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The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-α and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-α correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.

The pathogenesis involving non-alcoholic fatty liver disease (NAFLD) in the context of chronic HBV (CHB) virus infection requires to be understood for developing improved modalities of diagnosis and treatment. We retrospectively investigated the association between NAFLD and CHB virus infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between years 2013 and 2016, we studied 455 subjects in the current investigation. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the hepatitis B virus (HBV) viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. We found that there was a high concurrence of NAFLD among patients with CHB virus infection. The presence of metabolic syndrome and chronic inflammation in CHB virus-infected patients were two independent factors that led to the progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components.

n/a Funding Agencies|Swedish Research CouncilSwedish Research Council [AI52731]; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for VinnovaVinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine; Medical Research Council of Southeast Sweden; Department of Science and Technology-Science and Engineering Research Board, Government of India [CRG/2019/006096]

Objectives Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors. Methods Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection). Results Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C19*2 and CYP2C19*3 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C19*2, CYP2C19*3 and CYP2C19*17 loci. The participants heterozygous for both ABCB1 and CYP2C19*2 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects. Conclusions Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.

Summary Background Significance of monitoring adalimumab trough levels and anti‐adalimumab antibodies (AAA) for disease outcome in Crohn's disease (CD) patients remained unclear. Aim To evaluate the association of adalimumab trough levels and AAA at week 26 with clinical remission at week 52, the effect of azathiopurine on AAA and factors influencing trough levels in CD patients in the DIAMOND trial. Methods We performed this study using adalimumab trough levels, AAA at week 26 and 6‐thioguanine nucleotide (TGN) in red blood cells at week 12. A multiple regression model and receiver operating analysis was performed to identify factors influencing adalimumab trough levels and AAA, and adalimumab thresholds for predicting disease activity. Results There was a significant difference of adalimumab trough level at week 26 between patients with disease remission and without at week 52 (7.7 ± 3.3 μg/mL vs 5.4 ± 4.3 μg/mL: P 222.5 p mol/8 ×108 RBCs yielded sensitivity (100%) and specificity (60.6%) for AAA negativity. Conclusion Adalimumab trough levels and AAA occurrence were significantly associated with clinical remission. Higher 6TGN affected AAA negativity. The combination therapy is beneficial in some relevant aspects for CD patients. (UMIN Registration No. 000005146)

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2+CD4+T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA+ and nine were HBV DNA–. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69+ cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2+CD4+T cells, and the levels of cytokine expression correlated with functional cytokine levels.

Background Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks. Methods We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS−), dengue with warning signs (DWS+) and severe dengue (SD). Results Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P

Tuberculosis (TB) treatment monitoring is paramount to clinical decision-making and the host biomarkers appears to play a significant role. The currently available diagnostic technology for TB detection is inadequate. Although GeneXpert detects total DNA present in the sample regardless live or dead bacilli present in clinical samples, all the commercial tests available thus far have low sensitivity. Humoral responses against Mycobacterium tuberculosis (Mtb) antigens are generally low, which precludes the use of serological tests for TB diagnosis, prognosis, and treatment monitoring. Mtb-specific CD4(+) T cells correlate with Mtb antigen/bacilli burden and hence might serve as good biomarkers for monitoring treatment progress. Omics-based techniques are capable of providing a more holistic picture for disease mechanisms and are more accurate in predicting TB disease outcomes. The current review aims to discuss some of the recent advances on TB biomarkers, particularly host biomarkers that have the potential to diagnose and differentiate active TB and LTBI as well as their use in disease prognosis and treatment monitoring. Funding Agencies|Xiamen University Malaysia Research Funding (XMUMRF) [XMUMRF/2018-C2/ILAB/0001]; Swedish Research CouncilSwedish Research Council; Swedish Physicians against AIDS Research Foundation; VINNMER for VinnovaVinnova; Linkoping University Hospital Research Fund; ALF Grants Region Ostergotland; FORSS

Background: In view of the importance of chronic HBV (CHB) infection and the global burden of non-alcoholic fatty liver disease (NAFLD), it is imperative to understand the potential interplay between the two diseases. Methods: Here, we retrospectively investigated the association between NAFLD and CHB infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between year 2013 and 2016, we studied 449 subjects in the current investigation. Findings: CAP and LSM scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the HBV viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. Interpretations: Together, we found that there was a high concurrence of NAFLD among patients with CHB. The presence of metabolic syndrome and chronic inflammation in CHB patients were two independent factors that led to progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components. Plasma markers of liver steatosis and fibrosis progression are key to development of cell-targeted therapies exploiting specific molecular pathways. Funding Statement: This work was supported by a grant from the Frontier Research Grant (FRG), FG019-17AFR to Mohamed Rosmawati and Xiamen University Malaysia Research Funding (XMUMRF), XMUMRF/2018-C2/ILAB/0001. Marie Larsson is supported by the Swedish Research Council, the Swedish Physicians against AIDS Research Foundation; VINNMER for Vinnova, Linkoping University Hospital Research Fund, ALF Grants Region Ostergotland, FORSS. Declaration of Interests: The authors declare no conflicts interest. Ethics Approval Statement: The medical records of patients were extracted from the hospital database using patients’ unique hospital registration number. This study was approved by the Medical Ethics Committee of the University Malaya Medical Centre (MEC-938.42).

