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Neurocognitive development in HIV-positive children is correlated with plasma viral loads in early childhood.

ABSTRACT: Because of neurocognitive impairments in perinatally human immunodeficiency virus (HIV)-infected children and adolescents, this study aimed to demonstrate the effect of plasma viral loads and early initiation of sufficient combined antiretroviral therapy (cART) on neurocognitive development.In total, 14 perinatally infected HIV-positive children (median age 8.24 years [range: 6.0-16.74]) receiving lopinavir/ritonavir (LPV/r)-based ART underwent neurocognitive testing using the Wechsler Intelligence Score for Children, 4th Edition (WISC-IV). All 14 patients participated in a pharmacokinetic study in which they were hospitalized for an entire day. As a child's ability to concentrate varies over the course of the day, all tests were performed in the morning.The patients' neurocognitive development did not significantly differ from the normative collective pattern for any of the following composite scores that were examined: full-scale intelligence quotient (IQ) (mean: 106.5, P?=?.1060), verbal comprehension index (mean: 106.0, P?=?.1356), perceptual reasoning index (mean: 106.0, P?=?.1357), working memory index (mean: 106.3, P?=?.1171), and processing speed index (mean: 98.1, P?=?.6313). The overall full-scale IQ scores were significantly higher in children who began ART within the first year of life (P?=?.0379), whereas low lopinavir/r plasma levels (P?=?.0070) and high viral load area under the curves (AUCs) in the first 3 years of life, but not later, significantly correlated with reduced neurocognitive performance (Spearman r?=?-0.64, P?=?.0278).In this cohort of cART treated HIV-positive children and adolescents, neurocognitive performance correlated with early and sufficient viral load suppression within the first 3 years of life.

SUBMITTER: Weber V

PROVIDER: S-EPMC5466203 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Neurocognitive development in HIV-positive children is correlated with plasma viral loads in early childhood.

Weber Valentin V Radeloff Daniel D Reimers Bianca B Salzmann-Manrique Emilia E Bader Peter P Schwabe Dirk D Königs Christoph C

Medicine 20170601 23

Because of neurocognitive impairments in perinatally human immunodeficiency virus (HIV)-infected children and adolescents, this study aimed to demonstrate the effect of plasma viral loads and early initiation of sufficient combined antiretroviral therapy (cART) on neurocognitive development.In total, 14 perinatally infected HIV-positive children (median age 8.24 years [range: 6.0-16.74]) receiving lopinavir/ritonavir (LPV/r)-based ART underwent neurocognitive testing using the Wechsler Intellige ...[more]

PMID: 28591025

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Project description:Objective Even with successful combination antiretroviral therapy (cART), patients with human immunodeficiency virus positive (HIV+) continue to present structural alterations and neuropsychological impairments. The purpose of this study is to investigate structural brain connectivity alterations and identify the hub regions in HIV+ patients with fully suppressed plasma viral loads. Methods In this study, we compared the brain structural connectivity in 48 patients with HIV+ treated with a combination of antiretroviral therapy and 48 healthy controls, using diffusion tensor imaging. Further comparisons were made in 24 patients with asymptomatic neurocognitive impairment (ANI) and 24 individuals with non-HIV-associated neurocognitive disorders forming a subset of HIV+ patients. The graph theory model was used to establish the topological metrics. Rich-club analysis was used to identify hub nodes across groups and abnormal rich-club connections. Correlations of connectivity metrics with cognitive performance and clinical variables were investigated as well. Results At the regional level, HIV+ patients demonstrated lower degree centrality (DC), betweenness centrality (BC), and nodal efficiency (NE) at the occipital lobe and the limbic cortex; and increased BC and nodal cluster coefficient (NCC) in the occipital lobe, the frontal lobe, the insula, and the thalamus. The ANI group demonstrated a significant reduction in the DC, NCC, and NE in widespread brain regions encompassing the occipital lobe, the frontal lobe, the temporal pole, and the limbic system. These results did not survive the Bonferroni correction. HIV+ patients and the ANI group had similar hub nodes that were mainly located in the occipital lobe and subcortical regions. The abnormal connections were mainly located in the occipital lobe in the HIV+ group and in the parietal lobe in the ANI group. The BC in the calcarine fissure was positively correlated with complex motor skills. The disease course was negatively correlated with NE in the middle occipital gyrus. Conclusion The results suggest that the occipital lobe and the subcortical regions may be important in structural connectivity alterations and cognitive impairment. Rich-club analysis may contribute to our understanding of the neuropathology of HIV-associated neurocognitive disorders.

