Trends in AIDS-Related Opportunistic Infections among Men Who Have Sex with Men and among Injecting Drug Users,

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1 114 Trends in AIDS-Related Opportunistic Infections among Men Who Have Sex with Men and among Injecting Drug Users, Jeffrey L. Jones, Debra L. Hanson, Mark S. Dworkin, Jonathan E. Kaplan, and John W. Ward Adult/Adolescent Spectrum of HIV Disease Group,* Division of HIV/ AIDS Prevention Surveillance and Epidemiology, National Center for HIV, STD, and Tuberculosis Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia Incidence trends for the 13 most frequent AIDS-defining opportunistic infections (OIs) among men who have sex with men (MSM, n Å 15,588) and injecting drug users (IDUs, n Å 4475) were examined using data abstracted from medical records in ú90 hospitals and clinics in nine US cities during Among MSM, the most frequent OIs were Mycobacterium avium complex (MAC) disease, Pneumocystis carinii pneumonia (PCP), and cytomegalovirus (CMV) retinitis; decreasing (P.05) trends occurred for 11 OIs (MAC disease, PCP, CMV retinitis, Kaposi s sarcoma, esophageal candidiasis, CMV disease, extrapulmonary cryptococcosis, toxoplasmic encephalitis, tuberculosis, chronic herpes simplex, and disseminated histoplasmosis). Among IDUs, the most frequent OIs were PCP, MAC disease, and esophageal candidiasis; decreasing trends occurred for 5 OIs (PCP, esophageal candidiasis, tuberculosis, chronic herpes simplex, and chronic cryptosporidiosis) and an increase occurred in recurrent pneumonia. The differences in trends for MSM and IDUs may be due to differences in medical care and adherence to preventive medications. Opportunistic infections (OIs) are the principal cause of se- also help in setting priorities for preventive and therapeutic vere illness and death among human immunodeficiency virus interventions and provide information for planning future medi- (HIV) infected persons [1]; they significantly reduce the qual- cal care needs and research. Accordingly, we also examined ity of life and longevity, and they greatly influence medical trends in prescriptions of medications used for primary preven- care costs. Eighty-five percent of AIDS-defining OIs in the tion for Pneumocystis carinii pneumonia (PCP) and disseminated United States occur with marked immune suppression, characterized Mycobacterium avium complex (MAC) infection and in by a CD4 T lymphocyte count õ200 cells/ml [1]. prescriptions for antifungal medications, antiherpesviral medications, An estimated 200, ,000 HIV-infected persons in the and antiretroviral medications. United States have CD4 cell counts õ200/ml and are at high risk for OIs (Karon J, CDC, personal communication) [2]. AIDS-defining OIs are those infections that are included in Methods the Centers for Disease Control and Prevention (CDC) AIDS We used data from 9 Adult/Adolescent Spectrum of HIV Dissurveillance case definition [3]. In this evaluation, we examined ease surveillance system (ASD) project areas to examine trends the annual incidence and temporal trends for the 13 most fre- in OIs and prescription patterns for MSM and IDUs. We selected quently diagnosed AIDS-defining OIs among men who have these groups because they have the largest number of persons in sex with men (MSM) and injecting drug users (IDUs) in a ASD and therefore we were able to evaluate trends in the most large multicenter follow-up surveillance system. frequent AIDS-defining OIs, as well as in some less frequent condi- Trends in OIs provide information about whether preventive tions. ASD was started by CDC during 1990 in collaboration with medications or other preventive measures are having a signifimonitor state and local health departments as a surveillance project to the spectrum and frequency of HIV-associated diseases. cant impact on OI occurrence. Examining trends in OIs can The methods for ASD have been described previously [1, 4]. Briefly, at selected facilities in Atlanta, Dallas, Denver, Detroit, Los Angeles, San Antonio, Seattle, Houston, and New Orleans, HIV-infected persons at least 13 years