Socioeconomic Status and Survival of Persons with AIDS before and after the Introduction of Highly Active Antiretroviral Therapy
Rapiti, Elisabetta; Porta, Daniela; Forastiere, Francesco; Fusco, Danilo; Perucci, Carlo A.; for the Lazio AIDS Surveillance Collaborative Group
From the Department of Epidemiology, Lazio Region Health Authority, Rome, Italy.
Submitted October 1, 1999; final version accepted March 3, 2000.
Address correspondence to: Elisabetta Rapiti, Agenzia di Sanità Pubblica della Regione Lazio, Via Santa Costanza, 53, 00198, Roma, Italy.
Participants of the Lazio AIDS Surveillance Collaborative Group are listed in the Appendix.
We estimated the AIDS survival by neighborhood socioeconomic status before (1993–1995) and after (1996–1997) the introduction of highly active antiretroviral therapy in Rome, Italy, in a retrospective cohort of persons with AIDS followed through July 31, 1998. Participants included 1,474 persons with AIDS residing in Rome who were diagnosed in 1993–1997. We calculated hazard ratios (HRs) of death for two diagnostic periods (before and after highly active antiretroviral therapy was introduced) by neighborhood socioeconomic status categorized into four levels (level I = highest socioeconomic status), using the Cox model and adjusting for gender, age, intravenous drug use, CD4 cell count at diagnosis, AIDS-defining disease, and hospital of diagnosis. Thirty-four per cent of persons with AIDS (N = 503) had survived as of mid-1998. For persons with AIDS diagnosed in 1993–1995, we found little difference in the risk of death by neighborhood socioeconomic status. For 1996–1997, the risk of death was greater for persons with lower neighborhood socioeconomic status, especially for levels III and IV [HR = 2.81 (95% confidence interval = 1.38–5.76), and HR = 2.55 (95% confidence interval = 1.27–5.14), respectively, compared with level I]. Stratified analyses showed that the greatest difference was found for women and drug users. In conclusion, even in a country with universal health coverage that provides therapy at no cost, differences in survival of persons with AIDS have emerged by neighborhood socioeconomic status since highly active antiretroviral therapy was introduced. Inequalities in health-care access or in medical management, or poor adherence to treatment, could explain the observed heterogeneity.
Socioeconomic status (SES) is known to affect access to health care and the outcome of several diseases, yet the attempts to link SES and mortality in persons infected with the human immunodeficiency virus (HIV) have produced conflicting results. For example, two Canadian studies showed that lower SES was associated with a more rapid progression of HIV disease 1 and shorter survival after HIV infection, 2 and a study conducted in Philadelphia showed an association between lower income and higher incidence of AIDS and shorter survival. 3 By contrast, a study in Baltimore found little difference in disease progression or survival by SES among patients with HIV infection, 4 and a study recently conducted in San Francisco also failed to find an association between SES and survival. 5 Various reasons have been proposed to explain the differences in diverse social contexts, including the use of different proxies as a measure of SES and differences in the level of individual coverage of health insurance. 5 It has also been postulated that, in a period when therapies effective in significantly modifying the evolution of the disease were not available, it was difficult to see substantial differences in mortality even in the presence of marked differences in SES. 5
The new highly active antiretroviral therapies (HAARTs) have been shown to be effective in prolonging both incubation time of AIDS and survival after AIDS diagnosis in clinical trials and observational studies. 6–11 Reductions in disease progression were comparable among patients from different transmission groups and different clinical conditions. In those settings, however, individuals were provided with equal access to treatment. HAART is expensive and its administration is complex, and differences in the access to HAART could introduce substantial differences in the mortality of HIV-infected individuals. Several barriers in the access to treatment have been suggested in the United States and Canada, and there are hints that women and drug users are less likely to receive an appropriate treatment. 12,13
The aim of this study was to evaluate differences in survival after an AIDS diagnosis by SES in a population-based cohort before and after the introduction of HAART, in a country where AIDS therapy is provided by the National Health Service.