Project description:Quantification of HIV RNA in plasma is critical for identifying the disease progression and monitoring the effectiveness of antiretroviral therapy. While RT-qPCR has been the gold standard for HIV viral load quantification, digital assays could provide an alternative calibration-free absolute quantification method. Here, we reported a Self-digitization Through Automated Membrane-based Partitioning (STAMP) method to digitalize the CRISPR-Cas13 assay (dCRISPR) for amplification-free and absolute quantification of HIV-1 viral RNAs. The HIV-1 Cas13 assay was designed, validated, and optimized. We evaluated the analytical performances with synthetic RNAs. With a membrane that partitions ∼100 nL of reaction mixture (effectively containing 10 nL of input RNA sample), we showed that RNA samples spanning 4 orders of dynamic range between 1 fM (∼6 RNAs) to 10 pM (∼60k RNAs) could be quantified as fast as 30 min. We also examined the end-to-end performance from RNA extraction to STAMP-dCRISPR quantification using 140 μL of both spiked and clinical plasma samples. We demonstrated that the device has a detection limit of approximately 2000 copies/mL and can resolve a viral load change of 3571 copies/mL (equivalent to 3 RNAs in a single membrane) with 90% confidence. Finally, we evaluated the device using 140 μL of 20 patient plasma samples (10 positives and 10 negatives) and benchmarked the performance with RT-PCR. The STAMP-dCRISPR results agree very well with RT-PCR for all negative and high positive samples with Ct < 32. However, the STAMP-dCRISPR is limited in detecting low positive samples with Ct > 32 due to the subsampling errors. Our results demonstrated a digital Cas13 platform that could offer an accessible amplification-free quantification of viral RNAs. By further addressing the subsampling issue with approaches such as preconcentration, this platform could be further exploited for quantitatively determining viral load for an array of infectious diseases.

Project description:BACKGROUND:Despite recent progress, there exist gaps in the prevention of vertical HIV transmission program access and uptake in Cameroon. Female sex workers (FSW), many of whom are mothers, are disproportionately affected by HIV and have specific barriers to HIV testing and treatment access. Testing for HIV-exposed infants is crucial in monitoring for incident infection and timely intervention. This study explores the level of early childhood testing and also associations between antenatal care (ANC) attendance and other factors and early childhood HIV testing among FSW in Cameroon. METHODS:FSW were recruited to participate in an integrated biobehavioral survey in Cameroon between December 2015 and October 2016. Women were included in these analyses if they were living with HIV and had at least one living child. Both univariate and multivariable logistic regression were used to look at predictors of a child being tested for HIV before age five. RESULTS:A total of 481/2255 FSW were eligible for these analyses as they were HIV seropositive and had at least one living child at the time of the study. Women included in these analyses had a median age of 35(IQR 30-41). Nearly 70% reported none of their children had been tested for HIV before age five (326/481), and 3.5%(17/481) reported one or more of their children had been diagnosed with HIV. ANC attendance (adjusted OR 2.12, 95% CI: [1.02, 4.55]), awareness of HIV status (aOR 3.70[2.30, 5.93]), pregnancy intentions (aOR 1.89[1.16, 3.08]), and higher education (aOR 2.17[1.01, 4.71]) were all independently associated with increased odds of women having a greater proportion of children tested for HIV before age five. Regional differences in early childhood testing were also observed. CONCLUSION:Vertical transmission of HIV remains a challenge in Cameroon, and HIV testing among children of FSW living with HIV was very low. ANC attendance and promotion of the mother's health were associated with increased child HIV testing. For women at high risk of HIV and for whom engagement in the health system is low, strategies to promote and ensure ANC attendance are essential for their health and the health of their children.

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Neurocognitive development in HIV-positive children is correlated with plasma viral loads in early childhood.

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Neurocognitive development in HIV-positive children is correlated with plasma viral loads in early childhood.

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