CHAIN Report (Update Report # 26) Declining Mortality Rates and Service Interventions. Peter Messeri Gunjeong Lee

Transcription

1 CHAIN Report (Update Report # 26) Declining Mortality Rates and Service Interventions Peter Messeri Gunjeong Lee Joseph L. Mailman School of Public Health Columbia University May 23, 2000 HRSA Contract # BRH C.H.A.I.N. Report

2 ACKNOWLEDGMENTS A Technical Review Team (TRT) provides oversight for the CHAIN Project. In addition to Peter Messeri, PhD and Angela Aidala, PhD, both of Columbia University s Joseph L. Mailman School of Public Health, TRT members include Dorothy Jones Jessop, PhD (Chair), MHRA; Mary Ann Chiasson, DrPH, MHRA; Les Hayden, HIV CARE Services/MHRA; Joanne Hilger, NYC/DOH; Jeanne Kalinoski, HIV Planning Council; Arturo Llerandi-Phipps, PWA Advisory Group; and Rebecca Tiger, HIV Planning Council. This research was supported by grant number BRH from the U.S. Health Resources and Services Administration (HRSA). This study was supported by the HIV Health and Human Services Planning Council of New York under a Title I grant of the Ryan White Comprehensive AIDS Resources Emergency Act of 1990 through the New York City Department of Health. It was conducted under the auspices of Medical and Health Research Association of New York City, Inc. Its contents are solely the responsibility of the Joseph L. Mailman School of Public Health of Columbia University and do not necessarily represent the views of the funders.

3 Introduction Deaths due to AIDS in the United States peaked in 1995 and have fallen steadily in subsequent years. The Centers for Disease Control and Prevention (CDC) estimated 49,895 deaths among AIDS cases in 1995, which declined to 17,171 deaths in Men and women, African Americans, whites and Hispanics have all experienced sharp declines in AIDS deaths. New York City has experienced a parallel pattern of declining HIV/AIDS mortality. Chiasson et al. drew upon both vital statistics and AIDS case surveillance data and reported that annual HIV/AIDS deaths in NYC declined 63 percent between 1995 and 1997, from 7,046 deaths to 2,625 deaths. 2 Similar to the pattern for the United States, these declines occurred in all demographic groups. In both the United States and New York City the largest year-to-year decline occurred between 1996 and The dramatic decline in HIV/AIDS deaths is generally attributed to the introduction of combination antiretroviral therapies that became widely available in Moreover, the reduction in AIDS deaths across all major ethnic and racial group attests to the success of the health care system in general, and Ryan White funded services in particular, in disseminating these very expensive and complex medical regimens to the many subgroups that compose the HIV infected population. How the health care system has operated to achieve these outcomes, and the role of specific ancillary and supportive services, is not well understood. Vital statistics data and AIDS case surveillance data can take us only so far in exploring such relationships. These data sets can be used to measure the magnitude of change in deaths for broad demographic groups, but direct estimates of the linkage between reduced mortality risk and service interventions require more detailed data collected for individual cases. 1 CDC, HIV/AIDS Surveillance Report Table 26, Vol 11-1 June Chiasson, MA, Berenson, L., Li, W., Schwartz, S, Singh, T, Fortenza, S, Mojica, BA, Hamburg, M, Declining HIV/AIDS Mortality in New York City. JAIDS 21:59-64 (1999).

4 2 Such data are available through the CHAIN project. The study sample is a broadly representative cohort of people living with HIV in New York City. The cohort was first interviewed in 1994 and 1995 and has been re-interviewed at 6 to 12 month intervals. Linking mortality data from the New York City Department of Health s vital records and death certificates to this rich set of self-reported data collected at repeated interviews permits us to follow the complex causal chain from the provision of social and medical services and administration of medications through changes in health status, the delay and in some cases even reversal of disease progression, to reduction in mortality. In previous CHAIN reports we have examined the many facets of the comprehensive system of health and human services that are intended to improve the health and well being of people with HIV. CHAIN reports have shown, for example, that ancillary services improved engagement in medical care. They have documented the diffusion of combination therapy. They have shown that ethnic disparities in access to quality medical care and to new medications have diminished over time. CHAIN reports have examined the difficulties that the cohort is experiencing in following complex medical regimens and are assessing the impact of supportive services on helping clients maintain adherence to complex medical regimens. They have examined the need and utilization of specialized drug treatment, mental health and housing services. This is the first CHAIN report to turn its attention to the final patient outcome or endpoint of the many service interventions that have been the topics of earlier CHAIN reports-- the reduction in HIV-related mortality. This report covers four related topics: 1) A description of the social epidemiology of cohort mortality. Attention is directed at possible differences in mortality rates related to social and economic disadvantage, behavioral and environmental risk, and disease progression 2) A presentation of half-year mortality rates between 1995 and 1999 with specific attention to trends in possible ethnic and racial differences in these trends. 3) An analysis of the impact of medical interventions and ancillary services on reductions in mortality that examines the extent to which trends in ethnic disparities in mortality are related to the impact of medical care and service interventions.

