| |
PCP & End Stage Liver Disease are Leading Causes of Death
|
| |
| |
PCP Remains Leading Cause of Death; and End Stage Liver Disease is the leading cause of death in persons with >200 CD4s at Parkland Hospital in Dallas-- recommend dealing with liver disease and non-adherence
Clinical Infectious Diseases 2003;36:1030-1038. Mamta K. Jain et al. Division of Infectious Diseases, Department of Internal Medicine, of Texas Southwestern Medical Center, Dallas
".....At our hospital, PCP remains an important cause of death in the
highly active antiretroviral therapy (HAART) era, possibly because >50% of
HIV-infected patients who died were not receiving HAART....39% due to non-adherence... Non-adherence to HAART also appeared to be associated with nonadherence to PCP prophylaxis in this resource-limited patient population....11% because doctor saying they could not tolerate HAART due to underlying liver disease.. in developed countries, HAART and prophylaxis for opportunistic infections have markedly reduced opportunistic infection related deaths. Yet, at our safety-net hospital, which provides a Ryan White funded, state-of-the-art HIV outpatient clinic and a National Institutes of Health sponsored AIDS clinical trials unit, the HAART era brought a less-marked change.... the majority (89%) of patients who died at our hospital in 1999-2000 died of AIDS (as defined by a CD4 cell count of <200 cells/L)....77% in 1999-200 who died had <200 CD4s..
The authors emphasized that "strategies for the prevention and treatment of alcohol addiction, hepatitis B virus infection, and HCV infection" and "strategies to improve early diagnosis and maximize treatment adherence may lead to improved survival in high-risk populations" are needed and may have an important impact on survival in high-risk populations and on patients wuth liver disease.
"....patients not receiving HAART more frequently died of PCP, which was also the leading cause of death in patients in the pre-HAART era. However, the
patients who died in 1999-2000 while receiving HAART more frequently died of ESLD.... our data demonstrate that the leading cause of death in patients who died with a CD4 cell count of 200 cells/L was ESLD.......larger cohort studies are needed to determine the impact of HAART on deaths due to liver disease and other causes....
Based on the data reported it appeared that 50 of the 210 patients who died at the hospital had HCV, and 20 were HbsAg positive. 46 patients were heavy alcohol drinkers, and 37 had a history of liver disease.
"......many of the patients not receiving HAART were of ethnic minorities. Nine (75%) of 12 patients with newly diagnosed HIV infection before death and 12 (67%) of 18 nonadherent patients were black or Hispanic. Deaths among HIV-infected minorities increased at our hospital from 48% in 1995 to 61% in 19992000. National surveys show that the incidence of AIDS (per 100,000 persons) in 2000 was 3 times higher among Hispanic persons (30.4) and 9 times higher among black persons (74.2) than it was among white persons (7.9). Minorities may have limited access to medical care for economic, social, and cultural reasons. Lower socioeconomic status has been associated with a decreased duration
of survival in patients with AIDS. Efforts targeted at improving early diagnosis and adherence to medical therapy may decrease the mortality rate in this population.....
"I don't want to paint a gloomy picture," Jain, the author of this paper, said. "Definitely, the number of cases of patients dying with AIDS has decreased radically. But we were expecting to see a change in the types of diseases people were dying from, and we didn't see that. I think this study is important because, if you look at the HIV/AIDS literature, you see these dramatic changes, and people are living longer... but I think we kind of lose sight of the fact that there are still areas in the country that still are seeing a lot of the same problems that we did prior to HAART being available."
Last year, CDC estimated that up to one-third of the nation's 850,000-950,000 HIV-positive people do not appear to be receiving treatment.
Since the introduction of HAART, mortality due to AIDS-defining illnesses has decreased. The specific causes of mortality in the HIV-infected population continue to be investigated. A study from Cleveland, Ohio, that examined the cause of death in 255 HIV-infected persons showed that the percentage of patients who died of an AIDS-defining illness decreased in the HAART era, from 60% in 1995 to 30% in 1999, whereas a study from France suggested that 50% of deaths in the HAART era continue to be due to AIDS-defining illnesses. Some
studies of HIV-infected persons suggest that the proportion of nonAIDS-related deaths has increased in the HAART era, whereas other studies have found no such changes. An increasing proportion of deaths due to liver disease have been noted in some descriptive and cohort-based mortality studies but not in others. Mamta Jain and colleagues from the University of Texas Southwestern Medical Center conducted a retrospective chart review of patients who died at Parkland Memorial Hospital in Dallas, Texas, to evaluate specific causes of death in 1995 and in 1999-2000, reflecting the deaths before introduction of HAART and several years after widespread use of HAART began.
