Richard M. Selik

Trends in diseases reported on U.S. death certificates that mentioned HIV infection, 1987-1999.

Summary: To examine trends in the proportions of deaths with various diseases among deaths with HIV infection, we analyzed multiple‐cause death certificate data for all deaths in the United States from 1987 through 1999. Disease proportions were adjusted to control for demographic changes. Deaths reported with HIV infection increased from 15,331 in 1987 to 47,977 in 1995 and then decreased to 16,061 in 1999. Among these reported deaths, new trends during the period from 1995 through 1999 included decreases in the proportions with cytomegalovirus disease (from 6.8% to 2.8%), wasting/cachexia (9.8% to 6.8%), and dementia/encephalopathy (6.3% to 3.9%) and increases in the proportions with septicemia/septic shock (from 9.2% to 13.4%) and diseases of the liver (4.9% to 11.6%), kidney (6.3% to 9.1%), and heart (4.2% to 6.9%). Continuations of pre‐1995 trends included decreases in the proportions with nontuberculous mycobacteriosis (7.1% to 3.1%) and Kaposi sarcoma (5.3% to 2.6%). Advances in antiretroviral therapy probably caused deaths due to HIV infection to decrease after 1995. Consequently, the proportions of deaths with HIV that were caused by other conditions increased. Improved prophylaxis or treatment of some opportunistic infections could also have reduced the proportions of deaths with those diseases, whereas antiviral drug toxicity could have contributed to increases in the proportions with noninfectious organ diseases.

Acquired immune deficiency syndrome (AIDS) trends in the United States, 1978-1982.

This report summarizes results of surveillance for the acquired immune deficiency syndrome (AIDS) in the United States by the Centers for Disease Control through the first quarter of 1983. Surveillance has been predominantly passive, supplemented by active follow-up of requests to the Centers for Disease Control for pentamidine isethionate for treatment of Pneumocystis carinii pneumonia. The 1,299 reported cases showed trends of increasing incidence among all risk groups: homosexual men (72 percent), intravenous drug abusers (17 percent), persons of Haitian origin (5 percent), persons with hemophilia (1 percent), and others (6 percent). Cases were reported among residents of 35 states and the District of Columbia, with the majority from New York (49 percent) and California (22 percent). Of the 6 percent of patients without well-established risk factors for AIDS, many have suspected risk factors (e.g., blood transfusion or a sexual partner in a high-risk group).

Trends in infectious diseases and cancers among persons dying of HIV infection in the United States from 1987 to 1992.

