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.; Study Group, CoRP (2014). Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid disease progression. AIDS, 28(9), pp. 1261-1272. Lippincott Williams & Wilkins 10.1097/QAD.0000000000000293
|
Text
00002030-900000000-98358.pdf - Published Version Available under License Publisher holds Copyright. Download (805kB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology |
UniBE Contributor: |
Rauch, Andri |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0269-9370 |
Publisher: |
Lippincott Williams & Wilkins |
Language: |
English |
Submitter: |
Annelies Luginbühl |
Date Deposited: |
22 Aug 2014 07:26 |
Last Modified: |
05 Dec 2022 14:33 |
Publisher DOI: |
10.1097/QAD.0000000000000293 |
PubMed ID: |
24732774 |
BORIS DOI: |
10.7892/boris.51656 |
URI: |
https://boris.unibe.ch/id/eprint/51656 |
Actions (login required)
 |
Edit item |