of age are identified at their Received 17 June 1997; revised 2 January first health care encounter regardless of the stage of their HIV Presented in part: XI International Conference on AIDS, July 1996, Vancou- infection. Information is collected on demographic characteristics, ver, Canada (abstract We.C.3418). mode of HIV exposure, and any previous occurrences of conditions These surveillance data were collected under the federal assurance of confilisted in the AIDS surveillance case definition [3]. During succesdentiality in accordance with Sections 306 and 308(d) of the Public Health Service Act (42 USC 242k and 242m[d]). sive 6-month follow-up intervals, medical records are reviewed Reprints or correspondence: Dr. Jeffrey L. Jones, Mailstop E-47, Surveil- for illnesses, AIDS-defining conditions, prescriptions, laboratory lance Branch, Division of HIV/AIDS Prevention, NCHSTP, Centers for Dis- tests, including CD4 T lymphocyte counts, and medical care use. ease Control and Prevention, Atlanta, Georgia (jlj1@cdc.gov). More than 90 medical facilities that provide inpatient or outpa- * Group members are listed after text. tient care for HIV-infected patients were included in this analysis. The Journal of Infectious Diseases 1998;178: This article is in the public domain. All patients 13 years of age infected with HIV attending partici /98/ pating clinics were eligible for enrollment. In some sites, 25%

2 JID 1998;178 (July) AIDS Opportunistic Infections % of white men were systematically sampled, as described pre- were considered primary prophylaxis if given in intervals before viously [1]. Data from two ASD sites, New York City and Puerto the interval of observation of these OIs. PCP and MAC preventive Rico, were excluded from this analysis because these areas were prescriptions were assessed at CD4 T lymphocyte counts õ200 not added to ASD until 1992 or later and therefore we could not cells/ml and 75 cells/ml, respectively, because these were the examine trends for the full 6 years at these sites. levels recommended for prophylaxis in the US Public Health Service/Infectious Definitive and presumptive diagnoses were combined for this Diseases Society of America guidelines in effect analysis. The CDC classification was used for HIV exposure mode. at the time [9]. MSM who were also IDUs were not included in this analysis. Because there is not a general recommendation for primary Data used in this analysis were reported to CDC through July prophylaxis of fungal disease, antifungal prescriptions were assessed 1997 and were used to calculate annual incidence trends for the in the analysis whether they were used for prevention or 6-year period Data from 1990 were not included be- treatment of fungal disease at CD4 T lymphocyte counts õ200 cause many sites started late in the year. The number of months cells/ml. In ASD, medications are recorded if prescribed at any of prospective follow time were calculated for each year for per- time in each 6-month follow-up interval, and the specific dates or sons in care in ASD facilities. The calculated incidence is for the reasons medications are given are not recorded. first occurrence of each OI; persons were not considered to be at Outpatient care use rates were calculated to provide an indication risk for a specific OI if it had already occurred. The CD4 T lymphocyte of the frequency of medical care, because less frequent medirisk count associated with each observation was the minimum cal care might help explain lower prescription rates in one of the count in the previous 6 months. The median time from this CD4 T groups analyzed. Multivariate linear regression [10] was used to lymphocyte count to OI diagnosis was 2 months (mode, 0 months). assess differences in the frequency of annual outpatient care use These data were adjusted to standard populations from the AIDS by HIV exposure group (MSM and IDUs) while controlling for Reporting System (ARS) so that incidence could be calculated other potential confounders (CD4 T lymphocyte count, metropolitan from year to year in comparable populations within the MSM and