Objective: 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.
Design: 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.
Results: 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.
Conclusion: 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.
aAIDS Research Institute -IrsiCaixa-iInstitut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
bInstitute of Microbiology, University Hospital Center and University of Lausanne, Lausanne
cUniversity Clinic of Infectious Diseases, University Hospital Bern and University of Bern, Bern, Switzerland
dUniversidad Complutense de Madrid, Madrid, Spain
eMonogram Biosciences, South San Francisco, California, USA
fCentre d’Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), Badalona
gBanc de Sang i Teixits, Barcelona
hUniversitat de Vic (UVic-UCC), Vic
iInstitució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
*Judith Dalmau and Margalida Rotger contributed equally to this article.
†Amalio Talenti, Javier Martinez-Picado and Julia G. Prado contributed equally to the work.
Correspondence to Julia G. Prado, PhD, AIDS Research Institute – IrsiCaixa – Hospital Universitari Germans Trias i Pujol, Crta Canyet s/n, 08916 Badalona, Barcelona, Spain. Tel: +34 93 465 63 74 ext 171; e-mail: email@example.com
Received 18 December, 2013
Revised 26 March, 2014
Accepted 27 March, 2014
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