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HIV and Cognition: Indian Perspective

Dementia, as we all knows about it, an aging problem, which strikes the elderly people in society. When we look upon the Indian population, we can say that we are very young as 50% of our population is under forty years of age. As compared to developed countries, we have low prevalence and incidence rate of dementia.

When we look upon neuro-infection and dementia, we find four major classes of neuro-infection related to dementia.
1. Chronic Meningitis – Neurotuberculosis, fungal dementia, cryptococcal dementia, candidiasis, coccidiodomycosis, parasitic dementia and Neurocysticercosis.
2. Neurosyphilis – Tertiary Syphilis, Dementia paralytica and general paresis of the insane.
3. AIDS related Dementia – HIV encephalopathy, AIDS dementia complex and minor cognitive impairment.
4. Other infection includes whipple’s diseases and lyme diseases.

 

Special features of HIV/AIDS in India
 
In India, predominantly due to HIV C1 with very rare recombinant strains. Mode of transmission is mainly unprotective heterosexual intercourse about 85%, where contribution of homosexuality is negligible. Blood transfusion results in about 2.3% of all HIV cases. Of all the neuro-AIDS cases, neurological manifestation, opportunistic neuro-infection constitutes about 70-85%. In addition, HIV associated neoplasia are infrequent including primary lymphoma. HIV associated Dementia and HIV encephalitis are less common. Spinal pathology including vacuolar myelopathy is rare. Kaposi Sarcoma has not been reported in Indian population.
According to a study  conducted at National Institute of Mental Health and Neurosciences (NIMHANS), the Neuropsychiatric clinic has registered more than one thousand five hundred cases over last 20 years, which sums up to 150cases/year, which is a very large proportion. In the opportunistic neuro-infection associated with HIV/AIDS the major infection are Cryptococcal (32.2%) followed by Neurotuberculosis (31.9%). But, when we see the prevalence of HIV/AIDS Dementia it is only 1.4%. On comparing the data with developed countries, the difference found is just 2-4% in all categories except in case of dementia, which varies from 30-40% in western countries. This is a glaring difference and special feature of HIV/AIDS in India with context to other parts of the world.
While overviewing neurocognitive disorder in HIV, there are various types of manifestation i.e. 1. AIDS Dementia Complex also known as HIV associated cognitive motor complex or HIV associated dementia. 2. Minor cognitive impairment. 3. Asymptomatic neurocognitive disorder. When we look upon the therapeutic scenario for HIV/AIDS Dementia, after the introduction of Highly Active Antiretroviral Therapy (HAART) it reduced the prevalence percentage to almost half of its original both in India and worldwide.

 

Effects of HIV associated Neurocognitive disorder
The neurological conditions can manifest as behavioral changes such are apathy, irritability, psychomotor retardation and even some patients develop manic symptoms. Whereas the symptoms associated with HIV dementia are very distinct, these include Sub-cortical dementia, which affect the working memory eg. Short term memory, executive functions such as planning and cognition eg abstract thinking, initiating an action. When we analyze HIV associated dementia (HAND), we found several risk factors, and those include Effects of Substance Abuse, Opiod Substitution Therapy, Traumatic Brain Injury, Mental Illness, Sexual Risk Behavior, Drug Related Risk Behavior and Medication Adherence.
In order to precisely evaluate the clinical trait for HAND in Indian population, National bodies collaborated and conducted four individual and cohort studies between 1989 to 2006.

 

1. Dementia Associated with HIV : NIMHANS Study
Study registered 1239 patients with HIV related neurological complications. Only 19(1.5) cases were diagnosed of dementia with the mean age of 36.7±9.9years with male: female was 5:1. Majority of them shows memory impairment, behavioral disturbance in the form of apathy and incontinence. Imaging techniques shows ventricular enlargement, atrophy of caudate, putamen and nucleus accumbens. Early hyper-metabolism in basal ganglia and latter condition hypo-metabolism. HIV autopsy data (N=170) shows two cases associated with dementia. The data were cross referenced with other regions in the country and they also show consistency with the prevalence of 1-4% of HIV associated dementia. So this study proposed questions like is it due to viz. early death due to opportunistic infections, under reporting, inadequate methods of evaluation, socio-cultural ethos, clade”C” vs Clade “B” virus difference or any other protective factors are include in the pathogenesis.

