Background:  Concern about HIV-1 dual infection is increasing although reported prevalence remains low. In addition to the risk of additional acquired ART resistance, dual infection may result in accelerated disease progression and treatment failure. We therefore enhanced surveillance for dual infections during routine HIV-1 genotypic antiretroviral resistance testing (GART) in our genetically diverse cohort.  

Methods:  GART was performed using a protocol derived from the Viroseq kit (Celera) modified by the substitution of an in-house panel of sequencing primers with broad cross-clade binding ability. GART data were further examined for indications of dual infections using polymorphism frequency as an initial filter, and subsequent close analysis for a combination of mixed and discordant sequences within compiled contigs. Disentanglement of such sequences was followed by standard GART typing and analysis using REGA and the Stanford database.

Results:  We identified 3 inter-clade HIV-1 dual infections. All are men who have sex with men (MSM) who report sexual contacts exclusively in the UK. Patients 2 and 3 had dual infection on baseline genotype after diagnosis and have remained stable off ART to date. Patient 1 had a first genotype requested prior to initiation of ART due to declining CD4 count. There were no significant drug-resistance mutations in any of the viral sequences.

Conclusions:  These cases are the first to demonstrate the recent emergence of inter-clade dual HIV-1 infection due to sexual transmission between MSM in the UK. We have detected clades previously rare in MSM. This may reflect the changing epidemiology of HIV subtypes in London with increasing cross-over between otherwise distinct epidemiological groups. Dual infection has an established adverse effect on HIV disease outcome but inter-clade infections are of additional concern. Different clades may have differential responses to ART and drug-resistance pathways may differ, making treatment more difficult. There is an increased risk of HIV recombination to form new unique or circulating viral forms and implications for future vaccine design. These results suggest that safer-sex messages to patients must be reinforced and that public health initiatives targeting specific groups may have to take account of a larger degree of viral mixing. Continued surveillance for dual HIV-1 infection is required.