Jhptump A Immerykhri 155 2 Babii
Jhptump A Immerykhri 155 2 Babii
Jhptump A Immerykhri 155 2 Babii
TABLE 1. Charateristics of study participants by the time from HIV diagnosis to ART initiation (n [ 528)
up and ART are presented in the Supplementary material (Data treatment, respectively. Chi-squared tests, Wilcoxon–Mann–
S1). The study was approved by institutional ethics committees. Whitney tests, logistic regression models, Cox proportional-
Participants were classified by the timing of ART initiation hazard models, and mixed-effect spline models with random
after HIV diagnosis: 135 in the early-ART group (2 months), intercept and slope (square-root CD4+ count) were used
and 393 in the later-ART group (>2 months). The primary and where appropriate. We also assessed the sensitivity of our
secondary outcomes were the attainment of CD4+ count results for alternative ways to classify treatment groups ac-
900 cells/μL and 600 cells/μL during the first 36 months of cording to the timing of ART initiation after diagnosis of recent
TABLE 2. Primary and sensitivity analysis for the association between timing of ART and CD4+ T-cell recovery during the first
36 months of ART
Primary analysis
Time from HIV diagnosis to ART 0.46 (0.28– 0.75) 0.002 0.66 (0.47–0.93) 0.017 0.56 (0.34–0.92) 0.022 0.71 (0.56–0.90) 0.004
initiation (>2 versus 2 months)
Age at ART initiation (versus 16–29 years)
30–44 years 0.57 (0.35–0.95) 0.030 0.69 (0.48–0.99) 0.042 0.56 (0.34–0.91) 0.018 0.74 (0.58–0.94) 0.013
45 years 0.26 (0.12–0.56) <0.001 0.44 (0.25–0.77) 0.004 0.30 (0.17–0.54) <0.001 0.53 (0.38–0.74) <0.001
CD4+ count at ART initiation (versus <350 cells/μL)
350–499 cells/μL 2.48 (1.35–4.56) <0.001 2.31 (1.43–3.74) <0.001 3.50 (2.14–5.71) <0.001 2.47 (1.87–3.25) <0.001
500 cells/μL 9.50 (5.53–16.33) <0.001 7.10 (4.70–10.72) <0.001 9.70 (5.16–18.26) <0.001 4.82 (3.69–6.30) <0.001
Sensitivity analysis
Model 1: Time from HIV diagnosis to
ART initiation (versus 2 months)
>2–12 months 0.59 (0.30–1.13) 0.113 0.80 (0.51–1.24) 0.323 0.67 (0.35–1.29) 0.232 0.78 (0.57–1.06) 0.110
>12 months 0.42 (0.25–0.71) 0.001 0.61 (0.42–0.88) 0.008 0.52 (0.31–0.88) 0.014 0.69 (0.54–0.78) 0.003
Model 2: Time from HIV diagnosis to 0.48 (0.30– 0.76) 0.002 0.68 (0.49–0.94) 0.020 0.60 (0.38–0.94) 0.027 0.75 (0.61–0.94) 0.013
ART initiation (>4 versus 4 months)
Model 3: Time from HIV diagnosis to 0.99 (0.98–0.99) 0.007 0.99 (0.98–0.99) 0.017 0.99 (0.98–0.99) 0.012 0.99 (0.99–0.99) 0.015
ART initiation as continuous (months)
Abbreviations: ART, antiretroviral therapy; HIV, human immunodeficiency virus; OR, odds ratio; RR, rate ratio.
a
All analyses adjusted simultaneously for age, gender, ethnicity, education and baseline CD4+ count as indicated in Table 1.
Clinical Microbiology and Infection © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 22, 290.e5–290.e8
290.e7 Clinical Microbiology and Infection, Volume 22 Number 3, March 2016 CMI
infection: (1) >12 and 2–12 versus 2 months; (2) >2 versus effects of the timing of baseline CD4+ count on CD4+ T-cell
2 months; (3) as a continuous variable. All analyses were recovery.
performed using SAS 9.11 and SPSS 18. Another notable finding is that older age is associated with
decreased odds and rate of CD4+ T-cell recovery, which is
consistent with the existing literature [15,16]. Plasma viral load
Results suppression was achieved for most participants who were on
ART, with no significant differences between the two groups.
This was also observed in other studies [4,17].
There were no significant differences between the two groups
Several limitations should be noted. First, this is an obser-
for all variables at baseline (Table 1). During the first 36 months
vational study. Second, the BED assay may misclassify a pro-
of treatment, the proportions of participants achieving CD4+
portion of individuals as being recently infected, a previous
count 900 cells/μL or 600 cells/μL were significantly higher
study conducted in the same study area indicated that the
in the early-ART group than in the later-ART group and the
specificity of BED assay was 82.6% [18], where this level of
median time from ART initiation to such attainments was also
specificity suggests that some individuals who initiated ART
shorter in the early-ART group (Table 1).
shortly after diagnosis may not have been recently infected. In
The later-ART group had significantly lower odds and rate of
other words, there is the likelihood of underestimating the
achieving CD4+ count 900 cells/μL than the early-ART group.
effects of early ART initiation.
Sensitivity analysis showed a trend of decreased probability and
In conclusion, early initiation of ART leads to rapid and
rate of CD4+ recovery as time from HIV diagnosis to ART
better CD4+ T-cell recovery, but it does not offer a long-term
initiation increased. Furthermore, those individuals with base-
advantage in CD4+ counts. Nonetheless, given that the early
line CD4+ counts of 350 and 499 cells/μL or 500 cells/μL and
favourable immunological response is associated with better
who initiated ART at an age of <30 years were also indepen-
clinical outcomes, further investigations into the long-term
dently associated with decreased odds and rates of achieving
clinical benefits is warranted. BED assay is a useful tool for
CD4+ count 900 cells/μL or 600 cells/μL (Table 2).
detecting recent HIV infections to allow for early treatment,
After treatment, the estimated mean CD4+ counts increased
particularly in resource-constraint settings.
steeply during the first 6 months of treatment for both groups
but faster in the early-ART group (631 versus 502 cells/μL; p
<0.001), and then it reached a plateau in the early-ART group Acknowledgements
during 6 and 36 months of treatment but increased less steeply
in the later-ART group. The estimated mean CD4+ counts The authors wish to thank all who participated in this study and
converged after 30 months of treatment (622 versus 585 cells/ Dr Frank Y. Wong for his editorial assistance.
μL; p 0.349) (see Supplementary material, Fig. S1 in Data S1).
Transparency Declaration [10] Babiker A, Darbyshire J, Pezzotti P, Porter K, Prins M, Sabin C, et al.
CASCADE Collaboration. Short-term CD4 cell response after highly
active antiretroviral therapy initiated at different times from sero-
conversion in 1,500 seroconverters. J Acquir Immune Defic Syndr
The authors declare no potential conflicts of interest.
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