Eligibility for and outcome of treatment of latent tuberculosis infection in a cohort of HIV-infected people in Spain.

Abstract

Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion.
Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI).
A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9).
A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.

Full text

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RESEARCH ARTICLEOpen Access
Eligibility for and outcome of treatment of latent
tuberculosis infection in a cohort of HIV-infected
people in Spain
Asuncion Diaz1*, Mercedes Diez2, Maria Jose Bleda1, Mikel Aldamiz3, Miguel Camafort4, Xabier Camino5,
Concepcion Cepeda6, Asuncion Costa6, Oscar Ferrero7, Paloma Geijo8, Jose Antonio Iribarren5, Santiago Moreno9,
Maria Elena Moreno9, Pablo Labarga10, Javier Pinilla10, Joseba Portu3, Federico Pulido6, Carmen Rosa8,
Juan Miguel Santamaría7, Mauricio Telenti11, Luis Trapiella11, Monica Trastoy12, Pompeyo Viciana12
Abstract
Background: Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI)
in persons infected with the human immunodeficiency virus, but few studies have investigated the operational
aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for
TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to
investigate factors associated with treatment completion.
Methods: Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain.
Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95%
confidence interval (95% CI).
Results: A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%)
were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was
negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients
eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23
(18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients
(57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2
developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV
infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having
taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9).
Conclusions: A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of
treatment. Obstacles to successful implementation of this intervention need to be addressed.
Background
In Spain, there is an extensive overlap between the epi-
demiology of human immunodeficiency (HIV) and
Mycobacterium tuberculosis (M. tuberculosis) infections
[1]. The introduction of highly active antiretroviral treat-
ment (HAART) has led to a reduced incidence of tuber-
culosis (TB) among HIV positive people, but the risk of
developing TB remains much higher among this group
[2] than among those without HIV infection. Thus, as
suggested by studies performed in both high and low
prevalence areas [3-5], treatment of latent tuberculosis
infection (TLTBI) should be used in combination with
HAART to control TB in this population.
The efficacy of TLTBI in people co-infected with HIV
and TB has been extensively demonstrated [6,7], but no
treatment will have a demonstrable effect on public
health if the target population is not reached or if
* Correspondence: adiaz@isciii.es
1Unidad de Epidemiología del VIH/SIDA, Centro Nacional de Epidemiología,
Instituto de Salud Carlos III, Madrid, Spain
Full list of author information is available at the end of the article
Diaz et al. BMC Infectious Diseases 2010, 10:267
http://www.biomedcentral.com/1471-2334/10/267
© 2010 Diaz et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.

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treatment compliance is far from optimal, as seems to
be the case with TLTBI [8,9].
Although HIV is the main risk factor for developing
TB, few studies have investigated the operational aspects
of implementing TLTBI in the co-infected population
[10], and none has been performed in Spain. For this
reason we carried out a 3-year longitudinal study to
describe tuberculin skin testing (TST) and the preva-
lence of M. tuberculosis in HIV-infected people in Spain
and to investigate obstacles to successful completion of
TLTBI in the co-infected population.
A cohort of 1242 HIV-infected subjects was identified
during the study period, of whom 84 had past TB, 23
had current TB, and 87 had already been treated for
LTBI at study entry. Thus, only 1048 persons were eligi-
ble for TST, of whom 853 (81.4%) underwent testing.
The reasons for not undergoing TST were: test not pre-
scribed by the physician (185 cases), patient’s refusal
(7 cases), and unknown (3 cases). A detailed account of
reasons for non-prescription of TST and of M. tubercu-
losis prevalence in this cohort has already been pub-
lished [11,12].
The objective of this paper is to describe eligibility for
TLTBI, treatment prescription, initiation and completion
in HIV-infected subjects in Spain, and factors associated
with treatment completion. Since our aim was to assess
“routine clinical practice”, no attempt was made to
modify it in any way.
Methods
A cohort of HIV-infected people not previously followed
at an HIV clinic was prospectively identified between
March 2000 and February 2003 at 10 Spanish hospital-
based HIV clinics scattered across a wide geographical
area. In Spain, HIV care is always hospital based, and
antiretroviral treatment is not available outside this
setting.