Human immunodeficiency virus (HIV) infection results in various other infectious diseases and cancers. Trends in the proportion of HIV-related deaths caused by these secondary diseases may reflect the efficacy of measures for treating or preventing these diseases and may help identify diseases that need more attention. We used national vital statistics to examine these trends. Methods We obtained data from multiple-cause mortality tapes prepared by the National Center for Health Statistics from death certificates of U.S. residents from 1987 through 1992, which were filed in all 50 U.S. states and the District of Columbia [1]. We identified diseases by their codes in the International Classification of Diseases, Ninth Revision (ICD-9) [2] and identified HIV infection by supplemental codes introduced in 1987 [3]. Among deaths for which HIV infection was recorded as the underlying cause, infectious diseases and cancers that could be secondary to HIV infection were found as nonunderlying (immediate, intermediate, or contributing) causes of death; this classification allowed more than one such disease per death. To determine the percentage of HIV-related deaths caused by a given disease, we excluded from the denominator deaths for which information on secondary diseases was missing: deaths for which no disease but HIV infection was recorded and those for which the only other causes recorded were nonspecific (such as cardiac arrest), not associated with HIV infection (such as trauma), or likely to have preceded HIV infection (such as drug abuse). We examined trends in the annual percentage of deaths associated with each infectious disease or cancer that was reported in at least 1.0% of the denominator in the 6-year period. We used Poisson regression analysis [4] to test the statistical significance (P < 0.05) of the trend for each disease. Results From 1987 to 1992, HIV infection was the underlying cause of 140 461 deaths, of which 104 831 had possible secondary causes of death specified on the death certificates. The proportion represented by the latter (75%) remained stable as the number increased annually from 10 001 deaths in 1987 to 24 230 in 1992. These 104 831 HIV-related deaths provided the denominators for calculating the annual percentage of deaths associated with each disease. Most of these HIV-related deaths (60%) were reported with 1 secondary infectious disease or cancer; 19%, with 2; 6%, with 3 to 8; and 15%, with none (but with other secondary conditions). Twelve infectious diseases and 2 cancers were each reported in at least 1.0% of the HIV-related deaths. The annual number of deaths associated with each disease generally increased as the total number of HIV-related deaths increased, but the relative rates of increase differed among diseases. These varying rates caused distinctly different trends in their percentages (Table 1; Figure 1). The percentages of HIV-related deaths associated with the following three diseases decreased: pneumocystosis, from 32.5% to 13.8%; cryptococcosis, from 7.7% to 5.0%; and candidiasis, from 2.3% to 1.7%. The percentages of deaths associated with eight diseases significantly increased: nontuberculous mycobacteriosis, from 6.7% to 12.2%; cytomegalovirus disease, from 5.2% to 9.9%; bacterial septicemia, from 9.0% to 11.5%; diffuse non-Hodgkin lymphoma, from 3.9% to 5.7%; tuberculosis, from 2.9% to 4.1%; progressive multifocal leukoencephalopathy, from 0.8% to 1.9%; bacterial pneumonia, from 1.2% to 2.1%; and cryptosporidiosis or isosporiasis, from 0.7% to 1.2%. The percentages of HIV-related deaths associated with unspecified pneumonia, Kaposi sarcoma, and toxoplasmosis (ranges from 17.6% to 18.6%, 10.4% to 12.1%, and 4.9% to 5.5%, respectively) had no significant linear trends during the 6-year period. Table 1. Trends in the Percentage of Deaths Associated with Infectious Diseases and Cancers Reported on Death Certificates of Persons Dying of HIV Infection* Figure 1. Trends in the prevalence of infectious diseases and cancers reported among persons dying of human immunodeficiency virus infection in the United States from 1987 to 1992. As a result of these different trends, the ranking of the diseases by the percentage of HIV-related deaths in which they were reported has changed. Pneumocystosis was the most common of these diseases until 1991, when its frequency decreased below that of unspecified pneumonia (Figure 1). The rank of nontuberculous mycobacteriosis increased from sixth place to third during 1987 to 1992, cryptococcosis dropped from sixth to ninth place, and candidiasis dropped from eleventh to thirteenth place. Disease trends among black persons (including Hispanic blacks) were similar to trends among white persons (including Hispanic whites); trends among females were generally similar to those among males. Discussion From 1987 to 1992, the distribution of secondary diseases among persons dying of HIV infection changed markedly. Pneumocystosis, initially