Nutritional supplementation in HIV-infected individuals in South India: a prospective interventional study.

BACKGROUND: Malnutrition in human immunodeficiency virus (HIV)-infected individuals is associated with faster disease progression, higher mortality rates, and suboptimal response to antiretroviral therapy (ART). METHODS: We conducted a prospective interventional study to evaluate the effects of an oral macronutrient supplement among HIV-infected adults in South India. Patients attending Tuberculosis Research Centre clinics from June 2005 through December 2007 had baseline nutritional assessment and laboratory investigations performed. Patients at 1 center received nutritional counseling and standard care, whereas patients at 2 centers additionally received a macronutrient providing 400 cal and 15 g of protein daily. Study outcomes were changes in anthropometry, body composition, blood chemistry, and immune status at 6 months. RESULTS: In total, 636 ART-naive patients were enrolled in the study; 361 completed 6 months of follow-up (282 received supplements and 79 received standard care). Mean age +/- standard deviation (SD) was 31 +/- 7 years, mean weight +/- SD was 50 +/- 10 kg, and 42% were male. Significant increases in body weight, body mass index, midarm circumference, fat-free mass, and body cell mass were observed in the supplement group but not in the control group at 6 months; gains were greater in patients with CD4 cell counts <200 cells/microL. No changes were observed in lipid levels, whereas the CD4 cell count decreased in the control group. However, after adjusting for baseline differences, these changes were not statistically significantly different between the groups. CONCLUSIONS: Macronutrient supplementation did not result in significantly increased weight gain compared with standard care (including nutritional counseling) among patients with moderately advanced HIV disease. The effect of supplementation on specific subsets of patients and on preserving immune function needs further research.

Differential effects of polyadenylic: polyuridylic acid and lipopolysaccharide on the generation of cytotoxic T lymphocytes.

In a mixed leukocyte culture (MLC) reaction of allogenic mouse spleen cells differing for H-2K or H-2D, only a weak cytotoxic response is generated. This cytotoxic response is augmented significantly if bacterial lipopolysaccharide (LPS), 5 microgram/ml, or polyadenylic acid (poly A):polyuridylic acid (poly U), 20 microgram/ml, is present in the culture. The cytotoxic cells generated in the presence of these two agents are specific for sensitizing H-2K or H-2D antigen. Two lines of evidence suggest that these two agents exert their effect at different steps in the development of cytotoxic lymphocytes: (a) the effect of poly A:U depends on the presence of adherent cells, whereas the effect of LPS is independent of the presence of adherent cells and (b) LPS promotes the development of cytotoxic cells when ultraviolet light-treated stimulating cells are used in the MLC whereas poly A:U does not.

Emergence of drug resistant mutations after single dose nevirapine exposure in HIV-1 infected pregnant women in south India.

BACKGROUND & OBJECTIVES: Resistance to nevirapine (NVP) has been described with single dose preventive regimens in other populations. Our aim was to study the pattern and prevalence of HIV drug resistance (DR) at baseline (during pregnancy) and after delivery among antenatal women exposed to single dose NVP for prevention of parent to child transmission (PPTCT). METHODS: HIV-infected, ART-naive primigravidae between 18-25 years of age, attending government antenatal clinics in Chennai, Vellore or Madurai were recruited. Drug resistance testing was carried out during pregnancy and after Sd-NVP treatment (one month after delivery) by Viroseq sequencing. HIV-1 testing by DNA PCR was done in newborns at 30 days. RESULTS: Thirty one women were enrolled but only twenty six plasma specimens were analyzable (24 paired and two postnatal only). No major mutations were observed in any drug class at baseline though many polymorphisms were observed in both the reverse transcriptase and protease genes. Mutations to non-nucleoside reverse transcriptase inhibitors (NNRTI) were observed post-delivery in 33 per cent of women who were treated with Sd-NVP. None of the infants were HIV-positive. INTERPRETATION & CONCLUSIONS: Among pregnant ART-naive women, baseline HIV drug resistance was not observed. A high rate of development of NNRTI class resistance among women treated with single-dose NVP was observed. Our results emphasize the need to implement more effective PPTCT regimens, minimizing emergence of drug resistance and thereby preserving long-term treatment options for HIV-infected women in India.

Spoligotype Diversity of Mycobacterium tuberculosis over Two Decades from Tiruvallur, South India.

