All-cause and HIV-related mortality rates among HIV-infected patients after initiating highly active antiretroviral therapy: the impact of aboriginal ethnicity and injection drug use.
Martin, Leah J. ; Houston, Stan ; Yasui, Yutaka 等
Highly active antiretroviral therapy (HAART) has dramatically
reduced mortality among human immunodeficiency virus (HIV)-infected
individuals. (1,2) However, since the introduction of HAART, higher
rates of mortality have been observed among injection drug users (IDUs)
(3,4) and Aboriginal peoples (5) within this population.
Aboriginals are over-represented among HIV-positive test reports in
Canada and IDU is more commonly reported as a route of HIV exposure
among Aboriginals than non-Aboriginals. (6) Although IDU has been
associated with increased rates of mortality after starting HAART, (7,8)
less is known about the impact of Aboriginal ethnicity on mortality
after starting HAART and whether IDU may help to explain differences in
mortality between Aboriginal and non-Aboriginal HIV patients. One recent
Canadian study found Aboriginals to have significantly higher rates of
all-cause mortality after starting HAART after controlling for a history
of IDU; (5) however, the study did not investigate HIV related mortality
specifically and included only 88 Aboriginal subjects (14.1% of the
study population). As Mocroft et al. illustrate, it is inappropriate to
assume that higher all-cause mortality rates necessarily demonstrate a
poorer response to HAART; to investigate patients' responses to
HAART, it is important to examine HIV-related mortality rates
specifically. (9)
The objectives of this study were to compare all-cause and
HIV-related mortality rates between Aboriginal and non-Aboriginal HIV
patients after starting HAART, adjusting for factors known to influence
mortality among HIV patients. Because Aboriginal HIV patients have
higher rates of exposure to HIV via IDU and because we observed a strong
association between IDU and mortality, we also examined the relationship
between IDU and these two mortality outcomes.
METHODS
Data sources
This was a retrospective cohort study using data collected by the
Northern Alberta HIV Program (NAHIVP), a clinical database that has been
described in detail elsewhere. (10) In addition to data from NAHIVP, we
linked cause and date of death data from Alberta Health and Wellness to
the study database and used viral load data from the Alberta Provincial
Public Health Laboratory to replace missing baseline viral loads where
possible. The study procedures were approved by the University of
Alberta Health Research Ethics Board.
Study patients
We assembled a cohort of patients using the NAHIVP database who
satisfied the following eligibility criteria: 1) started HAART between 1
January 1999 and 30 June 2005 (baseline); 2) were previously
antiretroviral therapy (ART)-naive; and 3) were [greater than or equal
to] 15 years of age when starting HAART. Patients were excluded if they
were missing ethnicity data. To limit the study to patients who started
HAART for the purpose of treatment rather than to prevent vertical
transmission of HIV, we excluded patients if they started HAART [less
than or equal to] 26 weeks before being recorded as delivering a baby.
We assumed that starting HAART earlier in pregnancy or after delivery
would be for maternal indications. Patients were followed
retrospectively until December 31, 2005, which allowed follow-up time of
6 months to 7 years.
Definitions
We defined Aboriginals as Treaty and non-Treaty Aboriginals, Metis
and Inuit. One patient was defined as Aboriginal who was identified as
both Caucasian and Metis in the database. HIV exposure categories were
classified using an exposure category hierarchy. (11) Patients were
defined as IDUs if their HIV exposure was recorded as IDU or any other
exposure combined with IDU; patients with other exposures, including
unknown or missing exposures, were considered to have "other
exposures". We defined HAART as a combination of at least three
antiretrovirals, other than ritonavir, recorded as prescribed on the
same date. We excluded ritonavir under the assumption that, during the
study period (1999-2005), ritonavir would have been prescribed at low
dosages intended to boost other protease inhibitors, rather than at
clinically therapeutic levels. The HAART start date was the first date
that a HAART prescription was recorded in the database and, for the
purposes of these analyses, we assumed that patients continued on HAART.
