A positive tuberculin skin test (TST) is often defined by skin induration of ≥10 mm in people who are HIV-seronegative. However, to increase sensitivity for detection of Mycobacterium tuberculosis infection in the context of impaired immune function, a revised cut-off of ≥5 mm is used for people living with HIV infection. The incremental proportion of patients who are included by this revised definition and the association between this proportion and CD4+ cell count are unknown.
Methods
The literature was systematically reviewed to determine the proportion of people living with HIV (PLWH) without evidence of active tuberculosis in low and middle-income countries who tested TST-positive using cut-offs of ≥5 mm and ≥10 mm of induration. The difference in the proportion testing TST-positive using the two cut-off sizes was calculated for all eligible studies and was stratified by geographical region and CD4+ cell count.
Results
A total of 32 studies identified meeting criteria were identified, providing data on 10,971 PLWH from sub-Saharan Africa, Asia and the Americas. The median proportion of PLWH testing TST-positive using a cut-off of ≥5 mm was 26.8% (IQR, 19.8-46.1%; range, 2.5-81.0%). Using a cut-off of ≥10 mm, the median proportion of PLWH testing TST-positive was 19.6% (IQR, 13.7-36.8%; range 0–52.1%). The median difference in the proportion of PLWH testing TST-positive using the two cut-offs was 6.0% (IQR, 3.4-10.1%; range, 0–37.6%). Among those with CD4+ cell counts of <200, 200–499 and ≥500 cells/μL, the proportion of positive tests defined by the ≥5 mm cut-off that were between 5.0 and 9.9 mm in diameter was similar (12.5%, 12.9% and 10.5%, respectively).
Conclusions
There is a small incremental yield in the proportion of PLWH who test TST-positive when using an induration cut-off size of ≥5 mm compared to ≥10 mm. This proportion was similar across the range of CD4+ cell strata, supporting the current standardization of this cut-off at all levels of immunodeficiency.
Tuberculin skin tests (TSTs) have for a long time been used to define likely Mycobacterium tuberculosis (MTB) infection, identify those who may benefit from isoniazid preventive therapy and aid diagnosis of tuberculosis (TB) disease, especially in children. While interferon gamma release assays (IGRAs) were developed to improve the diagnostic accuracy for MTB infection, the World Health Organization (WHO) does not recommend routine use of IGRAs in resource limited settings due to cost, technical complexity and limited utility [1].
The sensitivity of TSTs for detecting MTB infection is impaired among people living with HIV (PLWH) due to an attenuation of cell-mediated responses, including a reduction in memory CD4+ T cells at the TST site [2]. While a cut-off of ≥10 mm of induration is often used to define a positive TST among those who are HIV sero-negative, a cut-off of ≥5 mm is instead recommended by the US Centers for Disease Control and Prevention among PLWH to increase the sensitivity [3]. This revised cut-off is based on unpublished data from New York City in the 1980’s among just 23 AIDS patients with known TB disease of whom two had a TST of 5–9 mm induration while 13 had an induration ≥10 mm [4]. However, the incremental proportion of individuals defined as TST-positive when using this revised cut-off and the variables such as CD4+ cell count that might be associated with this proportion are not known.
Cobelens and colleagues [5] investigated TST responses among a large number of PLWH who were diagnosed as having active smear-positive pulmonary tuberculosis (TB) in Tanzania. Although just 71.2% of patients tested TST-positive when using the recommended cut-off of ≥5 mm of induration, this did not differ substantially from the proportion defined as positive using a cut-off of ≥10 mm of induration (64.3%) with a difference of just 6.9%. Thus, the altered cut-off only marginally reduced the number of false-negative tests. The authors concluded from their data that loss of sensitivity of the TST in PLWH is predominantly attributable to anergy (ie an all-or-nothing phenomenon) rather than due to a gradual diminution in TST diameter during progressive immunodeficiency. However, this study was conducted solely among PLWH who had active TB and these findings cannot necessarily be extrapolated to those with latent MTB infection and any association with CD4+ cell count was not defined.
We previously conducted a systematic review of the literature to ascertain the proportions of PLWH who tested TST-positive using the conventional cut-off of ≥5 mm of induration [6]. In the present systematic review, we determined the proportions of PLWH testing TST-positive using cut-offs of ≥5 mm and ≥10 mm cut-off and the relationship with CD4+ cell count.