Geographically, most tuberculosis (TB) cases in 2018 were reported from India. This TB burden is compounded by MDR-TB and XDR-TB. The strategies for the management and control of TB in the community depend on an understanding of the mode of spread of the different strains of TB isolates in the community. To determine the distribution and trends of M. tb strains over the time period in the community due to treatment, we carried out the present study on changes over two decades. Design/Methods. A total of 1218 M. tb isolates (year: 2001-2018) from Tiruvallur, India, were genotyped by spoligotyping after DNA extraction and subjected to anti-TB drug susceptibility testing for the first-line anti-TB drugs. Results. On analysis with the SpolDB4 database, majority (2001-2003: 53.32% and 2015-2018: 46.3%) of the isolates belonged to East African Indian (EAI) lineage, and the orphans designated in comparison to SpolDB4 stood 33% among 2001-2003 strain collection and 46.3% among 2015-2018 strain collection. 10.2% (2001-2003) and 9.26% (2015 to 2018) of isolates were monoresistant to isoniazid (H). MDR strains were less common among EAI strains (3.2%) compared to non-EAI strains (10.32%). Conclusions. EAI is the most predominant lineage in Tiruvallur, despite the presence of highly transmissible lineages like Beijing for the last two decades. The prevalence of MDR-TB is below the national average of 2-3% among the new TB cases in the last two decades. The reason can be attributed to the well-established nature of the locally circulating strains in this region which are not associated with drug resistance.

5' regulatory and 3' untranslated region polymorphisms of vitamin D receptor gene in south Indian HIV and HIV-TB patients.

INTRODUCTION: Vitamin D receptor (VDR) gene polymorphisms in the 5' regulatory region (Cdx2 and A-1012G), coding region (FokI), and 3' untranslated region (UTR; BsmI, ApaI, and TaqI) were studied to find out whether these polymorphisms are associated with susceptibility to or protection against HIV-1 and development of tuberculosis (TB) in human immunodeficiency virus (HIV)-1-infected patients. STUDY SUBJECTS AND METHODS: The study was carried out in 131 HIV patients without TB (HIV+ TB-) and 113 HIV patients with TB (HIV+ TB+; includes 82 patients with pulmonary TB (HIV+ PTB+) and 31 with extra pulmonary TB), 108 HIV-negative pulmonary TB patients (HIV- PTB+), and 146 healthy controls. RESULTS: Among the 5' regulatory and coding region polymorphisms, significantly increased frequency of G/A genotype of Cdx-2 was observed in HIV+ TB- group compared to controls (p = 0.012, odds ratio (OR) 1.89 95% confidence interval (CI) 1.14-3.15). In the 3' UTR genotypes, a decreased frequency of b/b genotype of BsmI in total HIV patients (p = 0.014, OR 0.54 95% CI 0.32-0.89) and increased frequencies of A/A genotype of ApaI in HIV+ TB+ patients (p = 0.041, OR 1.77 95% CI 1.02-3.06) and t/t genotype of TaqI in HIV+ PTB+ patients (p = 0.05, OR 2.32 95% CI 0.99-5.46) were observed compared to controls. Haplotype analysis revealed significantly increased frequencies of 3' UTR haplotype B-A-t in HIV+ TB+ and HIV+ PTB+ groups (Pc = 0.030, OR 1.75 95% CI 1.14-2.66) and decreased frequencies of b-A-T haplotype in total HIV patients (Pc = 0.012, OR 0.46 95% CI 0.27-0.77), HIV+ TB- (p = 0.031 OR 0.48 95% CI 0.25-0.89), and HIV+ PTB+ groups (Pc = 0.04, OR 0.47 95% CI 0.23-0.89) compared to controls. CONCLUSIONS: The results suggest that VDR gene 3' UTR haplotype b-A-T may be associated with protection against HIV infection while B-A-t haplotype might be associated with susceptibility to development of TB in HIV-1-infected patients.

Effect of 1,25 dihydroxyvitamin D3 on intracellular IFN-gamma and TNF-alpha positive T cell subsets in pulmonary tuberculosis.

