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AIDS. 2014 Mar 13;28(5):699-708. doi: 10.1097/QAD.0000000000000130.

HIV-1-specific CD4(+) responses in primary HIV-1 infection predict disease progression.

Collaborators (178)

Breckenridge A, Clayden P, Conlon C, Conradie F, Kaldor J, Maggiolo F, Ssali F, Cooper DA, Kaleebu P, Ramjee G, Schechter M, Tambussi G, Miro JM, Weber J, Fidler S, Babiker A, Peto T, McLaren A, Beral V, Chene G, Hakim J, Babiker A, Porter K, Thomason M, Ewings F, Gabriel M, Johnson D, Thompson K, Cursley A, Donegan K, Fossey E, Kelleher P, Lee K, Murphy B, Nock D, Phillips R, Frater J, Ohm Laursen L, Robinson N, Goulder P, Brown H, McClure M, Bonsall D, Erlwein O, Helander A, Kaye S, Robinson M, Cook L, Adcock G, Ahmed P, Paton N, Fidler S, Kelleher A, Moore R, McFarlane R, Roth N, Finlayson R, Kiem Tee B, Read T, Kelly M, Doong N, Bloch M, Workman C, Grey P, Cooper DA, Kelleher A, Law M, Schechter M, Gama P, Mercon M, de Souza MB, Yoshida CB, Grangeiro da Silva JR, Sampaio A, Fernandes de Aguiar D, de Fátima Melo M, Garrido RQ, Tambussi G, Nozza S, Pogliaghi M, Chiappetta S, Torre LD, Gasparotto E, D'Offizi G, Vlassi C, Corpolongo A, Wood R, Pitt J, Orrell C, Cilliers F, Croxford R, Middelkoop K, Bekker LG, Heiberg C, Aploon J, Killa N, Fielder E, Buhler T, Rees H, Venter F, Palanee T, Stevens W, Ingram C, Majam M, Papathanasopoulos M, Ramjee G, Gappoo S, Moodley J, Premrajh A, Zako L, Grosskurth H, Kamali A, Kaleebu P, Bahemuka U, Mugisha J, Njaj HF, Miro JM, López-Dieguez M, Manzardo C, Arnaiz JA, Pumarola T, Plana M, Tuset M, Ligero MC, García MT, Gallart T, Gatell JM, Fisher M, Hobbs K, Perry N, Pao D, Maitland D, Heald L, Mulcahy F, Courtney G, O'Dea S, Reidy D, Leen C, Scott G, Ellis L, Morris S, Simmonds P, Gazzard B, Hawkins D, Higgs C, Anderson J, Mguni S, Williams I, De Esteban N, Pellegrino P, Arenas-Pinto A, Cornforth D, Turner J, Ainsworth J, Waters A, Johnson M, Kinloch S, Carroll A, Byrne P, Cuthbertson Z, Orkin C, Hand J, De Souza C, Weber J, Fidler S, Hamlyn E, Thomson E, Fox J, Legg K, Mullaney S, Winston A, Wilson S, Ambrose P, Taylor S, Gilleran G, Keeling S, Becker A, Boocock C.

Author information

1
aNuffield Department of Clinical Medicine, John Radcliffe Hospital bPeter Medawar Building for Pathogen Research cInstitute for Emerging Infections, The Oxford Martin School dOxford National Institute of Health Research Biomedical Research Centre, Oxford eMedical Research Council Clinical Trials Unit fMRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK gMwanza Intervention Trials Unit, Mwanza, Tanzania hDivision of Medicine, Wright Fleming Institute, Imperial College, London, UK. *Fiona Ewings and Jacob Hurst contributed equally to the writing of this article.

Abstract

OBJECTIVES:

Immune factors determining clinical progression following HIV-1 infection remain unclear. The SPARTAC trial randomized 366 participants in primary HIV infection (PHI) to different short-course therapies. The aim of this study was to investigate how early immune responses in PHI impacted clinical progression in SPARTAC.

DESIGN AND METHODS:

Participants with PHI recruited to the SPARTAC trial were sampled at enrolment, prior to commencing any therapy. HIV-1-specific CD4(+) and CD8(+) ELISpot responses were measured by gamma interferon ELISPOT. Immunological data were associated with baseline covariates and times to clinical progression using logistic regression, Kaplan-Meier plots, and Cox models.

RESULTS:

Making a CD4(+) T-cell ELISpot response (n = 119) at enrolment was associated with higher CD4(+) cell counts (P = 0.02) and to some extent lower plasma HIV RNA (P = 0.07). There was no correlation between the number of overlapping Gag CD8(+) T-cell ELISpot responses (n = 138) and plasma HIV-1 RNA viral load. Over a median follow-up of 2.9 years, baseline CD4(+) cell ELISpot responses (n = 119) were associated with slower clinical progression (P = 0.01; log-rank). Over a median of 3.1 years, there was no evidence for a survival advantage imposed by CD8(+) T-cell immunity (P = 0.82).

CONCLUSION:

These data support a dominant protective role for CD4(+) T-cell immunity in PHI compared with CD8(+) T-cell responses, and are highly pertinent to HIV pathogenesis and vaccines, indicating that vaccine-induced CD4(+) responses may confer sustained benefit.

PMID:
24549145
DOI:
10.1097/QAD.0000000000000130
[Indexed for MEDLINE]

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