Subjects were eligible for the study if 1) this was their
first visit to an HIV specialist, or 2) this was not the
first time an HIV specialist had examined them, but
they had not attended an HIV clinic in the preceding
2 years. To avoid the inadvertent inclusion of people
who had been followed up in HIV clinics not included
in the study, people taking antiretroviral drugs or noti-
fied as AIDS cases before study entry were excluded. A
more detailed description of the cohort can be found
elsewhere [12].
While guidelines for TB prevention in HIV-infected
people in Spain have been issued [13], the treating phy-
sicians, in accordance with their routine clinical practice,
made their own decisions about treatment eligibility,
regimens chosen for TLTBI and the number of follow-
up visits.
At study entry a physical examination was performed
by the visiting physician. TST was performed in accor-
dance with Spanish guidelines for HIV-positive
people [14].
All subjects without signs or symptoms of disease and
who had a positive Mantoux test at study entry or a
documented positive TST in the past were classified as
having latent tuberculosis infection (LTBI).
In accordance with Spanish guidelines [13] a person
was considered to be a candidate for TLTBI if he/she
did not have past/current TB and: a) was TST (+) and
had not taken TLTBI previously; b) was TST (-) but was
a known contact of a TB patient; or c) was TST (-) but
had a CD4 count of less than 500 cells/μL, anergy was
suspected and the treating physician considered that
TLTBI was necessary.
Treatment outcome was classified in the following
mutually exclusive categories: a) treatment completed: a
person who, in the clinician’s judgment, has completed
treatment; b) treatment interruption due to adverse
effects: a person who, on the physician’s advice, inter-
rupted treatment due to adverse effects; c) treatment
default: a person who interrupted treatment for reasons
other than adverse effects; d) development of TB: a per-
son who developed TB while in TLTBI; e) moved away:
a person who changed residence while in TLTBI and
whose outcome was unknown; f) death: a person who
died while in TLTBI independently of the cause.
By consensus among the participating clinicians, a
patient was considered to be adherent if he/she had
taken at least 80% of the total pills prescribed; however,
treatment adherence was assessed only in accordance
with the treating physician’s judgment.
Socio-demographic, epidemiological and clinical infor-
mation and data on follow-up visits and treatment out-
come were obtained from the clinical records.
Characteristics of subjects who were prescribed
TLTBI, those who initiated treatment, and those who
completed it were described. The chi-squared or Fisher’s
exact tests were used to evaluate the association
between qualitative variables. The odds ratio and its
95% confidence interval (OR, 95% CI) were used to
measure the association between different variables and
completion of TLTBI. The multivariate analysis was per-
formed using logistic regression following Hosmer and
Lemeshow model-building strategies and methods [15],
taking into consideration that the sample size was not
very large [16]. Data analysis was performed using the
STATA program (Version 10.0).
The study was performed following all the require-
ments of the Spanish legislation on data protection in
effect at the time, and was reviewed by the correspond-
ing boards of the institutions involved.
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Results
a) Eligibility for TLTBI and treatment initiation
Of the 853 HIV-infected subjects who underwent TST,
846 (99.2%) returned for the reading, and 121 (14.3% of
the tests read) were TST(+); none of them had signs or
symptoms of TB disease and were, thus, eligible for
TLTBI. Additionally, the treating physicians considered
that 57 TST(-) and three TST unknown patients were
also eligible for TLTB (Figure 1). Thus, of the 856 HIV-
positive people evaluated for TLTBI, 181 (21.1%) were
found to be eligible. However, only 122 of the latter
(67.4%) finally initiated treatment (Figure 1).
Reasons for not initiating treatment were: a) physi-
cians questioned patients’ compliance due to their social
situation (n = 20); b) medical contraindication (n = 19);
c) patient’s refusal (n = 17); and d) unknown causes (n
= 3). All patients who rejected TLTBI were Spaniards:
13 were intravenous drug users (IDU) and were infected
with Hepatitis C virus (HCV), 9 were unemployed, and
8 had poor or no education. Characteristics of subjects
eligible for treatment of LTBI and those who actually
initiated it are presented in table 1.
