Advances in Infectious Diseases, 2013, 3, 281-289
Published Online December 2013 (http://www.scirp.org/journal/aid)
http://dx.doi.org/10.4236/aid.2013.34043
Open Access AID
281
Mortality of HIV-I nfec ted Patients on Antiretroviral
Therapy in a Large Public Cohort in West Africa,
Burkina Faso: Frequency and Associated Factors
Armel Poda1,2*#, Arsène Hema2#, Jacques Zoungrana2, Nongodo Firmin Kaboré2,
Bebar Euloges Kamboulé2, Ibrahim Soré2, Guillaume Bado2, Abdoul-Salam Ouédraogo1,3,
Nicolas Meda4,5, Adrien Bruno Sawadogo2,3
1School of Medicine, University of Bobo Dioulasso, Bobo Dioulasso, Burkina Faso; 2Day Care Hospital for HIV-Patients of Bobo
Dioulasso, Department of Infectious Diseases, Souro Sanou Teaching Hospital, Bobo Dioulasso, Burkina Faso; 3Department of
Virology and Bacteriology, Souro Sanou Teaching Hospital, Bobo Dioulasso, Burkina Faso; 4School of Medicine, University of
Ouagadougou, Ouagadougou, Burkina Faso; 5Muraz Center, Bobo Dioulasso, Burkina Faso.
Received September 8th, 2013; revised October 8th, 2013; accepted October 15th, 2013
Copyright © 2013 Armel Poda et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background: In sub Saharan Africa, small size surveys have demonstrated early high mortality among infected patients
on antiretroviral therapies (ART). Few studies have been conducted in large cohorts of HIV-patients in public health care
system in West Africa. Objectives: Our study aims to determine mortality rate and its predictors in a cohort of patients
on ART in a public daycare hospital in Burkina Faso. Methods: We have carried out a retrospective cohort study. All
HIV-infected patients on ART between January 1st 2008 and December 31st 2011 were included in the study. Survival
probability was estimated by the Kaplan-Meier method. Cox regression analysis was used to identify associated factors
to mortality. Results: A total of 2243 HIV-infected patients were included in the study. During the follow-up, 218 pa-
tients representing 9.7% were lost. About 104 patients representing 4.6% were transferred and 1691 representing 75.4%
were still in the therapeutic cohort. There were 230 death cases for a total of 4282 persons-years, (5.4 deaths for 100
persons-years; 95% CI: 4.8 - 6.3). The survival probabilities after 6 months, 1 year and 2 years were 92.6%, 91% and
88.9% respectively. For the multivariate analysis, the following factors were independently associated to death: male
gender, BMI < 18.5 kg/m2, WHO stage 3 and 4, HIV-2, T-CD4 lymphocytes < 200/µl, haemoglobin rate < 8 g/dl and
creatinine clearance < 60 ml/m2. Conclusions: Our study provides for the first time mortality rates and its predictors
among HIV-patients on antiretroviral treatment in a large cohort in public health sector in Burkina Faso. It highlights
the importance of early HIV screening to limit ART initiation at advanced HIV infection stages.
Keywords: Antiretroviral Therapy; Burkina Faso; HIV; Mortality; West Africa
1. Introduction
Nowadays, antiretroviral treatments (ART) do not only
aim to reduce morbidity and mortality caused by HIV in-
fection and improving infected patients’ life. They also
aim to prevent HIV infection [1], therefore, they have the
interest of reaching universal access to ART goals (ART co-
verage superior or equal to 80% to those in need among in-
fected patients). Few African countries were able to make
it [2]. However, in sub Saharan Africa, the number of
patients on ART is increasing [2]. Landlocked West Afri-
can country, Burkina Faso is also part of this trend with
36,248 patients on ART in December 2011 [2]. Obviously,
ART have drastically reduced HIV-related morbidity and
mortality [2-6]. However, one can note residual mortality
among HIV-patients both in Southern and Northern coun-
tries [7]. The Souro Sanou Teaching Hospital is a public
reference health centre in Burkina Faso and in West Af-
rica for the ambulatory care to HIV-infected patients [8].
Few studies have been carried out among large cohorts in
West Africa on mortality during ART in public health
care system. In such conditions where patients on ART
*Corresponding author.
#These authors have contributed equally to the work.

