HIV-1 infection and AIDS

Belman, Anita

doi:10.1016/s0733-8619(02)00019-1

Cited by 19 publications

(17 citation statements)

References 125 publications

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“…HIV-infected children present with a wide range of disabilities, including generalized cognitive defects, 5 motor deficits, 6;7 and visual, 8–10 language, 7;11;12 or learning disorders 7;13 . These deficits are thought to result from the increased risk to central nervous system as the HIV virus can permeate the blood-brain barrier 14 .…”

Section: Introductionmentioning

confidence: 99%

Neurodevelopmental Benefits of Antiretroviral Therapy in Ugandan Children Aged 0–6 Years With HIV

Brahmbhatt

Boivin

Ssempijja

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Insufficient data on neurodevelopmental benefits of antiretroviral therapy (ART) in children. Methods Prospective study of 329 mothers and children aged 0–6 years to assess neurodevelopment. Results stratified by the maternal (M) and child (C) HIV status (MHIV−/CHIV−, MHIV+/CHIV−, and MHIV+/CHIV+). Gross Motor, Visual Reception, Fine Motor, Receptive and Expressive Language scores assessed by Mullen Scales of Early Learning. Global cognitive function was derived from an Early Learning Composite score (ELC). Standardized Weight and Height for Age z-scores were constructed and the lowest 15% cutoff defined disability. Generalized linear models were used to estimate Prevalence Rate Ratios (PRR) adjusted for the child’s age, weight and height. In HIV-positive children, generalized linear models assessed the impact of ART initiation and duration on neurodevelopment. Results Compared to MHIV−/CHIV− children, HIV+ children were more likely to have global deficits in all measures of neurodevelopment except gross motor skills, whereas in MHIV+/CHIV− children, there was impairment in receptive language (adj.PRR=2.67, CI: 1·08, 6.60) and the ELC (adj.PRR=2.94, CI: 1.11, 7.82). Of the children born to HIV positive mothers, HIV+ children did worse than - MHIV+/CHIV− only in Visual Reception skills (adj.PRR=2.86; CI: 1.23–6.65). Of the 116 HIV+ children, 44% had initiated ART. Compared to ART duration of <12 months, ART durations 24–60 months was associated with decreased impairments in Fine Motor, Receptive Language, Expressive Language and ELC scores. Conclusions Longer duration on ART is associated with reduction of some neurologic impairment and early diagnosis and treatment of HIV+ children is a priority.

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Section: Introductionmentioning

confidence: 99%

Neurodevelopmental Benefits of Antiretroviral Therapy in Ugandan Children Aged 0–6 Years With HIV

Brahmbhatt

Boivin

Ssempijja

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…48:166-172, 2007. Key words: mtDNA; DNA pol-g; NRTI OVERVIEW AIDS, a disease previously associated with rapid death, has become a chronic illness in the developed world where parents and children with HIV infection are surviving significant durations [Lwin and Melvin, 2001;Belman, 2002;Manfredi, 2004]. Nucleoside reverse transcriptase inhibitors (NRTIs) in combinations with other antiretrovirals (highly active antiretroviral therapy, HAART) are the cornerstones of AIDS therapy, turning HIV infection into a manageable clinical entity.…”

