CD4 cell count recovery in HIV/TB co-infected patients versus TB uninfected HIV patients.

Background: There is lack of data comparing the improvement in CD4 count following antitubercular (ATT) and antiretroviral therapy (ART) in patients presenting with Human Immunodeficiency Virus/Tuberculosis (HIV/TB) dual infection compared with CD4 matched cohort of TB uninfected HIV patients initiated on ART. We sought to test the hypothesis; TB additionally contributes to reduction in CD4 count in HIV/TB co-infected patients and this would result in greater improvement in count following treatment compared with CD4 matched TB uninfected individuals. Materials and Methods: In a retrospective cohort study design we studied the change in CD4 cell counts in two groups of patients - those with CD4 cell count >100 cells / mm 3 (Group 1) and <100/mm 3 (Group 2) at presentation. In each group the change in CD4 cell count in dually infected patients following six-month ATT and ART was compared to cohorts of CD4 matched TB uninfected patients initiated on ART. Results: In Group 1 (52 patients) dually infected subjects' CD4 count improved from 150 cells/ mm 3 to 345 cells/mm 3 (P=0.001). In the control TB uninfected patients, the change was from 159 cells/mm 3 to 317 cells/mm 3 (P=0.001). Additional improvement in dually infected patients compared to the control group was not statistically significant (P=0.24). In Group 2 (65 patients) dually infected subjects count improved from 49 cells/mm3 to 249 cells/mm 3 (P=0.001) where as in control TB uninfected patients improvement was from 50 cells/ mm 3 to 205 cells/mm 3 (P=0.001), there being statistically significant additional improvement in dually infected subjects (P=0.01). Conclusion: Greater increment in CD4 counts with ATT and ART in dually infected patients suggests that TB additionally influences the reduction of CD4 counts in HIV patients.

Immunophenotypic and intracellular cytokine profile of Indian patients with tuberculosis with and without human immunodeficiency virus co-infection.

Background. Tuberculosis (TB) occurs in more than 50% of human immunodeficiency virus (HIV) infected Indian patients. This study was carried out to determine the immunophenotypic and intracellular cytokine profile of patients with HIV-TB co-infection. Patients and Methods. Fifteen patients with HIV-TB co-infection and 15 each with TB alone and healthy individuals were studied. Immunophenotypic analysis and intracellular cytokines were measured using appropriate antibodies on a flowcytometer. Results. Percentage of CD3+ did not differ significantly in the three groups. The ratio of CD4+ : CD8+ was reversed among patients with TB and HIV-TB. CD19+ and CD25+ were present on fewer cells of healthy individuals but this was not statistically significant. Significantly higher percentage of cells of patients with TB and HIV-TB were CD69 positive. Interferongamma (INF-g ) and tumour necrosis factor-alpha (TNF-a) levels are significantly reduced in the CD4+ cells of patients with HIV-TB when compared with those with TB and healthy individuals. In CD8+ cells of patients with HIV-TB, levels of TNF-a are higher when compared with the other two groups. Interleukin-2 (IL-2) producing cells were not significantly different in any of the above subsets. Monocytes in individuals with HIV-TB had significantly higher interleukin-6 (IL-6) and TNF-a. Conclusions. T-helper cells among patients with HIV-TB have significantly lower cytokine production. T-suppressor cells and monocytes produce more TNF-a. These findings may be significant in view of recent attempts to treat HIV-TB coinfected patients with anti-TNF therapy.

Prevention of opportunistic infections in HIV infection by pentoxiphylline.

BACKGROUND & OBJECTIVES: Levels of tumour necrosis factor (TNF) are increased in patients with HIV infection leading to increased apoptosis and reduced CD4 cell life. Pentoxiphylline is a TNF inhibitor with properties that might make it useful for the treatment of HIV infection. These include improved cell mediated immunity and inhibition of viral replication. We carried out this study to determine the therapeutic utility of pentoxiphylline in improving constitutional manifestations, preventing opportunistic infections and sustaining CD4 counts among asymptomatic HIV infected individuals (i.e., those with no opportunistic infection). METHODS: Individuals with HIV infection who were over 18 yr of age and free of opportunistic infections were recruited in the study and followed up 4 weekly. CD4 counts were measured using a flowcytometer using anti-human CD4 intervals. Pentoxiphylline was prescribed in a dose of 400 mg thrice daily. RESULTS: Thirty three (18 males) patients with HIV infection were studied. During their follow up (mean 12.5 +/- 5.6 months) one patient each developed cryptococcal meningitis and fibrocavitary tuberculosis. Weight increased from 51.3 +/- 7.4 kg at baseline to 55.3 +/- 7.4 kg (P<0.05). Malaise, fatigue and appetite improved in all those with these complaints, except the two with opportunistic infections. Mean CD4 counts were 184 +/- 36.4/microl at baseline and increased to 210 +/- 28.6/microl3 at four weeks (P<0.05). The patients had stable CD4 counts over the follow up period since then, i.e., within 25 per cent of the previous levels. INTERPRETATION & CONCLUSION: Pentoxiphylline therapy in HIV infected individuals, who were free of opportunistic infections, improved their body weight, minimized opportunistic infections, increased and sustained CD4 counts. Given the low cost of the drug it could be recommended for the use in individuals who are at a high risk of developing opportunistic infections.