the most common of these diseases, accounted for one third of HIV-related deaths in 1987; by 1992, however, it accounted for less than half this proportion. The percentages of cryptococcosis and candidiasis decreased to a lesser extent, those of eight other diseases increased, and those of three others did not change significantly. The dramatic decrease in the percentage of HIV-related deaths associated with pneumocystosis is consistent with results of studies of persons with the acquired immunodeficiency syndrome (AIDS) and of cohorts of HIV-infected persons [5-7]. This decreasing frequency of death associated with pneumocystosis is probably due to two factors: 1) enhanced prevention, attributable to the increasing use of chemoprophylaxis, and 2) increased survival of persons with Pneumocystis carinii pneumonia, attributable to improved methods of diagnosis and treatment [8, 9]. Despite these advances, pneumocystosis continues to cause a relatively large percentage of HIV-related deaths, probably because many HIV-infected persons do not obtain medical care for HIV infection until the infection is in a late stage, when pneumocystosis may have already developed [10]. In addition, P. carinii pneumonia sometimes develops despite prophylaxis, especially as immunodeficiency becomes more severe [11]. The large decrease in the percentage of HIV-related deaths associated with pneumocystosis should be expected to increase the percentages of HIV-related deaths associated with other diseases, in the absence of other influences. However, the percentages of deaths from cryptococcosis and candidiasis also decreased, perhaps because of successful prophylaxis or treatment with new antifungal agents such as fluconazole. This drug was licensed by the U.S. Food and Drug Administration in 1990 and was first used in clinical trials a few years earlier [12, 13]. The percentages of HIV-related deaths associated with toxoplasmosis, Kaposi sarcoma, and pneumonia caused by unspecified organisms did not change despite the decreasing percentages of deaths associated with pneumocystosis, cryptococcosis, and candidiasis. The increasing use of chemoprophylaxis against pneumocystosis with drugs effective against toxoplasmosis could have prevented increases in the percentage of deaths associated with toxoplasmosis and may also have held down the increases in the percentages with bacterial pneumonia and septicemia [14]. The percentage of HIV-related deaths associated with Kaposi sarcoma could have been suppressed by the decreasing percentage of homosexual or bisexual men (who account for most cases of Kaposi sarcoma) among persons with AIDS and the decreasing percentage of homosexual men with Kaposi sarcoma among all homosexual men with AIDS [15, 16]. Unspecified pneumonias are probably a mixture of cases caused by various unidentified pathogens, including P. carinii. Prophylaxis against pneumocystosis would be expected to decrease this component of unspecified pneumonia, whereas other components might be increasing. The net result is an apparently stable trend overall for unspecified pneumonia. Any changes in clinical practice affecting the specificity of the diagnosis of pneumonia could also have influenced these trends. A limitation of our study is the fact that the relative proportions of the components of unspecified pneumonia are unknown. Nonetheless, because of the decreased percentage of HIV-related deaths associated with P. carinii pneumonia, unspecified pneumonia became the leading secondary cause of death among persons dying of HIV infection, accounting for almost one fifth of HIV-related deaths. Some cases of unspecified pneumonia may represent terminal events in patients whose inevitable deaths were caused primarily by other HIV-related diseases. For other cases, determining the causative organisms and the most effective methods for preventing and treating this vaguely described entity may substantially increase the survival of persons with HIV infection. As in our study, studies of persons with AIDS found increasing trends in the percentage of patients with a diagnosis of nontuberculous mycobacteriosis (Mycobacterium avium complex infection) [7]. It is too early to see the effect of newly licensed drugs such as rifabutin in preventing and treating M. avium complex infection [17]. For most of the diseases analyzed in our study, the similarity of trends among whites and blacks and among males and females suggests that advances in treatment and prophylaxis have affected all of these groups. However, racial or sexual inequities in access to such care may still exist [18]. The quality of our data depends on how accurately and thoroughly the causes of death were reported on death certificates. Previous studies suggest that deaths for which the underlying cause was reported as HIV infection represent only 66% to 86% of all deaths attributable to HIV infection among men aged 25 to 44 years and 55% to 80% of such deaths among women