The regimens prescribed for TLTBI were: a) isoniazid
6 months (6H): 51 patients (41.8%); b) isoniazid
9 months (9H): 26 (21.3%); c) isoniazid 12 months
(12H): 22 (18.0%); d) rifampin plus pyrazinamide
2 months (2RZ): 17 (13.9%); e) rifampin plus isoniazid
3 months (3RH): 5 (4.1%); and f) rifampin plus isoniazid
plus pyrazinamide 3 months (3RHZ): 1 patient (0.8%).
b) Treatment outcomes
Of the 122 patients who initiated TLTBI, 70 (57.4%)
completed treatment, 39 (32.0%) defaulted, 7 (5.7%)
interrupted treatment because of adverse effects,
2 (1.6%) developed TB, 2 (1.6%) died, and 2 (1.6%) chan-
ged residence and the final result was unknown.
Default rates were greater among IDUs than among
men who have sex with men (MSM) and heterosexuals:
44.0%, 23.5% and 18.1% respectively (p = 0.02).
Regarding treatment regimens, default rates for the
long-term regimens 12 H, 6 H, or 9 H were 40.9%,
39.2% and 30.8%, respectively. The corresponding
figures for the short-term regimens 2RZ, 3RH and
3RHZ were 5.9%, 20% and 0%.
Figure 1 Eligibility for treatment of latent tuberculosis infection, treatment initiation and result. TST: tuberculin skin testing; TLTBI:
treatment of latent tuberculosis infection
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Table 1 Characteristics of study subjects according to treatment of latent tuberculosis infection
Variables Eligible for TLTBIInitiated
TLTBI
Completed TLTBI
N(%)n(%) n(%)
Sex
Male
Female
141
40
(77.9)
(22.1)
92
30
(75.4)
(24.6)
52
18
(74.3)
(25.7)
Age group (years)
≤ 30
31-35
36-40
≥ 41
48
53
40
40
(26.5)
(29.3)
(22.1)
(22.1)
39
33
22
28
(32.0)
(27.0)
(18.0)
(23.0)
20
15
13
22
(28.6)
(21.4)
(18.6)
(31.4)
Country of origin
Spain
Other
154
27
(85.1)
(14.9)
101
21
(82.8)
(17.2)
58
12
(82.9)
(17.1)
Educational level
None/incomplete primary education
Primary education completed
Secondary/university education completed
Unknown
24
80
48
29
(13.3)
(44.2)
(26.5)
(16.0)
14
54
34
20
(11.5)
(44.3)
(27.9)
(16.3)
6(8.6)
(47.1)
(25.7)
(18.6)
33
18
13
Employment status
Employed
Unemployed
Other
Unknown
73
83
20
(40.3)
(45.9)
(11.0)
(2.8)
49
56
13
(40.2)
(45.9)
(10.6)
(3.3)
33
27
7
3
(47.1)
(38.6)
(10.0)
(4.3)54
HIV transmission route
IDU
MSM
Heterosexual sex
Other/unknown
101
22
53
(55.8)
(12.2)
(29.3)
( 2.8)
59
17
44
(48.4)
(13.9)
(36.1)
(1.6)
28
7
34
1
(40.0)
(10.0)
(48.6)
(1.4)52
Viral load (copies)
< 50
50-9,999
10,000-54,999
≥ 55,000
Unknown
17
57
45
58
(9.4)
(31.5)
(24.9)
(32.0)
(2.2)
8(6.6)
(35.2)
(24.6)
(32.0)
(1.6)
6(8.6)
(41.4)
(21.4)
(27.1)
(1.4)
43
30
39
29
15
19
142
CD4 (cells/μL)
< 100
100-199
200-499
≥ 500
22
24
75
60
(12.2)
(13.3)
(41.4)
(33.1)
11
16
52
43
(9.0)
(13.1)
(42.6)
(35.2)
5(7.1)
(14.3)
(40.0)
(38.6)
10
28
27
Hepatitis B carriers
Yes
No
Unknown
14
163
(7.7)
(90.1)
(2.2)
9(7.4)
(91.8)
(0.8)
3(4.3)
(95.7)
(0.0)
11267
041
Hepatitis C virus antibodies
Yes
No
Unknown
107
69
(59.1)
(38.1)
(2.8)
62
57
(50.8)
(46.7)
(2.5)
31
38
1
(44.3)
(54.3)
(1.4)53
TOTAL 181(100.0) 122(100.0) 70(100.0)
TLTBI: treatment of latent tuberculosis infection; IDU: Intravenous drug user; MSM: Men who have sex with men
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Out of the 39 defaulters, 23 (59%) abandoned treat-
ment in the first month, 16 of whom did not return
after the visit when TLTBI was prescribed (Table 2).