We studied the immunomodulatory effect of 1,25(OH)(2)D(3) on single cell expression of IFN-gamma and TNF-alpha cytokines in T cell subsets of pulmonary tuberculosis (PTB) patients (n=22) and normal healthy subjects (n=22). Peripheral blood mononuclear cells (PBMCs) were cultured with live Mycobacterium tuberculosis (MTB) with or without 1,25(OH)(2)D(3) (10(-7)M) for 48 h. T cell subsets positive for IFN-gamma and TNF-alpha were enumerated by flow cytometry and the culture supernatants were assayed for both the cytokines using ELISA. In both NHS and PTB patients, a significantly reduced percentage of IFN-gamma and TNF-alpha expressing CD3+, CD3+CD4+ and CD3+CD8+ T cells were observed in cultures stimulated with live MTB and treated with 1,25(OH)(2)D(3) compared to cultures without 1,25(OH)(2)D(3) (NHS; CD3+ IFN-gamma+: p<0.0001; CD3+TNF-alpha+: p=0.0292 and PTB; CD3+ IFN-gamma+: p=0.0292; CD3+ TNF-alpha+: p=0.0028). The levels of IFN-gamma and TNF-alpha in the culture supernatants of 1,25(OH)(2)D(3) treated cultures were also found to be significantly decreased in both groups (NHS; IFN-gamma: p=0.0001; TNF-alpha: p<0.0001) and (PTB; IFN-gamma: p<0.0001; TNF-alpha: p<0.0001). A positive correlation was observed between IFN-gamma and TNF-alpha expressing CD3+CD8+ T cells in MTB stimulated cultures treated with or without 1,25(OH)(2)D(3) in NHS (p=0.0001; p=0.001, respectively) and PTB patients (p=0.002; p=0.005, respectively). The present study revealed the suppressive effect of 1,25(OH)(2)D(3) on single cell expression of IFN-gamma and TNF-alpha by CD3+CD4+ and CD3+CD8+ T cells in pulmonary tuberculosis. This suppressive effect of 1,25(OH)(2)D(3) on proinflammatory and Th1 cytokine positive cells might have a role in reducing inflammation at the site of infection.

Impact of advocacy on the tuberculosis management practices of private practitioners in Chennai City, India.

BACKGROUND: Innovative schemes to ensure the participation of private practitioners (PPs) in the Revised National Tuberculosis Control Programme (RNTCP) are necessary to identify and treat all patients with tuberculosis (TB). We developed a novel public-private mix (PPM) model to encourage PPs to practise DOTS and participate in the RNTCP while retaining their patients. METHODS: The Resource Group for Education and Advocacy for Community Health (REACH) developed and implemented the programme in partnership with the Chennai local health authority and the Tuberculosis Research Centre, Chennai, India. PPs were sensitised to the RNTCP and DOTS through a one-to-one approach or group meetings, and were assisted in referring patients. Surveys were carried out at baseline and at the completion of the study to assess changes in attitudes and practices. RESULTS: Six hundred PPs underwent sensitisation about the RNTCP, after which the proportion of PPs adopting DOTS increased significantly (P < 0.001), and the majority (72.8%) used sputum testing for diagnosing TB. The proportion of PPs who used X-ray alone for diagnosis declined to 16.0% from a baseline of 45.4%. CONCLUSIONS: This PPM model, which emphasises sustained advocacy for DOTS and allows PPs to retain private patients, looks promising and needs to be tested at other sites.

Regulatory role of 1, 25-dihydroxyvitamin D3 and vitamin D receptor gene variants on intracellular granzyme A expression in pulmonary tuberculosis.

Vitamin D receptor (VDR) genotypes have been shown to be associated with differential susceptibility or resistance to tuberculosis. The influence of FokI, BsmI, ApaI and TaqI variants of VDR gene on 1, 25(OH)(2) D(3) modulated granzyme A expression of cytotoxic lymphocytes induced by culture filtrate antigen (CFA) of Mycobacterium tuberculosis was studied in 40 pulmonary tuberculosis (PTB) patients and 49 normal healthy subjects (NHS) by flow cytometry. In both the study groups, addition of 1, 25(OH)(2) D(3) (10(-7)M) significantly reduced the percentage of granzyme A positive cells in both unstimulated (NHS, p<0.0001; PTB, p=0.02) and stimulated culture conditions (CFA, NHS, p<0.0001; PTB, p=0.0001) which correlated positively with the IFN-gamma levels (unstimulated, p=0.01; CFA stimulated, p=0.004) in NHS. The ApaI aa genotype and bbaaTT extended genotype were associated with a significantly decreased percentage of granzyme A positive cells in NHS (p<0.05). Our results suggest that 1, 25(OH)(2) D(3) suppresses granzyme A probably by down-regulating Th1 cytokine response. Moreover, the VDR gene variants might regulate cytotoxic T-cell response via 1, 25(OH)(2) D(3) mediated suppression of granzyme A expression in tuberculosis.

Haplotype analysis of HLA-A, -B antigens and -DRB1 alleles in south Indian HIV-1-infected patients with and without pulmonary tuberculosis.