5 3 4) An analysis of the impact of combination therapies on mortality within different sociodemographic and behavioral risk groups. Key Findings 1. Through June of 1999, there have been 187 deaths among CHAIN participants or 27 percent of the original cohort of Consistent with national AIDS data and New York City AIDS surveillance and vital statistics data, the CHAIN cohort experienced a steady decline in deaths since the second half of Mortality rates, which were 145 deaths per thousand person-years during the second half of 1995, have steadily declined in each half-year interval through the first half of The sharpest decline in mortality occurred between 1996 and Large declines in mortality were experienced by African Americans, Hispanics, and nonhispanic whites. Nonetheless, after adjusting for age and CD4 count, African American participants had higher mortality rates than either Hispanics or nonhispanic whites. These differences are largely explained by lower use of combination therapy by African Americans. 4. Combination therapies that include a PI or NNRTI and administration of PCP prophylaxis to individuals with CD4 counts below 200 were associated with large and significant declines in mortality risks. CD4 counts, hospitalization, opportunistic infection and physical health functioning each independently predicted mortality risks. The effects of medication on reducing mortality risk were not substantially reduced after taking into account these factors. 5. CHAIN participants from vulnerable populations are benefitting from combination therapy. Substantial reductions in mortality risk associated with use of combination therapy were found for ethnic minorities as well as for people experiencing low educational attainment, unstable housing situations, current drug use, and low mental health functioning. 6. We estimate that 74 more CHAIN participants were alive as of June 1999 as a result of the cumulative impact of the availability of combination antiretroviral medications since 1996 than would have been alive without such interventions.

6 4 The Chain Survey and Data The Joseph L. Mailman School of Public Health of Columbia University is responsible for conducting the CHAIN Project surveys and reporting on findings from the survey data in collaboration with the New York City Department of Health and Medical and Health Research Association of New York City, Inc. (MHRA). The purpose of the surveys is to provide longitudinal information on study participants needs for health and human services, their use of health care and social service organizations, their satisfaction with services, and the impact of these services on changes in their physical, mental, and social well being. This information is prepared specifically for the NYC HIV Health and Human Services Planning Council to assess the full spectrum of services for HIV infected persons in NYC. The study is conducted under a subcontract from MHRA to Columbia University with the authorization of the NYC Department of Health and the HIV Planning Council. CHAIN sample design and participant recruitment At its inception in 1994, the CHAIN Project pursued a recruitment procedure designed to yield a broadly representative sample of people living with HIV in New York City. Study recruitment was conducted collaboratively with 43 randomly selected agencies, stratified to represent roughly equal numbers of medical care and social service sites as well as sites that were and were not recipients of Ryan White Title I grants. At 30 sites, staff contacted a random sample of clients. The names of clients who indicated an interest in participating were turned over to CHAIN staff for interviews. An open enrollment procedure was implemented at the remaining 13 agencies. All eligible clients present on a small number of recruitment days were invited by agency providers and CHAIN investigators to participate in the CHAIN study. Interviews were then scheduled with interested clients. A total of 648 individuals recruited from participating agencies completed baseline interviews. The agency-based sample was supplemented with 52 interviews conducted with HIV-positive individuals with little or no connection to medical and social services. These individuals were contacted at outreach sites and through nominations from CHAIN participants. More detailed information on sampling strategy and recruitment may be obtained upon request from MHRA (CHAIN Technical Report #1). At the time of original interview the CHAIN cohort closely matched the demographic characteristics of AIDS cases in New York City alive as of January 1, 1995.

7 5 Follow-up interviews Since the original (baseline) interview the Columbia research team has completed five additional rounds of interviews, and a seventh round is currently in the field. Intervals between interviews were originally between six and nine months. Since the fourth round of interviews the interval between interviews has increased to a year. The research team uses a number of resources and strategies to maintain contact with all surviving cohort members. Even when CHAIN participants miss an interview, we continue to follow them for later rounds. An individual who misses one interview is often re-interviewed at a subsequent round. As a result, sample attrition, for reasons other than death or migration out of New York City, is low. Among the 700 individuals from the original CHAIN cohort, 385 or 55 percent were interviewed for the fifth round of interviews -the last round of interview data used for this report. However, after excluding 170 individuals who had died and 41 individuals who had moved away from New York City before the start of the fifth round, the completion rate among surviving New York City residents increased to 79 percent (385[interviewed]/489[available]). Study sample Two different samples are used for the analyses presented in this report. All 700 participants of the original CHAIN cohort are included for the descriptive analysis of mortality. For this phase of the analysis, information on participant characteristics is drawn from first round interviews. For analyses that measure the effects of medical therapies and other interventions, the sample is restricted to the 577 CHAIN participants who were interviewed at least one more time after the original (baseline) interview. We excluded individuals who were interviewed at only the first round of interviews, since we have no information about them that post-dates the general introduction of combination therapy during the late fall of 1995 (first round interviews were completed in July 1995).