Mortality of HIV-Infected Patients on Antiretroviral Therapy in a Large Public Cohort in
West Africa, Burkina Faso: Frequency and Associated Factors
282
are increasing, we found it necessary to make investiga-
tions among the Bobo-Dioulasso cohort which includes
3089 patients on ART at the day of December 31st 2011.
The objective of this study was therefore to determine
mortality rates and related factors among a cohort of
ART patients in Burkina Faso, West Africa.
2. Methods
2.1. Study Area
The study was conducted at the Teaching Hospital in
Bobo-Dioulasso and specifically at the Day Care Hospi-
tal for HIV-patients. Bobo-Dioulasso is the second major
city after Ouagadougou the capital city, in Burkina Faso
2.2. Study Design
We conducted a retrospective cohort study. We included
all HIV patients on ART between January 1st 2008 and
December 31st 2011. These patients were followed up
from the initiation of the ART to June 30th 2012 (cut off
point).
2.3. Data Collection
Data have been collected during medical examinations
with ESOPE software (Epi concept). ESOPE is software
for monitoring patients with HIV infection in limited re-
sources countries. Data collected at the first visit includ-
ed: socio-demographic data, medical history, WHO clas-
sification, biological and clinical examinations, data such
as weight, height, etc. Samplings for biological examina-
tions were carried out on patients with empty stomach.
Examinations carried out at the first visit included hae-
mogram, TCD4 lymphocytes counting, and creatinine
checking. Data collected on ESOPE software were trans-
ferred to STATA-12 Corporation, Texas for analysis.
2.4. Statistical Analyses
Patients’ socio-demographic, clinical and biological char-
acteristics were described in number and percentage for
qualitative variables. Quantitative variables were de-
scribed through their medians and inter-quartile intervals
(IQR). The Pearson chi2 test was used to compare pro-
portions. The Student t test was used to test equality be-
tween the two averages (signification threshold 5%). To
calculate the mortality rate we used at the numerator the
total number of deaths that occurred during the follow up
and at the denominator how long patients were followed
up in the cohort from the first day of the treatment.
Survival probability was evaluated by the Kaplan-Me-
ier method. The association between socio-demographic,
clinical and immunologic factors of mortality was assess-
ed with the Iogrank test (signification threshold = 5%).
The effect of predictors significantly associated to the
prognosis was then studied through a multivariate analy-
sis with Cox proportional risks model.
2.5. Ethical Issues
This study was done in the process of routine clinical
care. Collected information was kept confidential and
names of patients were not included in the data collection
process.
3. Results
3.1. Characteristics of the Study Population
A total of 2243 HIV infected patients were on ART be-
tween January 2008 and December 2011. These included
636 males (28.4%) and 1607 females (71.6%) aged be-
tween 16 to 78 years with an average age of 37 (IQR 32 -
45) (Table 1). Married patients represented 54.3%, un-
educated ones were 46.4% and 58.1% were unem-
ployed.
HIV-1 was the most common infection (91.2%) and
was discovered in 59.1% of cases during an opportunistic
infection. At their first medical examination 54.6% of
patients were at 3 and 4 clinical stages, according to the
WHO classification. The average Body Mass Index (BMI)
was 20.5 kg/m2 (IQR 18 - 23) and 29.3% had a BMI <
18.5.
The pre-therapeutic biological assessment showed
7.1% of severe anaemia (hb < 8 g/dl); 10% of kidney
insufficiency (creatinine clearance < 60 ml/m2). The me-
dian number of T-CD4 lymphocytes at the initiation of
the ART was 186 cells/µl (IQR 95 - 268) and 6.4% of the
patients had more than 350 cells/µl.
The median time limit between the first medical visit
and the initiation of the ART was estimated to 44.0 days
(IQR 21 - 206) and the median duration of the treatment
was 20.0 months (IQR 9 - 35). The current medication
consisted in the association of two nucleoside reverse
transcriptase inhibitors (NRTIs) with a non-nucleoside
reverse transcriptase inhibitor (NNRTI). The most com-
mon Anti Retroviral regimens prescribed included AZT +
3TC + EFV (40.7%), AZT + 3TC + NVP (31.4%).
3.2. Cohort Follow-Up and Survival Progression
During the follow-up, we lost 218 patients (9.7%).
