High IL-7 plasma levels may induce and predict the emergence of HIV-1 virulent strains in pediatric infection

Kopka, Julieta; Mecikovsky, Débora; Aulicino, Paula; Mangano, Andrea; Rocco, Carlos; Bologna, Rosa; Sen, Luisa

doi:10.1016/j.jcv.2004.11.014

Cited by 10 publications

(4 citation statements)

References 30 publications

(28 reference statements)

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“…While we cannot exclude that the lack of detection of significant differences in IL-7 levels after ART may be due to the limited sample size and lack of statistical power, it is interesting to speculate that retention of CD8 + naïve T cells, as observed with innate effectors, may contribute to greater T cell recovery in infants than adults receiving ART after acute infection. In this sense, retention of IL-7 levels after ART could be a positive prognostic factor in infants despite of viremia in contrast to HIV-infected adults [ 58 , 59 ]. The interpretation that early ART in infants may result in greater benefits in immune reconstitution than adults is also supported by the fact that both NK cells and pDC subsets were retained irrespective of treatment strategy.…”

Section: Discussionmentioning

confidence: 99%

Early ART Results in Greater Immune Reconstitution Benefits in HIV-Infected Infants: Working with Data Missingness in a Longitudinal Dataset

et al. 2015

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BackgroundEarly initiation of anti-retroviral treatment (ART) decreases mortality as compared to deferred treatment, but whether it preserves immune cells from early loss or promotes their recovery remains undefined. Determination of complex immunological endpoints in infants is often marred by missing data due to missed visits and/or inadequate sampling. Specialized methods are required to address missingness and facilitate data analysis.MethodsWe characterized the changes in cellular and humoral immune parameters over the first year of life in 66 HIV-infected infants (0–1 year of age) enrolled in the CHER study starting therapy within 12 weeks of birth (n = 42) or upon disease progression (n = 24). A convenience cohort of 23 uninfected infants aged 0–6 months born to mothers with HIV-1 infection was used as controls. Flow cytometry and ELISA were used to evaluate changes in natural killer (NK) cells, plasmacytoid dendritic cells (pDC), and CD4+ or CD8+ T-cell frequencies. Data missingness was assessed using Little's test. Complete datasets for analysis were created using Multiple Imputation (MI) or Bayesian modeling and multivariate analysis was conducted on the imputed datasets.ResultsHIV-1-infected infants had greater frequency of CD4+ T cells with naïve phenotype, as well as higher serum IL-7 levels than HIV exposed/uninfected infants. The elevated data missingness was completely at random, allowing the use of both MI and Bayesian modeling. Both methods indicate that early ART initiation results in higher CD4+ T cell frequency, lower expression of CD95 in CD8+ T cell, and preservation of naïve T cell subsets. In contrast, innate immune effectors appeared to be similar independently of the timing of ART initiation.ConclusionsEarly ART initiation in infants with perinatal HIV infection reduces immune activation and preserves an early expansion of naïve T-cells with undiminished innate cell numbers, giving greater immune reconstitution than achieved with deferred ART. Both statistical approaches concurred in this finding.

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Section: Discussionmentioning

confidence: 99%

Early ART Results in Greater Immune Reconstitution Benefits in HIV-Infected Infants: Working with Data Missingness in a Longitudinal Dataset

et al. 2015

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“…IL-7 is a strong inducer of HIV-1 replication (45,57,58), leading to its proposed use as a therapy to purge the viral reservoirs in HIV-1-infected patients virally suppressed by antiretroviral therapy (45). Although there are no data on the ability of IL-7 to promote HIV-2 replication, it would be expected to be comparable given the similarity of the two viral promoter regions (long terminal repeats) (59).…”

Section: Discussionmentioning

confidence: 99%

Rate of Increase in Circulating IL-7 and Loss of IL-7Rα Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes

Albuquerque

Cortesão

Foxall

et al. 2007

The Journal of Immunology

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IL-7 is a nonredundant cytokine for T cell homeostasis. Circulating IL-7 levels increase in lymphopenic clinical settings, including HIV-1 infection. HIV-2 infection is considered a “natural” model of attenuated HIV disease given its much slower rate of CD4 decline than HIV-1 and limited impact on the survival of the majority of infected adults. We compared untreated HIV-1- and HIV-2-infected patients and found that the HIV-2 cohort demonstrated a delayed increase in IL-7 levels during the progressive depletion of circulating CD4 T cells as well as a dissociation between the acquisition of markers of T cell effector differentiation and the loss of IL-7Rα expression. This comparison of two persistent infections associated with progressive CD4 depletion and immune activation demonstrates that a better prognosis is not necessarily associated with higher levels of IL-7. Moreover, the delayed increase in IL-7 coupled with sustained expression of IL-7Rα suggests a maximization of available resources in HIV-2. The observation that increased IL-7 levels early in HIV-1 infection were unable to reduce the rate of CD4 loss and the impaired expression of the IL-7Rα irrespective of the state of cell differentiation raises concerns regarding the use of IL-7 therapy in HIV-1 infection.

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“…In vivo, a correlation between plasma levels of IL-7 and increased CXCR4 expression by PBMC has been observed in children infected with X4 viruses, although reversion of the viral phenotype to R5 induced by HAART was associated with reduced plasma levels of both viremia and IL-7 [13]. Although a positive correlation between CXCR4 levels and the prevalence of X4 viruses was observed, the levels of circulating IL-7 did not correlate with CXCR4 expression on PBMC of infected adults in an independent study [14].…”

Section: Il-7mentioning

confidence: 99%

New players in cytokine control of HIV infection

Alfano¹,

Crotti²,

Vicenzi³

et al. 2008

Curr HIV/AIDS Rep

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Cytokines are involved early in the pathogenesis of HIV infection and disease progression as a component of immunologic dysregulation and immunodeficiency and as determinants controlling virus replication. Several steps, before and after retroviral integration into host DNA in T cells and macrophages, are affected by cytokines whereas CCR5 and CXCR4 binding chemokines can interfere with viral entry. A growing number of potential players--including the gamma-common interleukin (IL)-7, IL-15, and IL-21 together with IL-17, IL-18, IL-19, IL-20, IL-23, and IL-27--are discussed in terms of their perturbation in HIV infection and of their effects on virus replication. Thus, an increasing intersection of HIV infection and the cytokine network represents a crucial determinant of virus replication and immunologic dysregulation and will likely play a key role in the development of effective strategies of HIV prevention and immunologic reconstitution.

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High IL-7 plasma levels may induce and predict the emergence of HIV-1 virulent strains in pediatric infection

Cited by 10 publications

References 30 publications

Early ART Results in Greater Immune Reconstitution Benefits in HIV-Infected Infants: Working with Data Missingness in a Longitudinal Dataset

Early ART Results in Greater Immune Reconstitution Benefits in HIV-Infected Infants: Working with Data Missingness in a Longitudinal Dataset

Rate of Increase in Circulating IL-7 and Loss of IL-7Rα Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes

New players in cytokine control of HIV infection

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