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Journal ArticleDOI

HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998

TL;DR: The proportion of new cases of HIV dementia with a CD4 count in a higher range since 1996 may be increasing, and the introduction of highly active antiretroviral therapy (HAART) may be responsible.
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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Journal ArticleDOI
TL;DR: Mental health affects progress towards the achievement of several Millennium Development Goals, such as promotion of gender equality and empowerment of women, reduction of child mortality, improvement of maternal health, and reversal of the spread of HIV/AIDS.

2,943 citations

Journal ArticleDOI
20 Feb 2009-AIDS
TL;DR: The first attempt to estimate the global burden of cryptococcal meningitis finds the number of cases and deaths to be very high, with most occurring in sub-Saharan Africa.
Abstract: OBJECTIVE: Cryptococcal meningitis is one of the most important HIV-related opportunistic infections especially in the developing world. In order to help develop global strategies and priorities for prevention and treatment it is important to estimate the burden of cryptococcal meningitis. DESIGN: Global burden of disease estimation using published studies. METHODS: We used the median incidence rate of available studies in a geographic region to estimate the region-specific cryptococcal meningitis incidence; this was multiplied by the 2007 United Nations Programme on HIV/AIDS HIV population estimate for each region to estimate cryptococcal meningitis cases. To estimate deaths we assumed a 9% 3-month case-fatality rate among high-income regions a 55% rate among low-income and middle-income regions and a 70% rate in sub-Saharan Africa based on studies published in these areas and expert opinion. RESULTS: Published incidence ranged from 0.04 to 12% per year among persons with HIV. Sub-Saharan Africa had the highest yearly burden estimate (median incidence 3.2% 720 000 cases; range 144 000-1.3 million). Median incidence was lowest in Western and Central Europe and Oceania (

1,891 citations

Journal ArticleDOI
19 Apr 2001-Nature
TL;DR: Human immunodeficiency virus-1 (HIV-1) can induce dementia with alarming occurrence worldwide, but discovery in brain of HIV-1-binding sites (chemokine receptors) provides new insights.
Abstract: Human immunodeficiency virus-1 (HIV-1) can induce dementia with alarming occurrence worldwide. The mechanism remains poorly understood, but discovery in brain of HIV-1-binding sites (chemokine receptors) provides new insights. HIV-1 infects macrophages and microglia, but not neurons, although neurons are injured and die by apoptosis. The predominant pathway to neuronal injury is indirect through release of macrophage, microglial and astrocyte toxins, although direct injury by viral proteins might also contribute. These toxins overstimulate neurons, resulting in the formation of free radicals and excitotoxicity, similar to other neurodegenerative diseases. Recent advances in understanding the signalling pathways mediating these events offer hope for therapeutic intervention.

1,184 citations

Journal ArticleDOI
01 Dec 2009-AIDS
TL;DR: The prevalence of HANDs without functional repercussion in daily life (asymptomatic neurocognitive impairment) is the most frequent subtype observed in this population, and the HIV dementia scale with a cutoff of 14 points or less seems to provide a useful tool to screen for the presence of Handeds.
Abstract: OBJECTIVE: To determine the prevalence of cognitive complaints and HIV-associated neurocognitive disorders (HANDs) in a cohort of aviremic HIV-positive patients. To evaluate the relevance of the HIV dementia scale to detect HANDs. DESIGN: Assessment of HANDs with neuropsychological tests. METHODS: Two hundred HIV-infected patients with undetectable HIV-1 RNA concentrations in the plasma, no history of major opportunistic infection of the central nervous system in the past 3 years, no current use of intravenous drugs, and no major depression answered a questionnaire designed to elicit cognitive complaints. Cognitive functions of 50 complaining and 50 noncomplaining HIV-positive patients were assessed. RESULTS: Patients had undetectable HIV-1 RNA concentrations for a median time of 48 months (range 3.2-136.6). The prevalence of cognitive complaints was 27%. The prevalence of HANDs was 84% among patients with cognitive complaints (asymptomatic neurocognitive impairment 24%, mild neurocognitive disorders 52%, and HIV-associated dementia 8%) and 64% among noncomplainers (asymptomatic neurocognitive impairment 60%, mild neurocognitive disorders 4%, and HIV-associated dementia 0%; P < 0.001). A score of 14 points or less on the HIV dementia scale yielded a positive predictive value of HANDs of 92% in complainers and 82% in noncomplainers. CONCLUSION: The prevalence of HANDs is high even in long-standing aviremic HIV-positive patients. However, HANDs without functional repercussion in daily life (asymptomatic neurocognitive impairment) is the most frequent subtype observed. In this population, the HIV dementia scale with a cutoff of 14 points or less seems to provide a useful tool to screen for the presence of HANDs.

