Analysis of transporter associated with antigen presentation (TAP) genes polymorphisms with HIV-1 infection.

Human leukocyte antigen (HLA) class I molecules of the human major histocompatibility complex (MHC) play an important role in modulating immune response. HLA class I molecules present antigenic peptides to CD8+ T cells and thereby play a role in the immune surveillance of cells infected with viruses. TAP1 and TAP2 are MHC-II-encoded genes necessary for the generation of a cellular immune response and polymorphism of these genes can influence the specificity of peptides preferentially presented by the MHC class I molecules and the outcome of the immune response. Several studies implicated genetic variation in TAP genes to various immune-mediated and infectious diseases. To determine the correlation between HIV-1 infection and the TAP1 and TAP2 genes polymorphisms, we performed PCR-RFLP assay of these genes in 500 HIV-1 seropositives and the matched seronegative individuals. Statistical analysis of the data disclosed no correlation between TAP1 (C/T intron 7) gene polymorphism and HIV-1/AIDS disease. However, the current results demonstrated that the heterozygous A/G [OR (95% CI) 1.39 (1.06-1.83), P = 0.0171] and homozygous G/G [OR (95% CI) 3.38(1.56-7.46), P = 0.0010] variants of TAP2 (A/G exon 11) (T665A) gene are positively associated with an increased risk of HIV-1/AIDS infection. This case-control analysis might suggest a possible role of TAP2 (A/G exon 11) (T665A) gene in the susceptibility to HIV-1 infection and disease outcome among North Indian patients.

Prevalence of multidrug resistance in Mycobacterium tuberculosis isolates from HIV seropositive and seronegative patients with pulmonary tuberculosis in north India.

BACKGROUND: Multidrug resistant (MDR) and extensively-drug resistant (XDR) tuberculosis (TB) are a serious threat to the national TB control programs of developing countries, and the situation is further worsened by the human immunodeficiency virus (HIV) pandemic. The literature regarding MDR/XDR-TB is, however, scanty from most parts of India. We carried out this study to assess the prevalence of MDR/XDR-TB in new and previously treated cases of pulmonary TB and in HIV seropositive and seronegative patients. METHODS: Sputum and blood specimens were obtained from 2100 patients suspected of pulmonary tuberculosis and subjected to sputum microscopy and culture for TB, and HIV serology at our tertiary care centre in north India. The culture positive Mycobacterium tuberculosis isolates were subjected to drug susceptibility testing (DST) for first line anti-tuberculosis drugs, and the MDR isolates were further subjected to second line DST. Various parameters of the patients' were analyzed viz. clinical presentation, radiology, previous treatment history, demographic and socioeconomic data and microbiology results. RESULTS: Of the 2100 patients, sputum specimens of 256 were smear positive for acid-fast bacilli (AFB), 271 (12.9%) grew Mycobacterium spp., and M. tuberculosis was isolated in 219 (10.42%). Of the 219 patients infected with M. tuberculosis, 20.1% (44/219) were found to be seropositive for HIV. Overall, MDR-TB was observed in 17.4% (39/219) isolates. There were 121 newly diagnosed and 98 previously treated patients, of which MDR-TB was found to be associated with 9.9% (12/121) and 27.6% (27/98) cases respectively. There was significantly higher association of MDR-TB (12/44, 27.3%) with HIV seropositive patients as compared to HIV seronegative patients (27/175, 15.4%) after controlling previous treatment status, age, and sex (odd's ratio, 2.3 [95% CI, 1.000-5.350]; p-value, 0.05). No XDR-TB was found among the MDR-TB isolates. CONCLUSION: The present study demonstrated a high prevalence of drug resistance amongst pulmonary TB isolates of M. tuberculosis from north India as compared to the WHO estimates for India in 2010, though this could possibly be attributed to the clustering of more serious or referred cases at our tertiary care centre. The prevalence of MDR-TB in HIV seropositive patients was significantly higher than seronegative individuals. The study emphasizes the need to monitor the trends of drug resistance in TB in various populations in order to timely implement appropriate interventions to curb the menace of MDR-TB.

A study on the association of autoantibodies, chemokine, and its receptor with disease activity in systemic lupus erythematosus in North Indian population.

Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by the production of autoantibodies against a spectrum of nuclear antigens. RANTES and its receptor CCR5 have been associated with the pathogenesis of SLE. The objective of this study is to analyze autoantibodies (DNA/RNA), allelic distribution of RANTES and the association of levels of RANTES and its receptor CCR5 in SLE patients in North Indian region. The RANTES-403 and RANTES-28 polymorphism in the promoter region of RANTES gene was studied in 80 patients and 80 healthy controls. The levels of chemokine RANTES, its receptor CCR5, anti-dsDNA, and anti-SSA antibodies levels were determined. Disease activity was assessed with the systemic lupus erythematosus disease activity index (SLEDAI) score. All the parameters were studied for statistical analysis by using t test (graph pad prism) and correlation by SPSS data. PCR-RFLP performed showed 28C/C and the 403G/G genotypes in both patients and controls, but no other genotypes such as 28C/G, 28G/G and 403A/G, 403A/A were found. Patients had higher levels of RANTES (1840.48 ± 739.42 vs. 835.44 ± 70.48 pg/ml; P < 0.0001) and its receptor CCR5 expression (26.49 ± 0.16 vs. 24.72 ± 3.02 %; P < 0.05) compared to controls. The levels of autoantibodies anti-dsDNA and anti-SSA were also higher in patients than controls. The patients showing elevated anti-dsDNA had negative correlation with SLEDAI score (P < 0.05) while borderline patients were not found to be correlated. In case of anti-Ro/anti-SSA antibody levels, the borderline patients showed a moderately significant negative correlation as compared to controls than patients with elevated autoantibody (P < 0.01). The levels of RANTES and CCR5 were also higher in case of patients than controls. But there was no significant correlation of RANTES and CCR5 with disease activity. We were unable to find an association of RANTES polymorphism with SLE in North Indian population in our sample. No significant difference in allele distribution of RANTES-28 and RANTES-403 in the sample of 160 individuals was detected. Of the two autoantibodies studied, anti-Ro/anti-SSA levels in borderline lupus patients appeared as an important parameter for monitoring/diagnosis of lupus patients.

Factors associated with health service satisfaction among people living with HIV/AIDS: a cross sectional study at ART center in Chandigarh, India.

People living with HIV/AIDS (PLHA) while availing anti-retroviral therapy (ART) services face administrative and procedural problems in hospitals which affect their level of satisfaction with service providers. There is very little information available regarding quality of services provided at ART centers in India. Hence this study was conducted between July 2007 and December 2008 at ART Center, Chandigarh to analyse the user's perception about quality of services provided and factors associated with satisfaction level. For this prospective cross-sectional study, 100 PLHA were randomly recruited at ART Center. Exit interviews were conducted with structured questionnaire containing four groups of questions and questions on waiting time and satisfaction level. A scoring system was devised. The satisfaction level was cross matched with group questions. Mean age of 100 PLHA was 36.46 years (SD = 8.46), 22% were females, 55% from rural background and 67% educated above primary level. The mean group scores of four groups of questions were: Information, access and guidance (58.8%), Interaction with service providers (92.96%), Physical facilities (70.85%), Confidentiality, discrimination and grievance redressal (70.31%). Eighty-eight per cent rated satisfaction level as satisfactory or above (30% very satisfactory, 58% satisfactory), 10% indifferent and 2% dissatisfied. Factors found to be associated with satisfaction level were patient provider interaction (p=0.002) [behaviour of staff (p=0.005)], physical facilities (p=0.005) [cleanliness (0.002), drinking water (0.006)], confidentiality (p=0.004), waiting time to meet the doctor (p=0.03) and total time spent in hospital (p < 0.001). Problem areas identified were low availability of signage, low awareness of grievance redressal system, sanitation/toilets, drinking water, waiting time to meet the doctor (mean = 53.3 minutes), and "total time spent in hospital" (mean = 143 minutes). Study provided user's perspective about quality of ART services provided in a tertiary care hospital of India and revealed the factors associated with PLHA satisfaction level. Better quality ART Services can be provided to PLHA by addressing these factors.

Causes of DMARD withdrawal following ADR within 6 months of initiation among Indian rheumatoid arthritis patients.

