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. Author manuscript; available in PMC: 2010 Jun 21.
Published in final edited form as: AIDS. 2010 Jun 1;24(9):1329–1339. doi: 10.1097/QAD.0b013e328339e245

Hospitalizations in a cohort of HIV patients in Australia, 1999–2007

Kathleen Falster a,b, Handan Wand a, Basil Donovan a, Jonathan Anderson a, David Nolan c, Kerrie Watson d, Jo Watson e, Matthew G Law a, the Australian HIV Observational Database
PMCID: PMC2888502  NIHMSID: NIHMS207180  PMID: 20559038

Abstract

Objectives

To describe hospitalization rates, risk factors and associated diagnoses in people with HIV in Australia between 1999 and 2007.

Design

Retrospective cohort study of people with HIV (n = 842) using data linkage between the Australian HIV Observational Database and administrative hospital morbidity data collections.

Methods

Incidence rate ratios with 95% confidence intervals were estimated using Poisson regression models to assess risk factors for hospitalization. Predictors of length of stay were assessed using generalized mixed models. The association between hospitalization and mortality was assessed using Cox regression.

Results

In 4519 person-years of observation, there were 2667 hospital admissions; incidence rate of 59 per 100 person-years. Hospitalization rates were 50–300% higher in this cohort than comparable age and sex strata in the general population. Older age (incidence rate ratio 1.46, 95% confidence interval 1.28–1.65 per 10-year increase) and prior AIDS (incidence rate ratio 1.71, 95% confidence interval 1.24–2.35) were significantly associated with hospitalization. Other predictors of hospitalization included lower CD4 cell counts, higher HIV RNA, longer duration of HIV infection and experience with more drug classes. Lower CD4 cell counts, older age and hepatitis C virus antibody positivity were independently associated with longer hospital stay. Non-AIDS diseases were the principle reason for admission in the majority of cases. Mortality was associated with more frequent hospitalization during the study period.

Conclusion

Hospitalization rates are higher in people with HIV than the general population in Australia and are associated with markers of advanced HIV disease despite the widespread use of combination antiretroviral therapy.

Keywords: AIDS, antiretroviral therapy, HIV, hospitalization, incidence

Introduction

Combination antiretroviral therapy (cART) has led to substantial declines in mortality and AIDS-related morbidity in HIV-infected individuals with access to these drugs [13]. Data on health service utilization in North America and Europe reflect this trend, with decreasing hospitalization rates since cART became available [412]. After the first few years of cART availability, however, some studies [6,9] found that hospital admissions started to increase again, particularly for non-AIDS conditions.

In an era of improved survival, many people with HIV infection will live to experience the impact of prolonged exposure to ART [1315], ageing and, often, coinfection with viral hepatitis. To effectively plan and provide for the evolving healthcare needs of people living with HIV infection, healthcare utilization and current and emerging comorbidities of importance need to be monitored in this population. In Australia, state health department hospital admission data collections are a useful source of information on morbidity and healthcare utilization in the population. In this study, we used linked data from hospital admission data collections in two Australian states and the Australian HIV Observational Database (AHOD) cohort to describe rates of, and reasons for, hospitalization in patients with HIV infection in Australia during the period 1999–2007. We also investigated risk factors for hospitalization and longer inpatient length of stay, and whether patients with a history of hospitalization have an increased risk of mortality.

Methods

Study population

AHOD is an observational, clinical cohort study of patients with HIV infection in Australia, which has been described elsewhere in detail [16]. Briefly, data are collected from 27 clinical sites in six of the eight states/territories of Australia, including hospitals, sexual health clinics and general medical practices that offer specialist HIV care. For this analysis, the study population was restricted to patients recruited to AHOD by 31 March 2007, who were recruited in the states of New South Wales (NSW) and Western Australia (where established data linkage infrastructure existed at the time this study commenced), provided written informed consent to data linkage and had at least one prospective follow-up visit after the baseline date.

Data collection

Prospective data collection in AHOD commenced in mid-1999, with retrospective data provided where available. Data for AHOD are transferred electronically to the National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia, every March and September from participating sites. Core variables include: date of birth, sex, name code (i.e. first two letters of first and last names), date of first positive HIV test, date of most recent clinic visit, HIV exposure category, hepatitis B virus (HBV) and hepatitis C virus (HCV) status, CD4 cell counts, HIV viral load, ART histories, AIDS-defining illness history and date and cause of death. All data are subject to standardized quality control procedures.

Hospital admissions within the AHOD cohort were ascertained via data linkage with the NSW Admitted Patient Data Collection and the Western Australia Hospital Morbidity Data Collection. These data collections cover all inpatient separations (discharges, transfers and deaths), including information about the patient's diagnosis and procedures undertaken, from all public and private hospitals in NSW and Western Australia, respectively. Each record represents an episode of care, which ends when a patient is discharged from hospital, dies or is transferred to another type of care. Date and cause of death data were obtained from death registers in both states.

In Australia, it is standard practice for HIV to be coded as a diagnosis for known cases of HIV infection, regardless of the reason for hospital admission. Therefore, HIV as a diagnosis code was used to identify suitable matches in this study. As the population in NSW is large, all linked hospital morbidity and death records for patients with HIV as a diagnosis code were selected from the NSW data linkage system prior to linkage with the AHOD cohort. The goal was to reduce the number of false-positive matches that may have arisen from using name codes instead of full names. In Western Australia, a HIV diagnosis code was confirmed for all matches after data linkage. Deterministic data linkage with the AHOD cohort was performed using matches on all, or part of, the following variables: name code, sex, date of birth and date of death (if deceased). Linked data were extracted and forwarded to the researchers in January–February 2009. For each episode of care, the date of admission and discharge, reason for separation, diagnosis [according to the International Classification of Diseases, 10th ed., Australian Modification (ICD10-AM)] and procedure codes, Major Diagnostic Category (aggregated ICD10-AM codes) and Australian Refined Diagnosis Related Group were included. Pregnancy- or childbirth-related episodes of care were excluded.

Ethical approval was obtained from all relevant institutional review boards. This study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 1983.

Definitions and outcome

The primary outcome variable was hospital admission. We defined a hospital admission as one or more episodes of care ending with a hospital discharge or death. Inpatient length of stay was calculated as the number of days from the date of admission in the first episode of care to the date of separation in the final episode of care for each hospital admission. The minimum inpatient length of stay was 1 day, and included same day admission and discharge. In this analysis, the Major Diagnostic Category variable was used to describe the principal reason for admission in an aggregated manner, with the exception of admissions that had opportunistic infections and AIDS-related cancers coded as the principal diagnosis. These were extracted and summarized as separate groups.