area, race, age, country of origin, sex, and year). Robust varifrom IDU groups. However, since the populations of MSM and IDUs ance methods were used to account for within-person correlation reported with AIDS have different compositions by race, country among patients followed for more than one 6-month follow-up of origin, and age, we chose to allow these factors to remain interval [11]. different in the two standard populations from ARS so that the incidence of OIs in these groups would more accurately reflect the incidence expected in persons reported with AIDS. The incidence Results of OIs used in the trends for MSM were weighted by age, race, In the 6-year period , there were 15,558 MSM and country of origin (US vs. foreign) to a standard population and 4475 IDUs in the study population. The descriptive charconsisting of the MSM reported to ARS in 1991 through 1996 in the nine ASD metropolitan areas (table 1). The incidence of OIs acteristics of the population are shown in table 1. Because used for trends in IDUs were weighted to a standard population a person may contribute ú1 year to each characteristic cate- (table 1) in a similar way as for MSM, except weighting by sex gory, both person-years and number of persons are presented was also done. in table 1. The 6-year lost-to-follow-up rate was 15.2% for When adjusting the data to the standard populations, the com- MSM and 15.4% for IDUs. The average annual incidence bined MSM-IDU CD4 T lymphocyte count (6 strata) and metropol- for each of the leading 13 OIs in , stratified by itan area distributions were used so these factors would not differ CD4 T lymphocyte count, is shown in figures 1 and 2 for for the two risk groups. The CD4 T lymphocyte distribution from MSM and IDUs, respectively. Among MSM with CD4 T persons with AIDS reported during was used in the lymphocyte counts õ100, the most frequent five AIDS-destandard populations because CD4 T lymphocyte reporting was fining OIs were MAC infection, PCP, cytomegalovirus most complete in these years (ú90%). The ARS standard popula- (CMV) retinitis, Kaposi s sarcoma, and CMV disease other tions were adjusted for reporting delays by the method described by Karon et al. [5], and the proportion of patients with unknown than retinitis, and in IDUs with CD4 cell counts õ100, they or unidentified risk exposure category was redistributed according were PCP, MAC infection, esophageal candidiasis, tubercu- to the method described by Green et al. [6]. losis, and recurrent pneumonia. The Cochran-Mantel-Haenszel statistic [7] was applied to the The annual incidence trends for the 13 most common OIs in observed data stratified by CD4 cell count, race, sex (IDUs), age, MSM and IDUs are shown in table 2. Among MSM, significant metropolitan area, and origin of birth to test for trend. For the decreasing trends occurred in 11 OIs: MAC disease, PCP, CMV overall average annual incidence of OIs among MSM and IDUs, retinitis, Kaposi s sarcoma, esophageal candidiasis, CMV disdata were additionally adjusted to the distribution by year of OI ease, extrapulmonary cryptococcosis, toxoplasmic encephalitis, diagnosis [8]. tuberculosis, chronic herpes simplex, and disseminated histo- The trends in medications used for PCP prophylaxis (trimethoplasmosis. In contrast, among IDUs, there were decreasing prim-sulfamethoxazole, dapsone, pentamidine) and MAC prophytrends for 5 OIs PCP, esophageal candidiasis, tuberculosis, laxis (clarithromycin, azithromycin, rifabutin) and for antifungal prescriptions (fluconazole, ketoconazole, itraconazole) were asone significantly increasing trend, for recurrent pneumonia. chronic herpes simplex, and chronic cryptosporidiosis and sessed in populations at risk for the first occurrence of PCP, MAC disease, and fungal infections, respectively. Among persons with MAC infection in IDUs increased after 1994 and especially PCP and MAC infection, prescriptions for preventive medications from 1995 to There were no significant differences in