We have shown earlier the association of human leucocyte antigen (HLA)-A11 with resistance and HLA-B40 and -DR2 with susceptibility to HIV and HIV-TB. In the present study, we have attempted to find out the HLA-DR2 subtypes and the possible HLA-A/-B/-DRB1 haplotype combinations that are associated with susceptibility or resistance to HIV and HIV with pulmonary tuberculosis (HIV+PTB+). HLA-DR2 subtyping was carried out by polymerase chain reaction-based sequence-specific oligonucleotide probe method. Overrepresentation of HLA-DRB1*1501 in HIV-positive PTB-negative (HIV+PTB-) patients (P = 0.004, P(c) = 0.06) and -DRB1*1502 in HIV-positive PTB-positive (HIV+PTB+) patients (P = 0.019) was observed as compared to healthy controls. Haplotype analysis revealed an increased frequency of HLA-A2-DRB1*1501 haplotype in HIV+PTB- patients (P = 0.008) and HLA-A2-DRB1*1502 among HIV+PTB+ patients (P = 0.01) compared to healthy controls. The haplotypes B40-DRB1*1501 and B40-DRB1*04 were found to be moderately increased in HIV+PTB(-) and HIV+PTB+ patients (P < 0.05). The study suggests that HLA-A2-DRB1*1501 haplotype may be associated with HIV infection while HLA-A2-DRB1*1502 haplotype might be associated with susceptibility to PTB in HIV patients. Moreover, HLA-B40-DRB1*1501 and HLA-B40-DRB1*04 haplotypes may be associated with susceptibility to HIV infection and to PTB in HIV patients.

CCR2, MCP-1, SDF-1a & DC-SIGN gene polymorphisms in HIV-1 infected patients with & without tuberculosis.

BACKGROUND & OBJECTIVES: Variability in the clinical outcome of persons exposed to and infected with HIV-1 and tuberculosis (TB) is determined by multiple factors including host genetic variations. The aim of the present study was to find out whether chemokine, chemokine receptor and DC-SIGN gene polymorphisms were associated with susceptibility or resistance to HIV and HIV-TB in south India. METHODS: CCR2 V64I (G/A), monocyte chemoattractant protein-1 (MCP-1) -2518 A/G, stromal cell derived factor-1alpha; (SDF-1alpha) 3'UTR G/A and DC-SIGN gene polymorphisms were studied by polymerase chain reaction based methods in HIV-1 infected patients without TB (n=151), with pulmonary TB (PTB) (n=81) and extrapulmonary TB (n=31), 155 PTB patients without HIV and 206 healthy controls. RESULTS: The genotype frequencies of CCR2 V64I, MCP-1 -2518 and DC-SIGN polymorphisms did not differ significantly between the study groups. A significantly increased frequency of GG genotype of SDF-1alpha polymorphism was observed among HIV+PTB+ patients compared to healthy controls (P=0.009, Pc=0.027). INTERPRETATION & CONCLUSIONS: Our data suggest that GG genotype of SDF-1alpha 3'UTR polymorphism may be associated with susceptibility to PTB in HIV-1 infected patients. A better understanding of genetic factors that are associated with TB could help target preventive strategies to those HIV patients likely to develop tuberculosis.

Incomplete immunological recovery following anti-tuberculosis treatment in HIV-infected individuals with active tuberculosis.

BACKGROUND & OBJECTIVE: Mycobacterium tuberculosis infection has been shown to result in increased HIV replication and disease progression in HIV-infected individuals through increased immune activation. The objective of this study was to correlate plasma levels of immune activation markers with the presence of tuberculosis (TB) in HIV-infected and uninfected individuals, and to study the changes following anti-tuberculosis treatment. METHODS: Plasma markers of immune activation - neopterin, beta-2-microglobulin (beta2M) and soluble tumour necrosis factor alpha receptor type I (sTNFalpha-RI) were measured by ELISA in 42 HIV positive TB patients (HIV+TB+) undergoing a six-month course of TB chemotherapy. Thirty seven HIV+ persons without active TB, 38 TB patients without HIV infection, and 62 healthy volunteers served as controls. RESULTS: Plasma levels of all three markers were elevated in HIV+ individuals, more so in those with active TB. When HIV+ individuals were further categorized based on CD4+ T cell counts, HIV+TB+ patients with CD4+ T cells counts

DOTS reaches socially marginalized population in the community: a study from a rural area of South India.