The present study was conducted in Indian rheumatoid arthritis (RA) patients prescribed disease-modifying anti-rheumatic drugs (DMARDs) to determine the incidence and type of adverse drug reactions (ADRs) leading to their withdrawal in the initial 6 months of therapy. This was considered important as pharmacogenetic variations in the pattern of RA in different populations and genetic differences in efficacy and safety to drugs demand separate studies to be conducted in different populations. Hospital records were used to identify 1,000 consecutive patients with RA fulfilling the American College of Rheumatology criteria and having at least 6-month follow-up. Age, gender, duration of arthritis, drug usage and ADR-related drug withdrawal were recorded from the charts. Most of the patients were put on single DMARD. Combined use of DMARD was less frequent and non-use of DMARD was common; however, disease control was good. The commonest DMARD used in our hospital was hydroxychloroquine 444 (44%) and the commonest combination used was methotrexate with hydroxychloroquine by 55 (6%). Sulphasalazine use showed preference to young and males. Supportive drugs used were NSAIDs by 883 (88%), corticosteroids by 646 (65%), paracetamol by 594 (59%) and amitriptyline by 88 (9%). Incidence of ADR-related DMARD withdrawal was maximum with leflunomide 2/15 (13.33%) followed by methotrexate 9/116 (7.76%), sulphasalazine 6/185 (3.24%), chloroquine 3/131 (2.29%) and hydroxychloroquine 8/444 (1.8%). Severity and symptomatology of disease, genetic pattern of patients, financial status, previous experience of the clinicians and patients, availability of drugs, patient expectations and compliance were the main factors that lead to a difference in pattern of therapy in our patients compared to other population.

Quality of Life, Social Support, Coping Strategies, and Psychiatric Morbidity in Patients with Rheumatoid Arthritis.

Background and Objectives Patients with rheumatoid arthritis (RA) have greater psychological morbidity, despite that research in this area is scarce from developing countries. This study was aimed to assess the association of quality of life, social support, coping strategies, and psychological morbidity in patients with RA. Materials and Methods In this cross-sectional study, 40 patients with RA, who were not receiving steroids or disease modifying antirheumatic drugs, were recruited through purposive sampling. Social support questionnaire, coping strategy check list, and World Health Organization quality of life-BREF (WHOQOL-BREF) were administered to assess social support, coping, and quality of life, respectively. Results More than half of the patients had psychiatric disorders (60%), with depression being the commonest disorder (52.5%). Internalization coping and disease severity indicators like tender joints counts, swollen joints counts, pain, and disease activity were found as significant predictors for psychiatric disorders, while externalization coping, quality of life (all domains), and physical functions were found to protect against psychiatric morbidity. Conclusions Coping, quality of life, disease severity, and physical functions predicted the psychiatric disorders in RA. Multipronged interventions to enhance quality of life with promoting adaptive coping and timely treatment may further improve their mental health and overall disease course.

Quality of life, social support, coping strategies, and their association with psychological morbidity among people living with HIV.

Objectives: Enhancement of quality of life and social support havebecome important therapeutic goals among people living with HIV. However, research from developing countries is sparse in this area. Index study was aimed to assess association of social support, coping, and quality of life with psychological morbidity among people living with HIV. Materials and Methods: In this cross-sectional study, 100 people with HIV were recruited through purposive sampling who were not receiving antiretroviral therapy. To assess social support, coping, and quality of life social support questionnaire, coping strategy check list and World Health Organization quality of life-HIV BREF were administered, respectively. Results: Quality of life domain scores fell in the moderate category and spirituality, religion, and personal belief domain had maximum score. Educated, married, employed, and male subjects reported better quality of life. Females reported greater use of internalization and emotional outlet coping strategies. Low social support, lower quality of life (in all domains and total score), and greater use of internalization coping strategy were significantly associated with psychiatric morbidity. Conclusion: Internalization coping, low social support, and lower quality of life were associated with greater psychiatric morbidity. Therefore, to improve their mental health and overall course of HIV, multipronged interventions should be implemented for promoting the adaptive coping, social support and quality of life.

Soluble granzyme B and cytotoxic T lymphocyte activity in the pathogenesis of systemic lupus erythematosus.

Activated cytotoxic T lymphocyte (CTL) mediated target cell death has been implicated in the development of systemic autoimmune disease like SLE. However, the role of soluble granzyme B and its relationship with CTL activity and disease activity is still unknown. In this study, we evaluated role of soluble granzyme B and cytotoxic T lymphocyte activity in SLE patients. The soluble granzyme B was measured in the serum by an enzyme-linked immunosorbent assay while cytotoxic T lymphocyte activity was measured by flow cytometry. The disease activity was determined by using SLE Disease Activity Index (SLEDAI) score. Cytotoxic T lymphocyte activity was increased and strongly associated with disease activity. The soluble granzyme B levels were higher in SLE patients and associated with various clinical features like reduced complement components; C3 & C4 and skin lesion. The soluble granzyme B levels were also sturdily related with severity of the disease. The findings of this study suggest that excessive secretion of soluble granzyme B and enhanced activity of cytotoxic T lymphocyte may play a vital role in the pathogenesis of SLE and organ damage. Also, evaluation of soluble granzyme B may be helpful in monitoring the clinical features associated with activated CTL in SLE.

