Limited evolution despite years of measurable viremia in a cART-treated seronegative HIV-1 positive individual

<jats:title>Abstract</jats:title><jats:p>Understanding the role that antibodies play in controlling HIV-1 infection and in the dynamics that underpin the formation of the HIV-1 reservoir are important steps towards combatting this global disease. To address these gaps, we performed whole-genome, deep sequence analysis of longitudinal plasma HIV-1 samples from an individual who remained absent of detectable anti-HIV-1 antibodies for 4 years post infection. These analyses reveal limited evolution despite months of measurable viremia during treatment with cART. By simultaneously analysing the viral and evolutionary dynamics of this unique individual with a mathematical model, we propose a role for antibodies in reducing viral infectivity. We further demonstrate how our data are consistent with a theory of rapid activation of latently infected cells prior to effective viral suppression. Our study supports and elucidates a recent finding that although the latent reservoir persists for years once virus is effectively suppressed, prior to this, viral strains within the reservoir turn over rapidly. The implications for a cure are major.</jats:p>