since 2000 , over 35,000 new cases of tuberculosis ( tb ) have been recorded annually in korea , raising concerns about an increasing incidence of multidrug - resistant tb ( mdr - tb ) ( 1 ) .
globally , the epidemiological synergy between hiv and tb co - infection and the deadly synergy between hiv and mdr - tb are major public health threats ( 2 ) .
the prevalence of human immunodeficiency virus ( hiv ) infection in korea is very low ( less than 0.1% ) , but hiv / tb co - infection is gradually increasing ( 3 , 4 ) .
although the relationship between hiv infection and tb is well understood , the association between hiv and mdr - tb is not clear ( 5 ) .
the aim of this study was to evaluate the prevalence of and risk factors for mdr - tb infection in hiv / tb co - infected patients .
this was a retrospective cohort study at the national medical center of korea , which has 540 beds , is managed under governmental supervision , and has one of the largest hiv care centers in korea .
eight hundred and fourteen hiv patients were registered from january 2005 to may 2011 . of these ,
55 clinically diagnosed tb patients with records of drug - susceptibility tests ( dsts ) were enrolled and analyzed .
patients whose drug - susceptibility profiles were unavailable and those transferred from other institutions without previous laboratory records were excluded .
acid - fast bacilli ( afb ) identification was carried out using bacteriological , molecular ( accupower mtb real - time pcr kit ; bioneer co. , daejeon , korea ) , and histopathological methods .
the dsts were performed using absolute concentration methods and/or the genotype mtbdr plus assay ( hain lifescience , nehren , germany ) .
mdr - tb was defined as in vitro resistance to at least isoniazid ( inh ) and rifampin ( rif ) .
extensively drug - resistant tuberculosis ( xdr - tb ) was defined as mdr - tb with additional resistance to any fluoroquinolone and any of the second - line anti - tb injectable drugs ( 6 ) .
traditional absolute concentration test data were used when the results of the 2 dst tests were not consistent .
clinical data including cd4 cell count and viral load were collected within 4 weeks of tb diagnosis .
acquired immune deficiency syndrome ( aids ) - defining clinical illnesses were determined using the us centers for disease control and prevention criteria ( 7 ) . to explore associated risk factors for mdr - tb in hiv / tb co - infected patients , demographic characteristics , clinical parameters and clinical outcomes
were compared between the mdr - tb group and the non - mdr - tb group .
univariate analysis was performed to assess the association between predictor variables and drug - susceptibility patterns of mycobacterium tuberculosis among hiv / tb co - infected cases .
p values were determined using the independent t - test or the mann - whitney u - test in the case of quantitative variables .
fisher 's exact test was performed to analyze the association between categorical variables and drug - susceptibility patterns of m. tuberculosis .
this study was approved by the institutional review board of the national medical center ( protocol no ; h-1105/011 - 004 ) .
this was a retrospective cohort study at the national medical center of korea , which has 540 beds , is managed under governmental supervision , and has one of the largest hiv care centers in korea .
eight hundred and fourteen hiv patients were registered from january 2005 to may 2011 . of these ,
55 clinically diagnosed tb patients with records of drug - susceptibility tests ( dsts ) were enrolled and analyzed .
patients whose drug - susceptibility profiles were unavailable and those transferred from other institutions without previous laboratory records were excluded .
acid - fast bacilli ( afb ) identification was carried out using bacteriological , molecular ( accupower mtb real - time pcr kit ; bioneer co. , daejeon , korea ) , and histopathological methods .
the dsts were performed using absolute concentration methods and/or the genotype mtbdr plus assay ( hain lifescience , nehren , germany ) .
mdr - tb was defined as in vitro resistance to at least isoniazid ( inh ) and rifampin ( rif ) . extensively drug - resistant tuberculosis ( xdr - tb )
was defined as mdr - tb with additional resistance to any fluoroquinolone and any of the second - line anti - tb injectable drugs ( 6 ) .
traditional absolute concentration test data were used when the results of the 2 dst tests were not consistent .
clinical data including cd4 cell count and viral load were collected within 4 weeks of tb diagnosis . acquired immune deficiency syndrome ( aids ) - defining clinical illnesses
were determined using the us centers for disease control and prevention criteria ( 7 ) . to explore associated risk factors for mdr - tb in hiv / tb co - infected patients , demographic characteristics , clinical parameters and clinical outcomes
were compared between the mdr - tb group and the non - mdr - tb group .
univariate analysis was performed to assess the association between predictor variables and drug - susceptibility patterns of mycobacterium tuberculosis among hiv / tb co - infected cases .
p values were determined using the independent t - test or the mann - whitney u - test in the case of quantitative variables .
fisher 's exact test was performed to analyze the association between categorical variables and drug - susceptibility patterns of m. tuberculosis .
this study was approved by the institutional review board of the national medical center ( protocol no ; h-1105/011 - 004 ) .
among the 814 hiv patients registered , 119 patients received anti - tb treatment . among these 119 , 55 patients had records of the dst results . in 55 subjects with available the dst results , eight had past medical history of anti - tb treatment and 47 were primary tb cases . including 6 xdr - tb patients ,
32.7% ( 18 of 55 ) were identified with mdr - tb . in 47 primary tb cases ,
29.7% ( 14 of 47 ) were mdr - tb ( i.e. , primary or transmitted mdr - tb ) . in 37 patients with non - mdr - tb , 34 had
there was no difference in demographic factors including age , gender , and body mass index ( bmi ) between the 2 groups ( table 1 ) .