645 citations


Cites background or result from "HIV-associated neurologic disease i..."

  • ...This number is somewhat higher than the prevalence of HANDs in patients described in previous reports [3,4,6– 8], but most of the studies [3,4,6,8] examining the prevalence of neurocognitive disorders in the HIVpositive population were performed before the revised nosology for HANDs was published, and thus ANI was possibly not accounted for....

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  • ...First, although the incidence of HIV-D has significantly decreased [3], its prevalence has increased [4], as HIV-positive patients live much longer than before the HAARTera [5]....

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Journal ArticleDOI
12 Sep 2007-AIDS
TL;DR: The association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there is a non-reversible component of neural injury that tracks with a history of disease progression, and suggests that restoring immunocompetence increases the likelihood of neurocognitive recovery.
Abstract: Objectives: HAART suppresses HIV viral replication and restores immune function. The effects of HAART on neurological disease are less well understood. The aim of this study was to assess the prevalence and incidence of neurocognitive impairment in individuals who initiated HAART as part of an AIDS clinical trial. Design: A prospective cohort study of HIV-positive patients enrolled in randomized antiretroviral trials, the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. Methods: We examined the association between baseline and demographic characteristics and neurocognitive impairment among 1160 subjects enrolled in the ALLRT study. Results: A history of immunosuppression (nadir CD4 cell count < 200 cells/ml) was associated with an increase in prevalent neurocognitive impairment. There were no significant virological and immunological predictors of incident neurocognitive impairment. Current immune status (low CD4 cell count) was associated with sustained prevalent impairment. Conclusion: The association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there is a non-reversible component of neural injury that tracks with a history of disease progression. The association of sustained impairment with worse current immune status (low CD4 cell count) suggests that restoring immunocompetence increases the likelihood of neurocognitive recovery. Finally, the lack of association between incident neurocognitive impairment and virological and immunological indicators implies that neural injury continues in some patients regardless of the success of antiretroviral therapy on these laboratory measures.

581 citations


Cites result from "HIV-associated neurologic disease i..."

  • ...infections [5,6], and neuropathological studies have confirmed these findings [7]....