Subjects and Methods
All data were taken from the AIDS Surveillance System of the Lazio Region (Italy), which since 1985, under a regional law, has recorded all AIDS cases. In Italy, only infectious disease hospital clinics perform AIDS diagnoses, and the case definition is that adopted in the European Community, based only on an AIDS-defining illness. 14 For each AIDS case, the Surveillance System records the individual’s name, gender, date and place of birth, date of AIDS diagnosis, hospital of diagnosis, probable risk factor of HIV, CD4 cell count at the time of diagnosis, and AIDS-defining illness. For the present analysis, we selected data referring only to people residing in the city of Rome (about three million inhabitants) at the time they were diagnosed with AIDS and included in the analysis only those ages 20–44 years (accounting for 74.2% of the total) who were diagnosed between January 1, 1993, and June 30, 1997. We consulted the Registry Office of the Municipality of Rome and the Municipalities to which subjects migrated to ascertain vital status. Patients were followed from the date of diagnosis to the date of death or to the end of the follow-up period (July 31, 1998). More complete details about the population and the study design have been published previously. 15
In Italy, the National Health Service guarantees universal coverage of health insurance , including for medical care and treatment for HIV-infected individuals; antiretroviral and prophylactic therapies are offered free of charge by hospital infectious disease wards. 16 Therapy with a combination of two antiretroviral agents replaced the use of monotherapy in Italy at the end of 1995; a minority of patients in experimental studies started to receive this therapy earlier. The HIV-1 protease inhibitors were licensed at the beginning of 1996, becoming widespread in triple therapies during the second quarter of 1997. 17 There are three main infectious disease hospitals in Rome that make diagnoses and report AIDS cases and provide specialized health care to persons with AIDS (PWA). Some patients, however, could have been reported by hospitals outside Rome. The criteria applied to medical care and clinical follow-up are based on international guidelines. 13
In Rome, a complex index of SES has been developed for each census block, the smallest territorial unit for which population data are available; details on the method used for calculating the index have been described elsewhere. 18 In brief, an overall measure of SES has been calculated in each census block by combining the following single census variables: proportion of individuals by educational level, proportion of individuals employed by occupational group, proportion of unemployed males of working age, proportion of one-person families, proportion of families of five or more persons, crowding index (person/room), and proportion of dwellings rented or owned. In the present study, we categorized these neighborhood SES values into four levels (the cutoff points were defined by the 20th, 50th, and 80th percentiles of the distribution), with the first level indicating the highest SES values. We matched each individual to the census block of residence and to the corresponding neighborhood SES level. For people living in a residential hospice at the time of diagnosis, we considered the previous residence.
To confirm our findings, we evaluated the association between neighborhood SES and survival using as indicators three of the single variables derived from the census data and included in the complex SES index (the proportion of persons with a university degree, the proportion of persons who completed only elementary school, and the proportion of unemployed males of working age). The cutoff points used to categorize these variables were defined by the 20th, 50th, and 80th percentiles.
We calculated survival time from AIDS to death, with 95% confidence intervals (95% CI), using the Kaplan-Meier method, for patients diagnosed in the period 1993–1995 and those diagnosed in the period 1996–1997. We used death from any cause as the outcome variable. To estimate the hazard ratio (HR) for death, with its associated 95% CI for the two periods of diagnosis, we applied Cox proportional regression models separately to the individuals diagnosed in the period 1993–1995 and to those diagnosed in the period 1996–1997. In addition to SES, as we reported elsewhere, 15 we considered the following variables for their possible independent effect on the survival of PWA: gender, age at diagnosis, CD4 cell count at diagnosis, intravenous drug use, AIDS-defining illness, and hospital of diagnosis. We included the continuous variable, CD4 cell count, after natural logarithmic transformation, as this improved the likelihood of the model. We constructed similar models substituting the other three SES indicators for the complex SES index. We also performed a stratified analysis by gender, including in each model an interaction term between SES and the period of diagnosis, to obtain the HR of death by SES for males and females in the two periods of diagnosis. Stratified analyses were also performed to obtain the HRs of death by neighborhood SES to evaluate differences in survival by intravenous drug use. We could not take sexual risk factors into account owing to the poor reliability of reporting of sexual contacts.