For the purpose of this analysis, viral load measures less than 400 copies/ml were replaced with the value 399 copies/ml and defined as undetectable because more sensitive assays were not uniformly available throughout the study period. Coinfection with HBV or HCV was defined as the detection of HBV surface antigen or HCV antibody, respectively. Patients who never tested positive for HBV surface antigen or HCV antibody were considered negative for the duration of the study. The date of each patient's first positive HIV test was used to estimate the duration of HIV infection as a time-dependent variable in this analysis. Patients were considered lost to follow-up if they were not dead and had no clinic visit recorded in AHOD in the 12 months prior to 31 March 2007.

Statistical analysis

Person-years were accrued from the date of enrolment in AHOD, except for patients recruited in NSW prior to 1 July 2000. For these patients, person-years were accrued from 1 July 2000, from which time the NSW Admitted Patient Data Collection recorded patient names. Person-years were terminated at the first of the following dates: date of death, the date 6 months after the last AHOD visit or 31 March 2007. In the analysis of risk factors for hospital admission, patients contributed person-years at risk only for periods when they were not hospitalized.

To investigate independent risk factors for hospital admission, incidence rate ratios (IRRs) were estimated with 95% confidence intervals (CIs) using random-effects Poisson regression methods to take into account within-person variation for repeated measures. The test for heterogeneity using the random-effects variance parameter estimate was significant (P < 0.01), indicating the suitability of the random-effects model. The following fixed covariates were tested: sex, HIV exposure, prior AIDS at baseline and HCV and HBV coinfection status. Age, time since first positive HIV test, CD4 cell count, log HIV RNA, AIDS-defining illness after baseline, calendar year and treatment exposure (including number of antiretroviral regimens and number of drug classes ever) were tested as time-dependent covariates in the models. Covariates were entered into the multivariate model if they had a P value of less than 0.10 in the univariate analysis and the model was adjusted for state. The final multivariate model was determined using a forward step-wise approach and only included covariates with a two-sided statistical significance (P < 0.05). The log-likelihood ratio statistic was used to assess contribution to the model. Missing data were excluded in tests for trend for ordinal categorical covariates or tests for homogeneity for nominal categorical covariates. All covariates with a P value of less than 0.10 in the univariate analysis that were not significant in the multivariate model are presented, adjusted for the final multivariate model.

We calculated crude hospital admission rates per 100 person-years, with 95% CI, for major diagnostic groups in three time periods (i.e. 1999–2001, 2002–2004 and 2005–2007). We explored whether hospitalization during the study period was an independent risk factor for mortality using Cox proportional hazards methods. Finally, we assessed predictors of inpatient length of stay using a generalized mixed model with a Poisson likelihood function [17,18].

Analyses were performed using Stata (version 10; StataCorp LP, College Station, Texas, USA) and R (version 2.5; R Foundation for Statistical Computing, Vienna, Austria).

Results

A total of 950 patients were recruited to AHOD in NSW (n = 657) and Western Australia (n = 293) and had complete data submitted by 31 March 2007. Of these, 842 patients consented to data linkage and had at least one follow-up visit after the baseline date for this study. During the study period, the follow-up rate in AHOD was 80%, and 58% of patients were admitted to hospital at least once (Table 1). The majority of patients were men (94%) and reported homosexual contact as a probable HIV exposure (82%). At baseline, the median age of the cohort was 41 years [interquartile range (IQR) 35–48] and the median time since the first positive HIV test was 7 years (IQR 4–12). One-fifth of patients had been diagnosed with an AIDS-defining illness prior to baseline, and 88% had prior ART experience. Patients who were admitted to hospital at least once during follow-up had a longer estimated duration of HIV infection, were slightly older and had a lower CD4 cell count and higher HIV RNA levels at baseline (Table 1). They were also more likely to have had a prior AIDS diagnosis, more ART regimens and been exposed to three drug classes.

Table 1. Baseline demographic and clinical characteristics of the 842 patients with HIV infection from New South Wales and Western Australia in the Australian HIV Observational Database cohort by hospitalization status, 1999–2007.

All patients Patients who were hospitalized at least once during follow-up Patients who were not hospitalized during follow-up Pa
Total patients, n (%) 842 488 354
Total person-years 4519 2782 1737
Female sex, n (%) 47 (6) 35 (7) 12 (3) 0.018
Age (years), median (IQR) 41 (35–48) 41 (36–49) 40 (35–46) 0.011
State, n (%) <0.001
 New South Wales 559 (66) 260 (53) 299 (84)
 Western Australia 283 (34) 228 (47) 55 (16)
Clinic type, n (%) <0.001
 Tertiary hospital 401 (48) 284 (58) 117 (33)
 Sexual health centre 150 (18) 76 (16) 74 (21)
 General medical practice 291 (35) 128 (26) 163 (46)
Hepatitis B virus coinfection, n (%) 0.594
 Negative/never tested 803 (95) 467 (96) 336 (95)
 Positive 39 (5) 21 (4) 18 (5)
Hepatitis C virus coinfection, n (%) 0.089
 Negative/never tested 745 (88) 424 (87) 321 (91)
 Positive 97 (12) 64 (13) 33 (9)
HIV exposure, n (%) 0.006
 Homosexual contactb 690 (82) 385 (79) 305 (86)
 Other 132 (16) 93 (19) 39 (11)
 Missing 20 (2) 10 (2) 10 (3)
Years since first positive HIV test, n (%) 0.042
 0–4 229 (27) 114 (23) 115 (32)
 5–7 167 (20) 101 (21) 66 (19)
 7–12 241 (29) 150 (31) 91 (26)
 ≥12 194 (23) 118 (24) 76 (21)
 Missing 11 (1) 5 (1) 6 (2)
 Median (IQR) 7 (4–12) 7 (3–11) 8 (4–12) 0.021
Prior AIDS, n (%) 174 (21) 123 (25) 51 (14) <0.001
CD4 cell count (cells/μl), median (IQR) 480 (309–675) 432 (260–624) 528 (377–730) <0.001
HIV viral load (log copies/ml), median (IQR)c 2.60 (2.60–3.84) 2.60 (2.60–4.04) 2.60 (2.60–3.52) 0.042
Prior ART, n (%) 738 (88) 435 (89) 303 (86) 0.123
Number of ART regimens ever, n (%) <0.001
 ≤1 275 (33) 137 (28) 138 (39)
 2–3 222 (26) 121 (25) 101 (29)
 4–6 176 (21) 105 (22) 71 (20)
 ≥7 169 (20) 125 (26) 44 (12)
Number of drug classes ever, n (%) 0.004
 ≤1 158 (19) 78 (16) 80 (23)
 2 393 (47) 221 (45) 172 (49)
 3 291 (35) 189 (39) 102 (29)
 4d
NRTI ever, n (%) 731 (87) 432 (89) 299 (84) 0.086
NNRTI ever, n (%) 430 (51) 263 (54) 167 (47) 0.054
Protease inhibitor ever, n (%) 552 (66) 339 (69) 213 (60) 0.005
Fusion inhibitor ever, n (%)d
Cumulative NRTI exposure (years), median (IQR) 3.0 (1.0–4.9) 3.2 (1.0–5.4) 2.6 (0.7–4.3) 0.002
Cumulative NNRTI exposure (years), median (IQR) 0.0 (0.0–1.5) 0.1 (0.0–1.3) 0.0 (0.0–1.5) 0.463
Cumulative protease inhibitor exposure (years), median (IQR) 1.3 (0.0–2.9) 1.6 (0.0–2.9) 0.8 (0.0–2.9) 0.025
Complete follow-up in AHOD cohort (%) 80 84 75 0.002
Median number of AHOD visits during study period (IQR) 28 (16–37) 33 (24–42) 21 (9–30) <0.001