Background Persistent inflammation caused by Chlamydia trachomatis in the female genital compartment represents one of the major causes of pelvic inflammatory disease (PID), ectopic pregnancy and infertility in females. Here, we examined the pro-inflammatory cytokine response following stimulation with three different types of C. trachomatis antigens, viz. chlamydial protease-like factor (CPAF), heat shock protein 60 (HSP60) and major outer membrane protein (MOMP). Methods A total of 19 patients with genital C. trachomatis infection and 10 age-matched healthy controls were recruited for the study. Peripheral blood mononuclear cells (PBMCs) isolated from genital C. trachomatis-infected females were cultured in the presence of CPAF, HSP60 and MOMP antigens, and cytokines were measured by ELISA assay. Results We reported that pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were robustly secreted following antigenic exposure. Notably, CPAP and MOMP were more potent in triggering IL-1β, as compared to HSP60. Elevated levels of the proinflammatory cytokines were also noted in the samples infected with plasmid-bearing C. trachomatis as compared to those infected with plasmid-free strains. Conclusions Our study highlights distinct ability of chlamydial antigens in triggering pro-inflammatory response in the host immune cells.

Fungal infections (mycoses) are likely to occur more frequently as ever-increasingly sophisticated healthcare systems create greater risk factors. There is a paucity of systematic data on the incidence and prevalence of human fungal infections in Malaysia. We conducted a comprehensive study to estimate the burden of serious fungal infections in Malaysia. Our study showed that recurrent vaginal candidiasis (>4 episodes/year) was the most common of all cases with a diagnosis of candidiasis (n = 501,138). Oesophageal candidiasis (n = 5850) was most predominant among individuals with HIV infection. Candidemia incidence (n = 1533) was estimated in hospitalized individuals, some receiving treatment for cancer (n = 1073), and was detected also in individuals admitted to intensive care units (ICU) (n = 460). In adults with asthma, allergic bronchopulmonary aspergillosis (ABPA) was the second most common respiratory mycoses noticed (n = 30,062) along with severe asthma with fungal sensitization (n = 39,628). Invasive aspergillosis was estimated in 184 cases undergoing anti-cancer treatment and 834 ICU cases. Cryptococcal meningitis was diagnosed in 700 subjects with HIV/AIDS and Pneumocystis jirovecii pneumonitis (PCP) in 1286 subjects with underlying HIV disease. The present study indicates that at least 590,214 of the Malaysian population (1.93%) is affected by a serious fungal infection annually. This problem is serious enough to warrant the further epidemiological studies to estimate the burden of human fungal infections in Malaysia.

Hepatitis C virus (HCV) causes persistent disease in ~85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses.We characterized the distinct T-cell phenotypes based on the expression of costimulatory molecules CD28 and CD27, senescence markers PD-1 and CD57, chronic immune activation markers CD38 and HLA-DR, and survival marker CD127 (IL-7R) by flow cytometry following activation of T cells using HCV peptides and phytohemagglutinin.HCV-specific CD4+ and CD8+ T cells from chronic HCV (CHC) patients showed increased expression of PD-1. Furthermore, virus-specific CD4+ T cells of CHC-infected subjects displayed relatively increased expression of HLA-DR and CD38 relative to HCV-specific CD8+ T cells. The CD4+ and CD8+ T cells from HCV-infected individuals showed significant increase of late-differentiated T cells suggestive of immunosenescence. In addition, we found that the plasma viral loads positively correlated with the levels of CD57 and PD-1 expressed on T cells.Chronic HCV infection results in increased turnover of late-senescent T cells that lack survival potentials, possibly contributing to viral persistence. Our findings challenge the prominence of senescent T-cell phenotypes in clinical hepatitis C infection.

Immune reconstitution inflammatory syndrome (IRIS) continues to be a complication in HIV/tuberculosis (TB) co-infected patients initiating highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the risk factors associated with developing IRIS to identify a possible biomarker to predict or diagnose IRIS in patients initiating HAART. A total of 175 HIV/TB co-infected patients initiating HAART were followed up longitudinally during September 2010 to May 2013 attending a HIV care clinic in Chennai. Patients were followed up longitudinally after HAART initiation and baseline demographic, laboratory parameters and treatment characteristics between patients with IRIS events and those without IRIS events were compared. Chi-square or Fisher's exact test for categorical variables and a Wilcoxon rank-sum test for continuous variables were performed using SPSS, version 12.0 software. Patients with IRIS had a significantly lower median baseline CD4+ T-cell count (P = 0.0039). There were no differences in terms of sex, CD4 T-cell %, plasma viral load, time interval between initiating ATT and HAART between the IRIS and non-IRIS patients. Low CD4+ T-cell count (

Tuberculosis (TB) and human immunodeficiency virus (HIV) infection interfere and impact the pathogenesis phenomena of each other. Owing to atypical clinical presentations and diagnostic complications, HIV/TB co-infection continues to be a menace for healthcare providers. Although the increased access to highly active antiretroviral therapy (HAART) has led to a reduction in HIV-associated opportunistic infections and mortality, the concurrent management of HIV/TB co-infection remains a challenge owing to adverse effects, complex drug interactions, overlapping toxicities and tuberculosis -associated immune reconstitution inflammatory syndrome. Several hypotheses have been put forward for the exacerbation of tuberculosis by HIV and vice versa supported by immunological studies. Discussion on the mechanisms produced by infectious cofactors with impact on disease pathology could shed light on how to design potential interventions that could decelerate disease progression. With no vaccine for HIV and lack of an effective vaccine for tuberculosis, it is essential to design strategies against HIV-TB co-infection.