8 6 CHAIN interviews CHAIN interviews are conducted in person by trained interviewers. Interview topics include sociodemographic characteristics, the full range of experiences with access and use of medical and social services, and quality of life. The interventions of major interest for this study are medical therapies. At each round of interviews, study participants are shown a card with the generic and trade names of prescription drugs in use and asked to indicate all drugs they are currently taking. This list includes all types of antiretroviral agents currently available. For each participant at each round of interview, we tabulated the number of NNRTI s and PI s currently being taken. Using these counts we classified each individual as (1) a current user of a combination therapy that included PI or NNRTI, (2) a current user of combinations that did not include a PI or NNRTI, and (3) not a current user of combination therapy. 3 At each round we also asked individuals whether they had received PCP prophylaxis between interviews. 4 We assessed the impact of this therapy for individuals who had CD4 counts below 200 at the preceding interview. A list of participant characteristics and other interventions selected for this study are summarized in Table 1. Dating time of death Deaths are routinely discovered during tracking for follow-up interviews. Both to confirm the death, its date and cause, and to check on status of individuals with whom we have lost contact, we received authorization to obtain copies of death certificates in 1997 and 1998 available through the New York City Department of Health death registry. During December 1999, a further check was conducted through an Internet website, ancestry.com, that maintains a Social Security Death Index. This database contains records of deaths reported to the Social Security Administration. Most of these cases were reported in connection with a death benefits claim. The search of New York City death certificates confirmed 142 deaths; 30 deaths were confirmed through the website search; and 15 deaths were reported by informants and have yet 3 This category included a small number of people who reported taking a single antiretroviral therapy. 4 Within the last six months for the first and fifth interviews.

9 7 to receive independent confirmation. We believe that mortality experience for this cohort is relatively complete through June 1999, although delays in reporting deaths may result in some upward revision, particularly for the first half of Table 1: Study Characteristics Characteristics Source of Data Definitions Demographics Gender Baseline Only Male/Female Race/Ethnicity Baseline Only African American/nonHispanic white /Hispanic Education Baseline Only Less than HS Diploma/HS Graduate Age Baseline Only Years Environmental & Behavioral Risks Current Drug Use All Interviews Use of heroin, crack/cocaine, problem drinking since last interview. Housing Stability All Interviews Stable/Doubled Up/One or more nights in unstable housing since last interview Resides in Poor Neighborhood Baseline Only Lives in zip code in which 40% + of families with income below poverty Health Status Physical Health R2-R5 b Medical Outcomes Study Summary Health Functioning Scale Mental Health Baseline Only Medical Outcomes Study Summary Mental Health Scale, Low functioning< 37. CD4 Count All Interviews 0-100/ / / /500+ AIDS All Interviews Report of CD4 count, disease condition or told by a clinician consistent with AID diagnosis Opportunistic Infections R2-R5 b Contracted O.I. since last interview Inpatient Visits R2-R5 b One or more hospital stays since last interview

10 8 Characteristics Source of Data Definitions Medical Care and Treatment Access to Primary Care R2-R5 b 2 or more visits between interview to provider that provide comprehensive and coordinated care PCP Prophylaxis R2-R5 b Received since last interview and CD4 count below 200 Combination Therapy R2-R5 b Currently taking (1)No combination/ (2)Combination without PI or NNRTI/ (3)Combination with PI or NNRTI Ancillary Services Case Management R2-R5 b Case manager-- 1. referred to medical care since last interview 2. Referred to social service since last interview Drug Treatment R2-R5 b Received therapeutic treatment for drug abuse since last interview Mental Health R2-R5 b Received professional mental health services since last interview Housing R2-R5 b Received housing services since last interview Notes: a. Baseline Only: Data obtained from first round interviews only. Treated as fixed or time invariant variable b. R2-R5: Collected from 2 nd through 5 th round of interviews. Values of such characteristics may change across interviews. c. For data collected at Round one and five, interval for retrospective information is six months. A date of death was established for all reported deaths. Whenever possible, dates from death certificates or the website were used in preference to the recall of informants. Findings Through June 7, 1999 a total of 187 CHAIN participants, 27 percent of the original cohort, are known to have died. A review of cause of death from 142 death certificates obtained so far shows that AIDS is the overwhelming cause of death listed. A small number of death