MethodsSearch strategy
The search strategy has been described in detail elsewhere [6]. In brief, we searched Embase, Global Health, Medline and Web of Science for relevant citations using a combination of MeSH and free text search terms according to a predetermined search criteria. The search was restricted to articles from January 1, 1990 to February 5, 2012 as an initial search demonstrated no relevant citations prior to this period. The first search set was created using comprehensive search terms for tuberculin skin test, latent tuberculosis and isoniazid preventive therapy and were combined using “or.” A second set was created for HIV/AIDS using comprehensive search terms. These two sets were then combined using “and.” Next, this set was combined with a low and middle-income country (LMIC) set (using the World Bank list of economies as of 01 July 2011) [7] using “and.” All citations were then limited to articles published in English and among humans.
Studies eligible for inclusion were those that were conducted in LMIC’s, included only PLWH who were at least 15 years of age, presented data for patients without evidence of active TB disease, and presented the proportion of those testing TST-positive current using a induration cut-off size of both ≥5 mm and ≥10 mm. Studies were also required to have at least 30 participants meeting the above criteria to limit imprecision around the point estimates. Studies utilizing two-step TST testing were excluded. All studies meeting the aforementioned criteria were included regardless of patient ART status at enrolment.
Citations identified through the search process were compiled into Endnote where duplicate citations were removed. Titles and abstracts were screened for study inclusion. Potentially relevant full-text citations were entered into an Excel spreadsheet and the full-texts were obtained. Two readers (ADK and SDL) carefully reviewed all full-text publications for study inclusion. Additional studies met the inclusion criteria following provision of additional data by the authors as previously described [6].
Data extraction
Study characteristics from eligible studies were abstracted directly into a structured Microsoft Excel spreadsheet. Variables recorded included: title, authors, year of publication, study period, study location, clinical setting, mean or median patient age, bacille Calmette et Guerin (BCG) vaccine scar status, ART status, special or potentially non-generalizable populations and the total number of eligible PLWH who underwent TST testing (and returned to have their results read) and the total number PLWH testing TST-positive using both a ≥5 mm and a ≥10 mm induration size. When TST-results using both a ≥5 mm and a ≥10 mm cut-off stratified by CD4+ cell counts (<200, 200–499 and ≥500 cells/μL) were available, these were also recorded.
The quality of studies was independently assessed by two reviewers (ADK and SDL) using a graded checklist [6]. A study receiving 70% of available points was considered to be of “good quality”, 50-70% was considered “medium quality” and less than 50% was considered “lower quality.” We also assessed the risk of bias in individual studies as well as across all included studies.
Statistical analysis
All statistical analysis was completed using STATA version 10.0. The difference in the proportion of those testing TST-positive using a ≥5 mm versus a ≥10 mm cut-off was calculated for all eligible studies and chi-squared tests were used to compare these proportions. Differences in the proportions of PLWH testing TST-positive by each cut-off size were then plotted using a forest plot and were stratified by geographic region and CD4+ cell count. Pooled estimates of overall data or stratified data were not derived due to substantial heterogeneity between studies as indicated by large I2 values [8].
Results
Of the 3,095 potential citations identified in the literature search, 254 were selected for full-text review (Figure 1). After concluding a full-text review, 24 articles met the pre-defined inclusion criteria and an additional 8 articles met inclusion criteria due to unpublished data provided by authors for a previous study. In all, 32 publications provided data from 34 unique study populations and were published between 1992 and 2011 (Additional file 1). Among included publications, 14 study populations were from Africa, 8 from the Americas and 12 from Asia. The TB prevalence in counties in which the studies were conducted ranged from 0.19-785 cases per 100,000 population and the majority (62%; 21/34) of study populations were from high-prevalence TB countries (estimated TB prevalence >100 cases per 100,000 population).
Overview of eligible studies containing data on the proportion of people living with HIV testing TST-positive using a ≥5 mm and ≥10 mm cut-off size.
