Government Hospital of Thoracic Medicine

Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI. 1. Ischemic symptom improvement is the primary indication for CTO-PCI. 2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI. 3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges. 4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs. 5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use. 6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation. 7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training.

We evaluated the effects of human immunodeficiency virus (HIV) disease on pharmacokinetics of antituberculosis medications by measuring concentrations of isoniazid and rifampin in blood and of pyrazinamide and ethambutol in urine. Peak concentration and exposure were reduced for rifampin, and rapid acetylators of isoniazid had lower drug levels. HIV and HIV-tuberculosis patients who have diarrhea and cryptosporidial infection exhibit decreased bioavailability of antituberculosis drugs.

The ART program in low- and middle-income countries (LMIC) like India, has a public health approach with the standardized regimen for all people living with HIV (PLHIV). Based on the evidence from high-income countries (HIC), the risk of an enhanced and accentuated onset of premature-aging or age-related diseases has been observed in PLHIV. However, very limited data is available on residual inflammation and immune activation in the populations who are on first-generation anti-HIV drugs like zidovudine and lamivudine that have more toxic side effects. Therefore, the aim of the present study was to evaluate the levels of systemic inflammation and understand the risk of age-associated diseases in PLHIV on long-term suppressive ART using a large number of biomarkers of the inflammation and immune activation. Blood samples were obtained from therapy naïve PLHIV (Pre-ART, n=43), PLHIV on ART for >5 years (ART, n=53), and HIV-negative healthy controls (HIVNC, n=41). Samples were analyzed for 92 markers of inflammation, sCD14, sCD163, and telomere length. Several statistical tests were performed to compare the groups under study. Multivariate linear regression was used to investigate the associations. Despite a median duration of eight years of successful ART, sCD14 (p<0.001) and sCD163 (p=0.04) levels continued to be significantly elevated in ART group as compared to HIVNC. Eleven inflammatory markers, including 4E-BP1, ADA, CCL23, CD5, CD8A, CST5, MMP1, NT3, SLAMF1, TRAIL and TRANCE, were found to be significantly different (p<0.05) between the groups. Many of these markers are associated with age-related co-morbidities including cardiovascular disease, neurocognitive decline and some of these markers are being reported for the first time in the context of HIV-induced inflammation. Linear regression analysis showed a significant negative association between HIV-1-positivity and telomere length (p<0.0001). In ART-group CXCL1 (p=0.048) and TGF- (p=0.026) have a significant association with increased telomere length and IL-10RA was significantly associated with decreased telomere length (p=0.042). This observation warrants further mechanistic studies to generate evidence to highlight the need for enhanced treatment monitoring and special interventions in HIV-infected individuals.

The absorption of rifampin, isoniazid, and D-xylose in patients with human immunodeficiency virus (HIV) infection and diarrhea, in patients with HIV infection and tuberculosis (TB), in patients with pulmonary TB alone, and in healthy subjects was studied. Percentage of dose of the drugs, their metabolites, and D-xylose excreted in urine were calculated. A significant reduction in the absorption of drugs and D-xylose in both the HIV infection/diarrhea and HIV infection/TB groups was observed (P<.05), and the correlation between them was significant. Our results indicate that patients with HIV infection and diarrhea and those with HIV infection and TB have malabsorption of rifampin and isoniazid.

BACKGROUND: Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with Bedaquiline and Delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+). METHODS: We prospectively determined the effectiveness and safety of combining two new drugs with two repurposed drugs - Bedaquiline, Delamanid, Linezolid, and Clofazimine for 24-36 weeks in adults with pulmonary MDR-TBFQ+ or/and MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as two consecutive negative cultures taken four weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during treatment period. RESULTS: Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: four deaths, seven treatment changes, two bacteriological failures, and one withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500msec. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority. CONCLUSION: After 24-36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully.

BACKGROUND: The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. METHODS: HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. RESULTS: Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14-47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7-16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9-23). Two patients died due to CNS TB-IRIS. Lower CD4(+) T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. CONCLUSION: Paradoxical TB-IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions.

BACKGROUND: Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India. METHODS: Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens. RESULTS: Of 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification. CONCLUSIONS: 4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB. TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2012/10/003060.

