AEGiS-Glasgow [O4] NNRTI mutations are efficiently transmitted within clusters of new HIV infections

Ninth International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 9-13 November 2008

NNRTI MUTATIONS ARE EFFICIENTLY TRANSMITTED WITHIN CLUSTERS OF NEW HIV INFECTIONS

J Int AIDS Soc 2008, 11(Suppl 1):O4 doi:10.1186/1758-2652-11-S1-O4

BG Brenner¹, T d'Aquin Toni¹, M Roger², JP Routy³, D Moisi¹ and MA Wainberg¹
¹McGill AIDS Centre, Jewish General Hospital, Montreal, Canada; ²Centre Hospitalier de l'Université de Montréal, Montréal, Canada; ³McGill University Health Centre, Montreal, Quebec, Canada

PURPOSE OF THE STUDY: We have shown that almost half of all primary/recent infections (PHI) in Quebec occur within clusters (J Infect Dis. 2007 Apr 1;195(7):951-9). Now, we have evaluated whether transmission of mutations associated with drug resistance also occurs within clusters.

METHODS: HIV-1 pol subtype B sequence data from early stage infections (<6 months post-PHI) were obtained from the Quebec PHI cohort and the provincial genotyping programs (n=859, 1998–2007). Phylogenetic analyses determined sequence interrelationships and clustering. Primary infections were classified as unique, small clusters (2–4 PHI) or larger clusters (≥5 PHI). The distributions of mutations conferring resistance to nucleoside and non-nucleoside RT inhibitors (NRTIs and NNRTIs) and protease inhibitors (PIs) were ascertained.

SUMMARY OF RESULTS: Clustering of new infections has increased from 49% to 56% from December 2005 to June 2007, and, in addition, the size of individual transmission clusters is growing over time. While the majority (95%, 403/423) of unique and small clusters identified pre-2006 represented dead end transmissions, PHI in 21 large clusters represented growing transmission cascades that increased from 6.6 ± 0.8 to 10.3 ± 1.1 PHI/cluster (n=132 and 215, respectively). High frequencies of NNRTI mutations (e.g. K103N/R, G190A, Y181C) were observed in large clusters (>5 PHI) compared with smaller ones (1–4 PHI) (12.1% vs. 3.3%, p<0.0001). In contrast, viruses harbouring NRTI mutations (in particular 215 revertants) were less frequent in clusters (7.9% vs. 3.4% vs. 1.2% and 5.8% vs. 1.7% vs. 1.1% for unique, small and large clustered transmissions, respectively) and PI mutations were also less common within clusters than in non-clustered new infections.

CONCLUSION: A significant proportion of new HIV infections in our community arise from untreated persons, who are often unaware of their serostatus, at early stages of infection, and this further results in onward transmission of both wild-type and drug-resistant infections. NNRTI mutations are detected within transmission clusters to a far higher extent than are mutations associated with other drug classes.

Brenner BG, Roger M, Routy JP, et al. “High rates of forward transmission events after acute/early HIV-1 infection”, J Infect Dis. 2007 Apr 1;195(7):951-9

2008-11-10
1758-2652-11-S1-O4

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