Epidemiologically linked transmission of HIV-1 illustrates the impact of host genetics on virological outcome

Abstract

The diversity of HIV-1 and human genetics complicates our ability to determine the impact of treatment during primary HIV-1 infection on disease outcome. Here, we show, in a small group infected with virtually identical HIV-1 strains and treated during primary HIV-1 infection, that patients expressing protective human leucocyte antigen alleles had lower viral loads following treatment discontinuation. These data suggest that genetic factors play an important role in the outcome of HIV-1 infection despite early therapy.

Figure 1. Epidemiologically-linked transmission of HIV-1

A) Longitudinal viral loads and CD4+ T cell counts are shown for all four subjects over a period of 900 days after presentation with primary HIV-1 infection. Lines in blue indicate the CD4+ T cell count, while lines in black indicate the viral loads in each subject. Grey shaded areas indicate the time on antiretroviral therapy in each subject. Inset shows the route of transmission of HIV-1 from subject “A” to subject “B” and “C”, while subject “D was subsequently infected by subject ”C”. B) HIV pol sequences from the four transmission subjects and nineteen other HIV chronic infected subjects from the same cohort were compared using a neighbour-joining phylogenetic tree. Sequences from the four subjects (boxed) cluster independently from sequences derived from other subjects. Scale bar indicates the genetic distance along the branches. Bootstrap values >600 are shown.