3 116 Jones et al. JID 1998;178 (July) Table 1. Descriptive characteristics of Adult/Adolescent Spectrum of Disease (ASD) project study population and AIDS Reporting System (ARS) population, ASD person-years ASD persons* ARS persons Characteristic MSM IDU MSM IDU MSM IDU Total 28,403 (100) 7383 (100) 15,588 (100) 4475 (100) 43,542 (100) 8845 (100) CD4 T lymphocytes/ml (14.7) 894 (12.1) 4768 (30.6) 1107 (24.7) 4783 (20.0) 4783 (20.0) (7.0) 333 (4.5) 3089 (19.8) 530 (11.8) 2519 (10.5) 2519 (10.5) (7.0) 372 (5.0) 3425 (22.8) 688 (15.4) 3559 (14.9) 3559 (14.9) (11.2) 736 (10.0) 4248 (27.3) 1114 (24.9) 7708 (32.2) 7708 (32.2) ,792 (38.0) 2559 (34.7) 7695 (49.4) 2323 (51.9) 2941 (12.3) 2941 (12.3) Missing count 6273 (22.1) 2489 (33.7) 9722 (62.4) 3118 (69.7) 2417 (10.1) 2417 (10.1) Year of observation (19.5) 1219 (16.5) 7768 (49.8) 1873 (41.9) 6183 (17.3) 1031 (14.4) (20.0) 1494 (20.2) 7846 (50.3) 2284 (51.0) 6240 (17.5) 1195 (16.7) (19.2) 1504 (20.4) 7743 (49.7) 2248 (50.2) 6003 (16.8) 1161 (16.2) (17.6) 1403 (19.0) 7086 (45.5) 2105 (47.0) 6195 (17.3) 1288 (18.0) (14.4) 1098 (14.9) 5893 (37.8) 1704 (38.1) 5873 (16.4) 1216 (17.0) (9.3) 664 (9.0) 4211 (27.0) 1166 (26.1) 5237 (14.7) 1258 (17.6) Race/ethnicity White 16,443 (57.9) 1800 (24.4) 8679 (55.7) 1091 (24.4) 25,365 (58.3) 2059 (23.3) Black 7759 (27.3) 5000 (67.7) 4548 (29.2) 2995 (66.9) 9835 (22.6) 5593 (63.2) Hispanic 3772 (13.3) 512 (6.9) 2132 (13.7) 344 (7.7) 7632 (17.5) 1118 (12.6) Asian 286 (1.0) 15 (0.2) 151 (1.0) 11 (0.2) 526 (1.2) 36 (0.4) Native American 87 (0.3) 51 (0.7) 49 (0.3) 28 (0.6) 115 (0.3) 31 (0.4) Other/unknown 57 (0.2) 5 (0.1) 29 (0.2) 6 (0.1) 69 (0.2) 9 (0.1) Sex Male 28,403 (100) 4153 (56.3) 15,588 (100) 2675 (59.8) 43,542 (100) 6300 (71.2) Female (43.7) (40.2) (28.8) Age at observation, years õ (19.3) 1065 (14.4) 4118 (26.4) 789 (17.6) 7674 (17.6) 1268 (14.3) ,857 (73.4) 5878 (79.6) 11,993 (76.9) 3715 (83.0) 31,648 (72.7) 6796 (76.8) ú (7.3) 440 (6.0) 1226 (7.9) 296 (6.6) 4219 (9.7) 781 (8.8) Birthplace US/Canada 26,639 (93.8) 7217 (97.8) 14,599 (93.7) 4353 (97.3) 33,714 (77.4) 7472 (84.5) Other 1685 (5.9) 158 (2.1) 946 (6.1) 114 (2.5) 5265 (12.1) 660 (7.5) Unknown 80 (0.3) 8 (0.1) 43 (0.3) 8 (0.2) 4563 (10.5) 713 (8.1) NOTE. Data are no. (%). * CD4 T lymphocyte count, year of observation, and age at observation are time-varying; a person may contribute to ú1 category (persons may not sum to total n). MSM and IDU cases diagnosed , ages 13, and from 9 ASD metropolitan areas were included. Adjustments were made for reporting delay; a proportion of cases with unknown or unidentified HIV-exposure category were redistributed as MSM or IDU. ARS cases were estimated for each year; lowest CD4 T lymphocyte counts from among combined MSM and IDU cases diagnosed were used (n Å 23,928). trends by race or sex, except that chronic herpes simplex was and IDUs (2% in 1991, 29% in 1996), although to a higher level decreasing among male IDUs (P õ.001) but not among female for MSM. IDUs (P Å.99) (data not shown). Among persons with CD4 T lymphocyte counts õ200 cells/ Prescription of medications used for PCP prophylaxis among ml, antifungal prescriptions were relatively stable in MSM (44% persons with a CD4 T lymphocyte count õ200 was relatively in 1991, 46% in 1996) and increased somewhat in IDUs (32% stable from 1991 through 1996 for MSM (88% in 1991, 80% in in 1991, 40% in 1996). Fluconazole prescriptions increased in 1996 [a high of 85% in 1993]) and increased somewhat for IDUs both MSM (20% in 1991, 40% in 1996) and IDUs (20% in 1991, (66% in 1991, 79% in 1996). Trimethoprim-sulfamethoxazole 36% in 1996). Acyclovir prescriptions at õ200 CD4 cells/ml did constituted an increasing proportion of PCP-preventive prescrip- not increase in MSM (42% in 1991, 36% in 1996) or IDUs tions for MSM (42% in 1991, 68% in 1996) and IDUs (42% in (19% in 1991, 19% in 1996). However, combination antretroviral 1991, 67% in 1996). Prescriptions of medications used for MAC therapy (defined as two or more drugs prescribed in an interval) prophylaxis among persons with CD4 T lymphocyte counts õ75 at õ500 CD4 cells/ml increased in MSM (12% in 1991, 52% cells/ml increased for both MSM (2% in 1991, 47% in 1996) in 1996) and IDUs (2% in 1991, 29% in 1996).