Among males we lost of follow-up 4.3% of cases and
among females we noted 4.8% of lost of follow-up.
Around 104 (4.6%) were transferred to different health
centres. Among males, 8.9% were transferred and among
females 10% were transferred (p = 0.44). 230 deaths rep-
resenting 10.3% were registered. Among males we Regis-
tered 15.4% of deaths and among females, 8.2% of
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Mortality of HIV-Infected Patients on Antiretroviral Therapy in a Large Public Cohort in
West Africa, Burkina Faso: Frequency and Associated Factors
283
Table 1. Basic characteristics of HIV infected patients in the
cohort taking ART at the Bobo-Dioulasso day hospital be-
tween 2008 and 2011.
Characteristics Male
(n = 636) Female (n = 1607) Total (n = 2243)
Age (years)
≤25 11 (1.7) 128 (8.0) 139 (6.2)
26 - 35 112 (17.6) 660 (41.0) 772 (34.4)
36 - 45 282 (44.4) 546 (34.0) 828 (36.9)
46 - 55 164 (25.8) 230 (14.3) 394 (17.6)
>55 67 (10.5) 43 (2.7) 110 (4.9)
Missing data 0 (0.0) 0 (0.0) 0(0.0)
Marital Status
Single 111 (17.5) 321 (20.0) 432 (19.3)
Married 456 (71.7) 762 (47.4) 1218 (54.3)
Widow 52 (8.2) 397 (24.7) 449 (20.0)
Divorced 16 (2.5) 127 (7.9) 143 (6.4)
Missing data 1 (0.1) 0 (0.0) 1 (0.0)
Education level
None 260 (40.9) 780 (48.5) 1040 (46.4)
Primary school 158 (24.8) 454 (28.3) 612 (27.3)
Secondary and higher school 216 (34.0) 372 (23.2) 588 (26.2)
Missing data 2 (0.3) 1(0.0) 3 (0.1)
Occupation
Unemployed 50 (7.9) 1248 (77.7) 1298 (57.9)
Farmer 117 (18.4) 14 (0.9) 131 (5.8)
Trader 95 (14.9) 118 (7.3) 213 (9.5)
Civil servant 263 (41.4) 117 (7.3) 380 (16.9)
Other 111 (17.4) 110 (6.9) 221 (9.9)
Missing data 0 (0.0) 0 (0.0) 0 (0.0)
AIDS screening circumstances
Voluntary screening 219 (34.4) 587 (36.5) 806 (35.9)
Clinical suspicion 414 (65.1) 912 (56.7) 1326 (59.1)
PTME 0 (0.0) 102 (6.4) 102 (4.6)
Missing data 3 (0.5) 6 (0.4) 9 (0.4)
BMI at the first visit (kg/m2)
BMI ≥ 18.5 417 (65.6) 1169 (72.7) 1586 (70.7)
BMI < 18.5 219 (34.4) 438 (27.3) 657 (29.3)
Missing data 0 (0.0) 0 (0.0) 0 (0.0)
WHO classification
Stage 1 112 (17.6) 393 (24.5)505 (22.5)
Stage 2 135 (21.2) 405 (25.2)540 (24.1)
Stage 3 294 (46.2) 648 (40.3)942 (44.0)
Stage 4 90 (14.2) 147 (9.1) 237 (10.6)
Missing data 5 (0.8) 14 (0.9) 19 (0.8)
Type of HIV
HIV1 562 (88.4) 1484 (92.4)2046 (91.2)
HIV2 23 (3.6) 33 (2.0) 56 (2.5)
HIV1 + 2 51 (8.0) 90 (5.6) 141 (6.3)
Missing data 0 (0.0) 0 (0.0) 0 (0.0)
Haemoglobin rate (g/dl)
Haemoglobin ≥ 8 548 (86.2) 1370 (85.2)1918 (85.5)
Haemoglobin < 8 42 (6.6) 117 (7.3) 159 (7.1)
Missing data 46 (7.2) 120 (7.5) 116 (7.4)
Creatinine clearance (ml/m2)
<60 66 (10.4) 153 (9.5) 219 (9.8)
60 - 89 258 (40.6) 586 (36.5)844 (37.6)
≥90 258 (40.6) 721 (44.9)979 (43.6)
Missing data 54 (8.5) 147 (9.1) 201 (9.0)
Initial CD4 (number/µl)
<200/µl 393 (61.8) 793 (49.3)1186 (52.9)
200 - 350/µl 211 (33.2) 654 (40.7)865 (38.5)
>350/µl 18 (2.8) 125 (7.8) 143 (6.4)
Missing data 14 (2.2) 35 (2.2) 49 (2.2)
Therapeutics .