SETTING: The currently recommended dosages of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol in children are extrapolated from adult pharmacokinetic studies, and have not been adequately evaluated in children. OBJECTIVE: To describe the pharmacokinetics of RMP, INH and PZA given thrice weekly in children with tuberculosis (TB), and to relate pharmacokinetics to treatment outcomes. METHODS: Eighty-four human immunodeficiency virus negative children with TB aged 1-12 years in Chennai and Madurai, India, were recruited. Phenotypic INH acetylator status was determined. Nutritional status was assessed using Z scores. During the intensive phase of anti-tuberculosis treatment, a complete pharmacokinetic study was performed after directly observed administration of drugs. At 2 and 6 months, drug levels were measured 2 h post-dose. Drug concentrations were measured using high performance liquid chromatography and pharmacokinetic variables were calculated. Multivariable regression analysis was performed to explore factors impacting drug levels and treatment outcomes. RESULTS AND CONCLUSIONS: Children aged <3 years had significantly lower RMP, INH and PZA concentrations than older children, and 90% of all children had sub-therapeutic RMP Cmax (<8 μg/ml). Age, nutritional status and INH acetylator status influenced drug levels. Peak RMP and INH concentrations were important determinants of treatment outcome. Recommendations for anti-tuberculosis treatment in children should take these factors into consideration.

Kidney stone affect 10-12% of the population in industrialized countries. The average life time risk of stone formation has been reported in the range of 5-10%. Recurrent stone formation is a common part of the medical care of patients with stone diseases. The aetiology of this disorder is multi factorial and is strongly related to dietary lifestyle habits or practices. Increased rates of hypertension, diabetes and obesity which are linked to nephrolithiasis, also contribute to an increase in stone formation. Hence, this study was undertaken to find out the prevalence among kidney stone patients. Aim and objectives: To assess the prevalence of kidney stone among patients visiting in OPD-1, Dept.ofMaruthuvam (Medicine), National Institute of Siddha and also to find out the risk factors influencing the development of kidney stones especially Family history, inadequate fluid intake, Stress, Over weight and Obesity, Dietary habits and lifestyle modifications, association with other diseases (diabetes, hypertension). Materials and methods: The study was conducted among 666 kalladaippu (kidney stone) patients. Details of factors influencing the formation of kidney stone were obtained using a pretested questionnaire. Results and conclusion: The study revealed a high prevalence of kidney stone is due to low fluid intake 72.07%(p=0.000),dehydration 67.56% (p=0.012) and dietary habits ofmixed diet 91.59%(p=0.000),, high intake of coffee and tea 57.50%, sodium 64.26%, sugar 49.84%. Life style modifications of smoking 36.03%, alcohol consumption 41.59%, lack of physical activity 42.79%, obesity 54.80% also revealed a high prevalence of this disease.