11 9 certificates list cancer or lymphomas(7), drug use (5) and coronary heart disease (3) as the primary cause of death Table 2 presents proportions of people in different subgroups who survived through June Among the personal characteristics examined, significant differences in mortality initially had appeared to be associated with CD4 counts and AIDS diagnosis. However, multivariate analysis (reflected in Table 2) shows that an AIDS diagnosis did not influence mortality independent of CD4 counts for deaths occurring after the second round of interviews. Table 2: Crude Mortality Rates for Selected Demographic Characteristics Characteristic N Cumulative Number of Deaths Proportion Surviving through June 30, 1999 Statistical Significance adjusting for age and CD4 count All CHAIN Participants % -- Gender Male Female % 75% No Race/Ethnicity African American Non-Hispanic White Hispanic % 71% 76% p<.05 Education Less than HS Diploma HS Graduate % 72% No Housing Status* Stable Doubled Up Unstable % 71% 79% No Current Drug Use* Yes No % 74% No

12 10 Characteristic N Cumulative Number of Deaths Proportion Surviving through June 30, 1999 Statistical Significance adjusting for age and CD4 count Low Mental Health Functioning* Yes No % 70% No Resides in Poor Neighborhood* Yes No % 74% No CD4 Count* % 73% 75% 91% 92% -- Diagnosed with AIDS* Yes No % 88% p<.01 Source: First round CHAIN interviews *Status based on reports at first round interviews Table 3: Demographic Correlates Mortality Adjusted for Baseline CD4 Counts (N=577) Hazard Ratios Race/Ethnicity African American Hispanic NonHispanic White Age 1.02* CD4 Count 0.52*** Source: Second through fifth Interviews *p<.1 ** p<.05 ***p<.01

13 11 Age (not presented) and race/ethnicity were the only sociodemographic characteristics to be associated with mortality. African Americans have a higher mortality rate when compared to whites and Hispanics of similar age and CD4 counts. A more detailed analysis indicates that excess deaths among African Americans is largest for the period immediately following the first interviews. Nonetheless higher African American mortality rates persists through the entire study period (see Tables 3 and 5). Given the absence of meaningful differences in mortality for other background characteristics, subsequent analyses include only race/ethnicity and age as demographic characteristics. Trends in Mortality Tables 4 and 5 and the accompanying figure display trends in mortality rate from 1995 through the first half of The sharp decline in mortality rates is clearly evident in Figure 1. The mortality rate for the first half of 1995 is artificially low and should be ignored when examining the trend in mortality. The sample was being assembled during this first half-year of the study. At that time the sample was undoubtedly healthier than the general population of HIV infected individuals. Some individuals died after being selected for participation in the CHAIN study but before they could be interviewed. The initial interviews with CHAIN participants were largely completed by July Therefore the CHAIN cohort more accurately reflects the mortality experience for HIV infected individuals surviving through the first half of Mortality was highest for the second half of 1995, 146 deaths per 1,000 persons year, and it has consistently declined in each successive half-year period. A low of 19 deaths per 1,000 person-years was reached during the first half of All three ethnic groups experienced large declines in mortality during the study period. White and African American CHAIN participants show large declines in mortality beginning in 1996 (Table 5). The decline in mortality for Hispanics appears to be delayed about a year. This apparent ethnic difference should be treated cautiously, however, due to the small number of annual deaths when the

14 sample is divided into ethnic and racial groups. When all AIDS mortality for New York City is examined, the secular pattern of decline is similar for all three ethnic groups The large year-to-year decline in mortality rates between 1995 and 1996 and between 1996 and 1997 corresponds to the secular trends in CHAIN participant s current use of Table 4: Half -Year Mortality Rates ( ) Interval Number of Deaths Cohort Alive at Start of interval Person- Years Deaths Per 1,000 person- years 1st Half nd Half st Half nd Half st Half nd Half st Half nd Half st Half Total for Source: Project tracking case management file and death certificate search for CHAIN Cohort members Notes: 3 individuals were excluded who were interviewed and died in combination therapy. Through 1995, use of combination therapy never exceeded 10 percent. Then during the first half of 1996, current use of combination therapy jumped to 33 percent and increased to 50 percent during the second of the year. By the second half of Chiasson et al. 1999, Figure 2.