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References
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Journal Article
TL;DR: In this paper, the authors reported a total of 22 waterborne-disease outbreaks associated with drinking water and recreational lake water, which caused an estimated total of 2,567 persons to become ill. No deaths were reported.
Abstract: Problem/condition Since 1971, CDC and the U.S. Environmental Protection Agency have maintained a collaborative surveillance system for collecting and periodically reporting data that relate to occurrences and causes of waterborne-disease outbreaks (WBDOs). Reporting period covered This summary includes data for January 1995 through December 1996 and previously unreported outbreaks in 1994. Description of the system The surveillance system includes data about outbreaks associated with drinking water and recreational water. State, territorial, and local public health departments are primarily responsible for detecting and investigating WBDOs and for voluntarily reporting them to CDC on a standard form. Results For the period 1995-1996, 13 states reported a total of 22 outbreaks associated with drinking water. These outbreaks caused an estimated total of 2,567 persons to become ill. No deaths were reported. The microbe or chemical that caused the outbreak was identified for 14 (63.6%) of the 22 outbreaks. Giardia lamblia and Shigella sonnei each caused two (9.1%) of the 22 outbreaks; Escherichia coli O157:H7, Plesiomonas shigelloides, and a small round structured virus were implicated for one outbreak (4.5%) each. One of the two outbreaks of giardiasis involved the largest number of cases, with an estimated 1,449 ill persons. Seven outbreaks (31.8% of 22) of chemical poisoning, which involved a total of 90 persons, were reported. Copper and nitrite were associated with two outbreaks (9.1% of 22) each and sodium hydroxide, chlorine, and concentrated liquid soap with one outbreak (4.5%) each. Eleven (50.0%) of the 22 outbreaks were linked to well water, eight in noncommunity and three in community systems. Only three of the 10 outbreaks associated with community water systems were caused by problems at water treatment plants; the other seven resulted from problems in the water distribution systems and plumbing of individual facilities (e.g., a restaurant). Six of the seven outbreaks were associated with chemical contamination of the drinking water; the seventh outbreak was attributed to a small round structured virus. Four of the seven outbreaks occurred because of backflow or backsiphonage through a cross-connection, and two occurred because of high levels of copper that leached into water after the installation of new plumbing. For three of the four outbreaks caused by contamination from a cross-connection, an improperly installed vacuum breaker or a faulty backflow prevention device was identified; no protection against backsiphonage was found for the fourth outbreak. Thirty-seven outbreaks from 17 states were attributed to recreational water exposure and affected an estimated 9,129 persons, including 8,449 persons in two large outbreaks of cryptosporidiosis. Twenty-two (59.5%) of these 37 were outbreaks of gastroenteritis; nine (24.3%) were outbreaks of dermatitis; and six (16.2%) were single cases of primary amebic meningoencephalitis caused by Naegleria fowleri, all of which were fatal. The etiologic agent was identified for 33 (89.2%) of the 37 outbreaks. Six (27.3%) of the 22 outbreaks of gastroenteritis were caused by Cryptosporidium parvum and six (27.3%) by E. coli O157:H7. All of the latter were associated with unchlorinated water (i.e., in lakes) or inadequately chlorinated water (i.e., in a pool). Thirteen (59.1%) of these 22 outbreaks were associated with lake water, eight (36.4%) with swimming or wading pools, and one(4.5%) with a hot spring. Of the nine outbreaks of dermatitis, seven (77.8%) were outbreaks of Pseudomonas dermatitis associated with hot tubs, and two (22.2%) were lake-associated outbreaks of swimmer's itch caused by Schistosoma species. Interpretation WBDOs caused by E. coli O157:H7 were reported more frequently than in previous years and were associated primarily with recreational lake water. This finding suggests the need for better monitoring of water quality and identification of sources of

1,471 citations

Journal ArticleDOI
TL;DR: The Multicenter AIDS Cohort Study was designed to elucidate the natural history of the infection causing acquired immunodeficiency syndrome (AIDS), identify risk factors for occurrence and clinical expression of the virus, and establish a repository of biologic specimens for future study.
Abstract: The Multicenter AIDS Cohort Study was designed to elucidate the natural history of the infection causing acquired immunodeficiency syndrome (AIDS), identify risk factors for occurrence and clinical expression of the infection, and establish a repository of biologic specimens for future study. A variety of recruitment techniques, including special assurance of confidentiality, were used to enroll participants. Nearly 5,000 homosexual men volunteered for semiannual interview, physical examination, and laboratory testing in four metropolitan areas. A significant majority of these men in each center (69-83%) reported having 50 or more lifetime sexual partners, and over 80% had engaged in receptive anal intercourse with at least some of their partners in the previous two years. By the time of the participants' initial evaluation (April 1984-April 1985), infection with the human immunodeficiency virus (HIV) had occurred in higher proportions of men in Los Angeles (51%) and Chicago (43%) than in Baltimore/Washington, DC (31%) and Pittsburgh (21%), presumably as a result of the higher number of partners and proportion with whom these men had engaged in high-risk practices (e.g., receptive anal intercourse). Follow-up evaluations are underway in this comprehensive longitudinal investigation of HIV infection.