The 7.5 kb cryptic plasmid of Chlamydia trachomatis has been shown to be a virulence factor in animal models, but its significance in humans still remains unknown. The aim of this study was to investigate the prevalence and potential involvement of the C. trachomatis cryptic plasmid in causing various clinical manifestations; including infertility, reproductive tract disintegrity, menstrual disorder, and polycystic ovarian syndrome (PCOS) among genital C. trachomatis-infected patients.A total of 180 female patients of child bearing age (mean 30.9 years old, IQR:27-35) with gynecological complications and subfertility issues, who visited Obstetrics and Gynecology clinics in Kuala Lumpur, Malaysia were recruited for the study. Prevalence of genital chlamydial infection among these patients was alarmingly high at 51.1% (92/180). Of the 92 chlamydia-infected patients, 93.5% (86/92) were infected with plasmid-bearing (+) C. trachomatis while the remaining 6.5% (6/92) were caused by the plasmid-free (-) variant. Our data showed that genital C. trachomatis infection was associated with infertility issues, inflammation in the reproductive tract (mucopurulent cervicitis or endometriosis), irregular menstrual cycles and polycystic ovarian syndrome (PCOS). However, no statistical significance was detected among patients with plasmid (+) versus plasmid (-) C. trachomatis infection. Interestingly, plasmid (+) C. trachomatis was detected in all patients with PCOS, and the plasmid copy numbers were significantly higher among PCOS patients, relative to non-PCOS patients.Our findings show a high incidence of C. trachomatis infection among women with infertility or gynecological problems in Malaysia. However, due to the low number of plasmid (-) C. trachomatis cases, a significant role of the plasmid in causing virulence in human requires further investigation of a larger cohort.

Background The 7.5 kb cryptic plasmid of Chlamydia trachomatis has been shown to be a virulence factor in animal models, but its significance in humans still remains unknown. The aim of this study was to investigate the prevalence and potential involvement of the C. trachomatis cryptic plasmid in causing various clinical manifestations; including infertility, reproductive tract disintegrity, menstrual disorder, and polycystic ovarian syndrome (PCOS) among genital C. trachomatis–infected patients. Results A total of 180 female patients of child bearing age (mean 30.9 years old, IQR:27–35) with gynecological complications and subfertility issues, who visited Obstetrics and Gynecology clinics in Kuala Lumpur, Malaysia were recruited for the study. Prevalence of genital chlamydial infection among these patients was alarmingly high at 51.1 % (92/180). Of the 92 chlamydia-infected patients, 93.5 % (86/92) were infected with plasmid-bearing (+) C. trachomatis while the remaining 6.5 % (6/92) were caused by the plasmid-free (−) variant. Our data showed that genital C. trachomatis infection was associated with infertility issues, inflammation in the reproductive tract (mucopurulent cervicitis or endometriosis), irregular menstrual cycles and polycystic ovarian syndrome (PCOS). However, no statistical significance was detected among patients with plasmid (+) versus plasmid (−) C. trachomatis infection. Interestingly, plasmid (+) C. trachomatis was detected in all patients with PCOS, and the plasmid copy numbers were significantly higher among PCOS patients, relative to non-PCOS patients. Conclusion Our findings show a high incidence of C. trachomatis infection among women with infertility or gynecological problems in Malaysia. However, due to the low number of plasmid (−) C. trachomatis cases, a significant role of the plasmid in causing virulence in human requires further investigation of a larger cohort.

Endometriosis is defined as presence of endometrial tissue outside the uterus. It can occur anywhere in the ovary. In the ovary it is usually presented as cyst, termed as endometriotic cyst or Chocolate cyst. Arias-Stella reaction is usually seen in gestational endometrium or in ectopic gestation site and rarely in non-pregnant uterus with hormonal intake. Co-existence of endometriosis and Arias-Stella reaction is very rare. We present a very rare case of endometriotic cyst of the ovary exhibiting Arias –Stella reaction which was seen in of non pregnant patient without any history of hormonal intake.

The mechanisms behind certain co-morbid conditions associated with chronic HIV disease still remain elusive. HIV-associated peripheral neuropathy is one among those rarely studied manifestations in HIV-1 infection. Numerous underlying factors associated with peripheral neuropathy have been described in HIV disease. Herein, we hypothesized certain heretofore undescribed potential mechanisms that lead to HIV associated neuropathy. Being a multifactoral manifestation, HIV-associated neuropathy is presumed to have an association with physiological factors namely, adrenal inadequacy/steroid resistance and lipodystrophy-induced cushion-effect loss in peripheral nerves. Therefore, management of the adrenals with steroids at the time-point of high inflammatory burden thereby preventing lipodystrophy by selecting the optimum treatment regimen could markedly alleviate the severity of HIV-associated neuropathic manifestations.

Objectives. Cold agglutinin (CA) titers are one among the first pathological indicators for diagnosing Mycoplasma pneumoniae disease. We prospectively studied the prevalence of CAs in 300 HIV-positive and 75 HIV-negative individuals with respiratory disease in Chennai, India. Methods. The cold agglutination test was used and retrospectively compared with the results of a particle agglutination test. Results. While CAs were positive in 51 HIV cases, particle agglutination test detected anti-M pneumoniae antibodies from 43 cases with HIV disease (P = .001). The seroprevalence of CAs was 2.6% (n = 2) among HIV-negative participants. The mean CD4 count in CApositive and -negative HIV cases was 107.4 + 121.2 and 259.2 + 247.2 cells/µL (P = .001), respectively. Conclusion. Our report suggests a basis for the existence of CAs in HIV-positive cases. Definitive diagnosis may be done only when CA detection is used in conjunction with a specific test.

Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory manifestation that occurs subsequent to initiation of highly active antiretroviral therapy in terminal (HAART) HIV infection, mainly due to the restoration of robust immune responses directed against latent microbial antigens. IRIS is believed to be multifactorial and less studied. Herein, we postulate that hypothalamo–pituitary–adrenal (HPA) dysregulation, a well-documented manifestation in HIV/AIDS, could possibly disturb the balance between pro-inflammatory and anti-inflammatory cytokines leading to clinical IRIS. Drugs, opportunistic infections, stress and numerous intrinsic and extrinsic factors have been described to be the possible causes of IRIS in HIV illness.

SummaryObjectiveThe role of oxidative stress in disease progression has been shown to be more complicated in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) compared to those who remain treatment-naïve. This study examined the changes in the antioxidant profile of HIV-infected subjects who remained HAART-naïve due to a high CD4 cell count and HIV-negative controls, over a 12-month follow-up period at YRG CARE, a tertiary HIV referral centre in southern India.MethodsWe prospectively studied 35 HIV-infected participants (18 on d4T+3TC+EFV (stavudine+lamivudine+efavirenz), eight on AZT+3TC+EFV (zidovudine+lamivudine+efavirenz), and nine who were antiretroviral therapy-naïve) and 20 HIV-negative controls. Antioxidant profile (total antioxidant status, glutathione reductase, glutathione peroxidase, uric acid, ceruloplasmin, zinc, and albumin), CD4 cell count, plasma viral load, dietary intake, and history of smoking and alcohol use were determined at baseline and at twelve months.ResultsAt 12 months, participants on HAART showed a significant increase in glutathione peroxidase (baseline: 1765 vs. 12 months: 2850U/l; p

Summary Objectives The prevalence of hepatitis B virus (HBV) is reportedly the main cause of hepatocellular carcinoma (HCC) in India, where hepatitis C virus (HCV)-associated HCC is believed to be relatively less prevalent. We verified the usefulness of alpha-fetoprotein (AFP) as a tumor marker and analyzed the influence of viral etiology on AFP levels in HCC. Methods Of a total of 1012 cases with liver disease, 202 were investigated for the presence of AFP (142 HCC cases, 30 cirrhosis cases, and 30 chronic liver disease (CLD) cases). In addition, serum samples from 30 healthy patients, 30 hepatitis B surface antigen (HBsAg) carriers, and 30 acute viral hepatitis cases were included as controls. AFP was quantitatively determined using a commercial ELISA (Quorum Diagnostics, Canada). Out of the 142 HCC cases screened for AFP, aflatoxin B1 (AFB1) detection was carried out in 38 HCC cases using an in-house immunoperoxidase test. Results In HBV and HCV co-infected HCC cases, the AFP positivity was 85.7%. In HBV alone-associated HCC, the positivity was 62.9%, and 54.5% of AFB1 positive HCC cases showed AFP positivity. In HBV and HCV negative HCC cases, the positivity was 20.5%, and in HCV-associated HCC it was 17.6%. The HBV/HCV co-infected group and HBV alone positive HCC cases had significantly elevated levels of AFP. When AFP positivity was analyzed based on the marker profile of HBV, 89.7% of AFP positive cases were HBV-DNA positive. Conclusions The overall positivity pattern of AFP in HCC does indicate that higher levels of AFP are observed with hepatitis virus positivity, especially with HBV. Further studies must be carried out to correlate the serum levels of AFP with the size, number, and degree of differentiation of HCC nodules.

Background We established the biochemical and hematological reference intervals among a south Indian healthy adult population attending an HIV referral centre in Chennai, southern India. Methods In a cross sectional study, 213 study subjects (129 male and 84 female) were studied between March and August 2005. All of the parameters were analyzed using standard hematological and biochemical techniques. Results Certain biochemical (viz. total bilirubin, alanine transaminase, albumin, creatinine, total protein, lipid profile, creatine phospokinase, uric acid and lactate) and hematological (mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and lymphocyte levels) parameters presented higher upper limits. In addition, the upper limits of white blood cell count, platelet count, hematocrit, red blood cell count and hemoglobin level were low in comparison to the currently reported ranges. Conclusion Ethnic variation in reference intervals was observed in certain biochemical and hematological analytes in a south Indian adult population.

Helicobacter pylori (H. pylori) -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs) and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs) associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD), 40 with peptic ulcer disease (PUD) and 15 with gastric cancer (GC) subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up-regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease.

Angiotensin II is one of the key regulatory peptides implicated in the pathogenesis of liver disease. The mechanisms underlying the salubrious role of α-tocopherol and β-carotene on liver pathology have not been comprehensively assessed. Here, we investigated the mechanisms underlying the role of Angiotensin II on hepatic damage and if α-tocopherol and β-carotene supplementation attenuates hepatic damage. Hepatic damage was induced in Apoe−/−mice by infusion of Angiotensin II followed by oral administration with α-tocopherol and β-carotene-enriched diet for 60 days. Investigations showed fibrosis, kupffer cell hyperplasia, hepatocyte degeneration and hepatic cell apoptosis; sinusoidal dilatation along with haemorrhages; evidence of fluid accumulation; increased ROS level and increased AST and ALT activities. In addition, tPA and uPA were down-regulated due to 42-fold up-regulation of PAI-1. MMP-2, MMP-9, MMP-12, and M-CSF were down-regulated in Angiotensin II-treated animals. Notably, α-tocopherol and β-carotene treatment controlled ROS, fibrosis, hepatocyte degeneration, kupffer cell hyperplasia, hepatocyte apoptosis, sinusoidal dilatation and fluid accumulation in the liver sinusoids and liver enzyme levels. In addition, PAI-1, tPA and uPA expressions were markedly controlled by β-carotene treatment. Thus, Angiotensin II markedly influenced hepatic damage possibly by restraining fibrinolytic system. We concluded that α-tocopherol and β-carotene treatment has salubrious role in repairing hepatic pathology.