During the period January 1, 1993 to June 30, 1997, 1,529 individuals residing in Rome between 20 and 44 years of age were reported to have been diagnosed with AIDS. We excluded 40 (2.6%) of these individuals because no home address was reported, and 15 (1.0%) additional individuals because no CD4 cell count was reported. The final population under study consisted of 1,474 PWA, 503 of whom (34.1%) were still alive on July 31, 1998.
The demographic and clinical characteristics of the population for the four levels of the complex neighborhood SES indicator are presented in Table 1. There were only small differences among the four levels of SES by gender, CD4 cell count at diagnosis, and period of diagnosis, but larger differences for age (with older people having a higher SES), drug use (with drug users having a lower SES), and AIDS-defining illness.
Figure 1 shows the Kaplan-Meier survival estimates by neighborhood SES for the two periods of diagnosis. At 18 months from diagnosis, the proportion of PWA still alive was 41% for those diagnosed in the period 1993–1995 (95% CI = 39–44) and 65% for those diagnosed in the period 1996–1997 (95% CI = 60–69). The corresponding HR of death in the second period compared with the first, after adjusting for all confounders, was 0.44 (95% CI = 0.37–0.52). For the first period, there were only small differences in survival among the four levels of SES, whereas for the second period, survival appeared to vary by SES.
Table 2 shows the HR and 95% CI for the second, third, and fourth levels of neighborhood SES, as compared with the first level, estimated using the Cox proportional regression model separately for the two periods of diagnosis. For the period 1993–1995, there was little difference in the risk of dying by SES, whereas in the period 1996–1997, individuals belonging to the last three levels of SES had a higher risk of dying (HR = 1.90, 2.81, and 2.55 for the second, third, and fourth levels, respectively). The same results emerged when we considered only the HIV-related deaths (94% of the total deaths).
We found similar results after stratifying by gender (Table 3). We observed an increased relative risk of dying only in the second period for both males and females. Females in the fourth SES level had a particularly high relative risk of dying (HR = 4.85).
When stratifying by drug use (Table 4), for the period 1996–1997, we observed a higher risk of dying among the drug users of the third neighborhood SES level (HR = 4.54) and the fourth level (HR = 4.68). We also observed differences among the fourth neighborhood SES levels for PWA not reporting drug use; these differences were found for both periods of diagnosis, although they became more marked for 1996–1997 (in the first period, HR = 1.65 for the third level and HR = 1.60 for the fourth level; in the second period, HR = 3.03 for the third level and HR = 2.21 for the fourth level).
Given the nature of the transition between ineffective and effective treatment, we tried to investigate the time period when the changes in survival actually occurred. We refined the analysis by dividing the diagnosis period 1996–1997 into three shorter periods: the first 6-month period of 1996, the second 6-month period of 1996, and the first 6-month period of 1997. We also truncated the period of observation at 12 months, the maximum length of follow-up for the third period group. We evaluated the HR of dying for the lowest SES level vs the first two levels together, because no event was observed in the highest level in the second 6-month period of 1996. We saw little difference in effect of SES in the first 6-month period of 1996 [HR = 0.99 (95% CI = 0.50–1.96) for the lowest level of SES]. The highest relative risk of dying was observed in the second 6-month period of 1996 (HR = 3.31; 95% CI = 1.01–10.8), whereas, for the first 6-month period of 1997, HR = 1.20 (95% CI = 0.46–3.12).
When using the proportion of individuals with a university degree, the proportion of those who completed only elementary school, and the proportion of unemployed males as SES indicators, the results were similar to those obtained with the complex neighborhood SES indicator. There were only small differences by neighborhood SES level in the HR of dying in the first period, yet in the second period, people in the lower levels of each indicator showed an increased risk of mortality, although the magnitude of the effect was smaller compared with that observed with the complex indicator (data not shown).