1,146 citations

Journal ArticleDOI
TL;DR: These definitions have been developed in conjunction with the International Classification of Diseases-10 (ICD-10, unpublished draft of the World Health Organization) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, unpublishedDraft of the American Psychiatric Association) and are not identical.
Abstract: Infection with human immunodeficiency virus-type 1 (HIV-1) has been associated with avariety of neurologic disorders thought to be caused, directly or indirectly, by HIV-1.1-6 Although these disorders have been described clinically, there is no consensus terminology or criteria for diagnosis. To develop consensus nomenclature and case definitions for HIV-1-associated neurologic conditions for research purposes, the American Academy of Neurology AIDS Task Force convened a working group of neurologists, neuropsychologists, psychiatrists, and sociologists that included representatives of the American Neurological Association, the World Federation of Neurology, the International Neuropsychological Society, the National Academy of Neuropsychology, the American Psychological Association, the American Psychiatric Association, the World Health Organization, and the Centers for Disease Control (CDC). These definitions have been developed in conjunction with the International Classification of Diseases-10 (ICD-10, unpublished draft of the World Health Organization) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV, unpublished draft of the American Psychiatric Association). Although consistent with the ICD-10, the definitions are not identical. HIV-2 may cause similar disorders, but the neurologic manifestations of HIV-2 are unknown and are not addressed in this article.

760 citations

Journal ArticleDOI
04 Nov 1998-JAMA
TL;DR: In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.
Abstract: Context.—Time to development of acquired immunodeficiency syndrome (AIDS) and time to death have been extended with the increased use of combination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods characterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level.Objective.—To assess the effectiveness of self-reported, long-term potent antiretroviral therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters).Design.—Cohort study. The cohort was compared for time to development of AIDS and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July 1995 to July 1997 when the major treatments were no therapy, monotherapy, combined therapy, and potent antiretroviral therapy, respectively. Survival analysis methods with time zero set as the date of seroconversion and incorporating staggered entries into each period were used. Mean CD4 cell change, stratified by infection duration, was determined for each period using a random effects model.Setting.—The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, Ill; Los Angeles, Calif; and Pittsburgh, Pa).Participants.—A total of 5622 men who were 18 years or older were enrolled into MACS. Of the 5622, there were 2191 HIV-positive individuals at enrollment. Of the 3431 men who were HIV-negative, 536 were observed to seroconvert and were followed up for up to 13 years. The group of 536 who seroconverted constituted the study population.Main Outcome Measures.—Time from seroconversion to development of AIDS and to death and change in CD4 cell count.Results.—A total of 231 seroconverters developed AIDS, and 200 men died. Using 1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04 (95% confidence interval [CI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% CI, 0.38-1.01) for the same periods. The relative time (the factor by which times are contracted or expanded) to development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and 1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time for 1993 to July 1995 was 1.01 (95% CI, 0.91-1.12) and for July 1995 to July 1997 was 1.21 (95% CI, 1.07-1.36) relative to 1990 to 1993. The rate of CD4 cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods.Conclusions.—In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.

735 citations

Journal ArticleDOI
15 Nov 1997-AIDS
TL;DR: The incidence of AIDS-defining events in patients with advanced HIV infection at Frankfurt University Hospital has declined by more than 70% from 1992 to 1996, with a trend for malignancies and single opportunistic infections, with the exception of mycobacterial diseases.
Abstract: Objective: To determine the incidence of AIDS-defining opportunistic infections and malignancies over a 5-year period from 1992 to 1996. Study population: Subcohort of 1003 homosexual men with HIV infection and CD4 count less than 200 x 10 6 cells/l from the Frankfurt AIDS Cohort Study. Methods: Data including the earliest date that a CD4 T-lymphocyte count < 200 x 10 6 /l was reached and the dates of AIDS-defining events were compiled from medical records. Incidence analyses for AIDS-defining events and death during the subsequent 5 years (1992-1996) were performed using rates per 100 person-years of exposure. Results: During the observation period, the number of patients per year with CD4 T-lymphocyte counts < 200 x 10 6 /l varied between 402 and 511. In 1992, 56.7%, of patients experienced at least one AIDS-defining illness, and 20.7% in 1996. The annual number of AIDS-defining events per 100 patient-years of observation declined from 143.5 in 1992 to 38.3 in 1996, and the number of AIDS-related deaths fell from 25.7 to 12.9. Analysis of the number of events confirmed this trend for malignancies and single opportunistic infections, with the exception of mycobacterial diseases. Conclusions: The incidence of AIDS-defining events in patients with advanced HIV infection at Frankfurt University Hospital has declined by more than 70%, from 1992 to 1996.

412 citations

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