4 JID 1998;178 (July) AIDS Opportunistic Infections 117 Figure 1. Average annual incidence of selected opportunistic infections in men who have sex with men by CD4 T lymphocyte count, MAC, Mycobacterium avium complex; Pneumocystis, Pneumocystis carinii; CMV, cytomegalovirus. CMV disease refers to disease other than retinitis; candidiasis, esophageal candidiasis; cryptococcosis, extrapulmonary cryptococcosis; toxoplasmosis, toxoplasmic encephalitis; cryptosporidiosis, chronic cryptosporidiosis; tuberculosis, pulmonary and extrapulmonary tuberculosis; histoplasmosis, disseminated histoplasmosis. The median number of outpatient visits per year for MSM was 9, compared with 6 among IDUs (P õ.001). Discussion These data indicate that decreases are occurring in many OIs but that these decreases are not occurring equally in all groups. The decrease in PCP among MSM cannot be attributed to an overall increase in PCP-preventive medication prescriptions because these prescriptions were relatively stable over the 6-year period. However, the decrease in PCP could be due to trimethoprim-sulfamethoxazole, because the proportion of persons taking this medication increased and because trimethoprim-sulfamethoxazole is both effective [12] and easy to administer as an oral preparation. PCP-preventive therapy was originally recommended in 1989 [13]. The in- crease in prescriptions for combination antiretroviral therapy may have also caused a decrease in PCP and other OIs by slowing the progression of HIV disease. A decrease in PCP has also been shown in cohort studies of MSM [14 17] and in other HIV-infected populations [18 20]. The decrease in toxoplasmic encephalitis in MSM may also be due to the increase in prescription of trimethoprim-sulfa- methoxazole. Trimethoprim-sulfamethoxazole has been shown to decrease the incidence of toxoplasmic encephalitis [21] and is recommended as the drug of choice for prophylaxis of this disease [9]. The decreases in esophageal candidiasis in MSM and IDUs and extrapulmonary cryptococcosis in MSM are probably due to the increased use of antifungal agents, such as fluconazole, that can prevent systemic fungal infections [22]. Use of these agents for less severe manifestations may prevent dissemina- tion of fungal pathogens. MAC infection decreased in MSM but not in IDUs. Although MAC-preventive medication prescriptions increased in both MSM and IDUs, they did not increase to as high a level in IDUs. The recommendations for MAC prophylaxis were pub- lished in 1993 and were updated in 1997 [23 25]. Combination antiretroviral therapy increased in both MSM and IDUs, but to a greater extent in MSM. The decreases in CMV retinitis and CMV disease other than retinitis in MSM may be due the effect of antiretroviral therapy slowing the progression of HIV disease. Chronic herpes sim- plex decreased in both MSM and IDUs, although acyclovir prescriptions were relatively stable in both groups. The decreases in chronic herpes simplex are particularly occurring in

5 118 Jones et al. JID 1998;178 (July) Figure 2. Average annual incidence of selected opportunistic infections in injecting drug users by CD4 T lymphocyte count, MAC, Mycobacterium avium complex; Pneumocystis, Pneumocystis carinii; CMV, cytomegalovirus. CMV disease refers to disease other than retinitis; candidiasis, esophageal candidiasis; cryptococcosis, extrapulmonary cryptococcosis; toxoplasmosis, toxoplasmic encephalitis; cryptosporidiosis, chronic cryptosporidiosis; tuberculosis, pulmonary and extrapulmonary tuberculosis; histoplasmosis, disseminated histoplasmosis. have had some impact on the diagnosis and abstraction of this condition. The limitations in using data from the ASD project to study incidence trends must be considered. ASD has a large, diverse population of HIV-infected persons that is similar to the US AIDS population by race and sex, but it does not represent the entire US population of persons with HIV infection or AIDS. Nevertheless, these data should be generalizable to the popula- tions from which they are drawn and to similar clinic populations in other locations. Information in ASD is limited to that obtained from medical record reviews. However, AIDS-defining OIs are severe illnesses that are very likely to be recorded in the medical chart. ASD records diagnosed OIs, and trends in OIs may be affected by changes in resources for medical care and diagnostic tests. In addition, autopsy studies show that some OIs may go undiagnosed [28, 29]. Finally, medications recorded in ASD are those prescribed in each 6-month interval regardless of duration, the reason medications are given is not recorded, and there is no assessment of adherence to medications. In summary, our findings indicate a decrease in the incidence of many opportunistic illnesses, but this decrease is not evident for all preventable OIs in all patient populations. The differences between MSM and IDUs are likely due to differences in the more recent years and may also be due to antiretroviral therapy slowing the progression of HIV disease. It is interesting that chronic