AHOD, Australian HIV Observational Database; ART, antiretroviral therapy; IQR, interquartile range; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-NRTI.

a

P value for Pearson χ2 test for categorical variables or Wilcoxon rank-sum test for continuous variables.

b

Injecting drug use also reported for some participants in this group.

c

All HIV viral load measures below 400 copies/ml were changed to 399 copies/ml (i.e. 2.60 log copies/ml) for the purpose of this analysis.

d

Patients were not on fusion inhibitors at baseline.

Hospitalization rates and risk factors

In total, 2667 hospital admissions were identified during the study period. Patients were at risk of hospitalization for 4519 of the total 4547 person-years of observation accrued during the study. The crude hospitalization rate was 59 per 100 person-years (95% CI 57–61). In comparable 10-year age strata, hospital admission rates were 1.5–3 times higher in men between 25 and 64 years of age in AHOD compared with the general Australian population [19].

Independent risk factors for hospitalization included prior AIDS at baseline (IRR 1.71, 95% CI 1.24–2.35), older age (IRR 1.46 per 10-year increase, 95% CI 1.28–1.65), higher HIV RNA (IRR 1.16 per 1 log increase, 95% CI 1.11–1.21) and calendar year (Table 2). Longer estimated durations of HIV infection (5–7, 7–12 and ≥12 years compared with 0–4 years) were also associated with an increased risk of hospitalization (IRR 2.48, 2.48 and 2.45; 95% CI 2.00–3.07, 1.92–3.20 and 1.82–3.31, respectively). Exposure to four drug classes (compared with ≤1) was also significantly associated with hospitalization (IRR 2.66, 95% CI 1.53–4.62), as was exposure to two drug classes, although to a lesser extent (IRR 1.36, 95% CI 1.05–1.76). Higher CD4 cell counts were significantly associated with a decreased risk of hospitalization (IRR 0.91 per 100 cell increase, 95% CI 0.89–0.93).

Table 2. Predictors of hospitalization among 842 patients with HIV infection from New South Wales and Western Australia in the Australian HIV Observational Database cohort, 1999–2007.

Person-years n Incidence rate per 100 person-years (95% CI) Univariate IRR (95% CI) p Multivariatea adjusted IRR (95% CI) p Pb
Total 4519 2667 59 (57–61)
Age (per 10-year increase)c 4519 2667 1.86 (1.65–2.09) <0.001 1.46 (1.28–1.65) <0.001
Sex
 Female 265 114 43 (36–52) 1.00
 Male 4254 2553 60 (58–62) 1.37 (0.78–2.42)
Hepatitis B virus coinfection
 Negative/never tested 4299 2596 60 (58–63) 1.00 1.00
 Positive 220 71 32 (26–41) 0.57 (0.30–1.09) 0.091 0.77 (0.40–1.49)
Hepatitis C virus coinfection
 Negative/never tested 3973 2374 60 (57–62) 1.00
 Positive 546 293 54 (48–60) 0.78 (0.53–1.16) 0.221
HIV exposure
 Homosexual contactd 3683 2250 61 (59–64) 1.00
 Other 744 371 50 (45–55) 0.78 (0.55–1.11) 0.170
 Missing 92 46 50 (37–67) 0.66 (0.28–1.52) 0.324
Time since first positive HIV test (years)c
 0–4 411 136 33 (28–39) 1.00 1.00 <0.001
 5–7 748 458 61 (56–67) 2.86 (2.31–3.53) <0.001 2.48 (2.00–3.07) <0.001
 7–12 1447 865 60 (56–64) 3.31 (2.62–4.18) <0.001 2.48 (1.92–3.20) <0.001
 ≥12 1873 1147 61 (58–65) 4.07 (3.15–5.27) <0.001 2.45 (1.82–3.31) <0.001
 Missing 39 61 154 (120–199)
Prior AIDS
 No 3544 1757 50 (47–52) 1.00 1.00
 Yes 975 910 93 (87–100) 2.23 (1.65–3.01) <0.001 1.71 (1.24–2.35) 0.001
CD4 cell count (per 100 cells increase, cells/μl)c 4519 2667 0.89 (0.87–0.92) <0.001 0.91 (0.89–0.93) <0.001
HIV viral load (per 1 log increase, copies/ml)c 4519 2667 1.09 (1.05–1.14) <0.001 1.16 (1.11–1.21) <0.001
Number of drug classes everc
 ≤1 552 239 43 (38–49) 1.00 1.00 <0.001
 2 1769 932 53 (49–56) 1.70 (1.33–2.18) <0.001 1.36 (1.05–1.76) 0.022
 3 2173 1415 65 (62–69) 2.04 (1.56–2.68) <0.001 1.16 (0.85–1.57) 0.345
 4 26 81 317 (255–394) 6.75 (4.03–11.33) <0.001 2.66 (1.53–4.62) 0.001
AIDS event after baselinec
 No 4378 2517 57 (55–60) 1.00 1.00
 Yes 141 150 106 (90–125) 1.63 (1.21–2.19) 0.001 1.11 (0.81–1.51)
Calendar yearc
 1999–2000e 461 280 61 (54–68) 1.00 1.00 <0.001
 2001 698 389 56 (50–62) 1.06 (0.90–1.24) 0.491 1.06 (0.90–1.24) 0.504
 2002 682 381 56 (51–62) 1.12 (0.95–1.31) 0.184 1.07 (0.91–1.27) 0.403
 2003 669 369 55 (50–61) 1.13 (0.96–1.33) 0.130 0.97 (0.81–1.16) 0.746
 2004 656 329 50 (45–56) 1.13 (0.95–1.33) 0.165 0.94 (0.78–1.13) 0.510
 2005 630 422 67 (61–74) 1.63 (1.39–1.91) <0.001 1.27 (1.05–1.54) 0.014
 2006–2007f 724 497 69 (63–75) 1.92 (1.63–2.24) <0.001 1.55 (1.27–1.89) <0.001

CI, confidence interval; IRR, incidence rate ratio.

a

Model adjusted for state.

b

P value for test for homogeneity for nominal, categorical covariates, test for trend for ordinal, categorical covariates.

c

Time-dependent covariate.

d

Injecting drug use also reported for some participants in this group.

e

Includes data from 1 July 1999 to 31 December 2000.

f

Includes data from 1 January 2006 to 31 March 2007.