Time limit between the first
examination and the initiation
of the ART (day), median (IQR)
35 (18; 174) 47 (21; 220)44 (21; 206)
2NRTI + 1NNRTI 541 (85.1) 1340 (83.4)1881(83.8)
2NRTI + 1PI 93 (14.6) 263 (16.4)356 (15.9)
3NRTI 2 (0.3) 4 (0.2) 6 (0.3)
Categorical variables are expressed as number (% total); continous variables
are expressed as median (interquartile range).
deaths (p < 10−3) and 1691 cases were still in the active
cohort, representing 75.4%. There were 230 deaths for a
total of 4282 persons-years (5.4 deaths for 100 persons-
years 95% CI: 4.8 - 6.3). Most deaths, 156 out of 230,
representing 68.1% occurred during the first six months
following the ART initiation. Survival probability after 6
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months, 1 year and 2 years was 92.6%, 91% and 88.9%
respectively.
3.3. Mortality Predictors
During the univariate analysis, socio-demographic fac-
tors associated to death included age and male gender.
Death risks were two times higher in men (p < 10−3) than
women (Figure 1) and 3.8 times higher among patients
more than 55 years old (p = 0.002).
AIDS clinical suspicion at screening (p < 10−3), severe
malnutrition with a BMI < 18.5 kg/m2 (p < 10−3), WHO 3
and 4 stages (p < 10−3) at the initiation of the antiretrovi-
ral treatment were the clinical factors associated to death.
Biological characteristics such as HIV-2 infection,
poor TCD4 lymphocytes (<200/µl), severe anaemia (hb <
8 g/dl), creatinine clearance < 60 ml/m2 were signifi-
cantly associated with death (Table 2).
The median time limit between the first medical visit
and the starting of the ART among dead patients was
comparable to that of living patients, that is, 18 versus 17
days p = 0.6.
At the multivariate analysis the following characteris-
tics at the initiation of the ART were independently asso-
ciated with death: male gender, BMI < 18.5 kg/m2, WHO
stage 3 and 4, HIV-2, T-CD4 lymphocytes < 200/µl,
haemoglobin rate < 8 g/dl and Creatinine clearance < 60
ml/m2 (Table 2).
4. Discussion
Our study provides for the first time both mortality rates
and death risk factors among patients on ART in a cohort
involving many participants in a governmental health
centre in Burkina Faso and in West Africa. Longitudinal
studies in West Africa were carried out either in govern-
mental health centres or among few participants. In our
retrospective cohort, we found a mortality rate of 5.4
deaths for 100 persons-years. Most death cases repre-
senting 68.1% occurred during the first six months fol-
lowing ART and there were 218 lost of follow-up repre-
senting 9.7%. It is highly recommended that patients
adhere to their treatment and follow-up visits to achieve
treatment efficacy. Several studies have demonstrated
that mortality in southern countries during the first six
months of ART initiation is higher than in northern coun-
tries with higher number of the patients lost of follow-up
[6,7,9].
The mortality rate, 5.4 deaths for 100 persons-years
that we found out was low compared to common rates in
resources-limited countries [10]. In a meta-analysis con-
cerning resources-limited countries like Asia, Africa,
Central and South America, mortality rates varied be-
tween 2.6% and 29.7%. The lowest rate was recorded in
0.00 0.05 0.10 0.15 0.20 0.25
Cumulative risk of death
020 40 60
Dur a tio n in M onths since AR T in itiati o n
Male Female
Figure 1. Risks and death curve according to gender among
the HIV infected patients cohort on antiretroviral treatment
at the Bobo-Dioulasso day hospital between 2008 and 2012.