15 13 approximately 70 percent of the cohort reported current use of combination therapies. The sharp increase in protease inhibitors lagged about six months behind the rapid rise in use of non-pi combinations. In short, the drop in mortality tracks closely the upward trend in use of combination therapies. Impact of medical therapies on declining mortality rates Table 6 presents a more direct assessment of the impact of medical therapies on declining mortality rates. This table presents results of a specialized statistical technique for analyzing length of survival, the proportional hazard analysis [see the appendix for a discussion of this methodology.] Table 6 presents hazard ratios for three regression equations that estimate the impact of combination therapy and PCP prophylaxis administered to individuals with CD4 counts below 200. For all models we adjust for differences in age at baseline and CD4 counts Table 5: Ethnic Annual Mortality Rates ( ) African American (N=`353) White (N=117) Hispanic (N=220) Year No. of Deaths Deaths Per 1,000 personyears No. of Deaths Deaths Per 1,000 personyears No. of Deaths Deaths per 1,000 personyears st Half Source: Project case management tracking and death certificate search for CHAIN cohort members. Notes: 2 Whites and 1 Latino were excluded who were interviewed and died in Table also excludes 7 individuals with other ethnic identification.

16 14 Figure 1 Trends in Mortality 160 Deaths Per 1,000 Person-Years h1 1996h1 1997h1 1998h1 1999h1 Half Year Interval African American White 160 Deaths Per 1,000 Person-Years HIspanic 1995h1 1996h1 1997h1 1998h1999h h1 1996h1 1997h1 1998h1999h1 Half Year Interval

17 15 between those using and not using combination therapy. CD4 counts is lagged by one interview. This avoids confounding the influence of low CD4 counts on the decision to initiate combination therapy and the beneficial consequences of combination therapy on disease progression were we to use a contemporaneous measure of CD4 counts. The hazard ratios measure the effects of demographic and health-related characteristics on the relative risk of experiencing death in a short time interval. A value of less than one indicates that an increase in the independent variable is associated with reduced risk of mortality. Values greater than one are associated with increased risk of mortality. The first model in Table 6 estimates the overall effect of these medications adjusting for CD4 counts and baseline age. Race and ethnicity are also included in these models to assess to what extent differential access to medications may explain race and ethnic disparities in mortality. Combination therapies with a PI or NNRTI and PCP prophylaxis exerted strong and significant effects on lowering mortality risks. Each medical treatment was independently associated with a 40 to 50 percent reduction in mortality risk. In contrast, combinations without a PI or NNRTI were associated with a modest and non-statistically significant reduction in mortality risk. Comparisons of the race and ethnic hazard ratios in Table 6 with those in Table 3 show that the size of the hazard ratio among African Americans is greatly diminished when we introduce use of medications into the models. These results are consistent with the possibility that higher rates of mortality among African Americans are due to lower use of combination therapy. The second and third models in Table 6 trace out the possible pathways through which use of medications are expected to reduce mortality risks. We first introduce those factors that might be the most immediate outcomes of medication: increased CD4 counts and reduced

18 16 occurrence of opportunistic infection 6. The third model tests whether combination therapy is further associated with hospitalization and improved physical functioning, two of the more short-term determinants of mortality risk. The effects of the medications in models 2 and 3 when compared to model 1 should be reduced (i.e., the hazard ratios would move closer to 1) if the effects of medication operated through one or more of these intermediate outcomes. Table 6: Proportional Hazard Models of Mortality (N=577). Model 1 Model 2 Model 3 Age 1.02* Ethnicity African American Hispanic NonHispanic White * 1.00 CD4 Count (Lagged) 0.46*** 0.65*** 0.63*** Combination Therapy With a PI or NNRTI Without a PI or NNRTI No Combination 0.54** ** PCP Prophylaxis 0.62**.56**.52*** Opportunistic Infection 1.89*** 1.08 Concurrent CD4 Count.60*** 0.67*** 1 or more Hospital Stays 2.77*** Summary Physical Health Score.97*** Source: Second through Fifth Interviews. *p<.1 **p<.05 *** p<.01 The results of these models offer mixed support for this line of reasoning. All four health status measures are associated with mortality in the expected direction. The diminished effect 6 We did not include viral loads as an independent variable. Self reported data collected thus far from CHAIN participants are both incomplete and not very reliable.