We report here that the Directly Observed Treatment, Short course (DOTS) is reaching all tuberculosis patients in the community irrespective of social classification based on the analysis from the tuberculosis prevalence survey and programme performance during 1999-2003 from a rural area in Tamilnadu, South India. New smear- positive cases treated under a DOTS programme were classified in two groups namely; scheduled caste living in colony and other population. The prevalence of smear- positive cases among the scheduled caste population was 1.9 times higher than the other population and this was reflected in the notification also. The successful treatment outcome was also similar in these two groups (75% and 78% respectively; overall 77%). From these findings it is concluded that people living in colony have equal access to DOTS as those in the village.

Nutritional status of persons with HIV infection, persons with HIV infection and tuberculosis, and HIV-negative individuals from southern India.

We compared the nutritional status of individuals with human immunodeficiency virus (HIV) infection alone, individuals with HIV infection and tuberculosis (after completion of antituberculosis treatment), and HIV-negative individuals and found that malnutrition, anemia, and hypoalbuminemia were most pronounced among HIV-positive patients with tuberculosis. Weight loss was associated with loss of fat in female patients and with loss of body cell mass in male patients.

HLA-DQB1 and -DPB1 allele profile in HIV infected patients with and without pulmonary tuberculosis of south India.

We made an attempt to find out whether Human Leucocyte Antigen (HLA)-DQB1 and -DPB1 alleles are associated with susceptibility or resistance to Human Immunodeficiency Virus (HIV) infection and development of pulmonary tuberculosis (PTB) in HIV infected patients. The allelic profile of HLA-DQB1 and -DPB1 was studied among HIV patients without pulmonary tuberculosis (HIV+PTB-) (n = 115), HIV patients with pulmonary TB (HIV+PTB+) (n = 59), HIV negative PTB patients (HIV-PTB+) (n = 110) and healthy controls (n=112) by polymerase chain reaction and sequence specific oligonucleotide probe method. Increased frequency of HLA-DQB1*050301 was observed in HIV+PTB- [p = 0.024, Odds Ratio (OR) 2.30, 95% Confidence Interval (CI) 1.11-4.90] and HIV+PTB+ patients (p = 0.044, OR 2.41, 95% CI 1.01-5.73) compared to healthy controls, suggesting that DQB1*050301 may be associated with susceptibility to HIV infection as well as development of PTB in HIV patients. Underrepresentation of HLA-DPB1*1501 was observed in HIV-PTB+ (p = 0.002, Pc = 0.034) and HIV+PTB+ (p = 0.036) patients compared to healthy controls, suggesting that DPB1*1501 may be associated with protection against PTB development both in HIV positive and negative subjects. Analysis on the amino acid variation in the peptide binding pocket at beta69 position of HLA-DPB1 molecules revealed that the beta69 arginine containing HLA-DPB1 alleles and the genotype lysine/arginine were underrepresented in HIV-PTB+ (allele: p = 0.003, Pc = 0.009; genotype: p = 0.0002, Pc = 0.001) and HIV+PTB+ (allele: p = 0.016, Pc = 0.048; genotype: p = 0.026). This suggests that HLA-DPB1 alleles with arginine may be associated with protection against development of PTB in both HIV infected as well as uninfected individuals. Further, the haplotypes HLA-DRB1*1502-DPB1*0201 and HLA-DQB1*0601-DPB1*0201 (Pc < 0.001) and HLA-DRB1*1502-DQB1*0601-DPB1*0201 (p = 0.006, OR 5.09, 95% CI 1.42-22.66) were significantly overrepresented in HIV+PTB+ patients compared to healthy controls suggesting that genetic susceptibility to PTB development in HIV patients may be modulated by interplay between HLA class II alleles, besides HLA class I alleles.

Genomic interrogation of ancestral Mycobacterium tuberculosis from south India.

Mycobacterium tuberculosis is a very important global pathogen. One quarter of the world's TB cases occur in India. The tuberculosis strains isolated from south Indian patients exhibit certain phenotypic characteristics like low virulence in guinea-pigs, resistance to isoniazid, thiophene-2-carboxylic acid hydrazide (TCH) and para-amino salicylic acid (PAS), and enhanced susceptibility to H2O2. Besides this, a large percentage of the isolates harbor only a single copy of IS 6110 which makes these strains distinct. Hence, we have studied the genotypic characteristics of these strains by using advanced techniques like Deletion Micro array, deletion PCR, allelic discrimination RT-PCR using several lineage specific markers and KatG G1388T (non-synonymous) polymorphism along with spoligotyping. The analysis of 1215 tuberculosis patient isolates from south India revealed that 85.2% belonged to the ancestral lineage of M. tuberculosis. Comparative whole-genome hybridization identified six new genomic regions within this lineage that were variably deleted.