EPIDEMIOLOGY OF ACQUIRED IMMUNE DEFICIENCY SYNDROME IN PERSONS AGED 50 YEARS OR OLDER

SummaryAcquired immune deficiency syndrome (AIDS) has afflicted persons of all ages, yet only recently has attention been devoted to AIDS in older persons. To examine the epidemiology of AIDS in persons ≧50 years old in the United States, we analyzed cases reported to the Centers for Disease Control. The number reported annually in persons ≧50 years old increased from 13 in 1981 to 3,562 in 1989. Through December 1989, 11,984 had been reported, representing 10% of all cases. Although male homosexual contact accounted for most cases in persons aged 50–69, blood transfusion became a more common means of exposure with increasing age, accounting for 28% of cases in persons aged 60–69 and 64% of cases in individuals aged ≧70. The proportion of women increased from 6.1% in persons with AIDS aged 50–59 to 28.7% of those aged ≧70. The proportion of AIDS diagnoses made in the same month as death increased from 16% in persons aged 50–59 to 37% in those aged ≧80, suggesting either more rapid progression of disease or increasing delay in diagnosis. As the incidence in older persons continues to increase, clinicians caring for older patients must become more familiar with AIDS.

Trends in perimortal conditions and mortality rates among HIV-infected patients.

Objectives:To describe trends in perimortal conditions (pathological conditions causing death or present at death but not necessarily the reported cause of death) during three periods related to the availability of HAART, pre-HAART (1992–1995), early HAART (1996–1999), and contemporary HAART (2000–2003); annual mortality rates; and antiretroviral therapy (ART) prevalence during 1992–2003. Design:Multicenter observational clinical cohort in the United States (Adult/Adolescent Spectrum of HIV Disease [ASD] project). Methods:Proportionate mortality for selected perimortal conditions, annual mortality rates, and ART prevalence were standardized by sex, race/ethnicity, age at death, HIV transmission category, and lowest CD4 cell count of ASD decedents. Multivariable generalized linear regression was used to estimate trends in proportionate mortality, as linear trends through all three HAART periods, mortality rates, and ART prevalence. Results:Of 9225 deaths, 58.6% occurred during 1992–1995, 29.5% during 1996–1999, and 11.9% during 2000–2003. Linear trends in proportionate mortality for noninfectious diseases (e.g., liver disease, hypertension, and alcohol abuse) increased significantly; proportionate mortality for AIDS-defining infectious diseases (e.g., pneumocystosis, nontuberculous mycobacterial disease, and cytomegalovirus disease) decreased significantly. Mortality rates decreased from 487.5/1000 person-years in 1995 to 100.6 in 2002. Of 36 256 patients from ASD, 75.7% (standardized average) were prescribed ART annually. Conclusions:Among HIV-infected patients, the majority of whom were prescribed ART, the increasing trend in common noninfectious perimortal conditions support screening and treatment for these conditions in order to sustain the trend in declining mortality rates.

Characteristics of Hiv Infection Among Hispanics, United States 2003-2006

Background:Hispanic subgroups of varied national origin differ culturally; overall, Hispanics in the United States are disproportionately affected by HIV infection. Methods:We analyzed cases of HIV infection that were diagnosed among Hispanics in 33 states and US-dependent areas during 2003-2006 and reported to the Centers for Disease Control and Prevention through June 2007. We used Poisson regression to calculate the estimated annual percent change in the number and rate of HIV diagnoses and used logistic regression to analyze the association between birthplace and a short (<12 months) HIV-to-AIDS interval. Results:HIV infection was diagnosed among 30,415 Hispanics. Of 24,313 with reported birthplace, 61% were born outside the continental United States. The annual number of diagnoses increased among Mexican-born males [estimated annual percent change = 8.8%; 95% confidence interval (CI) = 3.5 to 14.5] and Central American-born males (18.6%; 95% CI = 9.4 to 28.6) and females (24.6%; 95% CI = 8.8 to 42.7) but decreased among US-born Hispanic females (−8.2%; 95% CI = −13.3 to −2.8). A short HIV-to-AIDS interval was more common among Mexican-born Hispanics than among US-born Hispanics. Discussion:Diagnosis trends and HIV-to-AIDS intervals varied by place of birth. To decrease the incidence of HIV infection among Hispanics, prevention programs need to address cultural differences.

Effect of the human immunodeficiency virus epidemic on mortality from opportunistic infections in the United States in 1993.

To measure the effect of the human immunodeficiency virus (HIV) epidemic on mortality from opportunistic infections (OIs) in 1993, national multiple-cause death certificate data were examined using two approaches. First, for each OI, the percentage of deaths with HIV infection reported as the underlying cause was calculated. Second, the age-adjusted rate of death per million population was compared with the rate predicted from a model of rates in 1970-1980 or 1979-1981, as available. The percentage of deaths with HIV as the underlying cause and the ratio of observed to predicted death rates were as follows: toxoplasmosis, 91% and 86 (5.24/0.06); cryptosporidiosis/isosporiasis, 90% and infinite (1.61/0.00); progressive multifocal leukoencephalopathy, 87% and 19 (2.58/0.13); pneumocystosis, 82% and 18 (15.44/0.87); cytomegalovirus disease, 82% and 17 (12.60/0.74); nontuberculous mycobacteriosis, 79% and 18 (15.51/0.84); cryptococcosis, 76% and 4 (5.80/1.35); and histoplasmosis, 68% and 6 (1.36/0.23). Thus, the HIV epidemic has greatly increased mortality from several OIs.

