Early Immune Activation Predicts Central Nervous System Disease in HIV‐Infected Infants: Implications for Early Treatment

Kovács, Andrea

doi:10.1086/595886

Cited by 8 publications

(7 citation statements)

References 25 publications

(34 reference statements)

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“…It has been hypothesized that immune cell activation plays a central role in the neuropathogenesis of HIV disease, with CD8 + T-cells freely crossing the blood-brain barrier, activating infected cells and leading to a pro-inflammatory cascade that further damages the CNS [36]. In our adjusted analysis, we found that higher levels of CD8 + CD38 + HLA-DR + % were associated with lower Visual Reception and Gross Motor Scale scores on the MSEL.…”

Section: Discussionmentioning

confidence: 70%

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda

Ruiseñor-Escudero

Familiar‐Lopez

Sikorskii

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective To identify the nutritional and immunological correlates of memory and neurocognitive development as measured by the Mullen Scales of Early Learning (MSEL) and by the Color Object Association Test (COAT) among children in Uganda. Design This analysis uses baseline data collected between 2008 and 2010 from 119 HIV-infected children ages 1–6 years participating in a randomized controlled trial of an interventional parenting program in Kayunga, Uganda. Methods Peripheral blood draws were performed to determine immunological biomarkers. Unadjusted and adjusted linear regression models were used to relate MSEL and COAT scores to sociodemographic characteristics, weight-for-age Z-scores (WAZ), antiretroviral therapy (ART) status and immunological biomarkers. Results 111 children were included in the final analysis. Lower levels of CD4+ CD38+ T-cells (p=0.04) were associated to higher Immediate and Total Recall scores (p=0.04). Higher levels of CD8+ HLA-DR+ T-cells were associated with higher Total Recall score (p=0.04) of the COAT. Higher CD4+ CD38+ HLA-DR+ T-cells levels were associated with higher Gross Motor scores of the MSEL (p=0.02). WAZ was positively correlated to Visual Reception, Fine Motor, Expressive Language and composite score of the MSEL. Conclusions Overall, WAZ was a stronger predictor of neurocognitive outcomes assessed by the MSEL. CD4+ CD38+ T-cells were more specifically associated with memory-related outcomes. Future research should include immunological markers and standardized neurocognitive tests to further understand this relationship.

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Section: Discussionmentioning

confidence: 70%

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda

Ruiseñor-Escudero

Familiar‐Lopez

Sikorskii

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Although the pathogenic mechanism of CNS disease is not fully understood, immune activation seems to play a fundamental role, with CD8 + T-cells continually crossing the blood-brain barrier and promoting activation of infected cells, which in turn lead to a pro-inflammatory cascade, resulting in further damage (Kovacs, 2009 ). Research suggests that having higher CD8 + CD38 + HLADR + cells is associated with having poorer neurobehavioral outcomes (McCloskey et al .…”

Section: Discussionmentioning

confidence: 99%

“…HIV is a neurotropic virus that invades the central nervous system (CNS) early after infection, primarily via infected monocytes/macrophages and CD4 + lymphocytes (Kovacs 2009 ). The psychological effects of HIV on children are frequent, ranging from mild to severe (Mellins et al .…”

Section: Introductionmentioning

confidence: 99%

Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda

et al. 2015

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Background.HIV can affect the neuropsychological function of children, including their behavior. We aim to identify immunological correlates of behavioral problems among children living with HIV in Uganda.Methods.Children participating in a parent randomized control trial in Kayunga, Uganda were assessed with the Behavior Rating Inventory of Executive Function (BRIEF) and the Child Behavior Checklist (CBCL). We constructed simple and multiple linear regression models to identify immunological correlates of behavioral problems.Results.A total of 144 children living with HIV (50% male) with a mean age of 8.9 years [Standard Deviation (s.d.) = 1.9] were included in the analysis. Eighty-two children were on antiretroviral therapy. Mean CD4 cell count % was 35.1 cells/μl (s.d. = 15.0), mean CD4 cell activation 5.7% (s.d. = 5.1), mean CD8 cell activation was 17.5% (s.d. = 11.2) and 60 children (41.7%) had a viral load of <4000 copies/ml. In the adjusted models for the BRIEF, higher scores were associated with higher viral loads (aβ = 16.7 × 10−6, 95% CI −5.00 × 10−6 to 28.4 × 10−6), specifically on the behavioral regulation index. Higher mean CD8 activation % was associated with higher scores on the Externalizing Problems and Total Problems scales of the CBCL (aβ = 0.17, 95% CI 0.04–0.31 and aβ = 0.15, 95% CI 0.00–0.28, respectively).Conclusions.Poorer behavioral outcomes were associated with higher viral loads while higher CD8 activation was associated with poorer emotional and behavioral outcomes. Complete immunological assessments for children living with HIV could include commonly used viral and immunological parameters to identify those at higher risk of having negative behavior outcomes and who would benefit the most from behavioral interventions.

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“…Bacterial pneumonia is increased among HIV-infected individuals, especially injection drug users [44, 45], and cirrhosis may play a role in some who are coinfected with HCV. However, continued immune activation is also associated with encephalopathy, and some studies have suggested that microbial translocation related to gut-associated immunodeficiency may be a contributing factor [43, 46–48]. Furthermore, wasting syndrome may be a manifestation of chronic and severe gut-associated immunodeficiency that may be exacerbated by progressive HCV disease and/or alcohol use.…”

Section: Discussionmentioning

confidence: 99%

Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus

Kovács¹,

Karim

Mack

et al. 2010

J INFECT DIS

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Background Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression. Methods Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated. Results HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P < .001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P < .001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs <26%) of CD8+CD38+DR+ T cells (hazard ratio, 2.94 [95% confidence interval, 1.50–5.77]; P =.001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80–4.35]; P =.16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8+CD38−DR+, CD4+CD38−DR−, and CD8+CD38−DR− T cells were associated with a >60% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women. Conclusion HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial.

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Early Immune Activation Predicts Central Nervous System Disease in HIV‐Infected Infants: Implications for Early Treatment

Cited by 8 publications

References 25 publications

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda

Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda

Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus

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