Changing Trends in the Survival of Dialysis Patients with Human Immunodeficiency Virus in the United States
Tejinder S. Ahuja*,
James Grady and
Shilpi Khan*
*Department of Medicine, Division of Nephrology, and Department of Preventive Medicine and Community Health, Division of Epidemiology and Biostatistics, University of Texas Medical Branch, Galveston, Texas.
Correspondence to Dr. Tejinder S. Ahuja, 4.200 John Sealy Annex, 301 University Boulevard, Galveston, TX 77555. Phone: 409-772-1811; Fax: 409-772-5451; E-mail: tahuja{at}utmb.edu
ABSTRACT. HIV-infected patients with end-stage renal diseasehave a very high morbidity and mortality. In the last decade,survival of HIV-infected patients in the United States has remarkablyimproved. To determine whether similar improvement in survivalhas occurred in HIV-infected dialysis patients, their survivalwas evaluated by using the United States Renal Data System database.Survival of HIV-infected dialysis patients in the United Stateswas determined and the influence of year of initiation of dialysis,and demographic characteristics on the survival were analyzedby the Kaplan-Meier method. The effects of above variables onsurvival were also examined in a Cox proportional hazards model.Identified were 6166 HIV-infected patients with end-stage renaldisease who received dialysis in the United States. Eighty-ninepercent of the patients were black, 7.4% white, and 3% other.From 1990 to 1999, 1-yr survival of HIV-infected patients ondialysis improved from 56 to 74%, and the annual death ratesdeclined from 458 deaths to 240 deaths per 1000 patient-years.The hazard ratio declined significantly in patients who initiateddialysis in years 1999-2000 compared with patients who initiateddialysis 1990 (hazard ratio, 0.49; 95% confidence interval,0. 40 to 0.60). Survival of HIV-infected dialysis patients hasremarkably improved in the United States.
HIV infection is a common cause of end-stage renal disease (ESRD),especially in blacks, who develop a fulminant form of focalsegmental glomerulosclerosis termed HIV-associated nephropathy(HIVAN) or AIDS nephropathy (1–6). HIVAN has become thethird most common cause of ESRD in young African Americans (7).Initial reports suggested a very poor prognosis for HIV-infectedpatients on chronic maintenance dialysis, and it was an ethicaldilemma whether these patients should be offered long-term renalreplacement therapy (3,8). Although single-center reports havesuggested that these patients experience improvements in survival,the mortality and morbidity of HIV-infected dialysis patientsremains high (9–14).
In the recent years, use of potent antiretroviral drugs, improvedprophylaxis, and treatment of opportunistic infections haveled to dramatic improvement in survival of HIV-infected patients(15–17). However, the improved survival of these patientsmay not extend to the HIV-infected dialysis patients for thefollowing reasons. First, because the pharmacokinetics of themajority of antiretroviral drugs have not been thoroughly evaluatedin patients with renal failure, these patients are more likelyto be treated with suboptimal antiretroviral therapy. Second,the associated uremia with HIV infection may further impairthe immunological response of these already immunocompromisedpatients, thereby predisposing them to opportunistic infections.Finally, there is a theoretical possibility that hemodialysismay actually increase morbidity of HIV-infected ESRD patientsby enhancing viral replication through activation of white bloodcells and release of cytokines such as tumor necrosis factoralpha, interleukin 1, and interleukin 6; all of these cytokineshave been found to increase viral replication in vitro (18–22).
We therefore undertook the study presented here by using theUnited States Renal Data System (USRDS) database to determinewhether the survival of HIV-infected dialysis patients in theUnited States has improved.
Study Patients
The data were obtained from the USRDS Standard analysis files2000 (SAF.MEDEVID, SAF.PATIENTS, and RxGROUP). The USRDS includesdata on approximately 92% of patients receiving dialysis inthe United States (23). The accuracy of these data has beenvalidated previously (24). From a database of 1,090,121 patients,HIV-infected patients were identified by the codes 0429A, 0429Z,or 0449Z of the International Classification of Diseases, NinthRevision, Clinical Modification (ICD-9-CM). Demographic variablesused in the analysis include age, gender, and race (black, white,and other). Because dialysis data were available until May 1,2000, this date was used as a censor date for survival analysis.