Out of the seven patients with adverse reactions, five
developed hepatotoxicity within the first 2 months of
treatment (one for each regime except 3RHZ), one
developed exanthema in the fourth month of a 9 H regi-
men, and the last one developed gastric intolerance in
the tenth month of a 12 H regimen.
The two subjects who developed TB were MSM under
age 35 whose infection was detected within the first
month after treatment initiation.
Two patients died while in treatment. One was an
IDU co-infected with HCV who died in the first month
of TLTBI and the other was a MSM with a very low
CD4 count who died during the second month. Neither
of these deaths was related to TLTBI.
Factors associated with treatment completion
The 70 patients completing treatment had a mean age
of 37.1 (SD:8.8) years, and were mostly men (74.3%) and
Spaniards (82.9%). Almost 60.0% had acquired HIV
infection through sex. Regarding their initial clinical eva-
luation, 50.0% had less than 10,000 viral copies, and
almost 79% had more than 200 CD4 (Table 1).
Treatment completion was significantly greater among
people infected with HIV through heterosexual sex than
among IDU or MSM (77.3% vs. 47.5% and 41.2%
respectively) (p = 0.01).
The only patient treated with 3RHZ, as well as three
out of the five treated with 3RH finished the treatment.
Among people treated with 2RZ the completion rate
was 88.2%, and among those who had taken 9 H, 6 H
or 12 H, treatment completion rates were 53.8%, 56.9%
and 36.4% respectively.
The multivariate analysis to identify factors associated
with treatment completion excluded subjects who died
while in TLTBI, those who developed TB and those
who left treatment because of adverse effects, since
these persons could not complete treatment. Thus, only
the 111 patients who had completed treatment,
defaulted or moved away were included in this analysis.
Treatment completion was greater among patients
acquiring HIV through heterosexual sex as compared to
IDUs (OR:4.6; 95% CI: 1.4-14.7) and those treated with
2RZ as compared to those treated with 9 H (OR:8.3;
95% CI:2.7-24.9) (Table 3).
Discussion
This is the first study performed in Spain that describes
eligibility, initiation and outcome of TLTBI in routine
clinical practice among HIV-infected subjects. In total,
1242 people entered the study. Of these, 181 were eligi-
ble for treatment, 122 initiated it, and only 70 com-
pleted treatment. Thus, only 38.7% of people eligible for
TLTBI, actually finished the treatment. These findings
suggest that there are many obstacles to completing
TLTBI in the HIV-infected population.
Around one in five persons eligible for TLTBI did not
initiate it, either because the treatment was not pre-
scribed or because the patient refused to take it. In both
instances the patients’ social context seemed to be a
major determinant. Thus, some physicians did not pre-
scribe TLTBI because they expected the patient’s social
situation to make treatment compliance difficult; simi-
larly, most of the patients refusing treatment had unfa-
vorable social indicators.
Almost 11% of those potentially eligible for TLTBI did
not initiate it because of medical contraindications. This
figure is lower than the 17% found in a similar study
Table 2 Number of defaulters, by month when treatment of latent tuberculosis infection was abandoned and type of
regimen
Type of TLTBINo of people starting TLTBI Month DefaultingEarly
defaulters/Total defaulters
(%)
0*123456789 10 11 12
6H
51655226/20
(30.0%)
9H
263221 3/8
(37.5%)
12H
2261116/9
(66.6%)
2RZ
171 1/1
3RH
510/1
Total 16784211 39
TLTBI: Treatment of latent tuberculosis infection; H: isoniazid; R: rifampin; Z: pyrazinamide
* Patient did not return after the visit when TLTBI was prescribed
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performed in Italy [10], although in both studies hepati-
tis C was the most common contraindication.
