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 .