Reasons for hospitalization

Of the major diagnostic groups, gastrointestinal diseases had the highest crude hospitalization rates in all calendar year periods, except for 2005–2007, when the rate of kidney and urinary tract diseases was the highest (Table 3). A large proportion of the kidney and urinary tract-related admissions between 2002 and 2007 were for two patients who had dialysis recorded as the principal diagnosis code (189 of the 242 admissions). The crude hospital admission rate for neurological diseases increased during the study period, from 3.11 per 100 person-years (95% CI 2.24–4.31) in 1999–2001 to 5.91 per 100 person-years (95% CI 4.75–7.36) in 2005–2007. In contrast, hospital admission rates for mental health decreased from 4.31 per 100 person-years (95% CI 3.27–5.69) in 1999–2001 to 1.00 (95% CI 0.64–1.54) and 0.96 (95% CI 0.56–1.65) per 100 person-years in 2002–2004 and 2005–2007, respectively. More than half of mental health admissions had depression recorded as the principal diagnosis. Hospitalization rates for other major diagnostic groups remained relatively stable during the study period. Hospitalization rates for nonopportunistic infections/parasitic diseases, AIDS and non-AIDS-defining cancers were among the five most frequent major diagnostic groups in 1999–2001 and remained common reasons for admission during the study period.

Table 3. Hospitalization rates for major diagnostic groups among 842 patients with HIV infection from New South Wales and Western Australia in the Australian HIV Observational Database cohort, 1999–2007.

1999–2001 2002–2004 2005–2007



1159 person-years 2006 person-years 1354 person-years



n Rate per 100 person-years n Rate per 100 person-years n Rate per 100 person-years
All causes 669 57.73 (53.52–62.28) 1079 53.77 (50.66–57.08) 919 67.89 (63.64–72.43)
Major diagnostic groups
 Opportunistic infections 33 2.85 (2.02–4.01) 58 2.89 (2.23–3.74) 34 2.51 (1.79–3.52)
 Cancers, AIDS defininga 52 4.49 (3.42–5.89) 98 4.88 (4.01–5.95) 46 3.40 (2.55–4.54)
 Cancers, non-AIDS definingb 59 5.09 (3.94–6.57) 52 2.59 (1.97–3.40) 54 3.99 (3.06–5.21)
 Cardiovascular and other circulatory diseases 37 3.19 (2.31–4.41) 65 3.24 (2.54–4.13) 47 3.47 (2.61–4.62)
 Drug use and drug-induced organic mental disordersc 7 0.60 (0.29–1.27) 6 0.30 (0.13–0.67) 8 0.59 (0.30–1.18)
 Ear, nose, mouth and throat diseases 16 1.38 (0.85–2.25) 32 1.59 (1.13–2.26) 24 1.77 (1.19–2.65)
 Endocrine and metabolic diseases 9 0.78 (0.40–1.49) 15 0.75 (0.45–1.24) 15 1.11 (0.67–1.84)
 Eye diseases 10 0.86 (0.46–1.60) 11 0.55 (0.30–0.99) 15 1.11 (0.67–1.84)
 Gastrointestinal diseases 86 7.42 (6.01–9.17) 126 6.28 (5.27–7.48) 127 9.38 (7.88–11.16)
 Haematological diseases 25 2.16 (1.46–3.19) 26 1.30 (0.88–1.90) 12 0.89 (0.50–1.56)
 Hepatobiliary system and pancreas diseases 29 2.50 (1.74–3.60) 98 4.88 (4.01–5.95) 31 2.29 (1.61–3.26)
 Injuries, poisoning and toxic effects of drugs 20 1.73 (1.11–2.68) 26 1.30 (0.88–1.90) 18 1.33 (0.84–2.11)
 Kidney and urinary tract diseasesd 22 1.90 (1.25–2.88) 74 3.69 (2.94–4.63) 168 12.41 (10.67–14.44)
 Mental health diseases 50 4.31 (3.27–5.69) 20 1.00 (0.64–1.54) 13 0.96 (0.56–1.65)
 Musculoskeletal system and connective tissue diseases 32 2.76 (1.95–3.90) 70 3.49 (2.76–4.41) 64 4.73 (3.70–6.04)
 Neurological diseases 36 3.11 (2.24–4.31) 73 3.64 (2.89–4.58) 80 5.91 (4.75–7.36)
 Nonopportunistic infections/parasitic diseases 67 5.78 (4.55–7.35) 89 4.44 (3.60–5.46) 57 4.21 (3.25–5.46)
 Reproductive system diseases 9 0.78 (0.40–1.49) 24 1.20 (0.80–1.78) 18 1.33 (0.84–2.11)
 Respiratory system diseases 20 1.73 (1.11–2.68) 38 1.89 (1.38–2.60) 25 1.85 (1.25–2.73)
 Skin, subcutaneous tissue and breast diseases 24 2.07 (1.39–3.09) 32 1.59 (1.13–2.26) 24 1.77 (1.19–2.65)
 Other 26 2.24 (1.53–3.30) 46 2.29 (1.72–3.06) 39 2.88 (2.11–3.94)
a

Includes 146 hospital admissions (16 patients) wherein chemotherapy was recorded as the principal diagnosis.

b

Includes 14 hospital admissions (two patients) wherein chemotherapy was recorded as the principal diagnosis.

c

Includes alcohol and other drugs.

d

Includes 189 hospital admissions (two patients) with dialysis recorded as the principal diagnosis (43 in 2002–2004; 146 in 2005–2007).

Association between hospitalization and mortality

A total of 64 deaths occurred during the study period; the crude mortality rate was 1.4 per 100 person-years (95% CI 1.1–1.8) (Table 4). After adjusting for other significant risk factors, patients with at least four hospital admissions had an increased risk of mortality (hazard ratio 4.37, 95% CI 2.45–7.78) compared with those who were admitted to hospital one to three times during the study period. Conversely, patients with no hospital admissions had a 91% reduced risk of mortality (hazard ratio 0.09, 95% CI 0.03–0.27) compared with those admitted one to three times during the study period. Older age, lower CD4 cell counts and higher HIV RNA levels were also independently associated with mortality.