This study shows that, beginning in 1996, survival after diagnosis of AIDS differed by neighborhood SES, revealing a more than doubling in risk for the PWA with lower SES (third and fourth levels) as compared with those with the highest SES (first level). The differences were higher for women and for drug users.
The emergence of these differences in survival coincides with the introduction of the new antiretroviral therapies at the end of 1995, 17 which became widely available in Italy during 1996. The greatest differences observed among levels of neighborhood SES in the second half of 1996 could be explained by disparity in the administration of the new therapies by level of SES. In other words, among PWA there were “early adopters” of the new therapies in the highest social class group. Previous studies on AIDS survival have shown that in the era preceding HAART there were no large differences by SES; however, because there did not exist any therapy capable of substantially altering the clinical course of HIV infection and thus improving survival, it may have been more difficult to detect differences in survival by SES. 5 The new antiretroviral therapies might decrease HIV-related mortality enough to allow these differences to emerge more clearly, or might add to the differences related to HIV treatment. These agents are very expensive and require more complex management and care of HIV patients at different levels. Therefore, more financial, human, and technical resources are needed to ensure that PWA receive the full benefits of these treatments. In Italy, a lack of access to medical care, delayed access, or substandard offer of HIV therapy and management could explain the higher mortality of patients with a lower neighborhood SES. Two cross-sectional studies conducted in the United States and Canada on the offer of antiretroviral drugs and adherence to treatment showed that patients not participating in substance-abuse programs, active intravenous drug users, young persons, and women were less likely to receive treatment. 12,13 A study conducted in a hospital-based methadone program, which provided on-site HIV care in Harlem, showed a much higher utilization of HAART among HIV-infected intravenous drug users. 19
Another hypothesis that may explain the observed results, also related to the delivery of medical care, is the possibility that persons of lower neighborhood SES may have more difficulties in complying with the new regimens. Intravenous drug users are believed not to withstand the rigors of adherence to potent antiretroviral therapy regimens. 20–22 Comorbidities among drug users, such as chronic liver disease, together with psychosocial problems, complicate their medical care and their ability to fulfill physicians’ prescriptions. Finally, other explanations such as variable host resistance by SES may also affect treatment efficacy.
We did not have individual information on income or other socioeconomic variables. Nevertheless, an aggregate measure of SES has been used in several other studies. It has a high predictive validity and has been proposed as a valid surrogate for individual SES assessment. 23–25 Our aggregate indicator was derived from small areas of the city of Rome (one census block contains an average of 480 inhabitants), which are likely to be homogeneous in terms of SES. In a previous application of the indicator, a strong association was found between neighborhood SES level and mortality in the city of Rome. 18 Moreover, we found that the complex index discriminates better than its components.
It has been suggested that the so-called “downward drift” due to advancing disease can produce a decline in the socioeconomic level of PWA. 26 To define the neighborhood SES indicator, we used the place of residence at the time of the AIDS diagnosis. On a random sample of 100 patients, we identified their place of residence 5 years before they were diagnosed with AIDS and matched with the census block and the corresponding SES level. For 73 of these 100 patients, the neighborhood SES level was the same at the time of AIDS diagnosis.
Finally, we did not have individual treatment data, and our suggestion that survival improves after the introduction of new therapies is only “ecologic.” Our findings, however, are in line with worldwide evidence. 6–11
We thank Paola Michelozzi for her helpful suggestions and comments and Mark Kanieff for help with writing.
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Members of the Lazio AIDS Surveillance System and participating institutions that collaborated to the present study include the following: Angela Carboni and Alessandra Sperati, Department of Epidemiology Lazio Region Health Authority, Rome; Massimo Fantoni and Cosmo Del Borgo, Catholic University, Rome; Mario Falciano and Alessandro Macedonio, La Sapienza University, Rome; and Giuseppe Ippolito, Enrico Girardi, and Giuseppina Nurra, Spallanzani Hospital, Rome.
This article has been cited 3 time(s).
acquired immunodeficiency syndrome; socioeconomic status; survival; intravenous drug use; gender
© 2000 Lippincott Williams & Wilkins, Inc.
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