Immunological biomarkers predict HIV-1 viral rebound after treatment interruption

Nature Communications

Volumn 6, Issue , 2015, Pages

  Hurst, Jacob ^a,b   Hoffmann, Matthias ^a   Pace, Matthew ^a,b   Williams, James P ^a   Thornhill, John ^c   Hamlyn, Elizabeth ^d   Meyerowitz, Jodi ^a   Willberg, Chris ^a,e   Koelsch, Kersten K ^f   Robinson, Nicola ^a,b,e   Brown, Helen ^a,b,e   Fisher, Martin ^g   Kinloch, Sabine ^h   Cooper, David A ^f   Schechter, Mauro ⁱ   Tambussi, Giuseppe ^j   Fidler, Sarah ^c   Babiker, Abdel ^h   Weber, Jonathan ^c   Kelleher, Anthony D ^f   Phillips, Rodney E ^a,b,e   Frater, John ^a,b,e   more..

^a JOHN RADCLIFFE HOSPITAL   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

^d KING'S COLLEGE HOSPITAL NHS FOUNDATION TRUST   (United Kingdom)

^e NATIONAL INSTITUTES OF HEALTH   (United States)

^f UNIVERSITY OF NEW SOUTH WALES   (Australia)

^g Worthing Hospital   (United Kingdom)

^h UNIVERSITY COLLEGE LONDON   (United Kingdom)

ⁱ FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

^j SAN RAFFAELE HOSPITAL   (Italy)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; CD38 ANTIGEN; CD69 ANTIGEN; CD8 ANTIGEN; D DIMER; HLA ANTIGEN CLASS 1; HLA DR ANTIGEN; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 6; LAG 3 PROTEIN; PROGRAMMED DEATH 1 LIGAND 1; TIGIT PROTEIN; TIM 3 PROTEIN; UNCLASSIFIED DRUG; VIRUS DNA; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

BIOMARKER; DISEASE TREATMENT; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE SYSTEM; PERSISTENCE;

ADULT; ALLELE; ARTICLE; CD4 CD8 RATIO; CD4 LYMPHOCYTE COUNT; CELLULAR IMMUNITY; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MAJOR CLINICAL STUDY; NONHUMAN; PREDICTION; RECURRENT INFECTION; SEROCONVERSION; T LYMPHOCYTE; TREATMENT INTERRUPTION; TREATMENT WITHDRAWAL; VIRAL REBOUND; VIREMIA; VIRUS LOAD; VIRUS TRANSCRIPTION; BLOOD; GENETICS; HIV INFECTIONS; IMMUNOLOGY; PHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL; VIROLOGY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

ANTI-HIV AGENTS; BIOMARKERS; CD4 LYMPHOCYTE COUNT; HIV INFECTIONS; HIV-1; HUMANS; VIRAL LOAD; WITHHOLDING TREATMENT;

EID: 84944258447     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9495     Document Type: Article

References (36)