Impact of ERCC2 gene polymorphism on HIV-1 disease progression to AIDS among North Indian HIV patients.

HIV/AIDS remains to be one of the killing diseases of mankind. Host genetic response is one of the factor which determine susceptibility to HIV and disease progression to AIDS. The aim of the present study was to evaluate the impact of ERCC2 Lyc ( 751 ) Gln (excision repair cross complementing rodent repair deficiency, complementation group 2) polymorphism on HIV-1 susceptibility and disease progression to AIDS, as this gene has been reported to intervene in degrading retroviral cDNA before it integrates with the host DNA. This case control study included 300 HIV seropositive cases and an equal number of HIV seronegative controls. DNA was isolated from the blood samples of study subjects and genotyping of ERCC2 was conducted by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. The Gln/Gln genotype showed a significant variation between cases and controls (P = 0.047, OR 1.71, 95% CI 1.00-2.93), indicating a possible role of susceptibility in reference to controls and disease progression when compared within cases.

Dietary adequacy of HIV infected individuals in north India--a cross-sectional analysis.

BACKGROUND & OBJECTIVES: Dietary inadequacy is common in developing countries and so is in immune-deficient HIV infected individuals. Hence, an assessment of dietary patterns was done among a group of HIV infected individuals and compared with recommended dietary allowances. METHODS: One hundred consecutive HIV infected individuals were interviewed from the Immunodeficiency Clinic of a tertiary care center at Chandigarh. Dietary intake was assessed by 24 h recall method. Mean carbohydrate, protein and fat intakes were evaluated. Mean difference in the calorie intake from recommended dietary intake was then calculated. Mean absolute CD4 cell count was calculated and correlated with BMI and mean calorie intake. RESULTS: Mean weight and BMI of the individuals participated in the study was 58.6 ± 11.7 (range, 34 - 94) kg and 21.5 ± 3.7 (range, 13.6 - 36.7) kg/m [2] , respectively. Mean total calories intake was 1713 ± 292.8 (860 - 2525) calories/day and mean difference in the calories taken from the standard values was 249.5 ± 190.7 (10.6 - 967.5) calories/day. There was no significant correlation between CD4 cell count and total calories taken. INTERPRETATION & CONCLUSIONS: In HIV-infected individuals the energy intake was significantly lower than the recommended average intake. Hence, efforts should be taken to ensure that HIV-infected individuals have access to high-quality, nutritious food choices that promote optimal dietary patterns.

Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Myanmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

Differential diagnosis of disseminated Mycobacterium avium and Mycobacterium tuberculosis infection in HIV patients using duplex PCR.

Background: Disseminated Mycobacterium avium complex (MAC) and Mycobacterium tuberculosis infections have almost similar clinical presentations but require different therapeutic management. Materials & methods: A duplex PCR was designed based on the sequence variation between the genes encoding catalase-peroxidase (KatG) of M. avium complex and M. tuberculosis, so as to discriminate MAC, M. tuberculosis and mixed mycobacterial (MAC + M. tuberculosis) infections in HIV patients. Results: An accurate, single-step differential diagnosis of disseminated mycobacterial infections in HIV patients was achieved with specific detection of a single band each for M. avium (120 bp) and M. tuberculosis (90 bp) and two bands for the mixed (120 and 90 bp) infections. Conclusion:katG gene-based duplex PCR can facilitate quick differential diagnosis of disseminated MAC and M. tuberculosis infections in HIV patients.

Education effects on the International HIV Dementia Scale.

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) within the Indian subcontinent continues to spread. Although the primary clade of HIV in India differs from that of most Western countries, recent evidence suggests that the Indian clade (Clade C) also impacts neurocognitive functioning. India also has extremely high illiteracy rates that may confound detection of neurocognitive impairment, since many assessments to detect such impairment are heavily influenced by formal schooling. Among those with HIV/AIDS who have had limited educational opportunities and who are in the early stage of infection, the confounding effects of education on tests for neurocognitive impairment may be particularly salient. We therefore tested influence of HIV serostatus and education on a commonly used tool to screen for cognitive impairment, the International HIV Dementia Scale (IHDS), among Indian men and women in the catchment area of the Post Graduate Institute of Medical Education and Research (PGIMER) located in Chandigarh, India. Adjusted analyses showed that from a sample of 295 HIV-positive and HIV-negative individuals, only education was significantly associated with performance on the IHDS. HIV-negative and HIV-positive individuals, who were in the early stages of infection, performed similarly. Further development of this test to account for the effects of education on cut-off scores used to indicate possible dementia are needed, particularly for use in resource-limited settings such as India where low levels of education are widespread.