Parkland Memorial Hospital is a 990-bed county hospital and is the primary teaching institution for the University of Texas Southwestern Medical School. A retrospective chart review of all HIV-infected adults who died at Parkland Memorial Hospital in 1995 and 19992000 was conducted. Although perhaps not significant there was a trend towards a change in the patient population in the study at Parkland Hospital. In the study 50-60% of the patients were of black or Hispanic origin, 48% in 1995 vs 61% in 1999-2000,not a significant difference. In 1995 61% of the patients in the study were MSM vs 38% in 1999-2000, and this difference was significant. In 1995 22% of the patients were IDUs vs 32% in 1999-2000, but this change was not statistically signifiicant. There was also an increase in the percent of patients whose risk factor was heterosexual sex from 30% to 34%, but this was not statistically significant.
A total of 210 deaths of HIV-infected individuals were identified: 119 in 1995, 44 in 1999, and 47 in 2000; but the death rate due to PCP did not change from pre-HAART 1995 to 1999-2000. Researchers found an increase in the proportion of patients who died from an illness that was not related to acquired immunodeficiency syndrome (AIDS). Although there was a decrease in the prevalence of AIDS-defining illnesses, >85% of patients died with CD4 counts of <200 cells/L. The leading cause of death was Pneumocystis carinii pneumonia (PCP). During 1999-2000 46 of 88 patients (52%) were not receiving HAART: non-adherence (39%) to therapy and new diagnosis of HIV infection (26%) were the leading reasons why patients were not receiving antiretroviral therapy; 11% of the patients during 1999-2000 were not receiving HAART because they could not tolerate it due to the doctor's call of underlying liver disease; 9% were unable to tolerate HAART because of side effects or progression of AIDS. The leading causes of non-AIDS-related deaths in 1999-2000 were non-AIDS-defining infections and end-stage liver disease. At our hospital, PCP remains an important cause of death in the
highly active antiretroviral therapy (HAART) era, possibly because >50% of
HIV-infected patients who died were not receiving HAART. AIDS-defining
illnesses continue to be a major cause of mortality in the HAART era in
populations where access to care and adherence to HAART is limited.
The death rate due to PCP was the same in 1995 as it was in 1999-2000 (19% vs 17%), although death due to AIDS associated illness declined from 51% to 38% (p=.03). From 1995 to 1999-2000, there was a trend toward a decrease in
AIDS-defining illnesses as cause of death occurred. A significant decrease in deaths due to HIV-associated diseases occurred between period 1 and period 2. The proportion of patients who died as a result of PCP (probable or definite) did not change between the 2 periods. There were no deaths due to CMV, MAI, or toxoplasmosis in period 2. Because the proportion of deaths attributable to HIV-associated illnesses decreased from period 1 to period 2, nonAIDS-related illnesses increased. The leading nonAIDS-related causes of death in both time periods were infections and ESLD (10% vs 13%). Four patients in period 2 died of intracerebral hemorrhages (2 parenchymal and 2 subarachnoid). Other causes of death due to non-AIDS-related illnesses did not differ between the 2 time periods.
Study details
Data from medical records were collected regarding each patient's demographic characteristics, HIV risk factors, liver disease risk factors, CD4 cell count, and HIV load, as well as antiretroviral therapy and Pneumocystis carinii pneumonia (PCP) prophylaxis received. We determined the cause of death by a chart review on the basis of clinical, laboratory, and microbiologic data. Autopsy reports, when available, were also used to determine the cause of death. An attempt was made to assign one primary cause of death to each case. For patients who had several possible causes of death, 3 investigators (M.J., D.S., and D.B.) reviewed the records, including available autopsy reports, to determine the probable primary cause of death. Other possible causes of death were considered to be contributing causes of death.