The mean/median age among patients in eligible studies ranged from 22–42 years. The proportions of PLWH on ART at the time of TST assessment was reported for 18 study populations and an additional six study populations were assumed to be ART naïve as the studies were conducted prior to national ART implementation. Among these 24 populations, ART was received by a proportion of the participants in only 9 studies and this proportion varied from 1% to 100% (median 58%). Nine publications were of high quality, 12 studies of medium quality and 11 studies of low quality, as determined by a quality assessment checklist.
Difference in patients testing TST-positive using a ≥5 mm versus ≥10 mm cut-off size
Overall, there were 10,971 PLWH with TST results from 34 study populations; 4,880 were from sub-Saharan Africa, 2,247 from the Americas and 3,844 from Asia. All studies reported the proportion of individuals testing TST-positive using both a 5 mm and 10 mm cut-off (Table 1).
The proportion of people living with HIV who tested TST-positive using a ≥5 mm and ≥10 mm cutoff size and the difference between these two proportions
Study
Number of patients (n)
Number of patients TST-positive using ≥5 mm cut-off (%)
Number of patients TST-positive using ≥10 mm cut-off (%)
Difference in proportion of patients testing TST-positive (%)
P-value
Africa
Allen et al. [9]
284
73 (25.7)
60 (21.1)
4.6
0.1977
Aisu et al. [10]
1094
579 (52.9)
376 (34.4)
18.6
<0.0001
Duncan et al. [11]
106
35 (33.0)
32 (30.2)
2.8
0.6576
Fordham von Reyn et al. [12]
104
21 (20.2)
20 (19.2)
1.0
0.8616
Diagbouga et al. [13]
37
9 (24.3)
6 (16.2)
1.7
0.3857
Waddell et al. [14]
58
16 (27.6)
15 (25.9)
8.1
0.8338
Mtei et al. [15]
460
192 (41.7)
175 (38.0)
3.7
0.2524
Tegbaru et al. [16]
116
47 (40.5)
38 (32.8)
7.8
0.2201
Rangaka et al. [17]
67
35 (52.2)
33 (49.3)
3.0
0.7297
Karam et al. [18]
273
59 (21.6)
46 (16.8)
4.8
0.1581
Hanifa et al. [19]
33
18 (54.5)
14 (42.4)
12.1
0.3245
Leidl et al. [20]
89
42 (47.2)
35 (39.3)
7.9
0.2896
Oni et al. [21]
240
138 (57.5)
125 (52.1)
5.4
0.2332
Samandari et al. [22]
1919
468 (24.4)
383 (20.0)
4.4
0.0010
The Americas
Espinal et al. [23]
86
50 (58.1)
40 (46.5)
11.6
0.1269
Fordham von Reyn et al. [12]
121
3 (2.5)
2 (1.7)
0.8
0.6513
Garcia-Garcia et al. [24]
801
261 (32.6)
174 (21.7)
10.9
<0.0001
Miranda et al. [25]
98
16 (16.3)
12 (12.2)
4.6
0.4142
Balcells et al. [26]
109
12 (11.0)
7 (6.4)
4.1
0.2299
Gutierrez et al. [27]
104
20 (19.2)
13 (12.5)
6.7
0.184
Baboolal et al. [28]
64
6 (9.4)
0
9.4
0.0121
Moura et al. [29]
864
170 (19.7)
152 (17.6)
2.1
0.2661
Asia
Suwanagool et al. [30]
399
323 (81.0)
173 (43.4)
37.6
<0.0001
Yanai et al. [31]
217
46 (21.2)
32 (14.7)
6.5
0.0801
Yanai et al. [31]
129
21 (16.3)
15 (11.6)
4.7
0.281
Sawhney et al. [32]
396
103 (26.0)
62 (15.7)
10.4
0.0003
Gupta et al. [33]
752
157 (20.9)
137 (18.2)
2.7
0.1935
Swaminathan et al. [34]
631
269 (42.6)
227 (36.0)
6.7
0.0155
Davarpanah et al. [35]
173
64 (37.0)
23 (13.3)
23.7
<0.0001
Davarpanah et al. [36]
459
131 (28.5)
60 (13.1)
15.5
<0.0001
Jiang et al. [37]
46
27 (58.7)
17 (37.0)
21.7
0.0369
Zhang et al. [38]
93
3 (3.2)
3 (3.2)
0
1
Kabeer et al. [39]
180
33 (18.3)
27 (15.0)
3.3
0.3961
Nguyen et al. [40]
369
204 (55.3)
175 (47.4)
8.1
0.0274
The median proportion of PLWH testing TST-positive using a cut-off of ≥5 mm was 26.8% (IQR, 19.8-46.1%; range 2.5-81.0%). There was considerable heterogeneity with regard to regional differences in the proportion of patients testing TST-positive. The median proportions of patients testing TST-positive in sub-Saharan Africa, the Americas and Asia were 36.8% (IQR, 24.7-51.0%; range, 20.2-57.5%), 17.8% (IQR, 10.6-22.9%; range, 2.5-58.1%), and 27.3% (IQR, 20.3-45.8%; range, 3.2-81.0%), respectively.