19 17 of opportunistic infection from the second to third model is related to its association with hospitalization. To the extent that an opportunistic infection is life threatening it will lead to a hospitalization. Thus hospitalization may be regarded as a proxy for the severity of the O.I. Despite the predictive power of the health status variables, we do not find a diminished effect of the medication variables in successive models in Table 6. The reduction in the effect of PCP prophylaxis is negligible. Although the effect of PI combinations on mortality risk is no longer statistically significant, the decline in the size of the hazard ratio for this variable is small. Therefore, these models do not fully account for the processes through which use of these medications reduces mortality risk. Impact of medical care organization and ancillary services We next explored the possible direct and indirect impacts of the organization of medical care and ancillary services on reducing mortality risk. First, ancillary and supportive services have been demonstrated in previous CHAIN reports to promote entry and retention into coordinated and comprehensive HIV medical care and thus improve access to medical therapies. These services might operate in other ways to reduce mortality risk. Access to these services might improve adherence and therefore may be a proxy measure for more effective use of these medications. Finally, specialized ancillary services such as for housing and substance abuse treatment may ameliorate co-morbid conditions that may further compromise immune system functioning. We tested for effects of (1) access to medical care that met criteria for being coordinated and comprehensive, (2) case management services involving either referrals for medical care or social services, (3) housing services, (4) mental health services and (5) drug treatment. None of these services were found to exert a significant impact on reducing mortality risk. Case managers who made medical referrals, housing services, drug treatment and mental health services all had hazard values just under one, which indicated that each service was associated with lowering mortality. Because of the small effects of these services no further analyses were preformed.

20 18 The effectiveness of PI and NNRTI combinations for selected subgroups. Table 7 presents estimated hazard ratios adjusted for CD4 counts and age, for selected subgroups that represent vulnerable and under-served populations. The left column shows hazard ratios for each group for combinations without a PI or NNRTI. The right column shows the effects of combinations with PI and NNRTI. Because of the small number of deaths experienced for many of the smaller subgroups, attention should be paid to the general Table 7: Effects of Antiretroviral Therapy for Different CHAIN Subgroups (Hazard Ratios adjusted for age and CD4 Count) Subgroups Ethnic Groups African American Hispanic NonHispanic White Gender Male Female Education No HS Diploma HS Graduate Housing Situation Unstable Stable Substance Use Current Former or Never User Mental Health Status High Functioning(>36) Low Functioning (<37) Hazard Ratios For Combinations without a PI or NNRTI * Hazard Ratios For Combinations with a PI or NNRTI *.38** ***.30*.55**.46* ** Source: Second through fifth interviews. No combination therapy is reference group for the tabulated hazard ratios. *p<.1 ** p<.05

21 19 magnitude of the coefficients and less weight given to the level of statistical significance. The general pattern of coefficients in the right hand column suggests that all subgroups benefit from antiretroviral regimens that include a PI or NNRTI, but some secondary subgroup differences are evident. The effects of these medications are strongest for whites, but both African Americans and Hispanics enjoy a 50 percent reduction in mortality. Similarly, there was no increased mortality hazard associated with drug use, unstable housing, or low mental health functioning; in fact, all these groups displayed lower mortality hazards associated with use of PIs or NNRTIs. By contrast, women and those with low education appear to derive less benefit from PI and NNRTI combinations than other groups. However, these two groups show benefits from combinations without these medications not experienced by other groups. In short, within the precision of these data, it appears that the benefits of combination therapy are reaching broad segments of the HIV infected population. Discussion The CHAIN cohort has experienced a continuing sharp reduction in mortality since the second half of 1995, when the cohort was fully recruited. This trend is similar to declines in HIV/AIDS deaths for New York City and the entire nation. A few methodological cautions should be kept in mind when interpreting findings for policy purposes. Mortality rates for the CHAIN cohort of individuals are only broadly representative of the larger population of HIV positive residents of New York City. The CHAIN cohort is recruited at one point in time. As the cohort ages, the survivors become at greater risk of mortality than the HIV infected population as a whole, since the original sample is not replenished by newer HIV/AIDS cases that occurred after the study started. 7 Furthermore the small number of annual deaths limit the precision with which we can draw firm conclusions about subgroup differences in secular trends in mortality. Despite methodological differences, the proportional change in CHAIN mortality rate corresponds closely to percentage changes in New York City HIV/AIDS deaths assembled from 7 The CHAIN cohort was replenished in 1998 to address sample attrition and loss of representativeness. However the replenished sample was not included in this analysis.

22 20 vital statistics by Chiasson et al., (1999). From Table 8 we see that the percentage reduction in mortality for CHAIN and all of New York City are virtually the same for the 1995 and 1997 period. For both data sets, the rate of decline between the first halves of 1997 and 1998 is still substantial but not as large as for the previous period. The slow down is somewhat more for the New York City than the CHAIN cohort. This comparison offers some support that the experiences of the CHAIN cohort are roughly similar to all of New York City. Table 8: Comparison of CHAIN mortality rates and New York City HIV/AIDS deaths CHAIN Mortality Data All New York City HIV/AIDS Deaths Mortality Rate/ 1,000 person years Period to period % reduction in Mortality rate Number of HIV/AIDS deaths Period to period % reduction in deaths 2nd half rst half % % 1rst half % % Source: Chiasson et al. 1999, Figure 1, p. 60. This report provides direct evidence for the effectiveness of combination therapy for a broadly representative sample of New York City residents living with HIV. CHAIN data suggest that mortality rates have been reduced to a quarter of the pre-1997 rates, as CHAIN participants have benefitted from both combination therapy and PCP prophylaxis. The former medications are associated with a 50 percent reduction in short-term mortality and the latter about a 40 percent reduction. Study findings show that both hospitalization and physical health are strong independent predictors of mortality. The predictive power of the latter variable is particularly intriguing. It implies that a patient s subjective assessment of physical functioning