In this study, 6% of people who began TLTBI had to
interrupt it due to adverse effects. This proportion was
higher than the 3.7% found in an American study
where a 2RZ regimen was used [17], and lower that
the 10% found in the aforementioned Italian study,
where 6H/12 H regimens were used [10]. Results from
other Spanish studies-two clinical trials in HIV-
infected people and an observational study in non-HIV
infected people [18-20]-showed higher rates of adverse
effects: 15%, 9.7% and 12.4%, respectively. These differ-
ences may be due to different regimens being used or
to closer patient follow-up.
The proportion of defaulters in our study was higher
than the 22% and 27% found in the Spanish clinical
trials [18,19]. Defaulter rates in other non-Spanish
observational studies performed in HIV-infected patients
[10,17,21] vary considerably, ranging from 8% to 42%,
depending on the type of regimen chosen and whether
or not directly observed treatment (DOT) was used.
Defaulting was common with long-term regimens, but
it is interesting to note that most patients abandoned
early in the course of treatment, and more than 40% of
the defaulters failed to return for the first follow-up
visit. This finding, common to other studies [17,22],
may indicate that patients do not clearly understand the
benefits of TLTBI.
The treatment completion rate, 57.4%, is comparable
to those found in the Spanish clinical trials, 61% and
63.3% respectively [18,19]. As compared with findings
from international studies, the completion rate was simi-
lar to the 61% found in an observational study carried
out in United States with a 12 H regimen [17], but
worse than those in two other studies in Italy and Brazil,
which reported completion rates of 72.5% and 76.1,
using 6-12 H and 6 H regimes, respectively [10,3].
The finding that treatment completion was better in
patients who had acquired HIV through heterosexual
sex than among IDUs was not at all surprising, since
Spanish IDUs have also been found to have poor com-
pliance with antiretroviral treatment [23]. In fact, what
is surprising is that almost 50% of all IDUs initiating
TLTBI completed it, a figure similar to what has been
found in studies where DOT was used [24,25]. This
“good” result is explained by the positive selection
that had taken place among the IDUs during the clini-
cal process previous to treatment prescription: IDUs
were over-represented among subjects who did not
undergo TST [11] and constituted the majority of eli-
gible patients for whom TLTBI was not prescribed
(82.6%).
Table 3 Factors associated with completed TLTBI. Univariate and multivariate analyses (n = 111)
Univariate
Analysis
Multivariate
Analysis
VariablesCrude
OR
(95% CI) p valueAdjusted OR(95% CI)P value
Sex
Female
Male
11
1.2(0.9-1.6) 0.2442.1(0.9-4.9)0.081
Age group (years)
19-29
30-34
35-38
39-61
11
1.1
1.2
3.6
(0.4-2.9)
(0.4-3.5)
(1.1-11.9)
0.808
0.702
0.035
1.2
1.4
2.9
(0.3-5.1)
0.4-4.5)
(0.6-13.1)
0.789
0.599
0.173
HIV transmission route
IDU
MSM
Heterosexual
Other/Unknown
11
1.7
3.6
1.0
(0.2-12.3)
(1.3-9.8)
(0.1-13.7)
0.606
0.010
0.979
2.0
4.6
1.3
(0.3-12.2)
(1.4-14.7)
(0.2-7.6)
0.458
0.010
0.793
Type of TLTBI
9H
6H
12H
2RZ
3RH
11
0.9
0.6
9.6
1.9
(0.3-2.9)
(1.1-2.2)
(1.1-81.4)
(0.2-21.1)
0.861
0.423
0.037
0.591
0.6
0.6
8.3
1.7
(0.2-2.2)
(0.2-1.9)
(2.7-24.9)
(0.1-24.2)
0.505
0.382
0.000
0.702
OR: Odds ratio; CI: confidence interval
TLTBI: Treatment of latent tuberculosis infection; IDU: Intravenous drug user; MSM: Men who have sex with men; H: isoniazid; R: rifampin; Z: pyrazinamide
Multivariate model adjusted by hospital
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Treatment completion was significantly better with the
2RZ regimen than with the 9 H regimen. This result is
consistent with those of some clinical trials where
adherence to this regimen was between 73.4% and
80.0% [26-28]. In an observational study with this regi-
men where DOT was utilized, the completion rate
reached 93% [17]. Unfortunately, this regimen has been
associated with severe liver injury, mostly in HIV-nega-
tive but also in HIV-infected people, and some institu-
tions have withdrawn it from the list of recommended
regimens for the treatment of LTBI [29]. We found no
differences in the occurrence of adverse events with the
different regimens, but numbers were small.
