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Book ChapterDOI: 10.1007/978-1-4939-7290-6_3

HIV-1 Related Central Nervous System Diseases: Pathogenesis, Diagnosis, and Treatment – An Indian Scenario

01 Jan 2017-pp 43-53
Abstract: In the past several decades, various advances in medical sciences have improved the care of HIV-infected individuals globally. With the advent of antiretroviral therapy (ARV), the incidence of neurological opportunistic infections has been greatly reduced. However, the nonopportunistic condition like neurocognitive impairment is still prevalent among HIV-infected individuals. The studies from India conducted in late 1990s on neurological aspects of HIV have mostly concentrated on dementia or AIDS dementia complex. Over time, the neurocognitive consequences of HIV have gained the attention of Indian clinicians as they impair the quality of life, every day activities, employment, and adherence to the treatment. Despite the fact that the recent gains have increased the focus on the assessment of neurocognitive disorders associated with HIV, the data in India are meager. An attempt has been made in this chapter to analyze and present various central nervous system diseases associated with HIV-1 infection, prevalent in India, grounded on various hospital-based reports covering the country.

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Topics: Dementia (51%), Neurocognitive (50%)
References
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Open accessJournal ArticleDOI: 10.1073/PNAS.83.18.7089
Abstract: Dysfunction of the central nervous system (CNS) is a prominent feature of the acquired immune deficiency syndrome (AIDS). Many of these patients have a subacute encephalitis consistent with a viral infection of the CNS. We studied the brains of 12 AIDS patients using in situ hybridization to identify human immunodeficiency virus [HIV, referred to by others as human T-cell lymphotropic virus type III (HTLV-III), lymphadenopathy-associated virus (LAV), AIDS-associated retrovirus (ARV)] nucleic acid sequences and immunocytochemistry to identify viral and cellular proteins. Nine patients had significant HIV infection in the CNS. In all examined brains, the white matter was more severely involved than the grey matter. In most cases the infection was restricted to capillary endothelial cells, mononuclear inflammatory cells, and giant cells. In a single case with severe CNS involvement, a low-level infection was seen in some astrocytes and neurons. These results suggest that CNS dysfunction is due to indirect effects rather than neuronal or glial infection.

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Topics: Cellular localization (56%), HIV Antigens (55%), Virus (54%) ...read more

1,210 Citations


Open accessJournal ArticleDOI: 10.1001/ARCHNEUROL.2007.31
01 Jan 2008-JAMA Neurology
Abstract: Objective To evaluate whether penetration of a combination regimen into the central nervous system (CNS), as estimated by the CNS Penetration-Effectiveness (CPE) rank, is associated with lower cerebrospinal fluid (CSF) viral load. Design Data were analyzed from 467 participants who were human immunodeficiency virus (HIV) seropositive and who reported antiretroviral (ARV) drug use. Individual ARV drugs were assigned a penetration rank of 0 (low), 0.5 (intermediate), or 1 (high) based on their chemical properties, concentrations in CSF, and/or effectiveness in the CNS in clinical studies. The CPE rank was calculated by summing the individual penetration ranks for each ARV in the regimen. Results The median CPE rank was 1.5 (interquartile range, 1-2). Lower CPE ranks correlated with higher CSF viral loads. Ranks less than 2 were associated with an 88% increase in the odds of detectable CSF viral load. In multivariate regression, lower CPE ranks were associated with detectable CSF viral loads even after adjusting for total number of ARV drugs, ARV drug adherence, plasma viral load, duration and type of the current regimen, and CD4 count. Conclusions Poorer penetration of ARV drugs into the CNS appears to allow continued HIV replication in the CNS as indicated by higher CSF HIV viral loads. Because inhibition of HIV replication in the CNS is probably critical in treating patients who have HIV-associated neurocognitive disorders, ARV treatment strategies that account for CNS penetration should be considered in consensus treatment guidelines and validated in clinical studies.