When a cut-off of ≥10 mm was used, the median proportion of patients testing TST-positive was 19.6% (IQR, 13.7-36.8%; range, 0–52.1%). Strong regional differences in the proportion of patients TST-positive were again noted. Patients in sub-Saharan Africa had a median TST-positive proportion of 31.5% (IQR, 20.3-39.0%; range, 16.2-52.1%) compared to 12.4% (IQR, 5.2-18.6%; range, 0–46.5%) in the Americas and 15.4% (IQR, 13.3-36.3%; range, 3.2-47.4%) in Asia.
The median difference observed in the proportion of those testing TST-positive using a cut-off size of ≥5 mm versus ≥10 mm was 6.0% (IQR, 3.4-10.1%; range 0–37.6%). When stratified by geographic region, the median difference in the proportion of patients testing TST-positive using a 5 mm versus a 10 mm cut-off was 4.7% (IQR, 3.1-7.9%, range, 1.0-18.6%), 5.7% (IQR, 3.6-9.8%, range, 0.8-11.6%) and 7.3% (IQR, 4.4-17.0%, range, 0–37.6%) for Africa, the Americas and Asia respectively. The overall difference in the proportions of patients testing TST positive (Figure 2a) and stratified according to geographic region (Figure 2b) was demonstrated in forest plots.
Forest plot showing the difference in proportions (%, 95% CI) of people living with HIV testing TST-positive using a ≥5 mm versus a ≥10 mm cut-off size in (a) all study populations (n = 34) and (b) with data grouped according to region.
Association with CD4+ cell counts
Nine studies with a total of 5,107 PLWH reported the proportion of those testing TST-positive using both a ≥5 mm and a ≥10 mm cut-off size stratified by CD4+ cell counts at <200, 200–499, ≥500 (Table 2). These CD4+ cell count stratified data are shown in a forest plot (Figure 3). The median difference in the proportion of PLWH testing TST-positive using the two induration cut-off sizes was 2.0% (range, 0–10.7%; IQR, 0–7.8%), 3.5% (range, 1.5-7.8%; IQR, 2.7-4.4%) and 6.0% (range, 2.6-20.9%; IQR, 4.9-9.6%) among those with CD4+ cell counts <200, 200–499, ≥500 cells/μL, respectively. The corresponding proportions of positive tests defined by the ≥5 mm cut-off that were between 5.0 and 9.9 mm in diameter were 12.5% (IQR, 0–16.0), 12.9% (IQR, 7.6-15.2), 10.5% (IQR, 9.1-28.5), respectively [9-40].