Cytokine gene polymorphisms and cytokine levels in pulmonary tuberculosis.

Polymorphisms in the cytokine genes are known to influence cytokine levels and may be associated with outcome of infections. We investigated the polymorphisms in the cytokine genes namely IFN-gamma (+874 and +5644), IL-2 (-330 and +160), IL-4 (VNTR), IL-6 (-174), IL-10 (-1082 and -819) and IL-12B (+1188) in 188 normal healthy subjects (NHS) and 166 pulmonary tuberculosis patients (PTB) using polymerase chain reaction-based methods. To study the influence of cytokine gene polymorphisms on cytokine levels, phytohaemagglutinin and culture filtrate antigen of Mycobacterium tuberculosis-induced cytokine levels were measured by ELISA from 72-h-old peripheral blood mononuclear cell culture supernatants. Significantly decreased frequency of TT genotype of IL-2 -330 polymorphism (p=0.024, odds ratio (OR) 0.53, 95% CI 0.31-0.92) was observed in patients compared to NHS. The genotype frequencies of other polymorphisms were not different between patients and NHS. IL-12p40 levels were significantly decreased among NHS with AA genotype of IL-12B gene polymorphism compared to NHS with AC genotype (p<0.05). Increased levels of IL-12p40 were observed among patients with CC genotype of IL-12B gene compared to patients with other genotypes (p<0.01). The present study suggests that the TT genotype of IL-2 -330 polymorphism may be associated with the protection to PTB in south India. Further, +1188 polymorphism of IL-12B gene either alone or in combination with closely linked genes may regulate IL-12p40 production and may play a major role on acquired immunity to tuberculosis.

Excess mortality and risk factors for mortality among a cohort of TB patients from rural south India.

OBJECTIVES: To estimate the excess general mortality among tuberculosis (TB) patients in a rural area (Tiruvallur) and identify risk factors for TB-related mortality. SETTING: The study population consisted of all TB patients aged >or=15 years who were registered under the Revised National Tuberculosis Control Programme (RNTCP) during the years 2000 to 2003 at Velliyur TB unit (TU) in south India. DESIGN: This is a retrospective cohort study of 3405 patients treated under the DOTS strategy, followed up from the date of start of treatment till the date of interview (for the survivors) or the date of death (for those who died). RESULTS: There were 2710 (79.6%) survivors and 695 (20.4%) deaths. The excess general mortalities for the cohort, expressed as standardised mortality ratio (SMR), was 4.2 (95%CI 3.9-4.5). High SMR values were obtained for patients belonging to the 15-44 years age group (12.1), patients on Category II regimen (9.3), treatment failures (9.1) and defaulters (7.8). The adjusted hazards ratios (aHR) were high for patients aged 45-59 years (1.9), >or=60 years (3.1) and with incomplete treatment due to default or failure (6.4). CONCLUSION: TB is one of the main causes of mortality in the younger age group. Among TB patients, the major risk factors for mortality are old age (>or=45 years) and incomplete treatment.

Tuberculin skin test results in HIV-infected patients in India: implications for latent tuberculosis treatment.

OBJECTIVE: To evaluate the utility of the tuberculin skin test (TST) in detecting latent and active tuberculosis (TB) among human immunodeficiency virus (HIV) infected patients in South India. DESIGN: TSTs and CD4 counts were collected from 631 HIV-infected individuals without active TB and 209 antiretroviral and anti-tuberculosis treatment-naïve HIV-infected patients with TB. We calculated the proportion of TST-positive individuals, as well as the sensitivity, specificity, positive predictive value (PPV) and negative predictive value of TST in the diagnosis of TB. RESULTS: Among subjects without active TB, 28% with a CD4 count <100 cells/microl vs. 43% of the total cohort had a TST >5 mm (P = 0.14), while the proportions with induration >10 mm were 14% vs. 36%, respectively (P < 0.01). Among those with active TB, using a 5 mm cut-off, the sensitivity was 42% for those with CD4 counts <200 cells/mul compared to 70% for those with CD4 counts >or=200 cells/microl (P < 0.001). The PPV for detecting active TB was 29%. CONCLUSIONS: TST is a poor predictor of both latent and active TB in HIV-infected individuals in TB endemic countries. Programmes offering treatment for latent TB should consider including all HIV-positive patients regardless of TST status, or use other indicators, such as CD4 count.