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes increased production of proinflammatory chemokines and cytokines, including interleukin-18, which is a signature cytokine of the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared plasma levels of interleukin18 and other biomarkers of monocyte/macrophage activation in the prediction and characterization of TB-IRIS. Methods: Biomarkers were assayed pre-ART and during TB-IRIS, or equivalent timepoint, in a case‐control study of Malaysian HIV patients with paradoxical or unmasking TB-IRIS (n ¼15), TB no IRIS (n ¼14), and no TB or IRIS (n ¼15). Findings for interleukin18 were verified in another cohort of patients with paradoxical TB-IRIS (n ¼26) and their controls (n ¼22) from India. Results: Interleukin-18 was higher in TB-IRIS patients pre-ART and during the event in bothMalaysianpatients (P

Summary Background The true seroepidemiology of acute Mycoplasma pneumoniae infection in HIV infected individuals is ambiguous. Methods This study examined the serosurveillance of IgM antibodies to M. pneumoniae in HIV infected patients presenting with pulmonary symptoms at a tertiary AIDS care center in Chennai, Southern India, using cold-haemagglutination test and commercial enzyme linked immunosorbent assay in acute serum specimens. Results One hundred HIV infected patients had enrolled in the study; 21 (21%) were positive for M. pneumoniae IgM antibodies by ELISA and 34 (34%) showed evidence of cold hemagglutinins. Conclusion This serosurveillance study reports a 21% prevalence of M. pneumoniae IgM antibody among HIV infected patients with pulmonary symptoms by ELISA and non-specific diagnosis was confirmed in 34% of the cases screened. Determination of cold agglutination titer could be used as a substitute to other expensive procedures in limited resource settings and third-world nations to diagnose M. pneumoniae infections for prompt initiation of therapy, as CAT has been found to be 100% sensitive and 84% specific in the diagnosis of M. pneumoniae infection.

Non-neoformans cryptococci were previously considered to be saprophytes and nonpathogenic to humans.Cryptococcus laurentiiis frequently used as a biological means to control fruit rot. Interestingly,C laurentiihas recently been reported to be a rare cause of infection in humans. The authors report a case of pulmonary cryptococcosis caused byC laurentiiin a diabetic AIDS patient who was on antituberculosis and antiretroviral treatments. The sputum smear revealed capsulated yeast cells that were identified asC laurentii. Repeated pleural fluid culture revealed growth ofC laurentii. Both respiratory samples were negative for acid-fast bacilli.Moraxella catarrhalisandKlebsiella pneumoniaewere also found in the sputum, but not in the pleural fluid. The patient had a good response to oral fluconazole therapy at 600 mg/day for five weeks and was then discharged. The present article is the first to report on the rare pulmonary involvement ofC laurentiiin the Indian HIV population. These unusual forms of cryptococci create a diagnostic predicament in the rapid diagnosis of pulmonary cryptococcosis. A high degree of suspicion and improvement of techniques for culture and identification will contribute to the early diagnosis and treatment of unusual fungal infections.

Even in the era of successful combination antiretroviral therapy (cART), co-infection of Hepatitis C virus (HCV) remains one of the leading causes of non-AIDS-related mortality and morbidity among HIV-positive individuals as a consequence of accelerated liver fibrosis and end-stage liver disease (ESLD). The perturbed liver microenvironment and induction of host pro-inflammatory mediators in response to HIV and HCV infections, play a pivotal role in orchestrating the disease pathogenesis and clinical outcomes. How these viruses communicate each other via chemokine CCL2 and exploit the liver specific cellular environment to exacerbate liver fibrosis in HIV/HCV co-infection setting is a topic of intense discussion. Herein, we provide recent views and insights on potential mechanisms of CCL2 mediated immuno-pathogenesis, and HIV-HCV cross-talk in driving liver inflammation. We believe CCL2 may potentially serve an attractive target of anti-fibrotic intervention against HIV/HCV co-infection associated co-morbidities.

Background Foot infections are a frequent complication of patients with diabetes mellitus, accounting for up to 20% of diabetes-related hospital admissions. Infectious agents are associated with the worst outcomes, which may ultimately lead to amputation of the infected foot unless prompt treatment strategies are ensued. The present study sought to reveal the bacterial etiology of diabetic foot ulcers in South India, the diabetic capital of India. Methods A 10-month-long descriptive study was carried out to analyse the aerobic and anaerobic bacterial isolates of all patients admitted with diabetic foot infections presenting with Wagner grade 2–5 ulcers. Bacteriological diagnosis and antibiotic sensitivity profiles were carried out and analysed using standard procedures. Results Diabetic polyneuropathy was found to be common (56.8%) and gram-negative bacteria (57.6%) were isolated more often than gram-positive ones (42.3%) in the patients screened. The most frequent bacterial isolates were Pseudomonas aeruginosa , Staphylococcus aureus , coagulase-negative staphylococci (CONS), and Enterobacteriaceaes. Forty-nine cultures (68%) showed polymicrobial involvement. About 44% of P. aeruginosa were multi-drug-resistant, and MRSA was recovered on eight occasions (10.3%). Bacteroides spp. and Peptostreptococcus spp. were the major anaerobic isolates. Conclusions Our study supports the viewpoint put forth by previous South Indian authors that the distribution of gram-negative bacteria (57.6%) is more common than that of gram-positive ones (42.3%) and it is contrary to the viewpoint that diabetic foot infections are frequently monomicrobial. Furthermore, recovery of multi-drug-resistant P. aeruginosa isolates is of serious concern, as almost no one has reported the same from the South Indian milieu.

Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis.

Background Hepatitis C virus (HCV) represents one of the persistent viral infections afflicting humankind, and a significant proportion of chronic HCV disease progresses over time through liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). One potential mechanism underlying the chronic disease is believed to be viral escape from immune surveillance via upregulation of inhibitory molecules on immune cells by HCV. We investigated the diverse expression of various inhibitory molecules in PBMCs of healthy non-HCV controls and chronically HCV infected patients. Methods The expression of inhibitory molecules on PBMCs was investigated in chronic HCV infected patients relative to healthy non-HCV controls using standard immunological and molecular methods. The serum levels of indoleamine 2, 3 deoxygenase (IDO) and cyclooxygenase-2 (COX-2) were also investigated. Results The gene expression profile of chronically HCV infected patients was significantly different from control individuals. Our results showed upregulation of TIM-3 (p≤0.01), PD-1 (p≤0.01), FOXP-3 (p≤0.01), BLIMP-1 (p≤0.01), CD160 (p≤0.01), CTLA-4 (p≤0.01), TRAIL (p≤0.01), BTLA (p≤0.01) and LAG-3 (p≤0.01) with fold change of 1.3, 0.4, 14.6, 0.87, 6.6, 0.4, 14.7, 10.9 and 2.5 respectively in chronically HCV infected patients. The plasma IDO and COX-2 levels were significantly higher (p=0.001) in chronically HCV infected subjects relative to healthy control. Conclusion

Background Angiotensin II (Ang II) and high-fat diet are implicated in causing pathological changes in the vascular endothelium, brain, kidney and liver. The association of aneurysm leading to histopathological changes in the splenic compartment remains elusive. Further, the salubrious credentials of antioxidants, especially α-tocopherol and β-carotene in the resolution of splenic pathology have not been investigated. Methods Four-month-old Apoe−/− mice were used in the induction of aneurysm by infusing Ang II, and subsequently were orally administered with α-tocopherol and β-carotene-enriched diet for 60 days. Results We observed splenomegaly in Ang II-infused aneurysm and high-fat diet-supplemented mice as compared to normal mice. These observations were further confirmed through histopathological investigations, demonstrating splenic follicular hypertrophy. We observed a remarkable decrease in the size of spleen in α-tocopherol and β-carotene-treated Apoe−/− mice as compared with Ang II-treated animals. Furthermore, no marked changes in the histopathological splenic sections were seen in the β-carotene-treated group. However, hyperplasia and proliferation of immature lymphocytes in the follicles were observed in the α-tocopherol-treated animals. We found that CD4+ T-cell levels were increased in the high-fat diet group relative to the control group and were decreased in the β-carotene-treated animals. Conclusions Our study provides evidence that Ang II infusion and high-fat supplementation induces abdominal aortic aneurysm that has pathological implications to the spleen. The use of β-carotene but not α-tocopherol as an antioxidant markedly ameliorates the pathological changes in spleen.

Polymorphonuclear neutrophils (PMN) play a key role in host innate immune responses by migrating to the sites of inflammation. Furthermore, PMN recruitment also plays a significant role in the pathophysiology of a plethora of inflammatory disorders such as chronic obstructive pulmonary disease (COPD), gram negative sepsis, inflammatory bowel disease (IBD), lung injury, and arthritis. Of note, chemokine-dependent signalling is implicated in the amplification of immune responses by virtue of its role in PMN chemotaxis in most of the inflammatory diseases. It has been clinically established that impediment of PMN recruitment ameliorates disease severity and provides relief in majority of other immune-associated disorders. This review focuses on different novel approaches clinically proven to be effective in blocking chemokine signalling associated with PMN recruitment that includes CXCR2 antagonists, chemokine analogs, anti-CXCR2 monoclonal antibodies, and CXCR2 knock-out models. It also highlights the significance of the utility of nanoparticles in drugs used for blocking migration of PMN to the sites of inflammation.

Background: While the spectrum of opportunistic infections due to HIV infection has been widely discussed, there are very limited data available in south India on certain incident infections especially urinary tract infections (UTI) in HIV-infected subjects. Methods: Bacterial aetiology of 350 symptomatic UTI in HIV-infected subjects and the drug resistance pattern of the Escherichia coli isolates tested between June 2005 and July 2007 at the YRG Centre for AIDS Research and Education, a tertiary HIV Referral Centre in Chennai has been described here. Results:E. coli was the most common etiological agent of UTI in HIV patients, followed by Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus spp. and Staphylococcus epidermidis. Twenty-nine E. coli isolates were multi-drug-resistant and 83.3% of the isolates were resistant to sulfamethoxazole-trimethoprim. Conclusions: Urinary pathogens in HIV-infected patients demonstrate high antimicrobial resistance and with majority of therapy for UTIs being empiric, constant updates of the aetiological agents and their drug susceptibility pattern would largely be beneficial to clinicians in choosing the right drug.