Discussion by authors. Among HIV-infected persons hospitalized at Parkland Memorial Hospital, HAART has affected cause-specific HIV-related mortality only modestly. Nationwide, the leading causes of death before 1996 were PCP, MAI, CMV, and bacterial pneumonia. In developed countries, HAART and prophylaxis for opportunistic infections have markedly reduced opportunistic infectionrelated deaths. Yet, at our safety-net hospital, which provides a Ryan
Whitefunded, state-of-the-art HIV outpatient clinic and a National Institutes of Healthsponsored AIDS clinical trials unit, the HAART era brought a less-marked change. The proportion of deaths due to PCP was the same in 1999-2000
as it was in 1995. This observation differs from numerous published studies documenting a reduction in mortality from PCP. Several factors may explain why PCP remains a leading cause of death in our patient population.
First, despite the availability of HAART, the majority (89%) of patients in 19992000 died of AIDS (as defined by a CD4 cell count of <200 cells/L). Second, almost one-half of patients who died in 1999-2000 were not receiving
HAART because of non-adherence to medications or new diagnosis of HIV infection. Nonadherence to HAART also appeared to be associated with nonadherence to PCP prophylaxis in this resource-limited patient population.
Longitudinal data show the risk of death is significantly decreased in patients receiving primary PCP prophylaxis.
A significant increase in the proportion of nonAIDS-related deaths did occur between 1995 (period 1) and 1999-2000 (period 2). Unlike other studies that show an increase in the proportion of deaths due to liver disease, we did not find a significant change in the proportion of deaths due to this cause. Like other studies, we did not see an increase in the proportion of deaths due to nonAIDS-defining infections. However, these 2 etiologies were the most common nonAIDS-related causes of death in both time periods. We did see an increase in intracerebral hemorrhages not related to an underlying CNS lesion. Changes in diagnostic evaluation may account for these differences.
Death due to end-stage liver disease (ESLD) was defined as death of a patient with underlying liver disease and 1 of the following conditions: coagulopathy, bleeding esophageal varices, hepatic encephalopathy, hepatorenal syndrome, or spontaneous bacterial peritonitis.
A total of 210 deaths of HIV-infected persons were identified: 119 occurred in 1995, 44 in 1999, and 47 in 2000. Charts for 112 (94%) of 119 patients identified as being HIV infected who died in 1995 (period 1) and 88 (97%) of 91 in 19992000 (period 2) were available for review. The demographic characteristics, risk factors for HIV acquisition, and HIV carerelated profile of the study population are presented in table 1. The 2 groups were similar with respect to age and sex, but HIV risk factors were different in period 1 than they were in period 2, with men who have sex with men being more common in period 1. In period 1, 54 (48%) of 112 patients were of black or Hispanic origin, compared with 53 (60%) of 88 in period 2 (P = .09). No patients from period 1 received HAART, which was unavailable in 1995. Despite widespread availability after 1995, only 48% of patients from period 2 received HAART,
and 13 patients had HIV RNA levels of <400 copies/mL. The median CD4 cell counts (measured within 8 months of the time of death) were similar in both groups. CD4 cell counts were not available for 14 (13%) of 112 patients in
period 1 and 4 (5%) of 88 patients in period 2.
Our study is limited to inpatient deaths, and, therefore, we cannot calculate mortality rates or evaluate a causal association between HAART and HIV-associated deaths. As in any retrospective study, we cannot exclude bias, but we used consistent definitions to minimize potential bias. Although the case definition of probable PCP may have misclassified a few cases in 1995, the increase in definite PCP in 19992000 suggests that PCP remains an important
cause of death in our population. Larger prospective cohort studies in the HAART era are needed to define the impact of HAART on the changing pattern of deaths.
In our study, a trend toward a decrease in deaths due to AIDS-defining illness did occur in the HAART era compared with the pre-HAART era. However, PCP still remains an important cause of death. The leading nonAIDS-related deaths were due to nonAIDS-defining infections and ESLD in both time periods. In the subset of patients with CD4 cell counts of 200 cells/L, ESLD was the leading cause of death. Strategies for the prevention and treatment of alcohol addiction, hepatitis B virus infection, and HCV infection may have an important impact on deaths due to ESLD in HIV-infected patients receiving HAART. The majority of patients who died in the HAART era had a CD4 cell count <200 cells/L, and almost one-half of these patients who died were not receiving HAART at the time of death. Strategies to improve early diagnosis and maximize treatment adherence may lead to improved survival in high-risk populations.
|
|
| |
| |
|
|
|
