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Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid disease progression.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Dalmau Judith, Rotger Margalida, Erkizia Itziar, Rauch Andri, Reche Pedro, Pino Maria, Esteve Anna, Palou Eduard, Brander Christian, Paredes Roger, Phung Pham, Clotet Bonaventura, Telenti Amalio, Martinez-Picado Javier, Prado Julia G,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal AIDS (London, England)
Volume (Issue) 28(9)
Page(s) 1261 - 72
Title of proceedings AIDS (London, England)
DOI 10.1097/qad.0000000000000293

Open Access

URL http://dx.doi.org/10.7892/boris.51656
Type of Open Access Repository (Green Open Access)

Abstract

The study of HIV-1 rapid progressors has been limited to specific case reports. Nevertheless, identification and characterization of the viral and host factors involved in rapid progression are crucial when attempting to uncover the correlates of rapid disease outcome. We carried out comparative functional analyses in rapid progressors (n = 46) and standard progressors (n = 46) early after HIV-1 seroconversion (≤1 year). The viral traits tested were viral replicative capacity, co-receptor usage, and genomic variation. Host CD8(+) T-cell responses, humoral activity, and HLA immunogenetic markers were also determined. Our data demonstrate an unusual convergence of highly pathogenic HIV-1 strains in rapid progressors. Compared with standard progressors, rapid progressor viral strains show higher in-vitro replicative capacity (81.5 vs. 67.9%; P = 0.025) and greater X4/DM co-receptor usage (26.3 vs. 2.8%; P = 0.006) in early infection. Limited or absent functional HIV-1 CD8(+) T-cell responses and neutralizing activity were measured in rapid progressors. Moreover, the increase in common HLA allele-restricted CD8(+) T-cell escape mutations in rapid progressors acts as a signature of uncontrolled HIV-1 replication and early impairment of adaptive cellular responses. Our data support a dominant role for viral factors in rapid progressors. Robust HIV-1 replication and intrinsic viral properties limit host adaptive immune responses, thus driving rapid disease progression.
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