BACKGROUND: The co-factors underlying abnormal lactate level remains to be determined in resource-limited settings. In a cross-sectional study conducted between January 2004 and July 2006 we determined the proportion of HIV-infected persons with abnormal lactate levels and correlated the association of certain co-factors of abnormal lactate levels at a tertiary HIV care centre in Chennai Southern India. METHODS: Lactate was estimated by the enzymatic method using an Olympus AU 400 autoanalyzer. Absolute CD4+T lymphocyte count was determined by the Guava personal cell analyser (Guava Technologies Inc. Hayward CA USA). Subjects were classified to have normal or abnormal values of lactate based on the reference interval (0.3-2.2 mmol/L). A p value 0.05 was considered statistically significant. RESULTS: A total of 225 HIV-infected individuals (HAART experienced 213 (95%) and HAART naive (5%)) were included in the analysis. Mean age was 34+/-8 and 36+/-9 years for the individuals with normal and abnormal lactate levels respectively. Of these 185 (82%) had normal (0.3-2.2 mmol/L) and 40 (18%) had abnormal (>2.2 mmol/L) lactate levels. Significant difference in relation to female gender was observed between the normal and abnormal groups (p=0.03). Among the abnormal group 39 (97.5%) subjects were HAART experienced compared to 174 (94.1%) normal group. Among the abnormal group 24 (60%) individuals had a CD4 count of

Over the past decade, an increasing number of opportunistic fungal infections have been reported in immunocompromised subjects. Microascus spp. and their anamorphs Scopulariopsis spp. have been recovered from a wide geographical range. We report a case of Scopulariopsis brumptii in a 27-year-old man with AIDS presenting with breathlessness, pericardial effusion and hydrothorax in Chennai, southern India, in February 2007. Because of respiratory arrest, the patient was intubated. However, the patient developed obstructive shock and died due to cardiac dysfunctions. This report underlines the need for a direct, intensive approach to investigations in immunocompromised patients, especially those with AIDS.

Malignancies associated with the upper gastrointestinal (GI) tract are reported to be ex‐ tremely lethal. Most patients with gastric cancer (GC) in the United States are symptomatic and already have complex untreatable disease at the time of presentation. GC in general, is a senile malignancy (cancer of the aged) and is reportedly twice as common in blacks as in whites. Routine screening is not extensively performed, except in countries, which have a very high incidence of GC, such as Japan, Venezuela, and Chile. The three most common primary malignant gastric neoplasms are adenocarcinoma (95%), lymphoma (4%), and ma‐ lignant GIST (Gastrointestinal stromal tumor)(1%). Fortunately, dedicated research into its pathogenesis and detection of new risk factors, treatment, and advanced endoscopic techni‐ ques have led to early diagnosis of GC in the modern era.

Supplemental Digital Content is available in the text, HIV-infected individuals on antiretroviral therapy (ART) are at increased risk of cardiovascular disease (CVD). Given the relationship between innate immune activation and CVD, we investigated the association of single-nucleotide polymorphisms (SNPs) in TLR4 and CD14 and carotid intima-media thickness (cIMT), a surrogate measurement for CVD, in HIV-infected individuals on ART and HIV-uninfected controls as a cross-sectional, case-control study. We quantified the frequency of monocyte subsets (CD14, CD16), markers of monocyte activation (CD38, HLA-DR), and endothelial adhesion (CCR2, CX3CR1, CD11b) by flow cytometry. Plasma levels of lipopolysaccharide, sCD163, sCD14, sCX3CL1, and sCCL2, were measured by ELISA. Genotyping of TLR4 and CD14 SNPs was also performed. The TT genotype for CD14/−260SNP but not the CC/CT genotype was associated with elevated plasma sCD14, and increased frequency of CD11b+CD14+ monocytes in HIV-infected individuals. The TT genotype was associated with lower cIMT in HIV-infected patients (n = 47) but not in HIV-uninfected controls (n = 37). The AG genotype for TLR4/+896 was associated with increased CX3CR1 expression on total monocytes among HIV-infected individuals and increased sCCL2 and fibrinogen levels in HIV-uninfected controls. SNPs in CD14/−260 and TLR4/+896 were significantly associated with different markers of systemic and monocyte activation and cIMT that differed between HIV-infected participants on ART and HIV-uninfected controls. Further investigation on the relationship of these SNPs with a clinical endpoint of CVD is warranted in HIV-infected patients on ART.

Accumulating evidence indicates that immune impairment in persistent viral infections could lead to T-cell exhaustion. To evaluate the potential contribution of induction of negative costimulatory molecules to impaired T-cell responses, we primed naïve T cells with mature monocyte-derived dendritic cells (MDDCs) pulsed with HIV-1 in vitro. We used quantitative real-time polymerase chain reaction and flow cytometry, respectively, to compare the gene and surface-protein expression profiles of naïve T cells primed with HIV-pulsed or mock-pulsed DCs. We detected elevated expressions of negative costimulatory molecules, including lymphocyte activation gene-3 (LAG-3), CD160, cytolytic T-lymphocyte antigen-4 (CTLA-4), T-cell immunoglobulin mucin-containing domain-3 (TIM-3), programmed death-1 (PD-1) and TRAIL (tumor necrosis-factor-related apoptosis-inducing ligand) in T cells primed by HIV-pulsed DCs. The PD-1(+) T-cell population also coexpressed TIM-3, LAG-3, and CTLA-4. Interestingly, we also found an increase in gene expression of the transcriptional repressors Blimp-1 (B-lymphocyte-induced maturation protein-1) and Foxp3 (forkhead transcription factor) in T-cells primed by HIV-pulsed DCs; Blimp-1 expression was directly proportional to the expression of the negative costimulatory molecules. Furthermore, levels of the effector cytokines interleukin-2, tumor necrosis factor-α and interferon-γ, and perforin and granzyme B were decreased in T-cell populations primed by HIV-pulsed DCs. In conclusion, in vitro priming of naïve T-cells with HIV-pulsed DC leads to expansion of T cells with coexpression of a broad array of negative costimulatory molecules and Blimp-1, with potential deleterious consequences for T-cell responses.