Statistical Analyses
The Kaplan-Meier method was used to estimate the survival ofHIV-infected dialysis patients. The log rank test was used tocompare cumulative survival among these patients stratifiedby race, gender, and year dialysis was begun. An analysis wasalso conducted to compare survival of HIV-infected ESRD patientswith 1000 HIV-negative patients. These patients were randomlyselected and were matched for age, gender, race, and year ofinitiation of dialysis with the HIV-infected patients. A Coxproportional hazards model was used to evaluate the effect ofdemographic characteristics and year of initiation of dialysis.The reported P values in the Cox model are based on the Waldtest. All reported P values are two-sided. All values are mean± SD unless otherwise indicated. Statistical analysiswas performed with use of SAS system for Windows, version 8e(SAS Institute, Cary, NC). The Human Subject Research Committeeof the University of Texas Medical Branch Galveston institutionalreview board approved this study.
We identified 6179 patients with HIVAN or HIV infection andESRD by using the USRDS database. Thirteen patients were excludedfrom the analysis. In 8 of these 13 patients, information availablefor survival analysis was incomplete, and in 5 patients, renaltransplantation was the primary renal replacement therapy. Allof the patients included in the study were HIV infected at thetime of starting dialysis, and in 99%, the cause of ESRD listedwas HIVAN (ICD-9 code 0429A). The first and the last patientincluded in the study began dialysis in December 1985 and December1999, respectively. The mean follow-up period of the patientson dialysis was 21 ± 21. 48 mo. The mean age of the patientswas 39.4 ± 8.9 yr. Eighty-nine percent of the patientswere black, 7.4% were white, and 3.4% were other. Seventy-fourpercent were men, and 26% were women.
Figure 1 shows Kaplan-Meier estimates of survival of HIV-infectedESRD patients starting dialysis before 1990 and then biyearlyuntil May 2000. The survival rate at 12 and 24 mo of the patientsstarting dialysis before 1990 improved from 56 and 38% to 68and 54% compared with patients who started dialysis in the years1997 to 1998. One-year survival rate of patients who starteddialysis in 1999 to 2000 further improved to 74%. Table 1 summarizesthe estimated cumulative percent survival of these patients.In contrast to a minimal decline in annual death rates for theHIV-negative dialysis patients, the annual death rates of HIV-infecteddialysis patients declined from 458 deaths to 240 deaths per1000 patient-years from 1990 to 1999 (Table 2). The major improvementin survival of these patients occurred since 1997 (Tables 1 and 2).In the regression model, the only factor associatedwith a decrease in relative risk of death was later years ofinitiation of dialysis (hazard ratio [HR], 0.83; 95% confidenceinterval [CI], 0.81 to 0.85) Table 3.
Figure 1. Kaplan-Meier estimates of survival of HIV-infected patients from the start of dialysis from before 1990 and then biyearly until May 2000. The number of patients at various times is shown in the table below the figure.
Table 1. Estimated cumulative percentage survival of HIV-infected end-stage renal disease patients on dialysis according to the year of starting renal replacement therapy, gender, race, and dialysis modalitya
Table 2. Annual death rates for HIV-infected versus HIV-negative dialysis patients, period prevalent patients for the year per 1000 patient-years at risk
Table 3. Results of Cox proportional hazards model of survival of HIV-infected dialysis patients (n = 6166)
In another Cox model, we adjusted for the demographic variablesand used time as a categorical variable in biyearly periodssimilar to that in the life-table analysis. In this model, therelative risk for patients starting dialysis in the years 1999to 2000 was significantly lower (HR, 0.48, 95% CI, 0.40 to 0.50),compared with patients who started dialysis before 1990. Thesignificant change was again seen starting 1997, when the HRof the patients starting dialysis in years 1997 to 1998 declinedto 0.60 (95% CI, 0.52 to 0.69) from 0.92 (95% CI, 0.81 to 1.05),the previous biyearly period (1995 to 1996).
Race was not a factor in predicting survival on dialysis (Figure 2and Table 3). Although female dialysis patients appeared tohave better survival than male patients (Figure 3), the survivaladvantage was lost when the data were adjusted for the demographicvariables and year of initiation of dialysis in the regressionmodel (HR, 0.98; 95% CI, 0.91 to 1.05; Table 3). On examinationof the residual and global fitness measures for the variousCox models, no evidence of lack of fit or model inadequacy wasdiscovered.
Figure 2. Kaplan-Meier estimates of survival of HIV-infected dialysis patients by gender. The number of patients at various times is shown in the table below the figure.