23 21 and quality of life is a useful prognosticator of disease progression independent of objective clinical measures such as CD4 counts. There are concerns that the benefits of combination therapy may be short lived as individuals increasingly fail on these regimens. Through the first half of 1999 there is no evidence of an upturn in mortality rates, however, despite three years of experience with these medications. It is, of course, possible that the mortality rate for 1999 is artificially low because of delays in discovering all deaths that have occurred in the relatively recent past. Nor do these data speak directly to the adverse side effects and diminished quality of life that appear to be a commonplace occurrence when taking combination therapies. Other CHAIN Updates on adherence are examining the adverse effects of these medications. Continuing tracking of the CHAIN participants will serve to monitor possible upturns in mortality. The data also show that the declines in mortality have experienced rough parity among all three major ethnic and racial groups represented in this sample. Yet the data also indicate that African Americans continue to have higher mortality rates than either Hispanics or whites. African Americans appear to be at a disadvantage because they lagged behind whites in initial use of these medications, and they continue to be less likely to use combination therapies. In addition, even among the many African Americans who use these medications, there is a higher risk for mortality than their white counterparts. At this point we can only speculate on the reasons for the lower efficacy of these medications for African Americans (this low efficacy was also observed for Hispanics [see Table 7]}. Among the possible explanations, these data may indicate inadequate management of these medications by providers from whom African Americans typically seek treatment, or they may suggest differences related to maintaining adherence to these medications. Apart from race/ethnicity, none of the other demographic characteristics and risk factors tested in this study were associated with differential mortality risk. A few plausible reasons can be advanced to account for the absence of large subgroup differences. First, the sample sizes for such subgroups as current substance use and people living in unstable housing situations may be too small to detect stable differences. Second, while the characteristics we have selected are

24 22 salient risks for mortality in generally healthy populations, it is possible that HIV infection so dominates the health of individuals that it greatly diminishes the relative adverse impact of such risk factors. Although this analysis did not find an association betewen ancillary services and reduced mortality, it should not be concluded that ancillary services are not critical aspects of effective health care delivery. The influence of such services undoubtedly operated indirectly on mortality by improving the effectiveness of medical interventions received by the more vulnerable patient populations. Other analyses of CHAIN data show that ancillary services facilitate entry and retention into care, and we are currently engaged in an analysis of a more direct role of these services on adherence to antiretroviral medications. It is possible that the effects of ancillary services on mortality may be better assessed if, as we have done in the ancillary services report, the use of ancillary services is more carefully related with the need for these services. We plan to pursue a more refined analysis of ancillary services and mortality in future reports. To conclude this report, we provide a rough estimate of the cumulative impact of improvements in treatment since 1996 on the number of lives saved. Table 9 summarizes the steps we used to determine the number of CHAIN participants who are alive as of Jun 30, For this analysis, we project the number of additional deaths that would have occurred had mortality rates between 1997 and 1999 remained at the rates observed for 1995 and For this exercise we assume a 10 percent death rate per year. This is at the low end of mortality experienced during the first two years of the study and well in excess of mortality rates since the Row three of Table 9 reports the deaths post-1996 that would have occurred for the CHAIN cohort based on an assumed 5 percent mortality rate for each half-year interval. The projections were performed for the full cohort and then broken down by major racial and ethnic groups. Based on these calculations we estimated that 74 CHAIN participants were alive in June 1999 who would otherwise have died had the pre-1997 mortality rates persisted. This works out to an additional 106 survivors as of June 1999 per thousand people living with HIV at the start of Based on these calculations, improvements in medical care since 1997 were associated with a 17 percent increase in the size of the surviving CHAIN cohort.

25 Update #26: Declining Mortality Rates 23 Table 9 further shows that this methodology results in comparable lives saved for all three racial and ethnic groups. Further refinement of these methods is clearly desirable, but this exercise illustrates how CHAIN survey data can be used to demonstrate the benefits and costeffectiveness of Ryan White CARE Act services. The findings of this report offer indirect but compelling evidence of the considerable achievements of Title I and other public and private initiatives in creating a health care infrastructure for persons living with HIV that is able to bring the benefits of emerging medical therapies to many individuals who come from medically under-served communities. Within this general success, disparities remain. In particular, our data indicate the continuing need for programs that focus on African Americans and their service providers.