The proportion of people living with HIV who tested TST-positive using a ≥5 mm and ≥10 mm cutoff size stratified by CD4+ cell count categories <200, ≥200, 200–499 and ≥500 cells/μL
Study
Number of patients with CD4+ cell count <200
Number of patients TST positive using ≥5 mm cutoff (%)
Number of patients TST positive using ≥10 mm cutoff (%)
Number of patients with CD4+ cell count 200-499
Number of patients TST positive using ≥5 mm cutoff (%)
Number of patients TST positive using ≥10 mm cutoff (%)
Number of patients with CD4+ cell count ≥500
Number of patients TST positive using ≥5 mm cutoff (%)
Number of patients TST positive using ≥10 mm cutoff (%)
Gupta et al. [33]
50
8 (16.0)
7 (14.0)
326
71 (21.8)
66 (20.2)
307
65 (21.2)
56 (18.2)
Rangaka et al. [17]
8
2 (25.0)
2 (25.0)
31
17 (54.8)
16 (51.6)
18
11 (61.1)
10 (55.6)
Karam et al. [18]
145
11 (7.6)
10 (6.9)
85
25 (29.4)
22 (25.9)
43
23 (53.5)
14 (32.6)
Balcells et al. [26]
13
1 (7.7)
1 (7.7)
73
4 (5.5)
2 (2.7)
23
7 (30.4)
4 (17.4)
Swaminathan et al. [34]
150
64 (42.7)
48 (32.0)
313
138 (44.1)
117 (37.4)
160
67 (41.9)
62 (38.8)
Moura et al. [29]
137
13 (9.5)
13 (9.5)
386
70 (18.1)
61 (15.8)
341
87 (25.5)
78 (22.9)
Nguyen et al. [40]
75
31 (41.3)
24 (32.0)
206
116 (56.3)
100 (48.5)
88
57 (64.8)
51 (58.0)
Oni et al. [21]
51
25 (49.0)
21 (41.2)
137
79 (57.7)
73 (53.3)
50
33 (66.0)
30 (60.0)
Samandari et al. [22]
575
88 (15.3)
74 (12.9)
952
250 (26.3)
212 (22.3)
364
124 (34.1)
93 (25.6)
Discussion
This study found that among 10,971 patients without active TB in 34 different study populations, the incremental yield of patients defined as TST-positive when using a ≥5 mm cut-off rather than a ≥10 mm cut-off was just 6.0%. This suggests that using the modified cut-off had only a modest effect on increasing the proportion of PLWH who tested TST-positive. Importantly, this proportion was similar across the range of CD4+ cell count strata and also across different geographic regions.
Forest plot showing the difference in proportions (%, 95% CI) of people living with HIV testing TST-positive using a ≥5 mm versus a ≥10 mm cut-off size with data grouped according to CD4+ cell count strata (<200, 200–499 and ≥500 cells/μL).
Our findings of a 6% incremental proportion associated with the use of the revised TST cut-off among patients without active TB are very similar to those of Cobelens and colleagues [5] who reported a 7% increment among patients with active TB in Tanzania. This suggests that the small differences observed in the proportion of PLWH testing TST-positive using the two cut-off sizes are generalizable regardless of TB infection or disease status.
A recent systematic review and meta-analysis [41] investigated the utility of ≥5 mm and ≥10 mm TST cut-off sizes to predict the progression from latent infection to active TB disease. Among five studies in which the HIV status of patients was largely unknown, the unadjusted incidence rate ratio of tuberculosis in TST-positive patients was 1.43 (95% CI, 0.75-2.72) when a cut-off of ≥5 mm was used and 1.60 (95% CI, 0.94-2.72) when a cut-off ≥10 mm was applied. Thus, neither cut-off size better predicted the risk for progression to active TB disease. However, because the HIV status of the patients included in these studies was negative or largely unknown, it remains unclear whether these findings are generalizable to PLWH.
TSTs rather than IGRAs are the WHO-recommended assay for use in LMICs for detecting latent tuberculosis infection among PLWH prior to isoniazid preventive therapy [42]. Although use of TST is recommended, it remains unknown whether a ≥5 mm or ≥10 mm cut-off size better defines those who will benefit from IPT. A meta-analysis [43] among PLWH demonstrated that among those with a TST induration of ≥5 mm in diameter, IPT was associated with a TB risk reduction of 64% (95% CI, 39-78 %). However, all studies in this meta-analysis defined TST-positivity using a ≥5 mm cut-off size and thus it is not known whether those with a 5.0-9.9 mm induration gain benefit from IPT. An individual patient meta-analysis of data from randomized trials of isoniazid preventive therapy may be able to define this.
Strengths of this study include a comprehensive search strategy that utilized four different study databases. There were more than 10,000 patients from 34 unique study populations from many countries and geographic regions. Also, a number of variables potentially influencing differences in the proportion of TST-positive patients were recorded and summarized where possible. There were also several limitations. The reliability of TST assessment could not be assessed. Additionally, methods for excluding TB disease were not standardized among included studies. Heterogeneity in the data precluded the calculation of pooled summary estimates.
