Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques

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Abstract

Prolonged antiretroviral therapy (ART) is not likely to eradicate human immunodeficiency virus type I (HIV-I) infection. Here we explore the effect of therapeutic immunization in the context of ART during primary infection using the simian immunodeficiency virus (SIV251) macaque model. Vaccination of rhesus macaques with the highly attenuated poxvirus-based NYVAC-SIV vaccine expressing structural genes elicited vigorous virus-specific CD4+ and CD8+ T cell responses in macaques that responded effectively to ART. Following discontinuation of a six-month ART regimen, viral rebound occurred in most animals, but was transient in six of eight vaccinated animals. Viral rebound was also transient in four of seven mock-vaccinated control animals. These data establish the importance of antiretroviral treatment during primary infection and demonstrate that virus-specific immune responses in the infected host can be expanded by therapeutic immunization.

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Figure 1: Statistical analysis of the plasma virus load and proliferative response to p27 Gag and gp120 in the immunized ART-treated macaques from groups A(▪), B() and C().
Figure 2: Inverse correlation between LPR and viremia.
Figure 3: Induction of CD8+ t cell response by NYVAC-SIV-gpe immunization.
Figure 4: Viral load, p27 Gag and gp120 LPR in all animal groups before and during immunization and ART and after ART suspension.
Figure 5: Mamu-A*01-Gag 181-tetramer staining in ex vivo PBMC of macaques following ART discontinuation.

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Acknowledgements

We thank R. Klausner, M. Klein, R. Yarchoan and R. Little for discussion; R. Pal for the SIV251 stock; C. Mclaren for Stavudine; X. Wang for making the tetramers; the ABL staff for animal care; and S. Snodgrass for editorial assistance. M.Poudyal. was supported by the National Foundation for Biomedical Research as a Clinical Research Training Program Scholar.

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Correspondence to Genoveffa Franchini.

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