1. Palella, F. J. J. et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV outpatient study investigators. N. Engl. J. Med. 338, 853-860 (1998).
2. Wada, N. et al. Cause-specific mortality among HIV-infected individuals, by CD4() cell count at HAART initiation, compared with HIV-uninfected individuals. AIDS 28, 257-265 (2014).
3. Samji, H. et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS ONE 8, e81355 (2013).
4. Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295-1300 (1997).
5. Stöhr, W. et al. Duration of HIV-1 viral suppression on cessation of antiretroviral therapy in primary infection correlates with time on therapy. PLoS ONE 8, e78287 (2013).
6. Saez-Cirion, A. et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 9, e1003211 (2013).
7. Lodi, S. et al. Immunovirologic control 24 months after interruption of antiretroviral therapy initiated close to HIV seroconversion. Arch. Intern. Med. 172, 1252-1255 (2012).
8. Goujard, C. et al. HIV-1 control after transient antiretroviral treatment initiated in primary infection: role of patient characteristics and effect of therapy. Antivir. Ther. (Lond. ) 17, 1001-1009 (2012).
9. Goulder, P. J. & Walker, B. D. HIV and HLA class I: An evolving relationship. Immunity 37, 426-440 (2012).
10. SPARTAC Trial Investigators et al. Short-course antiretroviral therapy in primary HIV infection. N. Engl. J. Med. 368, 207-217 (2013).
11. Williams, J. P. et al. HIV-1 DNA predicts disease progression and posttreatment virological control. Elife 3, e03821 (2014).
12. Fidler, S. et al. Short-Course Antiretroviral Therapy in Primary HIV Infection. N. Engl. J. Med. 368, 207-217 (2013).
13. Fellay, J. et al. A whole-genome association study of major determinants for host control of HIV-1. Science 317, 944-947 (2007).
14. Pereyra, F. et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330, 1551-1557 (2010).
15. Friendly, M. Corrgrams: exploratory displays for correlation matrices. Am. Stat. 56, 316-324.
16. Bar-Joseph, Z. , Gifford, D. K. & Jaakkola, T. S. Fast optimal leaf ordering for hierarchical clustering. Bioinformatics 17(suppl 1): S22-S29 (2001).
17. El-Sadr, W. M. et al. CD4 count-guided interruption of antiretroviral treatment. N. Engl. J. Med. 355, 2283-2296 (2006).
18. Kiepiela, P. et al. CD8 T-cell responses to different HIV proteins have discordant associations with viral load. Nat. Med. 13, 46-53 (2007).
19. Tierney, C. et al. Prognostic value of baseline human immunodeficiency virus type 1 DNA measurement for disease progression in patients receiving nucleoside therapy. J. Infect. Dis. 187, 144-148 (2003).
20. Frater, J. et al. HIV-1 specific CD4 responses in primary HIV-1 infection predict disease progression in the SPARTAC trial. AIDS 28, 699-708 (2014).
21. Conway, J. M. & Coombs, D. A stochastic model of latently infected cell reactivation and viral blip generation in treated HIV patients. PLoS Comput. Biol. 7, e1002033 (2011).
22. Wang, S. & Rong, L. Stochastic population switch may explain the latent reservoir stability and intermittent viral blips in HIV patients on suppressive therapy. J. Theor. Biol. 360, 137-148 (2014).
23. Rouzine, I. M. , Razooky, B. S. & Weinberger, L. S. Stochastic variability in HIV affects viral eradication. Proc. Natl Acad. Sci. USA 111, 13251-13252 (2014).
24. Larkin, J. et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 23-24 (2015).
25. Jones, R. B. et al. Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. J. Exp. Med. 205, 2763-2779 (2008).
26. Tian, X. et al. The upregulation of LAG-3 on T cells defines a subpopulation with functional exhaustion and correlates with disease progression in HIVinfected subjects. J. Immunol. 194, 3873-3882 (2015).
27. Larsson, M. et al. Molecular signatures of T-cell inhibition in HIV-1 infection. Retrovirology 10, 31 (2013).
28. Okazaki, T. et al. PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. J. Exp. Med. 208, 395-407 (2011).
29. Duncan, C. J. et al. High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T Cell virological synapse. J. Virol. 88, 2025-2034 (2013).
30. Williams, J. et al. Low copy target detection by Droplet Digital PCR through application of a novel open access bioinformatic pipeline, 'definetherain'. J. Virol. Methods 202, 46-53 (2014).
31. Liszewski, M. K. , Yu, J. J. & O'Doherty, U. Detecting HIV-1 integration by repetitive-sampling Alu-gag PCR. Methods 47, 254-260 (2009).
32. Pasternak, A. O. et al. Highly sensitive methods based on seminested real-time reverse transcription-PCR for quantitation of human immunodeficiency virus type 1 unspliced and multiply spliced RNA and proviral DNA. J. Clin. Microbiol. 46, 2206-2211 (2008).
33. Pasternak, A. O. et al. Cellular levels of HIV unspliced RNA from patients on combination antiretroviral therapy with undetectable plasma viremia predict the therapy outcome. PLoS ONE 4, e8490 (2009).
34. Lewin, S. R. et al. Use of real-time PCR and molecular beacons to detect virus replication in human immunodeficiency virus type 1-infected individuals on prolonged effective antiretroviral therapy. J. Virol. 73, 6099-6103 (1999).
35. Saleh, S. et al. Expression and reactivation of HIV in a chemokine induced model of HIV latency in primary resting CD4 T cells. Retrovirology 8, 80 (2011).
36. Hamlyn, E. et al. Interleukin-6 and D-dimer levels at seroconversion as predictors of HIV-1 disease progression. AIDS 28, 869-874 (2014).