Background:  There is evidence for an increasing prevalence of transmitted drug-resistant HIV-1 in Europe and the U.S. However, the overall impact of this phenomenon on the spread of resistance within the community as a whole is, to some extent, dependant on the stability of these viruses within the plasma of infected individuals. To date it has not been demonstrated that secondary transmission of resistance can occur. 

Methods:  Contact tracing of partners of individuals infected with resistant virus in a prospective UK surveillance scheme was undertaken. Nested RT PCR and subsequent sequencing of HIV-1 pol, gag, and env genes was undertaken using the Beckman CEQ 2000. Sequence relatedness was inferred by phylogenetic analysis using  Clustal X, and  MEGA 2.  Neighbor-joining trees were constructed the using the Tamura Nei substitution model. Cloning of the C2,V3 region of the env gene from semen and blood samples  is underway to assess the degree of compartmentalisation of virus between blood and semen.  

Results:  5 partner pairs were identified in which transmission of resistance-associated mutations was suspected. All cases of transmission were strongly supported by phylogenetic analysis. In 1 case, 3 individuals linked epidemiologically were identified.  Person A was nucleoside analogue experienced, and a sample provided in 1995 showed the RT mutations: M41L, E44A/E, D67N/D, T69D/N/A, V118I/V, L210W, and T215D/N. He subsequently died in 1995. His sexual partner (person B) was first diagnosed HIV+ in 1994, and at that time, RT mutations M41L, E44D, V118I, L210W, and T215D were present in his plasma virus. He responded poorly to nucleoside analogue therapy, and stopped treatment in early 1998. 6 months following treatment interruption, his plasma and semen virus showed the presence of identical resistance-associated mutations to his pre-treatment sample, obtained 4 years previously.  In mid-1998, a sexual partner of person B (person C) underwent a documented seroconversion, his plasma virus showing RT mutations M41L, E44D, L210W and T215D.  Phylogenetic analysis of viruses from A, B, and C, in comparison with geographically and temporally related viruses, demonstrated close linkage between the viruses in all 3 genes (bootstrap support > 95%).

Conclusions:  We demonstrate a transmission chain of drug resistant HIV-1. Of interest, virus containing key RT mutations persisted over a 4-year period, despite intermittent nucleoside analogue therapy. This case illustrates the potential for further spread of drug resistant HIV-1.