Journal
AIDS
Volume 28, Issue 5, Pages 699-708Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000000130
Keywords
CD8+; progression; clinical; cell-mediated immunity; CD4+; primary HIV infection; ELISPOT
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Funding
- Wellcome Trust [069598/Z/02/Z]
- National Institute for Health Research Oxford Biomedical Research Centre
- Oxford Martin School
- Medical Research Council [G108/626, MC_U122886352, MC_UU_12023/16] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10093, NF-SI-0507-10313] Funding Source: researchfish
- MRC [MC_UU_12023/16, MC_U122886352, G108/626] Funding Source: UKRI
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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.
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