Baseline CD4 cell counts and viral loads were defined as those measures
that were taken closest to the HAART start date, [less than or equal to]
6 months before, and not after starting HAART. We classified causes of
death using the ninth and tenth revisions of the International
Statistical Classification of Diseases and Related Health Problems
(ICD-9 and 10). (12) We defined ICD-9 categories 042-044 and ICD-10
categories B20-B24 as HIV-related causes of death; all other known
causes were coded as non-HIV-related causes of death. Cause of death was
unavailable for five patients; therefore, one of the authors (SH)
reviewed their charts and determined cause of death to be HIV-related
for two patients and non-HIV-related for two patients. Cause of death
remained undetermined for one patient (an Aboriginal female IDU), who we
excluded from our analysis of HIV-related mortality.
Data analyses
Patient characteristics were tabulated and compared between
Aboriginals and non-Aboriginals and between IDUs and patients with other
exposures, using [chi square] and two-sided Fisher exact tests for
categorical variables and two-sided Wilcoxon rank sum test (normal
approximation) for continuous variables.
[FIGURE 1 OMITTED]
We assessed two main outcomes in our analyses: all-cause mortality
and HIV-related mortality. To examine unadjusted all-cause mortality
risk, we compared Kaplan-Meier estimates of survival probabilities by
Aboriginal ethnicity as well as by IDU grouping using the Log-Rank test.
We then used Cox proportional hazards models to estimate the adjusted
hazard rate ratios of mortality by Aboriginal ethnicity as well as by
the IDU grouping, adjusting for potential confounding variables
identified using the procedure described below. To examine HIV-related
mortality risk, we estimated cumulative incidence curves, as described
by Gooley et al., (13) by Aboriginal ethnicity and by the IDU grouping
(unadjusted analysis) and compared HIV-related mortality hazard rate
ratios using Cox proportional hazards models, adjusting for potential
confounding variables. Therefore, we created two multivariable Cox
proportional hazards models, one assessing all-cause mortality and one
assessing HIV-related mortality.
Potential confounding variables were identified as those associated
with all-cause (or HIV-related) mortality in unadjusted analyses with
p<0.20. Baseline age and baseline CD4 cell count were forced to enter
the models because other studies (7,8) have shown these variables to be
prognostic for mortality. We tested the interaction between Aboriginal
ethnicity and IDU in the final main effects multivariable models to
determine if the impact of Aboriginal ethnicity on mortality differed by
IDU status. The proportionality assumption of Cox proportional hazards
models was assessed using two time-varying covariates (Aboriginal
ethnicity by the log of survival time and IDU by the log of survival
time), which were each tested separately in unadjusted models that
included only the main effect and the time-varying covariate. P-values
were two-sided and those [less than or equal to] 0.05 were considered
statistically significant. Analyses were conducted with SAS[R] (version
9.1; SAS Institute Inc., Cary, NC) and R (version 2.6.2).
RESULTS
After removing duplicates and applying study eligibility criteria
(Figure 1), 548 individuals remained in the study population. We
excluded 36 patients who were missing ethnicity data, of whom 3 died
(8.3%). Compared to study patients, these 36 patients were less likely
to be IDU (28% vs. 47%, p=0.029), were less likely to start HAART in
1999-2001 vs. 2002-2005 (17% vs. 43%, p=0.0021), were followed for a
shorter time (median 1.9 vs. 3.3 years, p=0.0003), and died at an older
age (62.3 (n=3) vs. 40.9 years, p=0.017).
At baseline, the median age was 39.4 (interquartile range
(IQR)=32.9-45.0) years, median CD4 cell count was 210 cells/[micro]L
(IQR=100-320 cells/[micro]L, n=505), and median viral load was 100,000
copies/mL (IQR=18,000-350,000, n=529); 68 (12%) patients had baseline
viral loads <500 copies/mL. The single most common HIV exposure
category was IDU (227, 41%) followed by heterosexual contact (137, 25%),
men who have sex with men (MSM) (124, 23%), MSM/IDU (28, 5.1%), and
other (8, 1.5%); the exposure category was missing or unknown for 24
(4.4%) patients.