a multi-regional South American cohort and the highest
in sub Saharan Africa [10]. In Dakar, Senegal, on 404
adult patients from the antiretroviral treatment access ini-
tiative, the mortality rate was 12.5 deaths for 100 per-
sons-years in the first year and decreased to 6.6 for 100
persons-years in the second year [11]. In Ivory Coast, on
10,211 adult patients taking part in the Aconda Programme,
a non-governmental programme for the access to ART,
the mortality rate for a period of 18 months was 11.2%,
the proportion of lost to follow-up was 13.6% and 85%
for the survival probability with no consideration of the
rate of CD4 lymphocytes [12]. In Yaounde, Cameroon,
on 315 patients, a 9% mortality rate and 21.2 for 100 per-
sons-years mortality were noted [13]. In Ethiopia, among
a cohort of 1540 patients, the mortality rate varied from
15.4 for 100 persons-years in the South [14], to 2.03
(95% CI 1.64 - 2.51) for 100 persons-years in the East
[15]. However, lower mortality rates among patients on
ART are often recorded in northern countries [7].
Mortality among patients on ART in countries with
poor resources is often due to opportunistic infections
and immune reconstitution inflammatory syndrome [10,
16,17].
In our study, patients started ART mostly at an ad-
vanced immune-depression stage due to late screening.
For most patients, HIV screening was initiated on the
basis of a clinical suspicion. Therefore, it was not a real
screening. Patients who have discovered their HIV infec-
tion following a clinical suspicion have almost more than
two times risks to die than those who have been screened
when their infection was asymptomatic. This advanced
immune-depression with WHO 3 and 4 stages, weak T-
CD4 lymphocytes rates, low haemoglobin rate and a
BMI less than 18.5 kg/m2 at the initiation of ART were
often reported in African cohort [6,7,11,12,14,18,19] and
n other southern countries [10,20-23]. Late screening i
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Table 2. Factors associated with death among an HIV infected patients cohort on ART at the Bobo-Dioulasso day hospital
between 2008 and 2012.
Independent predictors RR [CI 95%] P Adjusted RR [CI 95%] P
Gender
Female 1 - 1 -
Male 1.98 [1.52 - 2.56] <10-3 1.75 [1.30 - 2.36] 10−3
Age (years)
≤25 1 - 1 -
26 - 35 1.83 [0.84 - 3.98] 0.13 1.54 [0.70 - 3.39] 0.28
36 - 45 1.53 [0.70 - 3.34] 0.28 1.07 [0.48 - 2.37] 0.87
46 - 55 2.72 [1.24 - 5.96] 0.01 1.78 [0.79 - 4.02] 0.16
>55 3.80 [1.62 - 8.89] 2.10-3 1.60 [0.64 - 3.96] 0.31
Marital status
Unmarried 1 -
Married 0.86 [0.66 - 1.12] 0.26
Level of education
None 1 -
Primary school 0.78 [0.56 - 1.07] 0.13
Secondary and above 0.91 [0.67 - 1.25] 0.56
Occupation
Unemployed 1 -
Working 1.15 [0.89 - 1.49] 0.29
BMI (kg/m²)
≥18.5 1 - 1 -
<18.5 3.96 [3.05 - 5.16] <10-3 2.04 [1.48 - 2.82] <10−3
WHO classification
Stage 1 & 2 1 - 1 -
Stage 3 & 4 2.65 [1.97 - 3.56] <10-3 1.56 [1.13 - 2.19] 8.10−3
Type of HIV
HIV1 & HIV 1 + 2 1 - 1 -
HIV2 2.30 [1.27 - 4.07] 6.10-3 2.39 [1.28 - 4.49] 6.10−3
Haemoglobin rate (g/dl)
≥8 1 - 1 -
<8 4.21 [3.02 - 5.87] <10-3 2.26 [1.57 - 3.25] <10−3
Creatinine clearance (ml/m2)
≥90 1 1 -
60 - 89 1.50 [1.09 - 2.07] 0.01 0.97 [0.68 - 1.39] 0.88
<60 5.30 [3.74 - 7.46] <10−3 2.40 [1.59 - 3.63] <10−3
Initial CD4 (nb/µl)
≥200 1 - 1 -
<200 3.11 [2.27 - 4.25] 10−3 2.30 [1.62 - 3.23] <10−3

Mortality of HIV-Infected Patients on Antiretroviral Therapy in a Large Public Cohort in
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and advanced immune-depression on ART initiation are
the major causes for early mortality of patients taking
ART among cohorts in countries with poor resources.
