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Immune and viral correlates of "secondary viral control" after treatment interruption in chronically HIV-1 infected patients.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (5), pp. e37792. Date of Electronic Publication: 2012 May 30. - Publication Year :
- 2012
-
Abstract
- Upon interruption of antiretroviral therapy, HIV-infected patients usually show viral load rebound to pre-treatment levels. Four patients, hereafter referred to as secondary controllers (SC), were identified who initiated therapy during chronic infection and, after stopping treatment, could control virus replication at undetectable levels for more than six months. In the present study we set out to unravel possible viral and immune parameters or mechanisms of this phenomenon by comparing secondary controllers with elite controllers and non-controllers, including patients under HAART. As candidate correlates of protection, virus growth kinetics, levels of intracellular viral markers, several aspects of HIV-specific CD4+ and CD8+ T cell function and HIV neutralizing antibodies were investigated. As expected all intracellular viral markers were lower in aviremic as compared to viremic subjects, but in addition both elite and secondary controllers had lower levels of viral unspliced RNA in PBMC as compared to patients on HAART. Ex vivo cultivation of the virus from CD4+ T cells of SC consistently failed in one patient and showed delayed kinetics in the three others. Formal in vitro replication studies of these three viruses showed low to absent growth in two cases and a virus with normal fitness in the third case. T cell responses toward HIV peptides, evaluated in IFN-γ ELISPOT, revealed no significant differences in breadth, magnitude or avidity between SC and all other patient groups. Neither was there a difference in polyfunctionality of CD4+ or CD8+ T cells, as evaluated with intracellular cytokine staining. However, secondary and elite controllers showed higher proliferative responses to Gag and Pol peptides. SC also showed the highest level of autologous neutralizing antibodies. These data suggest that higher T cell proliferative responses and lower replication kinetics might be instrumental in secondary viral control in the absence of treatment.
- Subjects :
- Adult
Aged
Anti-HIV Agents therapeutic use
Antibodies, Neutralizing immunology
Biomarkers metabolism
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
Chronic Disease
Female
Follow-Up Studies
HIV Infections pathology
HIV Infections virology
HIV-1 immunology
HIV-1 physiology
Humans
Intracellular Space drug effects
Intracellular Space metabolism
Intracellular Space virology
Male
Middle Aged
Viral Proteins metabolism
Virus Replication drug effects
Anti-HIV Agents pharmacology
HIV Infections drug therapy
HIV Infections immunology
HIV-1 drug effects
HIV-1 pathogenicity
Withholding Treatment
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22666392
- Full Text :
- https://doi.org/10.1371/journal.pone.0037792