HIV-1 Transmission Cluster with M41L ‘Singleton’ Mutation and Decreased Transmission of Resistance in Newly Diagnosed Swedish Homosexual Men

Abstract

To investigate the prevalence of HIV-1 with major drug resistance-associated mutations among 261 men who have sex with men (MSM) who were newly diagnosed as HIV-1-infected at Venhälsan, Stockholm, between 1992-2002. Major resistance-associated mutations were identified using an in-house method on stored plasma samples collected within 6 months of diagnosis. Additional samples were investigated from selected patients. Phylogenetic tree analyses were used to study evolutionary relationships between the viruses. Epidemiological data were retrieved from the partner notification investigations and the medical records. Informed consent as well as results from the resistance test were available for 201 out of 261 patients (77%) diagnosed during 1992-2002. Viruses from 28 of these 201 patients (14%) displayed major resistance-associated mutations; 27 of these viruses displayed only zidovudine/stavudine resistance-associated mutations. None of the patients displayed resistance mutations to protease inhibitors. The prevalence of resistance-associated mutations decreased over time; 20% in 1992-1996 versus 9% in 1997-2002 (P=0.04). A transmission cluster involving six patients with a singleton M41L mutation was identified. These viruses were phenotypically sensitive to zidovudine and stavudine. The M41L mutation, as well as most other resistance mutations, was stable for many years after transmission and may have been fixated by other putative compensatory mutations. In this Swedish population of MSM with newly diagnosed HIV-1 infection, the prevalence of resistance-associated mutations decreased over time. Reversion of resistance-associated mutations following transmission was slow and incomplete. A large transmission cluster with an interesting M41L singleton mutation was also observed.