Abstract
BackgroundThe evolution of HIV-1 and its immune escape to autologous neutralizing antibodies (Nabs) during the acute/early phases of infection have been analyzed in depth in many studies. In contrast, little is known about neither the long-term evolution of the virus in patients who developed broadly Nabs (bNabs) or the mechanism of escape in presence of these bNabs.ResultsWe have studied the viral population infecting a long term non progressor HIV-1 infected patient who had developed broadly neutralizing antibodies toward all tier 2/3 viruses (6 clades) tested, 9 years after infection, and was then followed up over 7 years. The autologous neutralization titers of the sequential sera toward env variants representative of the viral population significantly increased during the follow-up period. The most resistant pseudotyped virus was identified at the last visit suggesting that it represented a late emerging escape variant. We identified 5 amino acids substitutions that appeared associated with escape to broadly neutralizing antibodies. They were V319I/S, R/K355T, R/W429G, Q460E and G/T463E, in V3, C3 and V5 regions.ConclusionThis study showed that HIV-1 may continue to evolve in presence of both broadly neutralizing antibodies and increasing autologous neutralizing activity more than 10 years post-infection.
Highlights
The real impact of the humoral response to the human immunodeficiency virus type 1 (HIV-1) in the course of infection is still a matter of debate [1,2,3,4]
In the context of HIV-1 infection, neutralizing antibodies (Nabs) appear at the early stage of the infection in most of the patients but have been described as ineffective on the long term since they do not seem to be associated with control of viral replication and disease progression [7]
We have studied the viral population infecting a long term non progressor (LTNP) HIV-1 infected patient who had developed broadly Nabs (bNabs) at a level compatible with an elite neutralizer status after at least 8 years of infection, over 7 years of follow-up
Summary
The real impact of the humoral response to the human immunodeficiency virus type 1 (HIV-1) in the course of infection is still a matter of debate [1,2,3,4]. Several years after primary infection, only a limited percentage of HIV-1 infected patients are able to develop broadly Nabs (bNabs) albeit it appeared that there was a lack of effect of bNabs on disease progression [11,13,14]. Some of these patients were characterized as elite neutralizers due the exceptional breadth and potency of their antibodies [15]. The evolution of HIV-1 and its immune escape to autologous neutralizing antibodies (Nabs) during the acute/ early phases of infection have been analyzed in depth in many studies. Little is known about neither the longterm evolution of the virus in patients who developed broadly Nabs (bNabs) or the mechanism of escape in presence of these bNabs
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