Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection
Author(s)
Type
Journal Article
Abstract
Introduction: Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral
therapy (ART). Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune
senescence [1]. This ratio is improved by ART although normalization is uncommon (7%) [2]. The probability of normalization
of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI) [3]. We examined whether CD4/CD8 ratio
similarly normalized in immediate vs. deferred ART at PHI.
Methods: Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with
time (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (]1) adjusted for sex, risk group, ethnicity, enrolment from
an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART
initiation (ART started within six months of SC: early ART; ART initiatedsix months after SC: deferred). We also considered time
to CD4 count normalization (]900 cells/mm3
).
Results: In total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early ART,
100 deferred ART. At one year after starting ART, 114/253 (45%) early ART had normalized CD4/8 ratio, compared with 11/99
(11%) in the deferred group, whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99 (3%) in the
deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those
initiating later (HR, 95% CI 2.96, 1.755.01, pB0.001). The longer after SC ART was initiated, the reduced likelihood of achieving
normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.960.99 for each 30-day increase). CD4 count at ART initiation was also
associated with normalization, as expected (HR 1.002, 95% CI 1.0011.002, pB0.001). There was an association between
normal CD4/CD8 ratio and being virally suppressed (B400 copies HIV RNA/ml) pB0.001. CD4 count normalization was also
significantly more likely for those initiating early (HR 5.00, 95% CI 1.5216.41, p0.008).
Conclusions: The likelihood of achieving normalization of CD4/CD8 ratios was increased if ART was initiated within six months of
PHI. Higher CD4/CD8 ratio may reflect a more ‘‘normal’’ immune phenotype conferring enhanced prognosis and predict posttreatment
control.
Refer
therapy (ART). Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune
senescence [1]. This ratio is improved by ART although normalization is uncommon (7%) [2]. The probability of normalization
of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI) [3]. We examined whether CD4/CD8 ratio
similarly normalized in immediate vs. deferred ART at PHI.
Methods: Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with
time (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (]1) adjusted for sex, risk group, ethnicity, enrolment from
an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART
initiation (ART started within six months of SC: early ART; ART initiatedsix months after SC: deferred). We also considered time
to CD4 count normalization (]900 cells/mm3
).
Results: In total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early ART,
100 deferred ART. At one year after starting ART, 114/253 (45%) early ART had normalized CD4/8 ratio, compared with 11/99
(11%) in the deferred group, whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99 (3%) in the
deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those
initiating later (HR, 95% CI 2.96, 1.755.01, pB0.001). The longer after SC ART was initiated, the reduced likelihood of achieving
normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.960.99 for each 30-day increase). CD4 count at ART initiation was also
associated with normalization, as expected (HR 1.002, 95% CI 1.0011.002, pB0.001). There was an association between
normal CD4/CD8 ratio and being virally suppressed (B400 copies HIV RNA/ml) pB0.001. CD4 count normalization was also
significantly more likely for those initiating early (HR 5.00, 95% CI 1.5216.41, p0.008).
Conclusions: The likelihood of achieving normalization of CD4/CD8 ratios was increased if ART was initiated within six months of
PHI. Higher CD4/CD8 ratio may reflect a more ‘‘normal’’ immune phenotype conferring enhanced prognosis and predict posttreatment
control.
Refer
Date Issued
2014-11-01
Date Acceptance
2014-11-01
Citation
Journal of the International AIDS Society, 2014, 17 (4)
ISSN
1758-2652
Publisher
International AIDS Society
Journal / Book Title
Journal of the International AIDS Society
Volume
17
Issue
4
Copyright Statement
© 2014 Thornhill J et al; licensee International AIDS Society. This is an Open Access article distributed under the terms of the Creative Commons
Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Sponsor
National Institute for Health Research
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000344961700006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
NF-SI-0507-10313
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
1199 Other Medical And Health Sciences
Publication Status
Published