Figure 3. Kaplan-Meier estimates of survival of HIV-infected dialysis patients by race. The number of patients at various times is shown in the table below the figure.
The survival of the random matched group of HIV-negative dialysispatients was significantly better Figure 4. The 12- and 24-mosurvival of these patients was 87 and 79%, respectively, comparedwith 58 and 41% of HIV-infected patients.
Figure 4. Kaplan-Meier estimates of survival of HIV-infected patients compared with a matched group of HIV-negative patients. The number of patients at various times is shown in the table below the figure.
In the study presented here, we report that the survival ofHIV-infected ESRD patients on dialysis in the United Stateshas improved in the recent years. The major improvement in survivalhas occurred since 1997, when 1- and 2-yr survival of patientswho started dialysis in years 1997 to 1998 improved to 68 and54% from 52 and 37%, respectively, compared with patients whostarted dialysis in previous years (1995 to 1996). The 1-yrsurvival further improved to 74% in the patients who starteddialysis in years 1999 to 2000, an 18% increase in 1-yr survivalcompared with patients who started dialysis before 1990. Theannual death rate of HIV-infected patients declined from 458deaths to 240 deaths per 1000 patient-years. The major improvementhas occurred since 1997.
Early reports had described a dismal mean survival of HIV-infectedpatients with ESRD (3,8). Some small, single-center studieshave reported slightly better survival and the stage of HIVdisease as the main predictor of survival on dialysis (9–13).In a small number of HIV-infected hemodialysis patients, werecently reported that use of highly active antiretroviral therapyhas improved their survival (14). Although information regardingthe antiretroviral therapy patients received in the study presentedhere was not available, we can speculate that the improved survivalon dialysis observed is most likely the result of improved antiretroviraltreatment. The data suggest that improvement in survival ofHIV-infected ESRD patients has been more dramatic since 1997.Highly active antiretroviral therapy has been available muchbefore this time. However, because the pharmacokinetics of themajority of antiretroviral drugs have not been thoroughly evaluatedin patients with ESRD, the physicians could have been more hesitantto treat their patients with these drugs until more recently,when the experience with use of these medications has improved(25). Better management and prophylaxis against opportunisticinfections and technical advancements in dialysis delivery maybe other contributing factors in improvement in survival.
Although via life-table analysis we found that female dialysispatients had a better survival than male patients, the survivaladvantage was lost after adjusting for confounding factors inthe regression model. Gender not being a factor in survivalof these patients is consistent with a recent report of equalrates of progression to AIDS among men and women, despite thefact that initial viral loads were lower in women (26).
We did not find any differences in survival among differentraces. This is in contrast with the observations that blackpatients on dialysis have a better survival than whites (27,28).It is possible that unequal access to HIV care among the racescould have made null the survival advantage seen in black patientson dialysis.
Although the survival of HIV-infected dialysis patients hasimproved, it is still very low compared with age-, gender-,and race-matched HIV-negative patients. The 1- and 2-yr survivalof the HIV-negative patients was 87 and 79%, compared with 58and 41% of HIV-infected dialysis patients. The data supportthat further improvements in the survival of these patientsare likely to occur with development of better options for treatmentof HIV infection.
There are several limitations of our study. Most important ofall is the lack of information on plasma viral loads and totalCD4 counts of the patients. These critical data were not availablein the USRDS database and therefore could be a potential uncorrectedconfounding factors in the survival analysis. However, the factthat HIVAN is a manifestation of end-stage AIDS as reportedby Winston et al. (29) and the large number of patients in oursurvival analysis attenuates the effects of stage of HIV infectionon the survival data. The information on the antiretroviraltherapy these patients received was also not available to usin this database. We can only presume that the improving survivalis the result of better treatment options for these patients.
We conclude that survival of HIV-infected dialysis patientsin the United States has remarkably improved. However, survivalof these patients is still low compared with age- and gender-matchedHIV-negative patients. Therefore, further improvement in theirsurvival is likely to occur with improving treatment optionsfor HIV infection.
Acknowledgments
The data reported have been supplied by the USRDS. The interpretationand reporting of these data are the responsibility of the authorsand in no way should be seen as an official policy or interpretationof the US government.
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Received for publication November 6, 2001.
Accepted for publication April 11, 2002.
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Top
Abstract
Introduction
1990 (hazard ratio, 0.49; 95% confidence interval, 0. 40 to 0.60). Survival of HIV-infected dialysis patients has remarkably improved in the United States. 