India accounts for about one-fourth of the global burden of MDR-TB. This study aims to assess the prevalence and factors associated with tuberculosis drug resistance among patients from South India. MTBDRplus assay and MGIT liquid culture performed on 20,245 sputum specimens obtained from presumptive MDR-TB cases during a six-year period from 2013 to 2018 were analyzed retrospectively. Univariate and multivariate logistic regression analysis was carried out to evaluate factors associated with MDR, Rifampicin mono-resistance, and Isoniazid mono-resistance. MDR, Rifampicin mono- resistant and Isoniazid mono-resistant TB were found in 5.4%, 2.5%, and 11.4% cases of presumptive MDR-TB, respectively. Based on the rpoB gene, true resistance, hetero-resistance, and inferred resistance to Rifampicin was found in 38%, 29.3%, and 32.7% of the 1582 MDR cases, respectively. S450L (MUT3) was the most common rpoB mutation present in 59.4% of the Rifampicin resistant cases. Of the 3390 Isoniazid resistant cases, 72.5% had mutations in the katG gene, and 27.5% had mutations in the inhA gene. True resistance, heteroresistance, and inferred resistance accounted for 42.9%, 22.2%, and 17.3% of the 2459 katG resistant cases, respectively. True resistance, heteroresistance, and inferred resistance for the inhA gene were found in 54.5%, 40.7%, and 4.7% cases, respectively. MDR-contact (AOR 3.171 95% CI: 1.747-5.754, p-0.000) treatment failure (AOR 2.17595% CI: 1.703-2.777, p-0.000) and female gender (AOR 1.315 95% CI: 1.117-1.548, p-0.001), were positively associated with MDR-TB. Previous TB treatment did not show a significant positive association with MDR (AOR 1.113 95% CI: 0.801-1.546, p-0.523). Old age (AOR 0.994 95% CI: 0.990-0.999, p-0.023) and HIV seropositivity (AOR 0.580 95% CI: 0.369-0.911, p-0.018) were negatively associated with MDR-TB. Although Rifampicin mono-resistance had a positive association with treatment failure (AOR 2.509 95% CI: 1.804-3.490, p < .001), it did not show any association with previous TB treatment (AOR 1.286 95% CI: 0.765-2.164, p-0.342) or with history of contact with MDR-TB (AOR 1.813 95% CI: 0.591-5.560, p-0.298). However, INH mono-resistance showed a small positive association with the previous history of treatment for TB (AOR 1.303 95% CI: 1.021-1.662, p-0.033). It was also positively associated (AOR 2.094 95% CI: 1.236-3.548, p-0.006) with MDR-TB contacts. Thus INH resistance may develop during treatment if compliance has not adhered too and may be easily passed on to the contacts while Rifampicin resistance is probably due to factors other than treatment compliance. MDR-TB, i.e. resistance to both Rifampicin and Isoniazid, is strongly correlated with treatment failure, spread through contact, and not to treatment compliance. The temporal trend in this region shows a decrease in MDR prevalence from 8.4% in 2015 to 1.3% in 2018. A similar trend is observed for Rifampicin mono-resistance and Isoniazid mono-resistance, pointing to the effectiveness of the TB control program. The higher proportion of inferred resistance observed for Rifampicin compared with INH may indicate a surfeit of mechanisms that enable rifampicin resistance. Association of MDR-TB with age, gender, and HIV status suggest the role of the immune system in the emergence of the MDR phenotype.

Targeted metabolomics studies reported metabolic abnormalities in both treated and untreated people living with human immunodeficiency virus (HIV) (PLHIV). The present study aimed to understand the plasma metabolomic changes and predicted the risk of accelerated aging in PLHIV on long-term suppressive antiretroviral therapy (ART) in a case-control study setting and its association with the plasma proteomics biomarkers of inflammation and neurological defects. Plasma samples were obtained from PLHIV on successful long-term ART for more than five years (n = 22) and matched HIV-negative healthy individuals (n = 22, HC herein). Untargeted metabolite profiling was carried out using ultra-high-performance liquid chromatography/mass spectrometry/mass spectrometry (UHPLC/MS/MS). Plasma proteomics profiling was performed using proximity extension assay targeting 184 plasma proteins. A total of 250 metabolites differed significantly (p &lt; 0.05, q &lt; 0.1) between PLHIV and HC. Plasma levels of several essential amino acids except for histidine, branched-chain amino acids, and aromatic amino acids (phenylalanine, tyrosine, tryptophan) were significantly lower in PLHIV compared to HC. Machine-learning prediction of metabolite changes indicated a higher risk of inflammatory and neurological diseases in PLHIV. Metabolic abnormalities were observed in amino-acid levels, energetics, and phospholipids and complex lipids, which may reflect known differences in lipoprotein levels in PLHIV that can resemble metabolic syndrome (MetS).

BACKGROUND: Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered an adjunctive therapy to anti-tuberculosis treatment (ATT). We determined whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB). METHODS: In a randomized, 8-week, clinical trial, newly diagnosed, culture-positive PTB patients were randomized to standard ATT (HREZ = control arm) or standard ATT plus daily 1000 mg metformin (MET-HREZ = Metformin with Rifampicin [METRIF] arm) for 8 weeks during 2018-2020 at 5 sites in India. The primary end point was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. A Cox proportional hazard model was used to estimate time and predictors of culture conversion. RESULTS: Of the 322 patients randomized, 239 (74%) were male, and 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the control arm (hazard ratio, 0.8; 95% confidence interval [CI], .624-1.019). After 8 weeks of ATT, cavitary lesions on X-ray (7, 5.3% vs 18, 12.9%; relative risk, 0.42; 95% CI, .18-.96; P = .041) and inflammatory markers were significantly lower in the METRIF arm. Higher body mass index and lower sputum smear grading were associated with faster sputum culture conversion. CONCLUSIONS: The addition of metformin to standard ATT did not hasten sputum culture conversion but diminished excess inflammation, thus reducing lung tissue damage as seen by faster clearance on X-ray and reduced inflammatory markers. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2018/01/011176).