Chemokines and chemokine receptors in HIV infection: role in pathogenesis and therapeutics.

Chemokines are known to function as regulatory molecules in leukocyte maturation, traffic, homing of lymphocytes and in the development of lymphoid tissues. Besides these functions in the immune system, certain chemokines and their receptors are involved in HIV pathogenesis. In order to infect a target cell, the HIV envelope glycoprotein gp120 has to interact with the cellular receptor CD-4 and co-receptor, CC or CXC chemokine receptors. Genetic findings have yielded major insights into the in vivo roles of individual co-receptors and their ligands in providing resistance to HIV infection. Mutations in chemokine receptor genes are associated with protection against HIV infections and also involved in delayed progression to AIDS in infected individuals. Blocking of chemokine receptors interrupts HIV infection in vitro and this offers new options for therapeutic strategies. Approaches have been made to study the CCR-5 inhibitors as antiviral therapies and possibly as components of a topical microbicide to prevent HIV-1 sexual transmission. Immune strategies aimed at generating anti-CCR-5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV- protective immunity. It also remains to be seen how these types of agents will act in synergy with existing HIV-1 targeted anti viral or those currently in developments. Beyond providing new perspectives in fundamental aspects of the HIV-1 transmission and pathogenesis, chemokines and their receptors suggest new areas for developing novel therapeutic and preventive strategies against HIV infections. Studies in this review were identified through a search for relevant literature in the pubmed database of the national library of medicine. In this review, some developments in chemokine research with particular focus on their roles in HIV pathogenesis, resistance and therapeutic applications have been discussed.

Caspase 1 and caspase 8 in HIV infected patients with and without tuberculosis.

BACKGROUND: Caspase 8 is involved in apoptosis mediated by Fas and p55 tumor necrosis factor receptor ligation in HIV infection. Apoptosis is partially mediated by interleukin-1beta-converting enzyme (caspase-1). AIMS: We determined apoptosis, using caspase-1 and caspase-8, among patients with HIV infection, with and without tuberculosis (TB), those with TB alone and healthy individuals. SETTING AND DESIGN: Cross-sectional analysis of caspase-1 and caspase-8 among patients with HIV infection, with and without TB, those with TB alone and healthy individuals. MATERIALS AND METHODS: Nineteen HIV infected patients with TB (HIV+/TB+) and 20 with HIV infection without TB (HIV+/TB-) were studied. Fifteen individuals with TB alone were disease controls (HIV-/TB+) and 20 were healthy controls (HIV-/TB-). Caspases were measured by single-step ELISA using commercially available monoclonal antibodies. STATISTICAL ANALYSIS: Two-way ANOVA and Pearson's correlation coefficient. RESULTS: Mean CD4 counts of HIV+/TB+ were lower than HIV+/TB- (p<0.05). OD value of caspase 1 in HIV+/TB+ was 0.295+0.05, while that in HIV+/TB- it was 0.302+0.18. It was 0.293+0.07 in HIV-/TB+ and in HIV-/TB- the values were 0.287+0.06. OD value of caspase 8 in HIV+/TB+ was 0.307+ 0.07, lower than HIV+/TB- (0.927+0.25). It was 0.008+0.03 in HIV-/TB+ and in HIV-/TB-, 0.074+0.004. Values of caspase 8 in patients with HIV infection (with/without TB) were higher than those with TB alone or healthy individuals (p<0.01). Levels of caspase 8 in HIV+/TB- were higher than patients with HIV+/TB+ (p<0.01). CONCLUSION: Levels of caspase-1 are not different irrespective of presence or otherwise of TB and HIV infection. Fas-related apoptosis is higher in HIV infection. With concomitant TB, levels of caspase 8 were lower as compared with those without TB.

Beta2 microglobulin as a surrogate marker for HIV infection: good correlation with CD4 counts.