Of the 548 study patients, 194 (35%) were Aboriginal. Compared to
non-Aboriginals, Aboriginal patients were significantly more likely to
be female, be infected with HIV through IDU, start HAART at a younger
age, start HAART on a non-protease inhibitor-based regimen, have a lower
baseline CD4 count, and die (Table 1). Almost half of the patients (255,
47%) were IDU. Compared to patients with other exposures, IDUs were
significantly more likely to be Aboriginal, start HAART in 1999-2001,
have a longer duration of follow-up, and die (Table 1).
Overall, 55 patients (10%) died. Most deaths occurred among
Aboriginal patients (31, 56%) and IDUs (40, 73%). The single most common
cause of death was HIV disease (26, 47%), followed by external causes of
morbidity and mortality (16, 29%), which included accidents (8, 50%),
intentional self-harm (4, 25%), and events of undetermined intent (4,
25%). All 8 accidental deaths occurred among IDUs and three of the four
deaths caused by intentional self-harm occurred among non-Aboriginal
patients.
Compared to non-Aboriginals, Aboriginal patients had a higher
probability of all-cause mortality (p=0.0015) (Figure 2a) and a higher
crude all-cause mortality rate (hazard ratio (HR)=2.31, 95%
CI=1.36-3.94, p=0.0021) (Table 2). Controlling for IDU, baseline CD4
cell count, and baseline age, Aboriginal patients had an all-cause
mortality hazard rate 1.85 (95% CI=1.05-3.26, p=0.034) times higher than
non-Aboriginals (Table 2). Similarly, compared to patients with other
exposures, IDUs had a higher probability of all-cause mortality
(p=0.0003) (Figure 2b) and a higher crude all-cause mortality rate
(HR=2.82, 95% CI=1.56-5.11, p=0.0006) (Table 2). Controlling for
Aboriginal ethnicity, baseline CD4 cell count, and baseline age, IDUs
had an all-cause mortality rate 2.45 (95% CI=1.31-4.57, p=0.0050) times
higher than patients with other exposures (Table 2). The interaction
between Aboriginal ethnicity and IDU was not statistically significant
(p=0.55) and was not retained in the final model for all-cause
mortality.
[FIGURE 2 OMITTED]
Compared to non-Aboriginals, Aboriginal patients had a higher
cumulative incidence rate of HIV-related mortality (p=0.0001) (Figure
3a) and a higher crude HIV-related mortality rate (HR=4.76, 95%
CI=2.00-11.33, p=0.0004) (Table 2); among patients who died, Aboriginals
were more likely to die from an HIV-related cause (63% vs. 29%, Table
1). Until approximately 4 years after starting HAART, Aboriginals also
appeared to experience a higher cumulative incidence of non-HIV-related
mortality compared to non-Aboriginals; however, overall, the incidence
of non-HIV-related mortality did not differ by Aboriginal ethnicity
(p=0.75) (Figure 3b). Adjusting for IDU; sex; and baseline CD4 cell
count, viral load, age and calendar year, the HIV-related mortality
hazard rate was 3.47 times higher for Aboriginals compared to
non-Aboriginals (95% CI=1.36-8.83, p=0.0091) (Table 2). Compared to
patients with other exposures, IDUs had higher cumulative incidence
rates of HIV-related (p=0.039) and non-HIV-related (p=0.006) mortality
(Figure 3c, d), and a higher crude HIV-related mortality rate (HR=2.42,
95% CI=1.05-5.57, p=0.038) (Table 2); among patients who died, IDUs were
not more likely to die from an HIV-related cause (46% vs. 53%, Table 1).
Adjusting for Aboriginal ethnicity; sex; and baseline CD4 cell count,
viral load, age and calendar year, the HIV-related mortality hazard rate
was higher among IDUs than patients with other exposures, but this
result was not statistically significant (HR=1.65, 95% CI=0.67-4.04,
p=0.27) (Table 2). The interaction between Aboriginal ethnicity and IDU
was not statistically significant (p=0.14) and was not retained in the
final model for HIV-related mortality.
[FIGURE 3 OMITTED]
DISCUSSION
Aboriginal HIV patients suffer higher rates of all-cause and
HIV-related mortality compared to non-Aboriginal HIV patients after
starting HAART, even after controlling for IDU as an exposure category.
