The decline of incident cases of HIV-associated neurological disorders in San Francisco, 1991–2003

Abstract

Neuropsychological impairment as a result of HIV infection and the development of other central nervous system (CNS) disorders associated with HIV disease has been well documented since the early days of the epidemic [1]. Although the mechanism by which HIV causes cognitive–motor impairment is unresolved [2,3], cognitive decline has been demonstrated to be a ‘function of disease progression’ [4]. The prevalence of AIDS dementia is not known. However, the World Health Organization reported that “of 35 million HIV infected individuals worldwide, one-third of adults will develop a dementive illness” [4]. Estimates of the prevalence of the disorder range from 16 to 25%, with more recent data pointing towards 7–10% [2]. Among only those with advanced HIV disease, the prevalence of dementia has been estimated at 15–66% [2]. The prevalence of minor cognitive motor disorder has been estimated at 25–30%, and is usually seen in symptomatic HIV infection [4]. The annual incidence of AIDS dementia has been estimated at 7% [5]. The prevalence of the disorder has proved much more difficult to estimate. Nevertheless, because of the degree of morbidity associated with these disorders, a small change in their incidence or prevalence could mean a substantial change in the demands on the healthcare system. Since the advent of widely available highly active antiretroviral therapy (HAART) in 1996, several studies have reported a decrease in the incidence of AIDS dementia [6]. Among HAART-treated patients, a decrease in AIDS dementia has also been observed, along with improved cognitive functioning and neuroimaging markers [6]. Furthermore, autopsy analysis has revealed significant reductions in HIV-related brain lesions in HAART-treated patients compared with patients receiving either no therapy, monotherapy or dual therapy [7]. However, no difference in the presence of lesions was noted between untreated and treated patients who died in the post-HAART era, suggesting that the incidence of AIDS dementia among advanced-stage HIV patients may not decrease [7]. We report here on changes in the incidence of CNS disorders in San Francisco, a city in which AIDS case reporting has been shown to be over 95% complete [8], and where the proportion of individuals living with AIDS who receive HAART increased from 5% in 1995 to 76% in 2003 [9]. In San Francisco, the Department of Public Health conducts AIDS case surveillance activities, in which health department personnel review pathology, laboratory, and death reports to identify and report diseases among individuals with AIDS. The initial and subsequent occurrences of AIDS-related opportunistic infections, including cryptococcosis and HIV encephalopathy, are collected. We analysed the annual incidence of CNS diagnoses (AIDS dementia, cryptococcosis, toxoplasmosis, progressive multifocal leukoencephalopathy and primary brain lymphoma) among AIDS cases in San Francisco from 1991 to 2003. The annual incidence of AIDS dementia declined from 3.71 per 100 persons living with AIDS in 1992, to 0.34 per 100 persons living with AIDS in 2002 and to 0.24 per 100 persons living with AIDS in 2003 (Fig. 1). Although not as dramatic, declines in other CNS opportunistic illnesses were also observed. These data strongly support the notion that after the advent and wider use of HAART, the incidence of newly diagnosed AIDS dementia and other HIV-associated neurological problems in San Francisco has fallen sharply.Fig. 1: Incidencea of central nervous system diagnoses among AIDS cases 1991–2003b. All central nervous system causes;dementia;toxoplasmosis;cryptococcosis;brain lymphoma;progressive multifocal leukoencephalopathy. aIncidence per 100 individuals living with AIDS per year. bLikelihood ratio for trend, P < 0.001 for all central nervous system diagnoses.When interpreting these data it is important to note that diagnoses of CNS opportunistic illnesses may have been missed because of insufficient access to medical records at selected facilities, or to records of local AIDS cases who received some or all of their medical care at facilities outside San Francisco. Reports of opportunistic illnesses occurring in 2003 may be incomplete because of reporting delays, and thus the decline observed between 2002 and 2003 may not be as great as depicted. Nevertheless, consistent with reported declines in other opportunistic diseases among patients with HIV here in San Francisco [10], we conclude that the advent of HAART has resulted in a dramatic decrease in the incidence of each one of the five CNS disorders reported here among patients with AIDS. Whereas the actual mechanism of action of this protective effect is not fully understood, reduced viral load and protection against the destruction of immune competent cells associated with HAART appears to be responsible for reducing HIV-associated cognitive disorders and other CNS opportunistic diseases. Fewer new cases, as well as a decrease in the number of living cases with one or more of these debilitating CNS disorders, may indicate a decreasing burden on the system of care; an important consideration as we experience an increasing volume of patients living with chronic HIV infection into older age.