To determine if beta-2 microglobulin (beta2M) levels were elevated in our HIV infected patient population and if it could be used as a surrogate marker for disease progression. Thirty-eight HIV infected individuals and 26 age and sex-matched controls were studied. Measurement of CD4 cell count was carried out on a flowcytometer using anti-human CD4 monoclonal antibody and beta2M was measured by an enzyme immunoassay. Mean levels of HIV infected individuals were 1.29 +/- 0.52 mg/L and were significantly higher than 0.74 +/- 0.07 mg/L, the value of controls (p value <0.01). There was a negative correlation between CD4 counts and beta2M levels (r-value-0.79, p value <0.001). Beta2M levels in HIV infected individuals who have no opportunistic infection are elevated and these levels correlate with the CD4 counts. Beta2M can be used for the clinical follow-up of patients with HIV infection.

Human immunodeficiency virus infection in a patient with systemic lupus erythematosus.

We describe a 47 years lady with systemic lupus erythematosus (SLE) who was infected with human immunodeficiency virus (HIV), due to transfusion either by blood or platelet concentrate. There was a near remission in the disease and during the course of follow up she developed cryptococcal meningitis. The approach to the diagnosis of HIV infection in a patient with SLE, the effect of SLE on the virus and vice versa and some management issues in this setting are discussed.

Paucity of anti-hepatitis C virus antibodies in the serum of Indian patients with Sjogren's syndrome and inflammatory myositis.

Several extrahepatic manifestations have been associated with infection with Hepatitis C virus (HCV) infection. It has been associated with Sjogren's syndrome (SS) and inflammatory myositis (IM). The objective was to look at the prevalence of anti-HCV antibodies in the serum of SS and IM patients of Indian origin. Individuals satisfying the European Economic Community criteria for the diagnosis of SS and those satisfying the criteria of Bohan and Peter for the diagnosis of IM were recruited in the study. Routine evaluation for liver functions was made. Anti-HCV antibodies were tested by a third generation ELISA, using microplate HCV3.0 ELISA. Of the 23 patients with SS studied, 14 had extraglandular features. The commonest were anaemia and arthritis in six each, followed by in lymphopenia in two. One patient each had interstitial lung disease, hypothyroidism and chronic active hepatitis. Twenty-two patients with IM were studied alongside. None of the patients had abnormal liver functions. One patient with primary SS tested positive for anti-HCV antibodies. None of the patients with inflammatory myositis tested positive for anti-HCV antibodies. The presence of anti-HCV antibodies in our cohort of patients with SS and IM is low and more in keeping with the generally low prevalence of the infection in the Indian population.

Acute pancreatitis following propoxyfur (Baygon) ingestion.

Elevation of serum amylase and blood glucose is not uncommon following anticholinesterase poisoning. We report a young male who developed acute cholinergic crisis and acute pancreatitis following propoxyfur (Baygon) ingestion and recovered completely with conservative management.

Acute paraplegia following viper bite.

Neurological complications following viper bite are uncommon and are generally as a result of intracerebral or subarachnoid bleed and rarely due to cerebral infarction. We report a young male who following viperine bite developed local tissue swelling, haemorrhagic manifestations due to disseminated intravascular coagulation and later developed acute flaccid paraplegia as a result of dorsal spinal cord involvement.

Paradoxical reaction in HIV and tuberculosis coinfection.

Occurrence of paradoxical reaction following institution of antiretroviral therapy to patients with HIV and tuberculosis coinfection who are already on antitubercular therapy is distinctly uncommon. In this report we describe one such case and emphasize that such a reaction does not imply discontinuation of therapy.

Helicobacter pylori in Indian HIV infected patients.

Helicobacter pylori is a causative organism for chronic gastritis and associated with peptic ulcer disease. Infection may be asymptomatic as well. Human immuno-deficiency virus infection predisposes to a multitude of opportunistic infections, many of them resulting in gastrointestinal symptoms. We studied the prevalence of H pylori co-infection with HIV and its correlation with gastrointestinal symptoms in HIV infected patients. Seventy-three consecutive HIV infected patients presenting to the medical out patient department of Postgraduate Institute of Medical Education & Research, Chandigarh, India, were included in the study. Antibodies (IgG) to H pylori were tested by ELISA. There were 43 males, 30 females; mean age 26.1 +/- 4.7 years. Risk factors for acquiring HIV infection was predominantly heterosexual exposure. Eleven patients presented with gastrointestinal symptoms. Thirty-five of the 73 (47.9%) patients had serological evidence of H pylori infection. Six of them had gastrointestinal symptoms. These were odynophagia in 5, dyspepsia in 4 and recent diarrhoea in 2. Twenty-four patients with H pylori infection had AIDS. There was no difference in the prevalence of H pylori infection between patients with and without AIDS.

Linear scleroderma and autoimmune hemolytic anaemia.

Coexistence of localized scleroderma with other autoimmune disorders is not seen frequently. It has been reported to occur with myasthenia gravis, hemiatrophy and systemic lupus erythematosus. In this report we describe an association wherein linear scleroderma coexisted with autoimmune haemolytic anaemia.