This suggests that Aboriginal HIV patients experience inferior responses
to HAART compared to non-Aboriginals. This finding may be explained by
confounding variables we were unable to control for in this analysis,
such as poor adherence to therapy, which may be caused by ongoing
injection drug and other substance abuse behaviours, as opposed to
injection drug use only as a route of HIV exposure. Intermittent use of
HAART has been associated with increased rates of mortality. (14) In
addition, active drug use has been associated with poor adherence (15)
and intermittent and persistent drug users have been shown to have
higher mortality rates than non-users. (16) Furthermore, alcohol use has
been associated with poor adherence to HAART. (17) Rates of alcohol
dependence/ abuse have been shown to be higher among Aboriginals
compared to non-Aboriginals in Canada, (18) which may also be true for
the Aboriginal patients in our study, and may negatively impact their
adherence to therapy and thus their HAART outcomes. The higher rates of
HIV-related mortality observed among Aboriginal patients may also be
explained by poorer socio-economic conditions and social instability,
including factors such as lower income, unemployment, and unstable
housing, which have been associated with poor adherence to therapy.
(19-21) In general, Aboriginals have higher unemployment rates compared
to the general Canadian population (22) and Aboriginal HIV patients have
been shown to have higher rates of unstable housing23 and lower levels
of income. (5,23) These differences were likely represented in our study
population. More research is needed to understand the reasons for the
higher rates of HIV-related mortality observed among Aboriginal HIV
patients; adherence, active substance use, and socio-economic factors
should be measured in future studies.
IDU appears to be the strongest predictor of higher all-cause
mortality rates after starting HAART. Although HIV was the most common
cause of death among IDUs, after controlling for Aboriginal ethnicity
and other confounders, IDU was not a significant predictor of higher
HIV-related mortality rates. These results are consistent with findings
from the EuroSIDA study, which shows that, compared to patients with
other exposures, IDUs have higher rates of non-HIV-related mortality
after starting HAART, but similar rates of HIV-related mortality. (9)
The EuroSIDA authors, therefore, concluded that IDUs in their study
responded to HAART as well as patients with other exposures.
However, other research suggests that IDUs may receive less benefit
from HAART due to delayed treatment initiation, (24) treatment
interruptions, (25) and continued drug use, (16) which may also be
associated with lower levels of adherence. (15) In addition, hepatitis C
virus (HCV) co-infection, which is far more common among IDUs than those
infected with HIV via other transmission routes, (26) has been shown to
be an independent predictor of mortality among HIV-infected patients.
(27) Our results show that IDUs did not have significantly lower CD4
cell counts or higher viral loads at baseline compared to patients with
other exposures. This suggests that IDUs were provided HAART at similar
clinical periods during their illnesses and did not experience a
relative delay in treatment. However, interruptions in treatment may
have occurred more commonly among IDUs, which could have adversely
impacted their health. In our study, all 8 deaths due to accidents,
primarily accidental poisonings, occurred among IDUs. This is not
surprising, as drug overdoses are a common cause of death among IDUs,
(28) and it demonstrates that at least some individuals infected with
HIV through IDU continue substance abuse behaviours after starting
HAART. Our study did not assess adherence to therapy, continued drug
use, HCV co-infection, or socio-economic status, all of which may have
contributed to higher mortality rates among IDUs after starting HAART.
To our knowledge, this is the first study to investigate the
relationship between Aboriginal ethnicity and mortality after starting
HAART that has included such a large number of Aboriginal HIV patients,
has investigated HIV-related mortality as an outcome specifically, and
has attempted to exclude women who started HAART to prevent vertical
transmission of HIV.
This study has several limitations. First, ethnicity and HIV
exposure categories used in this analysis were self- or
physician-reported and misclassifications may have occurred, for
example, by categorizing individuals with unknown or missing exposure
categories as non-IDUs. However, this information is collected by
clinicians providing ongoing care to these patients, which gives us
confidence in its accuracy.
Second, the number of deaths that occurred in this study was low;
therefore, small changes in numbers may have relatively large impacts on
results. Because only a small number of HIV-related deaths occur after
starting HAART, it would be beneficial to conduct multi-provincial
studies investigating the association between Aboriginal ethnicity and
HIV-related causes of death across Canada.
