Dataset Information

Absolute CD4+ T cell count overstate immune recovery assessed by CD4+/CD8+ ratio in HIV-infected patients on treatment.

ABSTRACT:

Objectives

To analyse the correlation and concordance between aCD4, CD4%, CD4/CD8, their intra-patient variability, and to compare the immune recovery (IR) rates based on the three parameters in HIV-infected patients after starting antiretroviral therapy.

Methods

From a prospectively followed cohort, patients who maintained HIV-RNA suppression in ?95% of the determinations throughout the follow-up were selected. IR was defined as aCD4 >650/?l, CD4% ?38% or CD4/CD8 ?1.

Results

A total of 1164 patients with a median follow-up of 5 years were analysed. The increases in aCD4, CD4% and CD4/CD8 were highest during the first year and considerably lower thereafter regardless of baseline aCD4. The annual increases in aCD4 showed poor correlations with those of CD4% (r = 0.143-0.250) and CD4/CD8 (r = 0.101-0.192) but were high between CD4% and CD4/CD8 (r = 0.765-0.844; p<0.001). The median intra-annual coefficients of variation for aCD4, CD4/CD8 and CD4% were 12.5, 8.5 and 6.6, respectively. After five years, 66.7%, 41.6% and 42.1% of the patients reached aCD4 >650/?l, CD4% ?38%, and CD4/CD8 ?1, respectively, while only 31% achieved both aCD4 and CD4/CD8 target values.

Conclusions

The increases in aCD4 poorly correlate with those of CD4% and CD4/CD8. IR rates based on aCD4 significantly overstate those obtained by CD4% and CD4/CD8. CD4% and CD4/CD8 are more stable markers than aCD4 and should be taken into account to monitor the IR after treatment initiation.

SUBMITTER: Milanes-Guisado Y

PROVIDER: S-EPMC6197681 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Absolute CD4+ T cell count overstate immune recovery assessed by CD4+/CD8+ ratio in HIV-infected patients on treatment.

Milanés-Guisado Yusnelkis Y Gutiérrez-Valencia Alicia A Trujillo-Rodríguez María M Espinosa Nuria N Viciana Pompeyo P López-Cortés Luis Fernando LF

PloS one 20181022 10

<h4>Objectives</h4>To analyse the correlation and concordance between aCD4, CD4%, CD4/CD8, their intra-patient variability, and to compare the immune recovery (IR) rates based on the three parameters in HIV-infected patients after starting antiretroviral therapy.<h4>Methods</h4>From a prospectively followed cohort, patients who maintained HIV-RNA suppression in ≥95% of the determinations throughout the follow-up were selected. IR was defined as aCD4 >650/μl, CD4% ≥38% or CD4/CD8 ≥1.<h4>Results</ ...[more]

PMID: 30346965

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Project description:BackgroundThere is conflicting evidence on the immunologic benefit of treating helminth co-infections ("deworming") in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.Methodology/principal findingsTo estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (? = 42.8; 95% CI, -2.1 to 87.7) or after the first year of ART (? = ?-9.9; 95% CI, -24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (? = 63.0; 95% CI, 6.0 to 120.1) in females.Conclusions/significanceEmpiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

Project description:IntroductionRituximab (RTX) is a B cell-depleting agent approved for the treatment of granulomatosis with polyangiitis (GPA). RTX reduces antibody producing precursor plasma cells and inhibits B and T cells interaction. Infections related to T cell immunodeficiency are not infrequent during RTX treatment. Our study investigated CD4 cell count and CD4/CD8 ratio in GPA patients during the first two years of long-term RTX treatment.MethodsA single centre cohort study of 35 patients who received median total cumulative dose of cyclophosphamide (CYC) of 15 g and were treated with RTX 2 g followed by retreatment with either 2 g once annually or 1 g biannually. Serum levels of total immunoglobulin (Ig) and lymphocytes subsets were recorded at RTX initiation and at 3, 6, 12, 18 and 24 months. Low CD4 count and inverted CD4/CD8 ratio were defined as CD4 < 0.3 × 10(9)/l and ratio < 1.ResultsThe CD4 cell count and CD4/CD8 ratio decreased slightly following the initial RTX treatment and then increased gradually during maintenance treatment. While the proportion of patients with low CD4 cell count decreased from 43% at baseline to 18% at 24 months, the ratio remained inverted in 40%. Oral daily prednisolone dose at baseline, CYC exposure and the maintenance regimen did not influence the CD4 cell count and ratio. Being older (p = 0.012) and having a higher CRP (p = 0.044) and ESR (p = 0.024) at baseline significantly increased the risk of inverted CD4/CD8 ratio at 24 months. Inverted ratio at baseline associated with lower total Ig levels during the study.ConclusionsOverall, the CD4 and CD4/CD8 ratio increased during maintenance RTX therapy in GPA with no discernible impact of other immunosuppressive therapy. However the increase in CD4 was not followed by an increase in the CD4/CD8 ratio, especially in older patients. Inverted CD4/CD8 ratio associated with lower Ig levels, suggesting a more profound B cell depleting effect of RTX with a relative increase in CD8+ lymphocytes.

Dataset Information

Absolute CD4+ T cell count overstate immune recovery assessed by CD4+/CD8+ ratio in HIV-infected patients on treatment.

Objectives

Methods

Results

Conclusions

Publications

Absolute CD4+ T cell count overstate immune recovery assessed by CD4+/CD8+ ratio in HIV-infected patients on treatment.

Similar Datasets

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