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confidence: 99%

A brief overview of mechanisms of mitochondrial toxicity from NRTIs

Kohler

Lewis

2007

Environ and Mol Mutagen

143

103

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Nucleoside reverse transcriptase inhibitors (NRTIs) in combinations with other antiretrovirals (highly active antiretroviral therapy, HAART) are the cornerstones of AIDS therapy, turning HIV infection into a manageable clinical entity. Despite the initial positive impact of NRTIs, therapeutic experience revealed serious side effects that appeared to originate in the mitochondria and which ultimately manifested as dysfunction of that organelle. It may be reasonable to consider that as the AIDS epidemic continues and as survival with HIV infection is prolonged by treatment with HAART, long-term side effects of NRTIs may become increasingly common. This consideration may be underscored in children who are born to HIV-infected mothers who received NRTI therapy in utero during gestation. The long-term effect of that NRTI exposure in utero is not clear yet. This review examines some proposed mechanisms of NRTI mitochondrial toxicity, including genetic predisposition, defects in mitochondria DNA replication, the encompassing "DNA pol-gamma hypothesis," the relationship between mitochondrial nucleotide and NRTI pools, mitochondrial DNA mutation and dysfunction, and oxidative stresses related to HIV infection and NRTIs. Mechanisms of mitochondrial toxicity are reviewed with respect to key cell biological, pathological, and pharmacological events.

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“…Many antiretrovirals, such as zidovudine and stavudine, readily penetrate the BBB, enabling them to directly reduce the damage caused by HIV in the CNS by preventing the release of neurotoxic proteins through the inhibition of viral replication [27, 28]. The ART treatment strategy has proven remarkably effective as ART has been shown to reduce the prevalence of HIV-related neurologic disorders in US children to an estimated 10% [24] and is able to delay the onset of AIDS [9]. However, the complete prevention of encephalopathy cannot be expected with any currently available treatment regimen.…”

Section: Antiretroviral Therapymentioning

confidence: 99%

“…Although only microglia and macrophages are productively infected by HIV, neurons seem to bear the brunt of the damage, as is evident by the incidence of neuronal injury and apoptosis [6, 7]. A 2006 review by Kaul and Lipton provides an elegant overview of the mechanisms of HIV neuropathogenesis and the pathology of HIV-associated dementia [8], and the 2002 Belman review is a generous source of information on the pathology associated with HIV encephalopathy, as well as discussing topics such as mother-to-child transmission, antiretroviral therapy (ART) and disease management, and neurobehavioral/neuropsychiatric problems that are associated with pediatric HIV infections [9]. …”

mentioning

confidence: 99%

“…The most severe form of HIV-related neurologic damage is referred to as progressive encephalopathy (PE). PE is analogous to HIV-associated dementia in adults [9], and clinically presents as impairments in brain growth (microcephaly), marked and progressive motor dysfunction and an early plateau in the attainment of developmental milestones or a loss of milestones that have already been achieved [17]. Pediatric patients affected by static encephalopathy resulting from HIV infection can also demonstrate neurodevelopmental deficits, such as motor dysfunction, a delay in milestone attainment and learning disabilities [18].…”

mentioning

confidence: 99%

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The ART of HIV therapies: dopaminergic deficits and future treatments for HIV pediatric encephalopathy

Webb¹,

Mactutus²,

Booze³

2009

Expert Review of Anti-infective Therapy

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The concerted efforts of clinicians, scientists and caregivers of HIV-infected children have led to tremendous advances in our understanding of pediatric HIV/AIDS. Antiretroviral therapy (ART; formerly known as highly active antiretroviral therapy [HAART]) has significantly extended the longevity of HIV-infected children, but there are limitations to improvements in quality of life that may persist despite therapy. ART has remarkably reduced the incidence of neurologic deficits for the majority of infected children, but some patients do not experience these benefits and children living in poorer nations, who may not have access to antiretrovirals, are particularly at risk for developing neurologic deficits. This article reviews the neurologic symptoms of pediatric HIV infection that manifest as dopaminergic disruptions and explores potential future adjuvant therapies for HIV-related neurologic disorders in children.

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HIV-1 infection and AIDS

Cited by 19 publications

References 125 publications

Neurodevelopmental Benefits of Antiretroviral Therapy in Ugandan Children Aged 0–6 Years With HIV

Neurodevelopmental Benefits of Antiretroviral Therapy in Ugandan Children Aged 0–6 Years With HIV

A brief overview of mechanisms of mitochondrial toxicity from NRTIs

The ART of HIV therapies: dopaminergic deficits and future treatments for HIV pediatric encephalopathy

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