Finally, a clinical database was used as the primary data source in
this study, which has inherent limitations. Using these data, we could
not be certain that patients were ART-naive when starting HAART. In
particular, for the 68 (12%) patients with baseline viral loads <500
copies/mL, the HAART start date was likely earlier than the date entered
into the database. As well, deaths that occurred outside Alberta and
were not reported to NAHIVP would be missed in our analysis. In
addition, certain variables such as socioeconomic status measures,
adherence to therapy, HCV co-infection, presence of other co-morbid
conditions, and ongoing behaviours such as smoking and substance abuse
were not collected, or were not available in formats appropriate for
this analysis. These variables may have impacted mortality rates. Most
importantly, data assessing patients' adherence to HAART were not
available in our study dataset. However, because it is the most probable
reason for the difference in HIV-related mortality rates we observed
between Aboriginal and non-Aboriginal patients, adherence needs to be
investigated further. Although there is no agreed-upon gold standard for
measuring adherence, (29) other researchers comparing HAART treatment
outcomes between Aboriginal and non-Aboriginal HIV patients have used
prescription-refill data as an indirect measure of adherence; one study
found no significant differences in rates of adherence by Aboriginal
ethnicity (5) but another found a significantly lower rate of adherence
among Aboriginal patients. (23) These equivocal findings may be related
to different methods of measuring adherence (i.e., as a dichotomous vs.
continuous variable) or to measurement error associated with this
indicator of adherence. Pharmacy-refill data are considered to be a
useful measure of adherence in retrospective, population-based studies
when more accurate measures are not feasible. (30) In HIV research, they
have been shown to correlate with virological suppression (31) and
mortality. (14) However, one disadvantage of this method is that
patients who refill their prescriptions may not take their pills as
prescribed. Prospective studies are needed to compare adherence rates
between Aboriginal and non-Aboriginal patients; existing evidence from
pharmacy-refill data should be corroborated with more sensitive methods,
such as electronic monitoring, pill counts, directly observed therapy,
or a composite measure, as explored by Liu et al. (32) and recommended
by others. (33)
In summary, Aboriginal ethnicity is associated with higher rates of
all-cause mortality after starting HAART; this seems to be largely
explained by a significantly higher rate of death from HIV-related
causes among Aboriginals. IDU appears to be the strongest and most
significant predictor of higher all-cause mortality rates. Future
research should examine reasons for the high mortality rates we observed
among Aboriginals from HIV-related causes of death. Specifically, we
recommend three areas of research. First, the relationship between
Aboriginal ethnicity, IDU, and clinical outcomes of HAART, including
virological treatment success and failure, should be examined to
determine if the relationship we observed for mortality extends to these
clinical outcomes. Second, adherence to HAART should be prospectively
measured using sensitive methods to determine if Aboriginal ethnicity is
associated with poorer adherence to treatment. Finally, qualitative
studies should explore how Aboriginal HIV patients experience HAART
treatment to understand if they encounter challenges that have not yet
been well documented.
Acknowledgements: We thank the staff of the Northern Alberta
Program and J. Salmon for their assistance with the study data and
patients' charts; B.E. Lee from the Provincial Public Health
Laboratory for providing viral load data; and Q. Liu for helping us to
construct and test cumulative incidence curves. This study was funded by
the Alberta Heritage Foundation for Medical Research (AHFMR) Health
Research Fund. Dr. Martin was supported by an AHFMR full-time
studentship and a Canadian Institutes of Health Research Doctoral
Research Award.