Conclusion
In conclusion, using a ≥5 mm cut-off among PLWH resulted in only a modest increase in the proportion testing TST-positive when compared to a cut-off size of ≥10 mm and this finding concurs with a similar study that was conducted among patients with active TB. The difference in the proportion of PLWH testing TST-positive when using the two different cut-off sizes was similar across the range of CD4+ cell count strata suggesting use of this cut-off across the spectrum of immunodeficiency.
Competing interest
The authors have no conflicts of interest to declare.
Authors’ contributions
ADK initiated the study. ADK designed the search strategy. ADK ran the searches and selected and graded the studies with SDL. ADK, AG and SDL did the data synthesis. ADK and SDL wrote the manuscript and all other co-authors contributed to and approved the final draft.
Pre-publication history
The pre-publication history for this paper can be accessed here:
Characteristics of studies presenting data on the proportion of HIV-infected patients who tested TST-positive using a ≥5 mm and ≥10 mm cut-off size.
Click here for file
Acknowledgements
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the U.S. Centers for Disease Control and Prevention.
Funding
SDL is funded by the Wellcome Trust, London, UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
World Health OrganizationUse of tuberculosis interferon-gamma release assays (IGRAs) in low- and middle- income countries2011Geneva, Switzerland: World Health Organization170SarrazinHWilkinsonKAAnderssonJRangakaMXRadlerLVan VeenKLangeCWilkinsonRJAssociation between tuberculin skin test reactivity, the memory CD4 cell subset, and circulating FoxP3-expressing cells in HIV-infected personsJ Infect Dis20091370271010.1086/59673519199536Centers for Disease Control and PreventionTargeted tuberculin testing and treatment of latent tuberculosis infectionMMWR200013RR615115580784Centers for Disease Control (CDC)Tuberculosis and human immunodeficiency virus infection: recommendations of the Advisory Committee for the Elimination of Tuberculosis (ACET)MMWR198913236–8243–502494425CobelensFGEgwagaSMVan GinkelTMuwingeHMateeMIBorgdorffMWTuberculin skin testing in patients with HIV infection: limited benefit of reduced cutoff valuesClin Infect Dis20061363463910.1086/50643216886159KerkhoffADKranzerKSamandariTNakiyingi-MiiroJWhalenCCHarriesADLawnSDSystematic review of TST responses in people living with HIV in under-resourced settings: implications for isoniazid preventive therapyPLoS One201213e4992810.1371/journal.pone.004992823209621World Bank Website2011Available: http://data.worldbank.org/about/country-classifications/country-and-lending-groupsHigginsJPTThompsonSGQuantifying heterogeneity in a meta-analysisStatist Med2002131539155810.1002/sim.1186AllenSBatungwanayoJKerlikowskeKLifsonARWolfWGranichRTaelmanHVan De PerrePSerufiliraABogaertsJTwo-year incidence of tuberculosis in cohorts of HIV-infected and uninfected urban Rwandan womenAm Rev Respir Dis1992131439144410.1164/ajrccm/146.6.14391456559AisuTRaviglioneMCVan PraagEErikiPNarainJPBarugahareLTemboGMcFarlandDEngwauFAPreventive chemotherapy for HIV-associated tuberculosis in Uganda: an operational assessment at a voluntary counselling and testing centreAIDS1995132672737755915DuncanLEElliottAMHayesRJHiraSKTemboGMumbaGTEbrahimSHQuigleyMPobeeJOMcAdamKPTuberculin sensitivity and HIV-1 status of patients attending a sexually transmitted diseases clinic in Lusaka, Zambia: a cross-sectional studyTrans R Soc Trop Med Hyg199513374010.1016/0035-9203(95)90649-57747304Fordham Von ReynCArbeitRDTostesonANRistolaMABarberTWWaddellRSoxCHBrindleRJGilksCFRankiABartholomewCEdwardsJFalkinhamJOO’ConnorGTThe