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Topics: Viral load (57%)

741 Citations


Open accessJournal ArticleDOI: 10.1212/WNL.56.2.257
Ned Sacktor1, Robert H. Lyles2, Richard L. Skolasky2, C. Kleeberger2  +5 moreInstitutions (5)
23 Jan 2001-Neurology
Abstract: This study examined the temporal trends in the incidence rates of HIV dementia, cryptococcal meningitis, toxoplasmosis, progressive multifocal leukoencephalopathy, and CNS lymphoma from January 1990 to December 1998 in the Multicenter AIDS Cohort Study. The incidence rates for HIV dementia, cryptococcal meningitis, and lymphoma decreased following the introduction of highly active antiretroviral therapy (HAART). The proportion of new cases of HIV dementia with a CD4 count in a higher range (i.e., 201 to 350) since 1996 may be increasing.

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Topics: Multicenter AIDS Cohort Study (62%), Dementia (55%), Meningitis (55%) ...read more

585 Citations


Journal ArticleDOI: 10.1016/J.JNEUROIM.2004.08.042
Justin C. McArthur1Institutions (1)
Abstract: Several advances have led to improvements in the care and prognosis of HIV+ individuals. The first is an understanding of the direct relationship between HIV replication and subsequent immunological and clinical progression, reinforcing the need to completely suppress HIV replication to control disease progression. The second is the wider availability of HAART which can provide effective suppression of HIV. The third major change is the ability to monitor HAART through the reliable and widespread measurement of plasma HIV RNA levels, which has become a routine part of clinical care. Since the introduction of highly active antiretroviral therapy (HAART) in the 1990s, there have been significant declines in the incidence rates of opportunistic infections in developed countries. HAART has clearly improved survival for individuals with HIV/AIDS, and has reduced the incidence of HIV-associated dementia (HIV-D) by 40-50% (Brodt et al., 2002). The prevalence of sensory neuropathies in advanced HIV/AIDS now exceeds 20% (Schifitto et al., 2002), and may rise further with prolonged exposure to neurotoxic HAART. HIV-D and HIV-related sensory neuropathies (HIV-SN) have a combined prevalence of about 30-50% in advanced HIV disease, suggesting that HAART does not provide complete protection against neurological damage (Bouwman et al., 1998). HIV-associated dementia (HIV-D) remains a common cause of dementia worldwide, and with HIV-related sensory neuropathies (HIV-SN) represents the commonest neurological disorders associated with AIDS. Furthermore, the temporal progression of HIV-D appears to have been altered by HAART, with most patients now showing an attenuated form of dementia, which with treatment is slowly progressive or static (Dougherty et al., 2002). This overview will review some of the outstanding questions relating to HIV-dementia, including: (a) are there differing phenotypes or temporal patterns of progression in HIV-dementia? (b) what determines these temporal patterns? and (c), what has been the impact of therapy on HIV dementia?

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400 Citations


Journal ArticleDOI: 10.1080/13550280290101094
Ned Sacktor1Institutions (1)
Abstract: Highly active antiretroviral therapy (HAART) is effective in suppressing systemic human immunodeficiency virus (HIV) viral load and has decreased mortality rates and the incidence of systemic opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS). Multiple studies now suggest that the incidence rates of HIV-associated neurological disease and central nervous system (CNS) opportunistic infections also are decreasing. Since the introduction of HAART in 1996, the incidence of HIV dementia has decreased by approximately 50%. The mean CD4 cell count for new cases of HIV dementia is increasing, but it remains as a complication of moderate-advanced immunosuppression. The incidence of HIV-associated distal sensory polyneuropathy has decreased, although the incidence of antiretroviral drug-induced toxic neuropathy has increased. However, as patients with AIDS live longer as a result of HAART, the prevalence of peripheral neuropathy in HIV-seropositive patients may be increasing. The incidence rates of CNS opportunistic infections (cryptococcal meningitis, toxoplasmosis, progressive multifocal leukoencephalopathy) and primary CNS lymphoma have decreased since the introduction of HAART. As patients develop increasing resistance mutations to antiretroviral drugs and with subsequent decline in CD4 cell counts, in the near future, the incidence of HIV-associated neurological disease may begin to rise.

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378 Citations