Enhanced normalisation of CD4/CD8 ratio with earlier antiretroviral therapy at Primary HIV Infection.
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Accepted version
Author(s)
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.
Date Issued
2016-04-06
Date Acceptance
2016-04-06
Citation
Journal of Acquired Immune Deficiency Syndromes, 2016, 73 (1), pp.69-73
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
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
Subjects
Virology
1103 Clinical Sciences
Publication Status
Published