 

2. HIV 1, HIV2, Co-Infection and Neurological Progression
Prof. P.Satishchandra and Dr. Mahendra Kumar of University of Miami, received a NIH RO1 project grant to conduct a 5-year prospective study to find the co-relation between the infection and neurological progression. After following the strict inclusion and exclusion criteria biochemical studies were carried out and the subjects were followed up in 6th, 18th and 30th month, where detail clinical and neurological examination, CD4 testing, psychiatric assessment and neuro-psychological assessment was carried out. Over the follow up study it has being observed that CD4 count comes down with the progression of the disease. As the disease progresses the patients develop opportunistic infection but were intact psychologically and cognitively. After this study patients were prescribed HAART due to severe symptoms.

 

3. HIV 1 subtype C
This prospective study shows that, “there is a significant difference in the data obtained in India and in western countries.” So the question arise is it due to the HIV virus subtype? In order to investigate further, the research teams led by Dr. Satishchandra and Dr. Udaykumar start working upon TAT protein of HIV1 subtype C virus. After analyzing the protein and gene sequence it has been found that in Indian population the C virus is highly intact with very less recombinant variant and also that the C virus variant was defective for monocytic chemotactic activity. Loss of C-TAT chemotactic property may underlie reduced incidence of HIV associated dementia with HIV 1 C virus.

 

4. Impact of Neurological Opportunistic Infection on Cognition in HIV Positive Adults.
Another study which was conducted at NIMHANS, aimed to find out the co-relation between neuroinfection and cognition. After reviewing the data, which postulates the following point;
1. Cognitive deficits are a squeal of neuro-infection.
2. Cognitive deficit are present in HIV infection but largely studied in clade B infection.
3. Cognitive deficit also occur in HIV clade C infection.
To summarize we can state that, the facts which concern over HIV/NeuroAIDS and cognition include;
a. Opportunistic infections commonly associated with HIV/NeuroAIDS.
b. Neuological opportunistic infections (NOI) less prevalent(10-25%) in developed countries.
c. NOI more prevalent (85%) in developing countries
d. Surprisingly, all studies exclude HIV patients when they undertook study upon NOI.

ResearchBlogging.org

Hemelaar J, Gouws E, Ghys PD, Osmanov S, & WHO-UNAIDS Network for HIV Isolation and Characterisation (2011). Global trends in molecular epidemiology of HIV-1 during 2000-2007. AIDS (London, England), 25 (5), 679-89 PMID: 21297424

Siddappa NB, Dash PK, Mahadevan A, Jayasuryan N, Hu F, Dice B, Keefe R, Satish KS, Satish B, Sreekanthan K, Chatterjee R, Venu K, Satishchandra P, Ravi V, Shankar SK, Shankarappa R, & Ranga U (2004). Identification of subtype C human immunodeficiency virus type 1 by subtype-specific PCR and its use in the characterization of viruses circulating in the southern parts of India. Journal of clinical microbiology, 42 (6), 2742-51 PMID: 15184461

Satishchandra P, Nalini A, Gourie-Devi M, Khanna N, Santosh V, Ravi V, Desai A, Chandramuki A, Jayakumar PN, & Shankar SK (2000). Profile of neurologic disorders associated with HIV/AIDS from Bangalore, south India (1989-96). The Indian journal of medical research, 111, 14-23 PMID: 10793489


Gupta JD, Satishchandra P, Gopukumar K, Wilkie F, Waldrop-Valverde D, Ellis R, Ownby R, Subbakrishna DK, Desai A, Kamat A, Ravi V, Rao BS, Satish KS, & Kumar M (2007). Neuropsychological deficits in human immunodeficiency virus type 1 clade C-seropositive adults from South India. Journal of neurovirology, 13 (3), 195-202 PMID: 17613709

Ranga U, Shankarappa R, Siddappa NB, Ramakrishna L, Nagendran R, Mahalingam M, Mahadevan A, Jayasuryan N, Satishchandra P, Shankar SK, & Prasad VR (2004). Tat protein of human immunodeficiency virus type 1 subtype C strains is a defective chemokine. Journal of virology, 78 (5), 2586-90 PMID: 14963162

Baldewicz TT, Leserman J, Silva SG, Petitto JM, Golden RN, Perkins DO, Barroso J, & Evans DL (2004). Changes in neuropsychological functioning with progression of HIV-1 infection: results of an 8-year longitudinal investigation. AIDS and behavior, 8 (3), 345-55 PMID: 15475681

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  1. Well, if any infection is allowed to spread unchecked, collateral damage is bound to happen. That’s why around here, we go out even in the middle of the night for sinus infection antibiotics, if need be.

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