Polymorphisms of IL-6 174 G/C, IL-10 -592 C/A and risk of HIV/AIDS among North Indian population.

A growing body of evidence suggests that host genetic factors play an important role both in susceptibility to HIV infection and progression to AIDS. The present study aimed at evaluating the role of IL-6 and IL-10 gene polymorphisms on the risk of HIV susceptibility and disease progression among North Indian patients. The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques were applied to genotype IL-6 and IL-10. 300 seropositive and an equal number of age- and sex-matched seronegative control subjects were recruited for this study. There was statistically no significant variation in the frequencies of IL-6 and IL-10 genotypes among cases and controls. However, statistically non-significant association for risk of rapid disease progression was observed due to the combined effect of the IL-6 homozygous CC genotype and CC of IL-10, OR = 1.62, 95% CI = 0.38-6.91. Therefore, combined effects of the CC of IL-6 and CC of IL-10 might reduce the hosts ability to hinder viral replication after infection.

Association and impact of XPG Asp 1104 His gene polymorphism in HIV 1 disease progression to AIDS among north Indian HIV seropositive individuals.

Various efforts made to stop the deadly epidemic of HIV since its discovery in 1983 remain unsuccessful and this virus still continues to claim the lives of millions of individuals every year. The viral effect in the cell is complicated and the overall disease outcome is the result of interaction between a few viral proteins and complex host immune response. Because it has been reported that XPG (Xeroderma pigementesum group G) gene does play a role in reducing UV induced apoptosis and participate in Nucleotide Excision Repair (NER) process of DNA damage, it was hypothesized that polymorphism in this gene may have a role in HIV 1 disease progression to AIDS. The aim of the present study, therefore, was to find out the association between XPG gene polymorphism and its effect on the rate of HIV 1 disease progression to AIDS. 300 HIV seropositive cases and an equal number of age and sex matched controls were recruited for the study from north Indian population. The PCR-RFLP method was utilized to genotype 600 study subject for the XPG Asp (1104) His gene polymorphism. There was significant difference in the frequency of the His/His variant genotype (OR 1.95, 95% CI = 1.93-3.63, P = 0.04) between cases and controls indicating a probable role of this gene in host viral interactions.

Tuberculosis is the leading cause of lymphadenopathy in HIV-infected persons in India: results of a fine-needle aspiration analysis.

HIV infection is associated with a number of opportunistic infections and malignancies frequently involving the lymph nodes. Lymphadenopathy may occur at any stage of HIV infection. We aimed to determine the utility of fine-needle aspiration cytology in evaluating the causes of lymphadenopathy in HIV-infected individuals. Three hundred HIV-infected individuals with lymphadenopathy were included in the study. Fine-needle aspiration (FNA) was performed on peripheral or deep-seated lymph nodes. The material was used for cytological examination using May-Grunwald-Giemsa and haematoxylin and eosin staining. Special stains such as modified Ziehl-Neelsen staining for acid-fast bacilli and periodic acid-Schiff staining for fungi were also performed. The mean age of the study group was 35.0 ± 8.0 y (range 13-74 y). The median CD4 count was 152 cells/µl. Out of the 300 FNA reports, acid-fast bacteria were reported in 130 and cytological findings indicating mycobacterial infection in a further 43 patients. Cryptococcosis was reported in 4 individuals, histoplasmosis in 2 and aspergillosis in 1. Reactive hyperplasia was seen in 89 individuals. Lymphoma was noted in 7 individuals and suppurative inflammation in 5. In conclusion, tuberculosis is the predominant cause of lymphadenitis in HIV-infected individuals in India, especially in those with low CD4 cell counts.

Genetic and functional analysis of HIV-1 Rev Responsive Element (RRE) sequences from North-India.