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Received: January 9, 2010
Revisions requested: July 6, 2010
Revised ms: October 12, 2010
Accepted: October 24, 2010
Author Affiliations
Leah J. Martin, PhD, [1] Stan Houston, MD, FRCPC, [1,2] Yutaka
Yasui, PhD, [1] T. Cameron Wild, PhD, [3] L. Duncan Saunders, MBBCh, PhD
[1]
[1] Department of Public Health Sciences, School of Public Health,
University of Alberta, Edmonton, AB
[2] Division of Infectious Diseases, Department of Medicine,
University of Alberta, Edmonton, AB
[3] Centre for Health Promotion Studies, School of Public Health,
University of Alberta, Edmonton, AB
Correspondence: Dr. Leah J. Martin, E-mail: leah.martin@ualberta.ca
Previous Presentations: A previous version of this analysis was
presented in part at the 16th Annual Canadian Conference on HIV/AIDS
Research, Toronto, Ontario, Canada April 26-29, 2007 and this work was
presented at the XVII International AIDS Conference, Mexico City,
Mexico, August 3-8, 2008. This work was also included as a chapter in LJ
Martin's PhD thesis (2009).
Conflict of Interest: None to declare.
Table 1. Patient Characteristics by Ethnicity and Injection Drug Use
Exposure Category (N=548)
Characteristic Aboriginal Non-Aboriginal
(n=194, 35%) (n=354, 65%)
Years of follow-up 3.4 (2.2-5.1), 682.0 3.3 (1.6-5.1), 1213.0
time, median (IQR),
total Sex, no. (%)
Female 71 (37) 51 (14)
Male 123 (63) 303 (86)
HIV exposure category,
no. (%)
Injection drug use 131 (68) 124 (35)
Other exposures 63 (32) 230 (65)
Ethnicity
Aboriginal -- --
Non-Aboriginal -- --
CD4 cells/[micro]L at 195 (85-295), 220 (110-340),
baseline, median (IQR) (n=180) (n=325)
CD4 cells/[micro]L at
baseline, no. (%)
[less than or equal
to] 50 30 (15) 50 (14)
>50-200 63 (32) 101 (29)
>200-350 61 (31) 99 (28)
>350 26 (13.4) 75 (21)
Missing 14 (7.2) 29 (8.2)
HIV RNA copies/mL at 100,000 100,000
baseline, median (IQR) (22,000-390,000) (16,000-335,000)
(n=187) (n=342)
HIV RNA copies/mL at
baseline, no. (%)
<10,000 32 (16) 77 (22)
10,000-<100,000 59 (30) 90 (25)
[greater than or 96 (49) 175 (49)
equal to] 100,000
Missing 7 (3.6) 12 (3.4)
Initial HAART regimen,
no. (%)
Protease inhibitor
(PI)-based 40 (21) 108 (31)
Not PI-based 154 (79) 246 (69)
Year starting HAART,
no. (%)
1999-2001 87 (45) 147 (42)
2002-2005 107 (55) 207 (58)
Age at baseline, median
(IQR) 37.4 (31.7-42.7) 40.1 (33.6-45.7)
Age at baseline, no.
(%)
15-29 32 (16) 59 (17)
30-39 84 (43) 114 (32)
40-49 64 (33) 133 (38)
[greater than or 14 (7.2) 48 (14)
equal to] 50
Mortalities, no. (%)
Died 31 (16) 24 (6.8)
Alive 163 (84) 330 (93)
Cause of death, no. (%)
(n=54) ([dagger])
HIV-related causes 19 (63) 7 (29)
Non-HIV-related
causes 11 (37) 17 (71)
Age at death, median
(IQR) (n=55) 40.6 (33.7-46.1) 40.9 (37.7-50.4)
p-value Injection Drug Use
(n=255, 47%)
Years of follow-up 0.55 3.6 (2.1-5.3), 929.9
time, median (IQR), <0.0001
total Sex, no. (%)
Female 65 (25)
Male 190 (75)
HIV exposure category, <0.0001
no. (%)
Injection drug use -- *
Other exposures --
Ethnicity --
Aboriginal 131 (51)
Non-Aboriginal 124 (49)
CD4 cells/[micro]L at 0.037 220 (100-320),
baseline, median (IQR) (n=230)
CD4 cells/[micro]L at
baseline, no. (%) 0.23
[less than or equal
to] 50 38 (15)
>50-200 71 (28)
>200-350 80 (31)
>350 41 (16)
Missing 25 (9.8)
HIV RNA copies/mL at 0.46 99,000
baseline, median (IQR) (25,000-350,000)
(n=242)
HIV RNA copies/mL at 0.41
baseline, no. (%)
<10,000 39 (15)
10,000-<100,000 83 (33)
[greater than or 120 (47)
equal to] 100,000
Missing 13 (5.1)
Initial HAART regimen, 0.013
no. (%)
Protease inhibitor
(PI)-based 74 (29)
Not PI-based 181 (71)
Year starting HAART,
no. (%) 0.45
1999-2001 127 (50)
2002-2005 128 (50)
Age at baseline, median
(IQR) 0.0020 39.3 (33.0-45.0)
Age at baseline, no.