Table 4. Hospitalization as a predictor of mortality among 842 patients with HIV infection from New South Wales and Western Australia in the Australian HIV Observational Database cohort, 1999–2007.

Person-years No. of deaths Mortality rate per 100 person-years (95% CI) Univariate hazard ratio (95% CI) p Multivariatea adjusted hazard ratio (95% CI) p Pb
Total 4547 64 1.4 (1.1–1.8)
Hospital admissionsc,d
 None 2600 4 0.2 (0.1–0.4) 0.06 (0.02–0.18) <0.001 0.09 (0.03–0.27) <0.001
 1–3 1474 23 1.6 (1.0–2.4) 1.00 1.00
 ≥4 473 37 7.8 (5.7–10.8) 6.67 (3.80–11.70) <0.001 4.37 (2.45–7.78) <0.001
Age (years)d
 <45 2403 26 1.1 (0.7–1.6) 1.00 1.00
 ≥45 2144 38 1.8 (1.3–2.4) 1.59 (0.96–2.65) 0.073 1.88 (1.11–3.19) 0.019
Sex
 Female 267 3 1.1 (0.4–3.5) 1.00
 Male 4280 61 1.4 (1.1–1.8) 1.37 (0.42–4.44) 0.603
Hepatitis B virus coinfection
 Negative/never tested 4326 61 1.4 (1.1–1.8) 1.00
 Positive 221 3 1.4 (0.4–4.2) 0.98 (0.31–3.14) 0.976
Hepatitis C virus coinfection
 Negative/never tested 3997 55 1.4 (1.1–1.8) 1.00
 Positive 550 9 1.6 (0.9–3.2) 1.19 (0.59–2.41) 0.623
HIV exposure
 Homosexual contacte 3706 49 1.3 (1.0–1.8) 1.00
 Other 748 14 1.9 (1.1–3.2) 1.37 (0.73–2.58) 0.325
 Missing 93 1 1.1 (0.2–7.7) 0.88 (0.12–6.43) 0.900
Time since first positive HIV test (years)d
 0–4 413 3 0.7 (0.2–2.3) 1.00
 5–7 752 5 0.7 (0.3–1.6) 0.97 (0.23–4.12) 0.964
 7–12 1457 27 1.9 (1.3–2.7) 2.76 (0.81–9.42) 0.105
 ≥12 1886 29 1.5 (1.1–2.2) 2.29 (0.66–7.95) 0.191
 Missing 40 0
Prior AIDS
 No 3562 43 1.2 (0.9–1.6) 1.00 1.00
 Yes 985 21 2.1 (1.4–3.3) 1.77 (1.05–2.98) 0.033 0.87 (0.50–1.51) 0.614
CD4 cell count (cells/μl)d
 >200 4125 30 0.7 (0.5–1.0) 1.00 1.00 <0.001
 101–200 240 11 4.6 (2.5–8.3) 6.49 (3.24–12.98) <0.001 3.67 (1.78–7.57) <0.001
 ≤100 164 20 12.2 (7.9–18.9) 18.33 (10.31–32.58) <0.001 6.48 (3.35–12.52) <0.001
 Missing 18 3 17.1 (5.5–52.9)
HIV viral load (per 1 log increase, copies/ml)d
 ≤400 2633 24 0.9 (0.6–1.4) 1.00 1.00 0.012
 401–10 000 1052 8 0.8 (0.4–1.5) 1.15 (0.50–2.63) 0.748 1.05 (0.45–2.42) 0.911
 ≥10 001 842 29 3.5 (2.4–5.0) 4.92 (2.79–8.68) <0.001 2.01 (1.04–3.87) 0.038
 Missing 20 3 14.8 (4.8–45.8)
Number of drug classes everd
 ≤1 555 8 1.4 (0.7–2.9) 1.00
 2 1777 22 1.2 (0.8–1.9) 0.84 (0.37–1.89) 0.678
 3 2189 34 1.6 (1.1–2.2) 1.03 (0.47–2.26) 0.935
 4 26 0
AIDS event after baselined
 No 4402 54 1.2 (0.9–1.6) 1.00 1.00
 Yes 145 10 6.9 (3.7–12.9) 6.13 (2.98–12.62) <0.001 1.12 (0.52–2.39) 0.771
Calendar yeard
 1999–2000f 465 8 1.7 (0.9–3.4) 1.00
 2001 702 10 1.4 (0.8–2.6) 0.56 (0.10–3.17) 0.511
 2002 686 6 0.9 (0.4–1.9) 0.22 (0.03–1.89) 0.169
 2003 673 7 1.0 (0.5–2.2) 0.60 (0.07–5.33) 0.650
 2004 659 13 2.0 (1.2–3.4) 0.43 (0.04–4.40) 0.480
 2005 633 8 1.3 (0.6–2.5) 0.41 (0.04–4.35) 0.458
 2006–2007g 729 12 1.7 (0.9–2.9) 0.44 (0.04–4.88) 0.503

CI, confidence interval.

a

Model stratified by state.

b

P value for test for homogeneity for nominal, categorical covariates, test for trend for ordinal, categorical covariates.

c

During period of follow-up.

d

Time-dependent covariate.

e

Injecting drug use also reported for some participants in this group.

f

Includes data from 1 July 1999 to 31 December 2000.

g

Includes data from 1 January 2006 to 31 March 2007.

Inpatient length of stay

The inpatient length of stay in our study ranged from 1 to 191 days, with a mean of 4.6 days (standard deviation 10.0) and a median of 1 day (IQR, 1–4). Lower CD4 cell counts, higher HIV RNA, older age and HCV positivity were independently associated with a longer inpatient stay in this study (Table 5).

Table 5. Predictors of inpatient length of stay among 842 patients with HIV infection from New South Wales and Western Australia in the Australian HIV Observational Database cohort, 1999–2007.