no difference was found regarding the medical history ( including previous tb history , treatment adequacy , and use of highly active antiretroviral therapy [ haart ] ) prior to tb diagnosis .
however , patients ' immune status differed between the 2 groups : the median cd4 count was lower in the mdr - tb group than in the non - mdr - tb group ( 57 vs 121 cells/l ) , but this result was not statistically significant ( p = 0.251 ) .
notably , the frequency of additional aids - defining clinical illnesses other than tuberculosis before or at the time of tb diagnosis was significantly higher in the mdr - tb group ( 27.8% , 5 of 8) than in the non - mdr - tb group ( 5.4% , 2 of 37 ) ( p = 0.032 ) .
there were no significant differences between the two groups with regard to the well - reported risk factors for both mdr - tb and hiv , including smoking , drinking , and socioeconomic status as classified by the status of health insurance .
excluding 1 xdr - tb patient who died of head trauma , in - hospital mortality was significantly higher in the mdr - tb group ( 38.9% , 7 of 18 ) than in the non - mdr - tb group ( 13.5% , 5 of 37 ) ( p = 0.043 ) . in xdr - tb cases ,
this is the first study in korea to address the issue of mdr - tb among hiv / tb co - infected patients in a low hiv - prevalence and intermediate tb - burden setting .
the prevalence of mdr - tb among hiv / tb co - infected patients was 32.7% ( 18 of 55 ) in our center , which is significantly higher than that among the general population ( 9% in 2008 ) .
in addition , the rate of primary mdr - tb is 29.7% ( 14 of 47 ) , which is approximately 13 times higher than that in the general population ( 2.3% , 2003 - 2008 ) ( 8)
. a wide range of mdr - tb prevalence has been observed in different countries , which implies that there are many local confounders and common factors between mdr - tb and hiv ( 5 ) . on an individual level , it has been suggested that immunosuppression is a mechanism that may allow hiv infection to contribute to the development of mdr - tb .
molecular studies have suggested that mdr - tb strains are related to loss of fitness and have a tendency to spread in immunocompromised hosts ( 9 , 10 ) . in this
regard , cd4 cell count and aids - defining illness are well - established markers of immunosupression , and our results support the suggestion that immunosuppression is associated with mdr - tb infection .
the cd4 t - cell counts in the mdr - tb group were lower than those in the non - mdr - tb group , although this result was not statistically significant .
furthermore , aids - defining illnesses other than tb were observed more frequently in the mdr - tb group than in the non - mdr - tb group ( p = 0.032 ) , suggesting that immunosuppression by hiv infection may be associated with mdr - tb infection .
in korea , hiv patients tend to be stigmatized and isolated from society . as a result , they tend to be of low socioeconomic status , consume excessive alcohol , and smoke , all of which increase the risk of mdr - tb infection ( 5 , 11 ) .
however , our results show no significant difference in these factors between the 2 groups . the higher in - hospital mortality rate among hiv / mdr - tb - infected patients in our results is consistent with previous findings ( 12 , 13 ) . in this context , the early diagnosis and rapid recognition of dr - tb in hiv patients are necessary to improve prognoses . while dst using conventional methods
has a long turnaround time , a new molecular test is fast and sensitive ( 14 , 15 ) .
thus , we propose that this new test should always be performed in hiv patients who are suspected of having tb . as a retrospective single center study ,
more than half ( 64 of 119 ) of the hiv / tb co - infected patients were excluded because their dst data was not available . and the lack of information such as tb exposure history or use of second - line tb drugs may make it hard to analyze risk factors .
given that the prevalence of hiv / tb co - infection is very low , and it is relatively troublesome to confirm the drug susceptibility of m. tuberculosis in hiv / tb co - infected patients , however , our results could play a crucial role in understanding of hiv / tb co - epidemic in korea . in conclusion ,
the prevalence of mdr - tb among hiv / tb co - infected patients is significantly higher than that in the general population .
surveillance of drug - resistant tb among hiv infected patients is essential to reduce mortality and prevent the ongoing spread of drug resistance and should be conducted urgently . in addition , hiv - related immunosuppression may be associated with mdr - tb infection .
 much controversy surrounds the issue of whether hiv infection is a risk factor for developing multidrug - resistant tuberculosis ( mdr - tb ) . in this study 
 , we evaluated the prevalence of and risk factors for mdr - tb in hiv - infected patients at the national medical center of korea . 
 we reviewed the medical records of hiv / tb co - infected patients from january 2005 to may 2011 ; the drug susceptibility profiles were available for 55 patients . 
 of these , 32.7% had mdr - tb , which was approximately 3.6 times higher than the prevalence among the general population . 
 additionally , there were more additional aids - defining clinical illnesses in the mdr - tb group than in the non - mdr - tb group ( 27.8% vs 5.4% , p = 0.032 ) . 
 these results suggest that hiv infection and hiv - related immunosuppresion may contribute to the development of mdr - tb . 
INTRODUCTION
MATERIALS AND METHODS
Study site and subjects
Measurements
Statistics
Ethics statement
RESULTS
DISCUSSION