26 Update #26: Declining Mortality Rates 24 Table 9: Deaths Prevented between 1/1/97 and 6/30/99 1. Actual Deaths through 6/30/99 2. Actual Deaths through 12/31/96 3. Projected Deaths 1/1/97 through 6/30/99 4. Projected Deaths through 6/30/99 (2) + (3) 5. Lives saved through 6/30/99 (4)-(1) Additional individuals alive in 1999 per 1,000 HIV+ persons alive as of 1/1/95 Total African American NonHispanic White Hispanic Projected Mortality assumes a mortality rate of 5% for each half period between 1/1/97 and 6/39/99 (5 half periods) Additional survivors= (5)*1,000/(Baseline totals)

27 Update #26: Declining Mortality Rates 25 Appendix: Methods of Analysis The major analytical focus of this study is an assessment of the association between participant characteristics, use of selected medical and social services and the risk of death during the study period (1995 to June 1999). A statistically valid assessment of mortality risk involves use of statistical procedures that are more sophisticated then are usual for CHAIN reports. For this reason, a brief nontechnical summary of these methods is presented below. Three types of statistical analyses were performed for this report. The most straightforward analysis involved tabulation of the percentage of surviving individuals through June 30, 1999 for a selected set of sociodemographic, behavioral and environmental factors that are generally related to differences in mortality (see Table 1). We measured each of these factors based on first round interviews conducted between October 1994 and August Because comparisons of observed differences in survival may be confounded by group differences in disease progression and age, we conducted statistical tests of group differences in survival adjusting for baseline values for age and CD4 counts. A second analysis calculated half-year and annual mortality rates for the full CHAIN cohort and subgroups, most importantly the major race and ethnic groups represented in the cohort. When calculating mortality rates, it is necessary to adjust for the length of the time period (e.g a half year versus a year). It is also necessary to adjust for differences in individual exposure to mortality risk in periods of first interview or death. The numerator for the mortality rate is the number of people who have died in each half-year or annual interval. The denominator is the total years observed, person-years, for participants who were alive during each time interval and were interviewed in that interval or at an earlier time. The amount of time each individual contributes to the denominator is shortened if he or she is interviewed or died during that period. Mortality rates calculated following this process are reported as deaths per 1,000 person-years. It is much more complicated to estimate the impact of medical treatment and of other service interventions on mortality. There are two major complications. First, there are potentially many confounding factors that may simultaneously account for both use of services and differences in mortality risk. Decisions to treat or provide services are partly based on a patient or clients risk of mortality. Individuals with lower CD4 counts are both at greater risk of dying and more likely to receive medical and social services for this reason. A second complication is that both the use of services and other risk factors may change over time. Clearly, combination therapies became readily available only during Participants may both start, change, and withdraw from medications at different times and therefore alter their shortterm mortality risks. Similarly, disease progression will change both independently and as a result of these medications. Other risk factors and comorbid conditions such as contracting an opportunistic infection, current substance use and housing stability may also change over time. We take advantage of our multiple rounds of CHAIN interviews to measure time varying factors. We used a specialized multivariate procedure, the proportional hazard model, to measure the effects of service interventions. This technique permits us to adjust for potential confounding factors and model the time varying changes in treatment and other variables thought to affect mortality. A regression equation is specified and its coefficients are hazard ratios. A hazard

28 Update #26: Declining Mortality Rates 26 ratio is the probability of dying during a very short time interval. Smaller hazard rates are therefore associated with longer survival. The proportional hazard model estimates the relative risk of dying between different levels for each independent variable, controlling for all other variables in the equation. A value of one indicates the variable has no impact on mortality risk. A value greater than one indicates a proportionate increase in mortality risk or decreased survival, where as values less than one indicate increased survival. For example, 1.5 corresponds to a 50 percent increase in mortality risk, whereas.5 corresponds to a 50 percent reduction in the immediate risk of dying. For analyses of treatment effectiveness, the study sample was restricted to the 577 individuals who had at least one follow-up interview. Individuals who were interviewed only once were dropped, since it would have been extremely unlikely that they would have reported use of combination therapy. Their inclusion would have required the unrealistic assumption that they had never used combination therapy even if they had survived past the time when use of these medications had become commonplace. Nor could we adjust for other risk factors that might be expected to change over time. 8 8 For individuals in the analysis who are lost to follow-up before round five, the variables remain at the levels reported at the last completed interview. In theory this could be a problem if there were much change between round 5 and earlier interviews in the variables included in the analysis. We believe sample attrition is a minimal source of bias. Most decedents died within six months of their last interview, the typical interval between interviews. Only 10 individuals died a year or more after their last interview. Nor are there many survivors who are missing interviews. Over 80 percent of survivors for this analysis were interviewed at round 5.