Univariate β̂ (SE) p Multivariate β̂ (SE) p
Total
Age (per 5-year increase)a 0.05 (0.02) 0.028 0.08 (0.02) <0.001
Sex (female) −0.10 (0.21) 0.629
Hepatitis B virus coinfection −0.03 (0.27) 0.900
Hepatitis C virus coinfection 0.24 (0.14) 0.085 0.32 (0.14) 0.023
HIV exposure (Homosexual contactb) −0.02 (0.13) 0.878
Time since first positive HIV test (years)a
 0–4 Reference
 5–7 0.21 (0.12) 0.070
 8–11 0.13 (0.10) 0.205
 ≥12 0.14 (0.10) 0.136
Prior AIDS 0.17 (0.11) 0.108
CD4 cell count (per 100 cells increase, cells/μl)a −0.10 (0.02) <0.001 −0.08 (0.02) <0.001
HIV viral load (per 1 log10 increase, copies/ml)a 0.15 (0.02) <0.001 0.13 (0.02) <0.001
Number of drug classes evera
 ≤1 Reference
 2 0.03 (0.15) 0.835
 3 0.10 (0.15) 0.494
 4 −0.24 (0.33) 0.464
AIDS event after baselinea 0.17 (0.11) 0.108
Calendar yeara
 1999–2000c Reference Reference
 2001 −0.09 (0.13) 0.499 −0.02 (0.13) 0.891
 2002 −0.07 (0.14) 0.594 −0.03 (0.13) 0.849
 2003 0.19 (0.13) 0.133 0.20 (0.13) 0.114
 2004 −0.04 (0.14) 0.783 −0.01 (0.14) 0.938
 2005 −0.07 (0.14) 0.605 −0.006 (0.14) 0.966
 2006–2007d 0.16 (0.12) 0.195 0.25 (0.12) 0.044

Model adjusted for state.

a

Time-dependent covariate.

b

Injecting drug use also reported for some participants in this group.

c

Includes data from 1 July 1999 to 31 December 2000.

d

Includes data from 1 January 2006 to 31 March 2007.

Discussion

Our data indicate that older age, longer duration of HIV infection, treatment experience with four drug classes and indicators of advanced immune deficiency are independently associated with hospitalization in patients with HIV infection in Australia during the cART era. Of the major diagnostic groups, hospitalization rates for gastrointestinal diseases were highest for most of the study period. Longer inpatient length of stay was associated with older age, HCV coinfection and indicators of advanced immune deficiency. Hospitalization during follow-up was an independent risk factor for mortality. In comparable age and sex strata, hospitalization rates were around 50–300% higher in patients with HIV infection in our study than in the general Australian population.

Our finding that immunodeficiency was associated with hospitalization, inpatient length of stay and mortality in patients with HIV infection in Australia during the cART era is consistent with previous studies of health service utilization [46,11,12,2022] and mortality in HIV-infected populations [23,24]. Although antiretroviral drug-related toxicity may also have led to increased morbidity [15,25] and, therefore, hospitalizations in our cohort, our data suggest that immunodeficiency and virological failure were more important risk factors.

The majority of hospital admissions in the AHOD cohort between 1999 and 2007 were for non-AIDS conditions, in accord with previous studies [4,7,9]. Hospitalization rates for gastrointestinal diseases were higher than other major diagnostic groups in this study, except for 2005–2007. Although rates of gastrointestinal diseases were common in the US HIV Outpatients Study (1994–2005), renal-related admissions were lower than those in our study [4]. The higher rates of kidney and urinary tract-related admissions in the later period in AHOD can, for the most part, be explained by the frequent admission of two patients for dialysis between 2002 and 2007.

Despite the decline in incident AIDS-related cancers in Australia since the availability of cART [26], hospitalization rates for AIDS-defining cancers remained common between 1999 and 2007. For many of these hospitalizations, chemotherapy was recorded as the principal reason for admission. Hospitalization rates for non-AIDS cancers were similar to AIDS cancers in our study, consistent with the US HIV Outpatients Study in 2000–2005 [4].

There is evidence from previous studies [5,27,28] that liver-related hospitalizations have increased in HIV-infected individuals with HCV coinfection, a history of injection-drug user (IDU) or both since cART became available. HCV coinfection has also been identified as an independent risk factor for hospitalization [11,27]. Although HCV was not an independent risk factor for hospitalization in our study, it was associated with longer length of stay. The relatively low prevalence of HCV coinfection, IDU or both in AHOD compared with the John Hopkins University cohort in the US and the EuroSIDA cohort, may, in part, explain the different findings.

Our study has several strengths. First, AHOD is a multisite cohort with a relatively large sample size and follow-up rate of 80%. Second, data linkage enabled efficient collection of data on statewide hospital admissions in our cohort.

This study also had limitations. Ascertainment of hospital admissions were most likely affected by the use of name codes rather than full names as a matching variable in the data linkage; although previous studies linking Australian HIV/AIDS registries to death [29] and cancer [30] registries reported 82–99% sensitivity and 92–100% specificity. To reduce the likelihood of multiple matches in the populous state of NSW, we first restricted the linked hospital morbidity and death records to individuals with HIV recorded as a diagnosis. However, we cannot exclude that, in some instances, HIV was not coded as a diagnosis in the hospital data despite a patient being HIV positive. This misclassification would have resulted in under-ascertainment of hospitalizations in NSW and may, in part, explain the lower hospitalization rates in NSW compared with Western Australia. Service delivery may also have affected the different hospitalization rates between the two states; HIV services are more centralized in the smaller state of Western Australia where all AHOD patients are recruited via the tertiary hospital compared with NSW, where patients are recruited via general medical practices, sexual health centres and tertiary referral hospitals. To account for any differences between the states in our analysis, we adjusted for state in the multivariate models.

Another limitation of this study is the lower follow-up rate among patients who were not hospitalized during the study period. We assume that, similar to other clinical cohorts [31], those who remained under follow-up represent a sicker group of patients who utilize health services more frequently. In this case, our study may have overestimated the true hospitalization rates in people with HIV infection in Australia. Furthermore, AHOD is a highly treated study population and not necessarily representative of all patients with HIV infection in Australia. It is also essentially a closed cohort and, therefore, not ideal for studying changes over time. For this reason, the unexpected, increased IRRs for hospitalization in 2005 and 2006–2007 and the association with longer inpatient length of stay in 2006–2007 should be interpreted with caution.

To conclude, men receiving care for HIV infection in Australia are currently hospitalized at higher rates than men of similar age in the general population. Older, sicker individuals, as indicated by markers of advanced immunodeficiency, frequency of hospitalization or both, are at greater risk of hospitalization and death. Finally, many hospitalizations were for non-AIDS diseases, highlighting the importance of treating non-AIDS diseases and related risk factors in addition to those traditionally associated with HIV disease.

Acknowledgments

The Australian HIV Observational Database is funded as part of the Asia Pacific HIV Observational Database, a programme of The Foundation for AIDS Research, amfAR, and is supported in part by a grant from the United States National Institutes of Health National Institute of Allergy and Infectious Diseases (grant no. U01-AI069907) as part of the International epidemiologic Databases to Evaluate AIDS initiative, and by unconditional grants from Merck Sharp & Dohme, Gilead, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Pfizer, GlaxoSmithKline and Janssen-Cilag. The National Centre in HIV Epidemiology and Clinical Research is funded by the Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, The University of New South Wales. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above.

