Brief Report: Enhanced Normalization of CD4/CD8 Ratio with Earlier Antiretroviral Therapy at Primary HIV Infection

John Thornhill, Jamie Inshaw, Pontiano Kaleebu, David Cooper, Gita Ramjee, Mauro Schechter, Giuseppe Tambussi, Julie Fox, Miriam Samuel, Jose M. Miro, Jonathan Weber, Kholoud Porter, Sarah Fidler

Research output: Contribution to journalArticle

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 antiretroviral therapy (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 2 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 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 endpoint [adjusted hazard ratio (aHR) (95% CI) 0.52 (0.32 to 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 the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) 2.47 (1.67 to 3.67), P <0.001] than those initiating later. Interpretation: Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.
Original languageEnglish
Pages (from-to)69 - 73
Number of pages5
JournalJournal of Acquired Immune Deficiency Syndromes
Volume73
Issue number1
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

CD4-CD8 Ratio
Secondary Prevention
HIV Infections
Disease Progression
CD4 Lymphocyte Count
HIV
HIV Seropositivity
Therapeutics
Proportional Hazards Models
Biomarkers
T-Lymphocytes

Keywords

  • acute HIV infection
  • CD4/CD8 ratio
  • CD4:CD8
  • early antiretroviral therapy
  • primary HIV infection
  • seroconversion

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Brief Report: Enhanced Normalization 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 M.; Weber, Jonathan; Porter, Kholoud; Fidler, Sarah.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 73, No. 1, 01.09.2016, p. 69 - 73.

Research output: Contribution to journalArticle

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 2016, 'Brief Report: Enhanced Normalization of CD4/CD8 Ratio with Earlier Antiretroviral Therapy at Primary HIV Infection', Journal of Acquired Immune Deficiency Syndromes, vol. 73, no. 1, pp. 69 - 73. https://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 M. ; Weber, Jonathan ; Porter, Kholoud ; Fidler, Sarah. / Brief Report: Enhanced Normalization of CD4/CD8 Ratio with Earlier Antiretroviral Therapy at Primary HIV Infection. In: Journal of Acquired Immune Deficiency Syndromes. 2016 ; Vol. 73, No. 1. pp. 69 - 73.
@article{357346ff9d8c4f748ffd0fd57bbde474,
title = "Brief Report: Enhanced Normalization of CD4/CD8 Ratio with Earlier Antiretroviral Therapy at Primary HIV Infection",
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 antiretroviral therapy (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 2 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 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 endpoint [adjusted hazard ratio (aHR) (95{\%} CI) 0.52 (0.32 to 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 the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95{\%} CI) 2.47 (1.67 to 3.67), P <0.001] than those initiating later. Interpretation: Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.",
keywords = "acute HIV infection, CD4/CD8 ratio, CD4:CD8, early antiretroviral therapy, primary HIV infection, seroconversion",
author = "John Thornhill and Jamie Inshaw and Pontiano Kaleebu and David Cooper and Gita Ramjee and Mauro Schechter and Giuseppe Tambussi and Julie Fox and Miriam Samuel and Miro, {Jose M.} and Jonathan Weber and Kholoud Porter and Sarah Fidler",
year = "2016",
month = "9",
day = "1",
doi = "10.1097/QAI.0000000000001013",
language = "English",
volume = "73",
pages = "69 -- 73",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Brief Report: Enhanced Normalization of CD4/CD8 Ratio with Earlier Antiretroviral Therapy at Primary HIV Infection

AU - Thornhill, John

AU - Inshaw, Jamie

AU - Kaleebu, Pontiano

AU - Cooper, David

AU - Ramjee, Gita

AU - Schechter, Mauro

AU - Tambussi, Giuseppe

AU - Fox, Julie

AU - Samuel, Miriam

AU - Miro, Jose M.

AU - Weber, Jonathan

AU - Porter, Kholoud

AU - Fidler, Sarah

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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 antiretroviral therapy (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 2 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 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 endpoint [adjusted hazard ratio (aHR) (95% CI) 0.52 (0.32 to 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 the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) 2.47 (1.67 to 3.67), P <0.001] than those initiating later. Interpretation: Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.

AB - 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 antiretroviral therapy (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 2 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 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 endpoint [adjusted hazard ratio (aHR) (95% CI) 0.52 (0.32 to 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 the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) 2.47 (1.67 to 3.67), P <0.001] than those initiating later. Interpretation: Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.

KW - acute HIV infection

KW - CD4/CD8 ratio

KW - CD4:CD8

KW - early antiretroviral therapy

KW - primary HIV infection

KW - seroconversion

UR - http://www.scopus.com/inward/record.url?scp=84963682415&amp;partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963682415&amp;partnerID=8YFLogxK

U2 - 10.1097/QAI.0000000000001013

DO - 10.1097/QAI.0000000000001013

M3 - Article

VL - 73

SP - 69

EP - 73

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 1

ER -