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Enhanced normalisation of CD4/CD8 ratio with earlier antiretroviral therapy at Primary HIV Infection.

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Title: Enhanced normalisation of CD4/CD8 ratio with earlier antiretroviral therapy at Primary HIV Infection.
Authors: Thornhill, J
Inshaw, J
Kaleebu, P
Cooper, D
Ramjee, G
Schechter, M
Tambussi, G
Fox, J
Samuel, M
Miro, JM
Weber, J
Porter, K
Fidler, S
Item Type: Journal Article
Abstract: BACKGROUND: Total CD4 T-cell counts predict HIV disease progression, but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite ART, recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals. METHODS: CD4 count and CD4/CD8 ratio were analyzed using data from two cohorts: SPARTAC trial, and the UK HIV Seroconverters Cohort where Primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models we examined the effect of CD4/CD8 ratio at seroconversion on disease progression (CD4<350 cells/mm/ART initiation), and factors associated with time from ART initiation to CD4/CD8 normalization (ratio >1.0). FINDINGS: Of 573 seroconverters, 482 (84%) had abnormal CD4/CD8 ratios at HIV seroconversion. Individuals with higher CD4/CD8 ratio at seroconversion were significantly less likely to reach the disease progression end point (aHR [95% CI] = 0.52 [0.32, 0.82], p=0.005). The longer the interval between seroconversion and ART initiation (HR [95% CI] =0.98 per month increase [0.97, 0.99], p<0.001) the less likely CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize (HR [95% CI] =2.47 [1.67, 3.67], p<0.001) than those initiating later. INTERPRETATION: The majority of individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner ART is initiated in PHI the greater the probability of achieving normal CD4/CD8 ratio.
Issue Date: 6-Apr-2016
Date of Acceptance: 6-Apr-2016
URI: http://hdl.handle.net/10044/1/38425
DOI: https://dx.doi.org/10.1097/QAI.0000000000001013
ISSN: 0894-9255
Publisher: Lippincott, Williams & Wilkins
Start Page: 69
End Page: 73
Journal / Book Title: Journal of Acquired Immune Deficiency Syndromes
Volume: 73
Issue: 1
Copyright Statement: This is the author's accepted manuscript. The final published version can be found at Enhanced normalisation of CD4/CD8 ratio with earlier antiretroviral therapy at Primary HIV Infection. Thornhill, John; Inshaw, Jamie; Kaleebu, Pontiano; Cooper, David; Ramjee, Gita; Schechter, Mauro; Tambussi, Giuseppe; Fox, Julie; Samuel, Miriam; Miro, Jose Maria; Weber, Jonathan; Porter, Kholoud; Fidler, Sarah JAIDS Journal of Acquired Immune Deficiency Syndromes. https://dx.doi.org/10.1097/QAI.0000000000001013
Keywords: Virology
1103 Clinical Sciences
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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