The authors would like to thank Dr Marina van Leeuwen and Dr Preeyaporn Srasuebkul for advice on data preparation and statistical programming. The authors also acknowledge the assistance of the New South Wales Centre for Health Record Linkage and the Data Linkage Branch, Department of Health, Western Australia in the conduct of this study. The authors also thank participating sites and steering committee members (given below) and all patients who participated in this study.

K.F, J.A. and M.G.L. conceived and designed the study and K.F. drafted the analysis plan. K.F. coordinated the study, managed the data and drafted the manuscript. K.F. and H.W. conducted the statistical analyses. K.F., H.W., M.G.L. and B.D. interpreted the results. All authors commented on the analysis plan and drafts of the manuscript and approved the final manuscript draft for journal submission.

M.G.L. has received research grants, consultancy, travel grants or all from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen-Cilag, Johnson & Johnson, Merck Sharp & Dohme, Pfizer, Roche and CSL Ltd. J.A. has received research grants, consultancy, travel grants or all in the past 2 years from Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme and Pfizer. The other authors have no conflicts of interest.

The AHOD: D. Ellis, General Medical Practice, Coffs Harbour, NSW; J. Chuah*, M. Ngieng, Gold Coast Sexual Health Clinic, Miami, QLD; M. Bloch, T. Franic, S. Agrawal, N. Cunningham, Holdsworth House General Practice, Darlinghurst, NSW; R. Moore, S. Edwards, S. Carson, P. Locke, J. Anderson, Northside Clinic, North Fitzroy, VIC; D. Nolan, C. Forsdyke, J. Skett, Department of Clinical Immunology, Royal Perth Hospital, Perth, Western Australia; N.J. Roth*†, J. Nicolson, Prahran Market Clinic, South Yarra, VIC; D. Allen, P. Maudlin, Holden Street Clinic, Gosford, NSW; D. Smith, C. Mincham, C. Gray, Lismore Sexual Health & AIDS Services, Lismore, NSW; D. Baker*, R. Vale, East Sydney Doctors, Darlinghurst, NSW; D. Russell, S. Downing, Cairns Sexual Health Service, Cairns, QLD; D. Templeton, C. O'Connor, Royal Prince Alfred Hospital Sexual Health, Camperdown, NSW; D. Sowden, K. McGill, Clinic 87, Sunshine Coast & Cooloola HIV Sexual Health Service, Nambour, QLD; D. Orth; D. Youds, Gladstone Road Medical Centre, Highgate Hill, QLD; E. Jackson, Blue Mountains Sexual Health and HIV Clinic, Katoomba, NSW; T. Read, J. Silvers, Melbourne Sexual Health Centre, Melbourne, VIC; A. Kulatunga, P. Knibbs, Communicable Disease Centre, Royal Darwin Hospital, Darwin, NT; J. Hoy, K. Watson*, M. Bryant, The Alfred Hospital, Melbourne, VIC; M. Gotowski, S. Taylor, L. Stuart-Hill, Bligh Street Clinic, Tamworth, NSW; D. Cooper, A. Carr, K. Hesse, G. Keogh, R. Norris, St Vincent's Hospital, Darlinghurst, NSW; R. Finlayson, I. Prone, Taylor Square Private Clinic, Darlinghurst, NSW; M.T. Liang, Nepean Sexual Health and HIV Clinic, Penrith, NSW; M. Kelly, A. Gibson, AIDS Medical Unit, Brisbane, QLD; K. Brown, N. Skobalj, Illawarra Sexual Health Clinic, Warrawong, NSW; L. Wray, H. Lu, Sydney Sexual Health Centre, Sydney, NSW; W. Donohue, The Care and Prevention Programme, Adelaide University, Adelaide, SA; I. Woolley, M. Giles, Monash Medical Centre, Clayton, VIC; Dubbo Sexual Health Centre, Dubbo, NSW; P. Canavan*, National Association of People Living with HIV/AIDS; C. Lawrence*, National Aboriginal Community Controlled Health Organisation; I. Zablotska*, National Centre in HIV Social Research, University of NSW, Sydney; B. Mulhall*, School of Public Health, University of Sydney, Sydney, NSW; M. Law*, K. Petoumenos*, S. Marashi Pour*, C. Bendall*, K. Falster, National Centre in HIV Epidemiology and Clinical Research, University of NSW, Sydney; NSW. *Steering Committee member 2009, Current Steering Committee chair.

Cause of Death (CoDE) reviewers – D. Sowden, D. Templeton, A. Carr, J. Hoy, L. Wray, J. Chuah, K. Morwood, T. Read, N. Roth, I. Woolley, J. Anderson and M. Boyd.

