nucleoside reverse transcriptase inhibitors (NRTIs), 6.3%; non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3.5%; protease inhibitors, 1.9%]. TDR (P-trend = 0.015) and, in particular, NNRTI resistance (P = 0.002) increased from 2000 to 2008. Phylogenetic analyses revealed that 34.9% of newly diagnosed individuals, and 52.7% of those with recent infection were linked to transmission clusters. Clusters were more frequent in individuals with TDR than in those with sensitive strains (59.3 vs. 32.6%, respectively; P < 0.0001). Moreover, 84% of newly diagnosed individuals with TDR were part of clusters composed of only newly diagnosed individuals. CONCLUSION: Reconstruction of the HIV transmission networks using phylogenetic analysis shows that newly diagnosed HIV infections are a significant source of onward transmission, particularly of resistant strains, thus suggesting an important self-fueling mechanism for TDR.
Keywords AdultDrug Resistance, Viral/geneticsEpidemiologic MethodsFemaleHIV Infections/genetics/transmission/virologyHIV-1HumansMalePhylogeny
PMID: 19487906
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Research groups Swiss HIV Cohort Study
Unité HIV (46)
Groupe Laurent Kaiser (virologie clinique) (668)
Génomique Evolutionnaire Computationnelle (830)
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YERLY FERRILLO, Sabine et al. The impact of transmission clusters on primary drug resistance in newly diagnosed HIV-1 infection. In: AIDS, 2009, vol. 23, n° 11, p. 1415-23. https://archive-ouverte.unige.ch/unige:5456

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Deposited on : 2010-03-17

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