Characteristics of persons with heterosexually acquired HIV infection, United States 1999-2004.

OBJECTIVES In the United States a growing proportion of cases of heterosexually acquired HIV infections occur in women and in persons of color. We analyzed the association between race/ethnicity, whether diagnoses of HIV infection and AIDS were made concurrently, and the survival after diagnosis of heterosexually acquired AIDS. METHODS We used data from 29 states that report confidential name-based HIV/AIDS cases to the Centers for Disease Control and Prevention to calculate estimated annual percentage change in the number of actual diagnoses and analyzed the association between race/ethnicity and concurrent diagnoses of HIV and AIDS. We adjusted for reporting delays and absence of information about HIV risk factors. RESULTS During 1999 to 2004, diagnoses of heterosexually acquired HIV were made for 52 569 persons in 29 states; 33 554 (64%) were women. Among men and women, 38 470 (73%) were non-Hispanic Black; 7761 (15%), non-Hispanic White; and 5383 (10%), Hispanic. The number of persons with heterosexually acquired HIV significantly increased: 6.1% among Hispanic men (95% confidence interval=2.7, 9.7) and 4.5% among Hispanic women (95% confidence interval=1.8, 7.3). The number significantly decreased (-2.9%) among non-Hispanic Black men. Concurrent HIV and AIDS diagnoses were slightly more common for non-Hispanic Whites (23%) and Hispanics (23%) than for non-Hispanic Blacks (20%). CONCLUSIONS To decrease the incidence of heterosexually acquired HIV infections, prevention and education programs should target all persons at risk, especially women, non-Hispanic Blacks, and Hispanics.

Heterosexual and Homosexual Patients with the Acquired Immunodeficiency Syndrome: A Comparison of Surveillance, Interview, and Laboratory Data

Homosexual and heterosexual patients with the acquired immunodeficiency syndrome were compared by risk group. Race; diagnoses; history of sexually transmitted diseases, sexual behavior, and drug use; and socioeconomic indicators differed considerably among risk groups, suggesting different risk factors for acquisition of the syndrome. Patients in the homosexual, intravenous drug user, and Haitian risk groups differed in their serologic response to cytomegalovirus and syphilis testing, presumably due to lifestyle-related exposures. Differences in the rate of recovery of cytomegalovirus, serum levels of IgA and IgG, and antibody titers to Epstein-Barr virus were noted among patients with different diagnoses. We conclude that in studies of risk factors for the acquired immunodeficiency syndrome, patients should be analyzed by risk group and diagnoses.

This Place Is Killing Me: A Comparison of Counties Where the Incidence Rates of AIDS Increased the Most and the Least

BACKGROUND The objective of this study was to identify the socioeconomic and health characteristics of communities with the largest proportional increases in incidence rates of acquired immunodeficiency syndrome (AIDS). METHODS Reported AIDS cases (1981-1990 and 1995-1999) were used for a comparison between 20 US counties with the largest proportional increases in incidence rates of AIDS and 20 US counties with the smallest increases. Data were obtained from Community Health Status Indicators Reports of the Health Resources and Services Administration (HRSA) and from the US Census Bureau. RESULTS Counties with the largest increases in the incidence of AIDS had lower levels of income, education, and literacy; higher incidence rates of syphilis, age-adjusted mortality (all causes), and infant mortality; more low-birth-weight infants; and higher levels on all 9 specific mortality measures in the HRSA reports. CONCLUSIONS The incidence of AIDS increased the most in areas where many other health problems occurred. Research is needed to identify and address the root causes of ill health.