HIV infection in children – neurodevelopmental (autistic) outcomes and clinical pathologies – and their correlations to idiopathic autism
note: in a recent small scale preliminary study by Whittemore Peterson Institute around 40% of children with autism tested postive for XMRV murine retrovirus DNA, with nearly 60% showing presence of antibodies to the virus (unpublished data). According to latest research the presence of XMRV retrovirus in general healty population is 4%. Larger scale studies are currently under way.
There is a striking correlation between neurodevelopmental symptoms found in children infected with HIV retrovirus and those children diagnosed with idiopathic Autism Spectrum Disorders (of still unknown aetiology). Furthermore, the underlying biomedical pathologies found in HIV-positive children are in many ways identical to biomedical pathologies found in children diagnosed with ‘common’ idiopathic autism.
The mechanisms of HIV-injury on host cellular systems have been identified in recent years and these pathologies often very closely match those found in autism, such as chronic microglial activation, cellular calcium overload, oxidative stress, vasoconstriction, glutathione depletion, chronic inflammation of gastrointestinal and central and peripheral nervous systems etc (see list below).
Many treatment agents used in treating autism, whether with studied and proven beneficial effects or anecdotal reports of reducing autistic symptoms in some affected individuals, have antiretroviral mode of action and have been shown to inhibit the retroviral activity and/or reduce HIV viral load.
Neurodevelopmental findings in children infected with HIV retrovirus
Impairments in language, especially expressive language, behavioural symptoms: irritability, lack of social skills, repetitive actions (rocking etc).
Severity of autistic symptoms in HIV positive children is correlated to levels of retroviral load/replication, as well as CD4+ levels. Symptoms of autism – deficits in language, behaviour and social skills – in HIV infected children often recover upon administration of single or combination antiretroviral treatments, at least to some degree. Sometimes recovery is complete, with total remission of autistic symptoms.
HIV infected children sometimes develop normally and regress later, usually between 1.5-2 years of age. This is linked to increased HIV viral load.
Latent retrovirus can be reactivated by vaccinations. In addition to this, live virus vaccines, especially MMR, often come with a warning for HIV infected individuals with low CD4+ counts – inability to mount appropriate immune responses results in vaccine virus persistence. For example polio vaccine strain has been found in gastrointestinal tract of vaccinated individuals. No antibody production to Dtp or measles live virus vaccine. These findings have lead to proposals that both immunotherapy and vaccination of HIV-infected individuals should be accompanied by administration of an antiviral drug(s). In addition, it is suspected that exposure to antigenic stimulation through vaccinations may enhance the susceptibility of uninfected subjects to HIV-1
(reactivation of endogenous retroviruses by external stressors, including vaccinations, has been proposed as causal in other autoimmune diseases, such as multiple sclerosis and arthritis)
Gastrointestinal findings in HIV positive children parallel gastrointestinal abnormalities found in idopathic autism:
Leaky gut and malabsorbtion of nutrients
Dysregulated production of digestive enzymes (impaired pancreatic function)
Abnormal immune reactions to gliadin and casein
Inability to digest complex carbohydrates
Inability to absorb fats and proteins
Gastrointestinal pathogen overload: secondary intestinal viruses, bacterial overload.
Abnormal immune reactivity to candida albicans.
Impaired fine and gross motor skills in HIV positive children
Impaired sensory – auditory and visual processing
Subclinical hypothyroidism (in adults, no data on children)
Pathological mechanisms in HIV infection
HIV retrovirus causes calcium overload and mitochondrial dysfunction (also found in idiopathic autism)
HIV causes oxidative stress and glutathione depletion (also found in autism)
HIV causes microglial activation and inflammation (also found in autism)
HIV combined with bacterial agents causes breakdown of the blood brain barrier (bbb breakdown suspected in autism)
HIV causes glutamate exitotoxicity (dyregulated GABA/glutamate mechanisms observed in autism)
HIV causes vasoconstriction – tightening of blood vessels that supply oxygen to brain (observed in autism)
HIV inhibits methylation (abnormal methylation found in autism)
Many modalities currently used for treating autism have proven or suspected antiretroviral effects:
– chelation of metals inhibits HIV virus integration into human DNA. Retroviruses in general are desintegrated by chelation agents in vitro. Several chelators have been patented as antiretroviral agents. Several agents with chelating properties, such as alpha lipoic acid (ALA) and NAC have been shown to reduce viral load in HIV positive individuals
– Tetracycline antibiotics (one currently on trial for autism) inhibit HIV in vitro through same mechanism as chelation agents.
– HIV is inhibited by glutathione and agents that raise glutathione
– Acyclovir/valacyclovir (antiviral agent with anti-herpevirus activity, with anecdotal reports of amelioration of autistic symptoms) has been shown to reduce HIV viral load in HIV positive individuals. The mechanisms are not clear.
– Hyperbaric oxygen has been shown to inhibit HIV and reduce viral load.
– Pancreative enzymes trial showed beneficial effect in HIV positive.
– Methylation agents such as cobalamins and SAMe directly inhibit HIV activity and maintain its latency.
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Measles/MMR vaccine for infants born to HIV-positive mothers [Intervention Protocol], B Unnikrishnan et al, The Cochrane Library 2009, Issue 1
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See Infectious Agents for further references to mechanisms behind HIV-induced neurological dysfunction such as cellular and mitochondrial calcium overload in the brain (also present in ‘common’ autism)
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Advances in two-metal chelation inhibitors of HIV integrase Authors: Johns, Brian A; Svolto, Angilique C Source: Expert Opinion on Therapeutic Patents, Volume 18, Number 11, November 2008 , pp. 1225-1237(13)
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The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation McMahon MA, et al J Biol Chem. 2008 Nov 14;283(46):31289-93. Epub 2008 Sep 24.
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