(%) 0.024
15-29 37 (15)
30-39 98 (38)
40-49 100 (39)
[greater than or 20 (7.8)
equal to] 50
Mortalities, no. (%) 0.0006
Died 40 (16)
Alive 215 (84)
Cause of death, no. (%)
(n=54) ([dagger]) 0.013
HIV-related causes 18 (46)
Non-HIV-related
causes 21 (54)
Age at death, median
(IQR) (n=55) 0.43 40.4 (35.0-45.2)
Other Exposures p-value
(n=293, 53%)
Years of follow-up 3.2 (1.6-4.7), 965.1 0.034
time, median (IQR), 0.090
total Sex, no. (%)
Female 57 (19)
Male 236 (81)
HIV exposure category, --
no. (%)
Injection drug use --
Other exposures --
Ethnicity <0.0001
Aboriginal 63 (22)
Non-Aboriginal 230 (79)
CD4 cells/[micro]L at 210 (110-330), 0.91
baseline, median (IQR) (n=275)
CD4 cells/[micro]L at
baseline, no. (%) 0.26
[less than or equal
to] 50 42 (14)
>50-200 93 (32)
>200-350 80 (27)
>350 60 (20)
Missing 18 (6.1)
HIV RNA copies/mL at 100,000 0.58
baseline, median (IQR) (11,000-360,000)
(n=287)
HIV RNA copies/mL at 0.0025
baseline, no. (%)
<10,000 70 (24)
10,000-<100,000 66 (23)
[greater than or 151 (52)
equal to] 100,000
Missing 6 (2.1)
Initial HAART regimen, 0.32
no. (%)
Protease inhibitor
(PI)-based 74 (25)
Not PI-based 219 (75)
Year starting HAART,
no. (%) 0.0017
1999-2001 107 (37)
2002-2005 186 (63)
Age at baseline, median
(IQR) 39.5 (32.8-45.0) 0.83
Age at baseline, no.
(%) 0.038
15-29 54 (18)
30-39 100 (34)
40-49 97 (33)
[greater than or 42 (14)
equal to] 50
Mortalities, no. (%) <0.0001
Died 15 (5.1)
Alive 278 (95)
Cause of death, no. (%)
(n=54) ([dagger]) 0.64
HIV-related causes 8 (53)
Non-HIV-related
causes 7 (47)
Age at death, median
(IQR) (n=55) 42.4 (33.7-53.8) 0.22
* Not applicable
([dagger]) Note: One death of unknown cause was excluded from this
calculation
Table 2. Univariable and Multivariable Cox Proportional Hazards Models
Assessing All-cause and HIV-related Mortalities After Starting HAART
Variable All-cause Mortality
(N=548)
Unadjusted 95% CI
Hazard
Ratio
Ethnicity (Aboriginal vs. non-Aboriginal) 2.31 1.36-3.94
Sex (Female vs. male) 1.39 0.78-2.48
HIV exposure category (Injection drug use vs.
other exposures) 2.82 1.56-5.11
CD4 cells/[micro]L at baseline
[less than or equal to] 50 (ref) 1.00 --
>50-200 0.58 0.28-1.20
>200-350 0.42 0.19-0.92
>350 0.39 0.16-0.91
Missing baseline CD4 count 0.55 0.19-1.54
HIV RNA copies/mL at baseline
<10,000 0.55 0.24-1.27
10,000-99,999 0.98 0.53-1.79
[greater than or equal to] 100,000 (ref) 1.00 --
Missing baseline viral load measure 1.23 0.37-4.06
Age at baseline
15-29 (ref) 1.00 --
30-39 1.49 0.66-3.36
40-49 1.37 0.60-3.13
[greater than or equal to] 50 1.71 0.59-4.97
Initial HAART regimen (protease inhibitor
(PI) vs. non-PI based) 0.98 0.55-1.76
Baseline calendar year (1999-2001 vs.