Our study has some limitations. The small number of
study participants prevented an in depth analysis of fac-
tors associated with treatment prescription and treat-
ment initiation. Such analyses would have provided a
better understanding of physician-and patient-related
variables associated with treatment prescription or treat-
ment initiation. Furthermore, small sample sizes could
have sometimes resulted in less precise estimates.
Conclusions
This study shows that, despite the high prevalence of
M. tuberculosis and TB disease in the HIV-infected
population in Spain [12] and the potential benefit of
treating LTBI [30], the outcome of TLTBI in routine
clinical practice is far from desirable: less than half of
the patients eligible for treatment actually take it. Rea-
sons for this situation are diverse, but social or struc-
tural causes seem to play a far greater role than medical
reasons.
The study results have some public health implica-
tions: a) adequate enablers should be used to facilitate
TLTBI among IDUs; b) health staff should try to help
patients understand the importance of TLTBI; and c)
further research is needed to fully understand patient
and physician behavioral factors influencing initiation
and completion of TLTBI.
Acknowledgements
This work was funded by a grant (3041/99) from the Foundation for AIDS
Research and Prevention in Spain (Fundación para la Investigación y la
Prevención del SIDA en España-FIPSE). The authors are grateful to Kathy
Fitch for English review.
Author details
1Unidad de Epidemiología del VIH/SIDA, Centro Nacional de Epidemiología,
Instituto de Salud Carlos III, Madrid, Spain.2Secretaria del Plan Nacional
sobre el sida, Ministerio de Sanidad y Política Social, Madrid, Spain.3Servicio
Medicina Interna, Hospital Txagorritxu,Vitoria, Spain.4Servicio Medicina
Interna, Hospital Mora d’Ebre, Instituto de Investigación Sanitaria “Pere
Virgili”, Universidad “Rovira i Virgili”, Mora d’Ebre, Spain.5Servicio de
Enfermedades Infecciosas, Hospital Ntra Sra de Aranzazu, San Sebastián,
Spain.6Unidad VIH, Hospital Doce de Octubre, Madrid, Spain.7Servicio
Enfermedades Infecciosas, Hospital de Basurto, Bilbao, Spain.8Servicio
Medicina Interna, Hospital Virgen de la Luz, Cuenca, Spain.9Servicio de
Enfermedades Infeccciosas, Hospital Ramón y Cajal, Madrid, Spain.10Servicio
de Medicina Interna, Hospital San Millán, Logroño, Spain.11Unidad de
Enfermedades Infecciosas, Hospital Universitario Central de Asturias, Oviedo,
Spain.12Servicio Enfermedades Infecciosas, Hospital Virgen del Rocío, Sevilla,
Spain.
Authors’ contributions
AD worked on data collection and management, carried out the
epidemiological analysis, prepared the figure and most of the tables, wrote
the first version of the manuscript and contributed to all successive versions.
MD was the main study researcher. She had the original idea, developed the
study protocol, supervised field work and data collection, and wrote the
statistical analysis plan and the final version of the manuscript. MJB
performed data collection and management, quality control and statistical
analysis, and reviewed all the manuscript drafts. MA, MC, XC, CC, AC, OF, PG,
JAI, SM, MEM, PL, JP, JP, FP, CR, JMS, MT, LT,MT and PV were the physicians
responsible for patient recruitment and follow-up in the participating
hospitals. They all participated in development of the study protocol,
collection of epidemiological and clinical data, and critical review of all
versions of the manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 17 February 2010 Accepted: 14 September 2010
Published: 14 September 2010
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Pre-publication history
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Cite this article as: Diaz et al.: Eligibility for and outcome of treatment
of latent tuberculosis infection in a cohort of HIV-infected people in
Spain. BMC Infectious Diseases 2010 10:267.
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