international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study GroupAIDS1996131025103210.1097/00002030-199610090-000148853737DiagbougaSFumouxFLedruESanouPTBarroDMarchalGLack of direct correlation between CD4 T-lymphocyte counts and induration sizes of the tuberculin skin test in human immunodeficiency virus type 1 seropositive patientsInt J Tuberc Lung Dis1998133173239559403WaddellRDVon CFRBabooKSMwingaAChintuCZumlaAThe effects of BCG immunization and human immunodeficiency virus infection on dual skin test reactions to purified protein derivative and Mycobacterium avium sensitin among adults in ZambiaInt J Tuberc Lung Dis19991325526010094328MteiLMateeMHerfortOBakariMHorsburghCRWaddellRColeBFVuolaJMTvarohaSKreiswirthBPallangyoKReyn VonCFHigh rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in TanzaniaClin Infect Dis2005131500150710.1086/42982515844073TegbaruBWoldayDMesseleTLegesseMMekonnenYMiedemaFvan BaarleDTuberculin skin test conversion and reactivity rates among adults with and without human immunodeficiency virus in urban settings in EthiopiaClin Vaccine Immunol20061378478910.1128/CVI.00098-0616829616RangakaMXDiwakarLSeldonRVan CutsemGMeintjesGAMorroniCMoutonPSheyMSMaartensGWilkinsonKAWilkinsonRJClinical, immunological, and epidemiological importance of antituberculosis T cell responses in HIV-infected AfricansClin Infect Dis2007131639164610.1086/51823417516410KaramFMbowFFletcherHSenghorCSCoulibalyKDLefevreAMNgom GueyeNFDieyeTSowPSMboupSLienhardtCSensitivity of IFN-γ release assay to detect latent tuberculosis infection is retained in HIV-infected patients but dependent on HIV/AIDS progressionPLoS One200813e144110.1371/journal.pone.000144118197251HanifaYGrantADLewisJCorbettELFieldingKChurchyardGPrevalence of latent tuberculosis infection among gold miners in South AfricaInt J Tuberc Lung Dis200913394619105877LeidlLMayanja-KizzaHSotgiuGBasekeJErnstMHirschCGolettiDToossiZLangeCRelationship of immunodiagnostic assays for tuberculosis and numbers of circulating CD4+ T-cells in HIV infectionEur Respir J20101361962610.1183/09031936.0004550919608590OniTBurkeRTsekelaRBanganiNSeldonRGideonHPWoodKWilkinsonKAOttenhoffTHMWilkinsonRJHigh prevalence of subclinical tuberculosis in HIV-1-infected persons without advanced immunodeficiency: implications for TB screeningThorax20111366967310.1136/thx.2011.16016821632522SamandariTAgizewTBNyirendaSTedlaZSibandaTShangNMosimaneotsileBMotsamaiOIBozemanLDavisMKTalbotEAMoetiTLMoffatHJKilmarxPHCastroKGWellsCD6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trialLancet2011131588159810.1016/S0140-6736(11)60204-321492926EspinalMAReingoldALLavanderaMEffect of pregnancy on the risk of developing active tuberculosisJ Infect Dis19961348849110.1093/infdis/173.2.4888568319García-GarcíaMLValdespino-GómezJLGarcía-SanchoCMayar-MayaMEPalacios-MartínezMBalandrano-CamposSEscobar-GutiérrezAPerugaAWeissenbacherMDanielsEUnderestimation of Mycobacterium tuberculosis infection in HIV-infected subjects using reactivity to tuberculin and anergy panelInt J Epidemiol20001336937510.1093/ije/29.2.36910817138MirandaAMorganMJamalLLasersonKBarreiraDSilvaGSantosJWellsCPainePGarrettDImpact of antiretroviral therapy on the incidence of tuberculosis: the Brazilian experience, 1995–2001PLoS One200713e82610.1371/journal.pone.000082617786198BalcellsMEPérezCMChanqueoLLassoMVillanuevaMEspinozaMVillarroelLGarcíaPA comparative study of two different methods for the detection of latent tuberculosis in HIV-positive individuals in ChileInt J Infect Dis20081364565210.1016/j.ijid.2008.03.00518534887GutierrezEGomesVPiconeCSugaHAtomiyaAActive tuberculosis and Mycobacterium tuberculosislatent infection in patients