16th International HIV Drug Resistance Workshop 12-16 June 2007, Barbados

POPULATION-BASED SURVEILLANCE SHOW TRANSMISSION CASCADES OF HIV-1 VARIANTS HARBOURING DRUG RESISTANCE

Antivir Ther. 2007; 12:S44 (abstract no. 37)

BG Brenner ^1,2, D Moisi¹, M Roger³, JP Routy², J Cox², MA Wainberg^1,2 and the Quebec Primary HIV Infection (PHI) Study Group
¹McGill AIDS Centre, Jewish General Hospital, Quebec, Canada; ²Centre Hospitaliers de l’Université de McGill, Canada; ³L’Université de Montréal, Quebec, Canada

BACKGROUND: Our recent study used a population-based genotyping strategy to show that >50% of primary infections segregate into clusters, suggestive of high rates of forward transmission events (J Infect Dis. 2007 Apr 1;195(7):951-9). This study ascertained the cumulative implications of clustering on transmitted drug resistance.

METHODS: HIV-1 pol subtype B sequences from early stage infections (<6 months post-PHI) were obtained from the Quebec PHI cohort and the provincial genotyping programs (n=778, 1998–2006). Phylogenetic and maximum likelihood analyses were performed to determine interrelationships among early stage infections and identify sequence clustering having high bootstrap values (>98%) and genetic distances of >0.015%. Comparative analysis linked sequences of genotyped PHI with infections from chronically-infected potential transmitter populations (n=990). The distributions of mutations conferring resistance to thymidine analogues (TAMs), nucleoside and non-nucleoside RT inhibitors (NRTIs and NNRTIs), and protease inhibitors (PIs) were ascertained.

RESULTS: Viral sequences were obtained from primary infections (~4.9 mean months post-seroconversion). Phylogenetic analysis showed that infections segregated into 338 unique primary infections, 82 small clusters (2.6 ±0.8 PHI, n=216) and 23 large clusters (9.2 ± 1.0 PHI, n=224) representing 43.3%, 27.8% and 28.9% of transmission events, respectively. TAMs and 215 revertants were significantly less frequent in clustered transmissions (8.3% versus 5.0% versus 0.8% and 6.2% versus 1.9% versus 0.4%, P=0.0001 and P=0.0002, respectively). In contrast, transmission cascades led to higher frequencies of NNRTIs (K103N/R and G190A) in large clusters (>5 PHI), as compared to small clusters (1–4 PHI), (14.3% versus 5.6%, P<0.0001). Chronic infections that coclustered with PHI included wild-type (WT) infections, as well as sixteen chronic infections harbouring M184V where WT ancestral forms were transmitted. Four NNRTI transmission cascades were noted.

CONCLUSIONS: In a North American setting offering universal access to health care, antiretroviral therapy and genotyping, the majority of new infections arise from untreated persons at early stages of infection, often unaware of their HIV serostatus. This may result in onward transmission of HIV drug-resistant infections. Prevention and diagnostic strategies, as well as routine genotyping, are needed for early stage infections.

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2007-06-12
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