Throughout the survey we found out that men were
nearly two times more exposed to death risks than wo-
men. A strong relationship between male gender and
mortality when taking ART was reported in other African
cohorts [11,24,25]. In our centre, there was no significant
difference between men and women lost to follow up. In
Kenya, a survey demonstrated that the rate of men in
follow up programmes is lower than that of women [26].
Besides, men have a bad observance of the ART [27].
However, a survey in China showed that death risk on
ART is higher when the patient does not regularly have
medical visits and that women do not regularly attend
checkups as men [28].
Through our results, death risk was higher among
HIV-2 infected patients compared to HIV-1 and HIV-1 +
2 infected patients in a multivariate analysis. A study
conducted in Ouagadougou, Burkina Faso shows that si-
milar results are reported in non-governmental centres
treating HIV infected patients [29]. In this study among
patients with advanced immune-depression, there is a hi-
gher mortality rate and a lower immune restoration among
HIV-2 patients compared to HIV-1 patients.
In one hand, results on immunity restoration were dis-
covered in Gambia [30] and Ivory Coast [12]. On the
other hand, in the Gambian survey mortality was higher
among HIV-1 patients compared to HIV-2 and HIV-1 + 2
patients [30]. In the study carried out in Ivory Coast,
there is no statistical difference in the mortality rate re-
garding the type of HIV [12]. In a prospective cohort
survey conducted in Guinea Bissau between 1990 and
2007, 223 HIV-1 infected patients participated in the
study. Those with a HIV-2 infection in addition to HIV-1
presented a slow progression towards AIDS and had a
higher TCD4 lymphocytes rate [31].
We also noticed that 9.8% of patients in our cohort had
a creatinine clearance < 60 ml/m2 at the ART initiation.
In Zambia, a survey came out to the same proportions.
Similarly, the authors of the study found a very close
relation between the high rate of creatinine at ART initia-
tion and death occurrence [32]. However, it is demon-
strated that in countries with poor resources, where there
are not always etiologic investigations in case of high
creatinine, the initiation of ART improved patients’ kid-
ney function [33]. Factors associated to kidney impair-
ment among HIV infected patients initiating ART com-
bine diabetes, high blood pressure, heart diseases, tradi-
tional treatment and HIV-related factors such as low
TCD4 lymphocytes, high viral load, WHO stage III and
IV, and low BMI [34,35]. Nowadays according to WHO
recommendations [36] tenofovir is widely used in Africa,
so there are many problems with patients suffering from
a kidney insufficiency when starting an ART. Though it
is very efficient and well tolerated [36-38], tenofovir
worsens existing kidney lesions among African cohorts
[39-41].
Finally, in our study, age and level of education were
not considered as risk factors. In Ethiopia, patients with a
primary school education level have higher death risks
than uneducated ones [14].
Our study has weaknesses: the Bobo-Dioulasso day
hospital is a national reference teaching hospital with an
experienced team. It provides free services including bio-
logical assessment and most opportunistic infection treat-
ments. Our results are not representing the situation in
the overall country, especially the HIV care in remote
health districts where there are few practitioners and peo-
ple have limited resources. However, a survey done by
DWB-Holland tries to show that mortality in both verti-
cal and integrated programmes is similar [42]. Because
of the retrospective aspect of our study, data collection
and the quality of some information have limitations.
Some data are also missing and some factors such as
viral load, opportunistic infections, death causes, and ob-
servance assessment were not taken into account. Finally,
the number of those lost to follow up and the fact that we
have no information on them could be a factor which
does not make for the true assessment of mortality rates.
5. Conclusion
In our cohort, the mortality rate was 5.4 deaths per 100
person-years. Male gender, BMI <18.5 kg/m2, WHO
stages 3 and 4, the number of T-CD4 lymphocytes <
200/μl, hemoglobin rate < 8 g/dl, creatinine ≥120 µmol/l
were factors independently associated with death. This
study provides for the first time, mortality rates and death
risk factors for patients on ART in a cohort with a large
number of participants in a government centre in Burkina
Faso and West Africa. It emphasizes once again the need
for screening and early initiation of ART.
6. Acknowledgements
The authors thank all patients of the Day Hospital of Bo-
bo Dioulasso, the male nurses, and all non-medical staff
of our department.
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