References

  • 1.Egger M, Hirschel B, Francioli P, Sudre P, Wirz M, Flepp M, et al. Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. BMJ. 1997;315:1194–1199. doi: 10.1136/bmj.315.7117.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, Monforte AdA, et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet. 2003;362:22–29. doi: 10.1016/s0140-6736(03)13802-0. [DOI] [PubMed] [Google Scholar]
  • 3.Palella FJ, Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338:853–860. doi: 10.1056/NEJM199803263381301. [DOI] [PubMed] [Google Scholar]
  • 4.Buchacz K, Baker RK, Moorman AC, Richardson JT, Wood KC, Holmberg SD, Brooks JT. Rates of hospitalizations and associated diagnoses in a large multisite cohort of HIV patients in the United States, 1994–2005. AIDS. 2008;22:1345–1354. doi: 10.1097/QAD.0b013e328304b38b. [DOI] [PubMed] [Google Scholar]
  • 5.Floris-Moore M, Lo Y, Klein RS, Budner N, Gourevitch MN, Moskaleva G, Schoenbaum EE. Gender and hospitalization patterns among HIV-infected drug users before and after the availability of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2003;34:331–337. doi: 10.1097/00126334-200311010-00012. [DOI] [PubMed] [Google Scholar]
  • 6.Gebo KA, Diener-West M, Moore RD. Hospitalization rates in an urban cohort after the introduction of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2001;27:143–152. doi: 10.1097/00126334-200106010-00009. [DOI] [PubMed] [Google Scholar]
  • 7.Gebo KA, Fleishman JA, Moore RD. Hospitalizations for metabolic conditions, opportunistic infections, and injection drug use among HIV patients: trends between 1996 and 2000 in 12 states. J Acquir Immune Defic Syndr. 2005;40:609–616. doi: 10.1097/01.qai.0000171727.55553.78. [DOI] [PubMed] [Google Scholar]
  • 8.Hellinger FJ. The changing pattern of hospital care for persons living with HIV: 2000 through 2004. J Acquir Immune Defic Syndr. 2007;45:239–246. doi: 10.1097/QAI.0b013e3180517407. [DOI] [PubMed] [Google Scholar]
  • 9.Krentz HB, Dean S, Gill MJ. Longitudinal assessment (1995–2003) of hospitalizations of HIV-infected patients within a geographical population in Canada. HIV Med. 2006;7:457–466. doi: 10.1111/j.1468-1293.2006.00408.x. [DOI] [PubMed] [Google Scholar]
  • 10.Mocroft A, Barry S, Sabin CA, Lepri AC, Kinloch S, Drinkwater A, et al. The changing pattern of admissions to a London hospital of patients with HIV: 1988–1997. Royal Free Centre for HIV Medicine. AIDS. 1999;13:1255–1261. doi: 10.1097/00002030-199907090-00016. [DOI] [PubMed] [Google Scholar]
  • 11.Mocroft A, Monforte A, Kirk O, Johnson MA, Friis-Moller N, Banhegyi D, et al. Changes in hospital admissions across Europe: 1995–2003. Results from the EuroSIDA study. HIV Med. 2004;5:437–447. doi: 10.1111/j.1468-1293.2004.00250.x. [DOI] [PubMed] [Google Scholar]
  • 12.Paul S, Gilbert HM, Lande L, Vaamonde CM, Jacobs J, Malak S, Sepkowitz KA. Impact of antiretroviral therapy on decreasing hospitalization rates of HIV-infected patients in 2001. AIDS Res Hum Retroviruses. 2002;18:501–506. doi: 10.1089/088922202317406646. [DOI] [PubMed] [Google Scholar]
  • 13.Fontas E, van Leth F, Sabin CA, Friis-Moller N, Rickenbach M, d'Arminio Monforte A, et al. Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis. 2004;189:1056–1074. doi: 10.1086/381783. [DOI] [PubMed] [Google Scholar]
  • 14.Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356:1723–1735. doi: 10.1056/NEJMoa062744. [DOI] [PubMed] [Google Scholar]
  • 15.Friis-Moller N, Sabin CA, Weber R, d'Arminio Monforte A, El-Sadr WM, Reiss P, et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. 2003;349:1993–2003. doi: 10.1056/NEJMoa030218. [DOI] [PubMed] [Google Scholar]
  • 16.Australian HIV Observational Database. Rates of combination antiretroviral treatment change in Australia, 1997–2000. HIV Med. 2002;3:28–36. doi: 10.1046/j.1464-2662.2001.00094.x. [DOI] [PubMed] [Google Scholar]
  • 17.Breslow NE, Clayton DG. Approximate inference in generalized linear mixed models. J Am Stat Assoc. 1993;88:9–25. [Google Scholar]
  • 18.Schall R. Estimation in generalized linear models with random effects. Biometrika. 1991;78:719–727. [Google Scholar]
  • 19.AIHW. Australian hospital statistics 2007–08. Canberra, Australia: Australian Institute of Health and Welfare (AIHW); 2009. Health services series no. 33. Cat. no. HSE 71. [Google Scholar]
  • 20.Fielden SJ, Rusch ML, Levy AR, Yip B, Wood E, Harrigan RP, et al. Predicting hospitalization among HIV-infected antiretroviral naive patients starting HAART: determining clinical markers and exploring social pathways. AIDS Care. 2008;20:297–303. doi: 10.1080/09540120701561296. [DOI] [PubMed] [Google Scholar]
  • 21.Gardner LI, Klein RS, Szczech LA, Phelps RM, Tashima K, Rompalo AM, et al. Rates and risk factors for condition-specific hospitalizations in HIV-infected and uninfected women. J Acquir Immune Defic Syndr. 2003;34:320–330. doi: 10.1097/00126334-200311010-00011. [DOI] [PubMed] [Google Scholar]
  • 22.The HIV Research Network. Hospital and outpatient health services utilization among HIV-infected patients in care in 1999. J Acquir Immune Defic Syndr. 2002;30:21–26. doi: 10.1097/00126334-200205010-00003. [DOI] [PubMed] [Google Scholar]
  • 23.Egger M, May M, Chene G, Phillips AN, Ledergerber B, Dabis F, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet. 2002;360:119–129. doi: 10.1016/s0140-6736(02)09411-4. [DOI] [PubMed] [Google Scholar]
  • 24.May M, Sterne JA, Sabin C, Costagliola D, Justice AC, Thiebaut R, et al. Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies. AIDS. 2007;21:1185–1197. doi: 10.1097/QAD.0b013e328133f285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Weber R, Sabin CA, Friis-Moller N, Reiss P, El-Sadr WM, Kirk O, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006;166:1632–1641. doi: 10.1001/archinte.166.15.1632. [DOI] [PubMed] [Google Scholar]
  • 26.van Leeuwen MT, Vajdic CM, Middleton MG, McDonald AM, Law M, Kaldor JM, Grulich AE. Continuing declines in some but not all HIV-associated cancers in Australia after widespread use of antiretroviral therapy. AIDS. 2009;23:2183–2190. doi: 10.1097/QAD.0b013e328331d384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Gebo KA, Diener-West M, Moore RD. Hospitalization rates differ by hepatitis C status in an urban HIV cohort. J Acquir Immune Defic Syndr. 2003;34:165–173. doi: 10.1097/00126334-200310010-00006. [DOI] [PubMed] [Google Scholar]
  • 28.Martin-Carbonero L, Soriano V, Valencia E, Garcia-Samaniego J, Lopez M, Gonzalez-Lahoz J. Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients. AIDS Res Hum Retroviruses. 2001;17:1467–1471. doi: 10.1089/08892220152644160. [DOI] [PubMed] [Google Scholar]
  • 29.Nakhaee F, McDonald A, Black D, Law M. A feasible method for linkage studies avoiding clerical review: linkage of the national HIV/AIDS surveillance databases with the National Death Index in Australia. Aust N Z J Public Health. 2007;31:308–312. doi: 10.1111/j.1753-6405.2007.00076.x. [DOI] [PubMed] [Google Scholar]
  • 30.Grulich AE, Wan X, Coates M, Day P, Kaldor JM. Validation of a nonpersonally identifying method of linking cancer and acquired immune deficiency syndrome register data. J Epidemiol Biostat. 1996;1:207–212. [Google Scholar]
  • 31.Lau B, Gange SJ, Moore RD. Interval and clinical cohort studies: epidemiological issues. AIDS Res Hum Retroviruses. 2007;23:769–776. doi: 10.1089/aid.2006.0171. [DOI] [PubMed] [Google Scholar]

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