HIV-1 Rev protein regulates the expression of HIV-1 transcripts by binding to a highly structured stem loop structure called the Rev Responsive Element (RRE) present in the genomic and partially spliced RNAs. Genetic variation in this structure is likely to affect binding of Rev protein and ultimately overall gene expression and replication. We characterized RRE sequences from 13 HIV-1 infected individuals from North India which also included two mother-child pairs following vertical transmission. We observed high degree of conservation of sequences, including the 9-nt (CACUAUGGG) long sequence in stem-loop B, required for efficient binding of Rev protein. All of our 13 RRE sequences possessed G to A (position 66) mutation located in the critical branched-stem-loop B which is not present in consensus C or B sequence. We derived a consensus RRE structure which showed interesting changes in the stem-loop structures including the stem-loop B. Mother-Child RRE sequences showed conservation of unique polymorphisms as well as some new mutations in child RRE sequences. Despite these changes, the ability to form multiple essential stem-loop structures required for Rev binding was conserved. RRE RNA derived from one of the samples, VT5, retained the ability to bind Rev protein under in vitro conditions although it showed alternate secondary structure. This is the first study from India describing the structural and possible functional implications due to very unique RRE sequence heterogeneity and its possible role in vertical transmission and gene expression.

Genetic and functional characterization of human immunodeficiency virus type 1 VprC variants from north India: presence of unique recombinants with mosaic genomes from B, C and D subtypes within the open reading frame of Vpr.

The human immunodeficiency virus type 1 (HIV-1) epidemic in India is predominantly caused by genetic subtype C, though other minor subtypes have also been reported. One of the major accessory proteins of HIV-1, namely Vpr, is known to influence key steps in viral replication, cell cycle progression, promoter activation, apoptosis and pathogenesis. Therefore, we carried out a genetic and functional analysis of the Vpr variants from eight HIV-1-infected individuals from north India. The sequence analyses revealed that six of eight samples clustered with ancestral subtype C. Remarkably, five of these showed a conserved and region-specific L64P mutation, located in the predicted third alpha-helix. This change adversely affected their ability to activate the HIV-1 long terminal repeat promoter without compromising their ability to cause apoptosis. Bootscan, phylogenetic and SimPlot analysis of the remaining two samples (VprS2 and A6) revealed very interesting mosaic genomes derived from B, C and D subtypes. The N-terminal half of the VprS2 gene consisted of genomic segments derived from subtypes B/D, C and D but the C-terminal half was derived predominantly from subtype C. Interestingly the N-terminal half of sample A6 also showed similar B/D, C and D inter-subtype recombinant structure but the C-terminal half was entirely derived from the consensus B subtype. Multiple breakpoints in a short stretch of 291 nt encoding the Vpr gene strongly suggest that this region is a potential hot-spot for the formation of inter-subtype recombinants and also highlight the importance of the rapidly evolving HIV-1 epidemic in the north Indian region due to multiple genetic subtypes.

Profile of hematological abnormalities of Indian HIV infected individuals.

BACKGROUND: Hematological abnormalities are a common complication of HIV infection. These abnormalities increase as the disease advances. Bone marrow abnormalities occur in all stages of HIV infection. METHODS: Two hundred HIV infected individual were screened for hematological abnormalities from March 2007-March 2008. Absolute CD4 cell count analysis was carried out by flowcytometry. Depending on the results of the primary screening further investigations were performed, like iron studies, hemolytic work up, PNH work up and bone marrow evaluation. Other investigations included coagulation profile, urine analysis, blood culture (bacterial, fungal, mycobacterial), serology for Epstein Barr virus (EBV), Cytomegalovirus (CMV), Hepatitis B and C, and Parvo B19 infection. RESULTS: The most common hematological abnormality was anemia, seen in 65.5% (131/200) patients. Iron deficiency anemia was seen in 49.2% (/200) cases while anemia of chronic disease occurred in 50.7% (/200) cases. Bone marrow evaluation was carried out in 14 patients out of which staging marrow was performed in 2 cases of non-Hodgkin's lymphoma (NHL) and did not show any bone marrow infiltration. In remaining 12 cases bone marrow was done for evaluation of pancytopenia. Among patients with pancytopenia 50% (6/12) showed granulomas (4 were positive for AFB, 2 were positive for fungal cryptococci), 25% (3/12) showed hemophagocytosis. There was a strong negative correlation between anemia and CD4 counts in this study. Thrombocytopenia was seen in 7% (14/200) cases and had no significant correlation with CD4 counts. No patient had absolute neutrophil count (ANC) < 800 cells/microL. No case of coagulation abnormalities was found. CONCLUSION: Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Patients should be investigated for hematological manifestations and appropriate steps should be taken to identify and treat the reversible factors.