cryptosporidiosis is decreasing in IDUs but not MSM. MSM may be more likely to acquire cryptosporidiosis sexually than are IDUs. The finding that IDUs had fewer annual outpatient visits than MSM suggests that their health care is more sporadic and that adherence to prophylaxis may be lower among IDUs. Although the incidence of tuberculosis is higher in IDUs than in MSM, it is reassuring that tuberculosis declined in both MSM and IDUs. The number of tuberculosis cases in the United States peaked in 1992 [26], the year before the highest tuberculosis incidence in our study population. Overall, the annual incidence of disseminated MAC was lower in IDUs than in MSM, even though IDUs were less likely to receive MAC-preventive therapy. Perhaps tuberculosis, which occurred more frequently in IDUs than MSM (figures 1 and 2), offered some protection against MAC, as was shown in a report by Horsburgh et al. [27]. If so, the finding that there was an increase in MAC among IDUs in 1995 and 1996 could be partially related to the marked decrease in tuberculosis in the same time period. The increase in recurrent pneumonia in IDUs occurred since The fact that recurrent pneumonia was added to the AIDS surveillance case definition in 1993 may

6 JID 1998;178 (July) AIDS Opportunistic Infections 119 Table 2. Incidence of AIDS OIs by mode of HIV exposure and year of observation, Exposure category, OI Overall P* Trend MSM Mycobacterium avium complex Decreasing Pneumocystis carinii pneumonia Decreasing Cytomegalovirus retinitis Decreasing Kaposi s sarcoma Decreasing Esophageal candidiasis Decreasing Cytomegalovirus disease Decreasing Recurrent pneumonia None Chronic cryptosporidiosis None Extrapulmonary cryptococcosis Decreasing Toxoplasmic encephalitis Decreasing Pulmonary, extrapulmonary tuberculosis Decreasing Chronic herpes simplex Decreasing Disseminated histoplasmosis Decreasing IDU Pneumocystis carinii pneumonia Decreasing Mycobacterium avium complex None Esophageal candidiasis Decreasing Pulmonary, extrapulmonary tuberculosis Decreasing Recurrent pneumonia Increasing Extrapulmonary cryptococcosis None Cytomegalovirus retinitis None Toxoplasmic encephalitis None Kaposi s sarcoma None Cytomegalovirus disease None Chronic herpes simplex Decreasing Chronic cryptosporidiosis Decreasing Disseminated histoplasmosis None NOTE. Data are cases/100 person-years, estimated by weighting according to risk-specific AIDS Reporting System proportions of CD4 cell counts (MSM and IDU combined), race, sex, age, metropolitan area (MSM and IDU combined), and origin of birth. See table 1 for number of persons and person-years of observation. * Test for linear trend using Cochran-Mantel-Haenszel statistic applied to observed data stratified by CD4 cell count, race, sex (IDU), age, metropolitan area, and origin of birth. Direction of significant trends (P õ.05). Includes other AIDS-defining disseminated Mycobacterium species except M. tuberculosis. exposures to disease (for example, tuberculosis), medical care, References and adherence to prophylactic treatment regimens. Future re- 1. Farizo KM, Buehler JW, Chamberland ME, et al. Spectrum of disease in search should focus on these parameters in all groups of HIV- persons with human immunodeficiency virus infection in the United States. JAMA 1992;267: infected persons. 2. Centers for Disease Control and Prevention. Projections of the number of persons diagnosed with AIDS and the number of immunosuppressed HIV-infected persons United States, MMWR Morb Mortal Adult/Adolescent Spectrum of HIV Disease Group Wkly Rep 1992;41(RR-18): Centers for Disease Control and Prevention revised classification system for HIV infection and expanded surveillance case definition for Melanie Thompson, AIDS Research Consortium of Atlanta; AIDS among adolescents and adults. MMWR Morb Mortal Wkly Rep Frank Sorvillo, Los Angeles County Department of Health Ser- 1992;41(RR-17):4 19. vices, Los Angeles; Susan Buskin, Seattle King County Departlymphocytes 4. Hanson DL, Chu SY, Farizo KM, Ward JW. Distribution of CD4 / T ment of Public Health, Seattle; Susan Kreitner, Texas Department at diagnosis of acquired immunodeficiency syndrome defining and other human immunodeficiency virus related illnesses. of Health, Austin; Eve D. Mokotoff, Michigan Department of Arch Intern Med 1995;155: Public Health, Detroit; Arthur Davidson, Denver Department of 5. Karon JM, Devine OJ, Morgan WM. Predicting AIDS incidence by extrap- Health and Hospitals; Susan Troxler, Louisiana Department of olating from recent trends. In: Castillo-Chavez C, ed. Mathematical and Health, New Orleans; Kaye Reynolds, Department of Health and statistical approaches to AIDS epidemiology. Vol 83: Lecture notes in Human Services, Houston; Samuel Martinez, Puerto Rico Depart- biomathematics. Berlin: Springer-Verlag, 1989: ment of Health, Bayamon, Puerto Rico; Judith Sackoff, New York 6. Green TA, Karon JM, Nwanyanwu OC. Changes in AIDS incidence trends City Department of Health. in the United States. J Acquir Immune Defic Syndr 1992;5:

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