Background: A great deal of effort has been devoted to understanding the role of AIDSassociated mycoplasmas in recent years. However, the role of Mycoplasma pneumoniae in HIV disease remains unclear. Methods: We studied 300 adult HIV infected persons (200 with community-acquired pneumonia (CAP) and 100 with no respiratory illness) and 75 HIV uninfected persons with CAP and analysed the prevalence of respiratory pathogens. Results: Prevalence of M. pneumoniae was 17% by induced sputum and 11.3% by throat swab culture in HIV positive subjects. Seroprevalence of anti-M. pneumoniae IgM was 11.7% by ELISA and 14.3% by gelatin microparticle agglutination test. Prevalence of M. pneumoniae among HIV negative cases was relatively low. Streptococcus pneumoniaewas predominant (28%) among subjects with lower respiratory disease, whereas Staphylococcus aureus (15%) was more common among cases with upper respiratory illness. Rales (P=0.001), pharyngeal erythema (P=0.02), cervical adenopathy (P=0.004) and crepitations (P=0.001) showed significance in relation to M. pneumoniae positivity. Statistical significance was observed with regard to total lymphocyte count (P=0.02) and erythrocyte sedimentation rate (P=0.04), and M. pneumoniae positivity. Conclusion: The prevalence of M. pneumoniae in HIV infected subjects was relatively higher than HIV uninfected subjects with respiratory disease.

Department of Infectious Diseases,YRG Centre for AIDS Research and Education (YRG CARE),VHS Hospital Campus, IT Corridor, Taramani,Chennai 600 113, India.Tel.: +91 (44) 22542929E-mail: sundaram@yrgcare.orgDear Editor,Electrolyte disturbance can be associated with numerousmorbid conditions especially among HIV-infected individualsreceiving highly active antiretroviral therapy (HAART) (1- 4).Electrolyte imbalance is described to be the prime cause ofdeath due to myriad infectious ailments involving thegastrointestinal tract, exemplified by Asiatic cholera, rota virusinfection, shigellosis, salmonellosis, leptospirosis, malaria andparasitic diarrhoea. Unless restored, electrolyte imbalance canbe serious and might interfere with a patient’s immuneresponse. T erminal HIV disease is characterized by the onsetof numerous opportunistic infections (OI) and neoplasms andindividuals in terminal AIDS are vulnerable to numerousintracellular infections, where the corresponding aetiologicalagents reportedly use the intracellular elements (e.g. iron) andmetabolites to survive and replicate, which likely alters theevents related to cellular metabolism (5). This couldsubsequently lead to a plethora of functional sabotage eventsin cellular and immune functions (5). Maintenance of anoptimum amount of electrolyte (ionic homeostasis) in theintracellular as well as the extracellular compartment (blood,interstitial fluid etc.) is paramount to healthy living. Electrolyteimbalance could be attributed to numerous factors both fromthe host as well as from the parasite point of view andprincipally reflects a disturbance in the host’s cellular metabolicpathways possibly after establishment of an infection.In the post-HAART era, information of the prevalence ofelectrolyte imbalance is limited both in developed world aswell as in resource-limited settings and has never beenadequately investigated. One study has identified abnormallylow bicarbonate levels (1) and another documented HIV-associated nephropathy (2) among HAART-treated HIVpositive persons. Few others have documented that HIV-infected individual with underlying OIs treated with HAARTregimens developed biological abnormalities includinghyponatraemia, hyperkalaemia or hypokalaemia and acidosis(3, 4). Besides, sodium and potassium imbalances arebelieved to be associated with a plethora of chronic ailments,such as malnutrition, alcoholism, diabetes mellitus and otherinfectious causes especially in AIDS. A detailed literaturesurvey revealed the availability of very limited past data onthe prevalence of electrolyte imbalances in HIV infectedindividuals. Further, the underlying risk factors for biologicalabnormalities are poorly defined. Hence in a cross-sectionalstudy we investigated the proportion of HIV infected personswith abnormal serum electrolytes and identified the possibleco-factors of these biological abnormalities among personsattending YR Gaitonde Centre for AIDS Research andEducation (YRG CARE), a tertiary referral centre in SouthernIndia, between January 2004 and July 2006. Data werecollected with the approval of YRG CARE’s freestandinginstitutional review board.YRG CARE, since 1993, has provided medical andpsychosocial care and support to over 12,000 HIV-infectedpersons in the south of India. The study was approved by theInstitutional Review Board (IRB) of YRG CARE. Writteninformed consent was obtained from all the participants. Weinvestigated 464 HIV-infected persons who were either HAARTnaive or HAART experienced. Demographics, clinicalcharacteristics and co-factors (age, gender, hepatitis B and Cstatus and exposure to HAART) were included in the analysis.Laboratory investigations such as electrolytes (sodium,potassium, chloride and bicarbonate) and absolute CD