2002-2005) 0.79 0.44-1.43
Adjusted 95% CI
Hazard
Ratio
Ethnicity (Aboriginal vs. non-Aboriginal) 1.85 1.05-3.26
Sex (Female vs. male) -- * --
HIV exposure category (Injection drug use vs.
other exposures) 2.45 1.31-4.57
CD4 cells/[micro]L at baseline
[less than or equal to] 50 (ref) 1.00 --
>50-200 0.60 0.29-1.26
>200-350 0.40 0.18-0.87
>350 0.44 0.19-1.05
Missing baseline CD4 count 0.53 0.19-1.51
HIV RNA copies/mL at baseline
<10,000 -- --
10,000-99,999 -- --
[greater than or equal to] 100,000 (ref) -- --
Missing baseline viral load measure -- --
Age at baseline
15-29 (ref) 1.00 --
30-39 1.26 0.55-2.87
40-49 1.24 0.53-2.88
[greater than or equal to] 50 2.02 0.68-6.01
Initial HAART regimen (protease inhibitor
(PI) vs. non-PI based) -- --
Baseline calendar year (1999-2001 vs.
2002-2005) -- --
HIV-related Mortality
(N=547)
Unadjusted 95% CI
Hazard
Ratio
Ethnicity (Aboriginal vs. non-Aboriginal) 4.76 2.00-11.33
Sex (Female vs. male) 1.79 0.80-4.02
HIV exposure category (Injection drug use vs.
other exposures) 2.42 1.05-5.57
CD4 cells/[micro]L at baseline
[less than or equal to] 50 (ref) 1.00 --
>50-200 0.53 0.22-1.31
>200-350 0.15 0.04-0.57
>350 0.07 0.01-0.54
Missing baseline CD4 count 0.49 0.13-1.81
HIV RNA copies/mL at baseline
<10,000 0.30 0.07-1.30
10,000-99,999 0.67 0.26-1.73
[greater than or equal to] 100,000 (ref) 1.00 --
Missing baseline viral load measure 2.42 0.70-8.38
Age at baseline
15-29 (ref) 1.00 --
30-39 3.59 0.82-15.79
40-49 2.14 0.45-10.07
[greater than or equal to] 50 2.00 0.28-14.24
Initial HAART regimen (protease inhibitor
(PI) vs. non-PI based) 0.74 0.30-1.85
Baseline calendar year (1999-2001 vs.
2002-2005) 0.26 0.10-0.66
Adjusted 95% CI
Hazard
Ratio
Ethnicity (Aboriginal vs. non-Aboriginal) 3.47 1.36-8.83
Sex (Female vs. male) 1.18 0.50-2.77
HIV exposure category (Injection drug use vs.
other exposures) 1.65 0.67-4.04
CD4 cells/[micro]L at baseline
[less than or equal to] 50 (ref) 1.00 --
>50-200 0.56 0.22-1.42
>200-350 0.17 0.041-0.68
>350 0.14 0.016-1.21
Missing baseline CD4 count 0.24 0.034-1.62
HIV RNA copies/mL at baseline
<10,000 0.68 0.14-3.19
10,000-99,999 1.19 0.43-3.31
[greater than or equal to] 100,000 (ref) 1.00 --
Missing baseline viral load measure 6.47 0.99-42.27
Age at baseline
15-29 (ref) 1.00 --
30-39 1.77 0.37-8.42
40-49 1.14 0.22-5.91
[greater than or equal to] 50 1.17 0.15-9.41
Initial HAART regimen (protease inhibitor
(PI) vs. non-PI based) -- --
Baseline calendar year (1999-2001 vs.
2002-2005) 0.29 0.11-0.79
* Note: Other than baseline age and baseline CD4 count, variables with
p-values [greater than or equal to] 0.20 were not included in the
multivariable model.