BACKGROUND: A rapid and specific test is urgently needed for tuberculosis (TB) diagnosis especially among human immunodeficiency virus (HIV) infected individuals. In this study, we assessed the sensitivity of Interferon gamma release assay (IGRA) in active tuberculosis patients who were positive for HIV infection and compared it with that of tuberculin skin test (TST). METHODOLOGY/PRINCIPAL FINDINGS: A total of 105 HIV-TB patients who were naïve for anti tuberculosis and anti retroviral therapy were included for this study out of which 53 (50%) were culture positive. Of 105 tested, QuantiFERON-TB Gold in-tube (QFT-G) was positive in 65% (95% CI: 56% to 74%), negative in 18% (95% CI: 11% to 25%) and indeterminate in 17% (95% CI: 10% to 24%) of patients. The sensitivity of QFT-G remained similar in pulmonary TB and extra-pulmonary TB patients. The QFT-G positivity was not affected by low CD4 count, but it often gave indeterminate results especially in individuals with CD4 count < 200 cells/microl. All of the QFT-G indeterminate patients whose sputum culture were positive, showed < or = 0.25 IU/ml of IFN-gamma response to phytohemagglutinin (PHA). TST was performed in all the 105 patients and yielded the sensitivity of 31% (95% CI: 40% to 22%). All the TST positives were QFT-G positives. The sensitivity of TST was decreased, when CD4 cell counts declined. CONCLUSIONS/SIGNIFICANCE: Our study shows neither QFT-G alone or in combination with TST can be used to exclude the suspicion of active TB disease. However, unlike TST, QFT-G yielded fewer false negative results even in individuals with low CD4 count. The low PHA cut-off point for indeterminate results suggested in this study (< or = 0.25 IU/ml) may improve the proportion of valid QFT-G results.

The dose of efavirenz during concomitant rifampin (RMP) administration is a matter of debate. We studied the influence of RMP coadministration on the steady-state pharmacokinetics of efavirenz in human immunodeficiency virus type 1 (HIV-1)-infected patients in South India. Fifty-seven HIV-tuberculosis (TB)-coinfected and 15 HIV-1-infected patients receiving combination antiretroviral therapy (CART) with an efavirenz (600 mg once daily)-containing regimen were recruited. HIV-TB-coinfected patients were receiving treatment with RMP-containing regimens. A complete pharmacokinetic study was conducted with 19 HIV-TB patients on two occasions (with and without RMP). Trough concentrations of efavirenz were measured in the remaining 38 patients during RMP coadministration. The 15 HIV-infected patients underwent complete pharmacokinetic sampling on one occasion. Plasma efavirenz was estimated by high-performance liquid chromatography, and genotyping of CYP2B6 G516T polymorphism was performed by sequencing. Peak and trough concentrations and exposure to efavirenz were significantly higher in TT than in GT and GG genotype patients (P < 0.001). Although RMP coadministration decreased the peak and trough concentrations and exposure to efavirenz by 17.8, 20.4, and 18.6%, respectively, the differences were not statistically significant. The trough concentration of efavirenz was subtherapeutic (less than 1.0 microg/ml) in 6 (8%) of 72 patients. In this South Indian population of HIV-infected patients, CYP2B6 G516T polymorphism but not RMP coadministration significantly influenced the pharmacokinetics of efavirenz; patients with the TT genotype had very high blood levels of efavirenz. While a small proportion of patients had subtherapeutic efavirenz levels, the clinical implications are uncertain, as all had good immunological responses to CART.