with HIV/AIDSHIV Med20091356457210.1111/j.1468-1293.2009.00730.x19785665BaboolalSRamoutarDAkpakaPEComparison of the QuantiFERON®-TB Gold assay and tuberculin skin test to detect latent tuberculosis infection among target groups in Trinidad & TobagoRev Panam Salud Publica201013364220857019MouraLCXimenesRARamosHLFilhoDBMFreitasCDSilvaRMCoimbraIBatistaJDLMontarroyosURMilitãoDFPAlbuquerqueMAn evaluation of factors associated with taking and responding positive to the tuberculin skin test in individuals with HIV/AIDSBMC Publ Health20111368710.1186/1471-2458-11-687SuwanagoolSChuenaromVPechthanonLSonjaiALeelarasameeAPathrakomCA comparative study of tuberculin skin test reactivity between asymptomatic HIV-1 seropositive subjects and healthy volunteersAsian Pac J Allergy Immunol1995131391448703242YanaiHUthaivoravitWMastroTDLimpakarnjanaratKSawanpanyalertPMorrowRHNieburgPUtility of tuberculin and anergy skin testing in predicting tuberculosis infection in human immunodeficiency virus-infected persons in ThailandInt J Tuberc Lung Dis1997134274349441097SawhneyMSharmaYKSignificance of tuberculin testing in HIV infection: An Indian perspectiveMedical Journal Armed Forces India20061310410710.1016/S0377-1237(06)80047-XGuptaANayakURamMBhosaleRPatilSBasavrajAKakraniAPhilipSDesaiDSastryJBollingerRCByramjeeJMedical College-Johns Hopkins University Study Group: Postpartum tuberculosis incidence and mortality among HIV-infected women and their infants in Pune, India, 2002–2005Clin Infect Dis20071324124910.1086/51897417578786SwaminathanSSubbaramanRVenkatesanPSubramanyamSKumarSRMayerKHNarayananPRTuberculin skin test results in HIV-infected patients in India: implications for latent tuberculosis treatmentInt J Tuberc Lung Dis20081316817318230249DavarpanahMRastiMMehrabaniDAllahyariSNeiramiRSaberiFirooziMAssociation between PPD and QuantiFERON gold TB test in TB infection and disease among HIV infectedIran Red Crescent Med J2009137175DavarpanahMRafieeGMehrabaniDThe prevalence of M. tuberculosis infection and disease in HIV positive individuals in Shiraz, Southern IranIran Red Crescent Med J200913199202JiangWShaoLZhangYZhangSMengCXuYHuangLWangYWangYWengXZhangWHigh-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-gamma release assay among HIV-infected individuals in BCG-vaccinated areaBMC Immunol2009133110.1186/1471-2172-10-3119476627ZhangMWangHLiaoMChenXGranerMZhuXZhangJYangQLuHZhouBChenXDiagnosis of latent tuberculosis infection in bacille Calmette-Guérin vaccinated subjects in China by interferon-gamma ELISpot assayInt J Tuberc Lung Dis2010131556156321144240KabeerBSASikhamaniRRajaAComparison of interferon gamma–inducible protein-10 and interferon gamma–based QuantiFERON TB Gold assays with tuberculin skin test in HIV-infected subjectsDiagn Microbiol Infect Dis20111323624310.1016/j.diagmicrobio.2011.07.01221996360NguyenDTMHungNQGiangLTDungNHLanNTNLanNNYenNTBBangNDNgocDVTrinhLTTBeasleyRPFordCEHwangL-YGravissEAImproving the diagnosis of pulmonary tuberculosis in HIV-infected individuals in Ho Chi Minh City, Viet NamInt J Tuberc Lung Dis2011131528153410.5588/ijtld.10.077722008768RangakaMXWilkinsonKAGlynnJRLingDMenziesDMwansa-KambafwileJFieldingKWilkinsonRJPaiMPredictive value of interferon-γ release assays for incident active tuberculosis: a systematic review and meta-analysisLancet Infect Dis201213455510.1016/S1473-3099(11)70210-921846592World Health OrganizationGuidelines for intensified tuberculosis case-finding and isoniazid preventative therapy for people living with HIV in resource-contrained settings20111187AkoloCAdetifaIShepperdSVolminkJTreatment of latent tuberculosis infection in HIV infected personsCochrane Database Syst Rev2010CD00017120091503