Decline in beta-2 microglobulin levels after antitubercular therapy in tubercular patients with HIV infection.

BACKGROUND: Infection with Mycobacterium tuberculosis results in a state of immune activation, more so, when there is concomitant HIV infection. Beta-2 microglobulin (B2M) is a useful marker to study the state of immune activation among the HIV infected. Objective. To study the modulation of B2M levels among patients with HIV/TB coinfection, to correlate it with the CD4 count and also to study the change in these levels after four weeks of therapy. MATERIAL AND METHODS: Twelve patients with HIV infection and having concomitant TB diagnosed on the basis of positive acid fast bacilli were studied both at baseline and then at four weeks. Fourteen HIV infected individuals who had no overt opportunistic infection at the time of the study were also studied along with fourteen age and sex matched healthy volunteers. CD4 counts were performed using a flowcytometer. B2M was measured using a commercially available ELISA kit. RESULTS: B2M levels in HIV/TB coinfected patients were 1.62+/-0.45 mg/L (range 1-2.7 mg/L) and were significantly higher (p<0.0002) when compared with healthy controls, whose levels were 0.74+/-0.05 mg/L (range 0.48-81 mg/L). The levels in HIV infected individuals free of opportunistic infections were 1.2+/-0.16 mg/L (range 0.78-1.92 mg/L) and were significantly lower than the levels in HIV/TB coinfected (p<0.017), but significantly higher than the levels in healthy controls (p<0.01). Four weeks of antitubercular therapy resulted in a decline in B2M to 1.08+/-0.26 mg/L (range 0.8-1.74 mg/L) and was statistically significant (p<0.012). There was no correlation between the CD4 counts and the pre-treatment levels of B2M among these patients. CONCLUSION: Patients with HIV/TB coinfection had significantly higher levels of B2M than individuals with HIV infection without associated opportunistic infection and healthy controls. Four weeks of anti-tuberculous therapy resulted in a significant decline in these levels.

Use of static lung mechanics to identify early pulmonary involvement in patients with ankylosing spondylitis.

AIM: To assess if a detailed analysis of lung mechanics could help in early recognition of pulmonary abnormalities in patients with ankylosing spondylitis. METHODS: Static pulmonary mechanics were studied in 17 patients (16 men and one woman) of ankylosing spondylitis with no obvious clinical or radiological evidence of pulmonary involvement. Lung pressure-volume relationship was generated using a whole body plethysmograph, and a monoexponential equation fitted to this data. RESULTS: Total lung capacity (TLC) was reduced in one (5.9%) and static lung compliance (Cst) in nine (52.9%) patients. Four (23.5%) patients had normal TLC, yet Cst and shape constant (K) were reduced. Five (29.4%) patients had reduced TLC and Cst; four of them had low K. One (5.9%) patient had normal TLC but elevated Cst and K. CONCLUSIONS: Pulmonary involvement in patients with ankylosing spondylitis is probably diffuse and begins much earlier than generally presumed. Evaluation of static lung mechanics can identify pulmonary involvement early in the course of disease in several of these patients.

Hepatitis B virus co-infection in HIV infected patients.

AIM: Human immunodeficiency virus (HIV) and Hepatitis B virus (HBV) share the same routes of transmission. Co-infection with the two viruses has been reported to occur in upto 90% of HIV infected patients, depending on the prevailing risk factors for acquiring infection in a given population. We studied our HIV positive patients for the prevalence of HBV co-infection in them. METHODS: Eighty consecutive HIV positive patients underwent ELISA for HBsAg and antiHBc antibodies. HBeAg was tested for in all HBsAg positive patients. Polymerase chain reaction for HBV DNA was carried out in 40 randomly selected patients who showed no serological evidence of HBV infection. RESULTS: There were 56 males and 24 females (mean age 33.2 +/- 8.3 years). Twenty seven (33.8%) patients (23 males, 4 females) had evidence of co-infection with HBV. Of these 6 (22.2%) were HBsAg positive, 22 had antiHBc antibodies and HBV DNA was positive in one. Four patients had evidence of replicating virus (3 HBeAg+ve, 1 DNA+ve). All 4 had normal transaminases and advanced HIV infection. HBV co-infection was significantly higher among males (p < 0.05). There was no significant difference in the liver functions of HBV positive and negative individuals. The risk factor for acquiring infection was heterosexual exposure in al HBV+ve patients except one. CONCLUSIONS: Hepatitis B virus co-infection was seen in 33.8% of our HIV positive patients. Males were more likely to be co-infected. All except one of the patients acquired infection through heterosexual exposure.