We studied the effect of rifampicin on steady-state pharmacokinetics of nevirapine and the impact of increasing the dose of nevirapine on its peak (Cmax) and trough (Cmin) levels in 13 HIV-infected patients on regular antiretroviral treatment with nevirapine-containing regimens (200 mg twice daily). A baseline pharmacokinetic study was conducted and repeated after 1 week of daily rifampicin (450/600 mg). The study was repeated in 7 of 8 patients who had subtherapeutic Cmin nevirapine levels after increasing nevirapine dose to 300 mg twice daily. Liver function was monitored. Rifampicin caused significant reductions in Cmax (42%), Cmin (53%), and exposure (46%) of nevirapine (P <.01). The Cmin of nevirapine fell below the therapeutic range of 3 microg/ml in 8 of 13 patients. An increase of nevirapine to 300 mg twice daily raised Cmin to therapeutic range in all 7 patients without exceeding the toxic level of 12 microg/mL. There were no clinical or laboratory adverse events. Our findings suggest that decreased bioavailability of nevirapine because of rifampicin coadministration could be overcome by increasing the dose of nevirapine from 200 to 300 mg twice daily without short-term adverse events. Further studies to evaluate the long-term safety of higher dose of nevirapine are required.

India has approximately 5.2 million persons infected with HIV. Although antiretroviral therapy (ART) is being widely introduced in public clinics, many HIV-infected persons still seek care via the private sector. A cross-sectional survey was conducted in 2004 at six public and private sites to characterize the knowledge, attitudes, and practices (KAP) of ART among patients with HIV receiving care in India. Of 1667 persons surveyed, 609 (36%) had heard of ART and 19% of these persons reported that ART could cure HIV. Twenty-four percent reported that they were currently taking ART, with 18% of these patients not actually on ART according to their provider. Major barriers to taking ART were cost (33%), lack of knowledge of ART (41%), and deferral by physician (30%). More than half of all public and private patients had not heard of CD4 (57%) or viral load testing (80%), and even fewer had received these tests (32% and 11%, respectively). Private clinic attendees were almost 4 times more likely to be on ART (35% versus 9%, p < 0.0001), more likely to be male, have a higher education, be partnered, have a higher income, and have had a CD4 or viral load (p < 0.0001). Overall, low levels of ART knowledge and access were observed among HIV infected patients, with access to ART being particularly low among patients attending public clinics. In order to make widespread dissemination of ART effective in India, further educational and programmatic efforts are likely needed to optimize access, treatment awareness, and compliance among patients with HIV.

Mucocele is the most common lesion of the oral mucosa, which results from the accumulation of mucous secretion due to trauma and lip biting habits or alteration of minor salivary glands. Mostly they are two types based on histological features which as follows: Extravasation and retention. Mucoceles can appear at anywhere in the oral mucosa such as lip, cheeks and the floor of the mouth, but mainly appear in the lip. Diagnosis is mostly based on clinical findings. The most common location of the extravasation mucocele is the lower lip. Mucoceles most probably affect young patients but can affect all the age groups. They may have a soft consistency, bluish, and transparent cystic swelling, history of bursting and collapsing due to which resolves themselves then refilling which may be repeated. The treatment of choice is surgical removal of the mucocele.

Interferon gamma (IFNgamma)-based in-vitro assays have suboptimal sensitivity, especially in immunocompromised individuals, which emphasizes the need for alternative markers for tuberculosis (TB) diagnosis. We compared TB antigens-specific IFNgamma and IFNgamma-inducible protein-10 levels in culture of whole blood samples from HIV-TB patients. We report that IFNgamma-inducible protein-10 detects a greater number of HIV-TB cases than IFNgamma and suggest that IFNgamma-inducible protein-10 may be a better alternative marker for latent TB infection diagnosis among immunocompromised individuals.

Plasma concentrations of the non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine are known to exhibit a high degree of inter-patient variability.

Tuberculosis (TB) elimination is possible with the discovery of accurate biomarkers that define the stages of infection. Drug-resistant TB impair the current treatment strategies and worsen the unfavourable outcomes. The knowledge on host immune responses between drug-sensitive and drug-resistant infection is inadequate to understand the pathophysiological differences and disease severity. The secreted proteins, cytokines display versatile behaviour upon infection with Mycobacterium tuberculosis (MTB) and their imbalances often tend to assist disease pathology than protection. Therefore, studying these soluble proteins across TB infection spectrum (drug-resistant TB, drug-sensitive TB, and latent TB) may unveil the disease mediated responses and unique stage specific cytokine signatures. Thus, we sought to determine the plasma cytokine levels from healthy, latently infected, drug-sensitive, and drug-resistant TB individuals. Our study revealed top 8 cytokines (IL-17, IL-1α, IL-2, IL-10, IL-5, IFN-γ, TNF-α and IL-6) and their biomarker abilities to discriminate different stages of infection.