How many people living with HIV will be additionally eligible for antiretroviral treatment in Karnataka State, India as per the World Health Organization 2013 guidelines?

BACKGROUND: The National AIDS control programme (NACP) in India is currently following the World Health Organization (WHO) 2010 antiretroviral therapy (ART) guidelines. In 2013, the WHO revised its recommendations for initiating ART among people living with HIV (PLHIV) by increasing the threshold for ART initiation to a CD4 count ≤500 cells/uL. For certain patient groups, ART is recommended irrespective of CD4 count (PLHIV with active tuberculosis, hepatitis B virus infection, pregnant and breast feeding women, children aged under five years and those living in a sero-discordant relationship). In this operational research, we assess the effect of applying this recommendation on the number of PLHIV additionally eligible for ART. METHODS: This was a cross-sectional analysis of routinely collected programme data from all PLHIV registered in Karnataka State (population 60 million), India in 2012. RESULTS: Of 37,044 PLHIV, 27,074 (73%) were eligible for initiating ART as per WHO-2010 criteria. As per the WHO-2013 criteria (CD4 count ≤500 and all pregnant women and under-five children irrespective of CD4 count), an additional 5104 (14%) HIV-infected people would be eligible for initiating ART. There were no data to inform the additional patient load due to sero-discordance. CONCLUSION: Adopting the WHO-2013 guidelines for India has important resource implications. However, given the significant patient and programmatic benefits of adopting the new guidelines, this has been considered favourably by the NACP in India and steps are being planned to integrate ART care into the general health system to cope with the increased numbers of patients

Retention in pre-antiretroviral treatment care in a district of Karnataka, India: how well are we doing?

Setting: Antiretroviral treatment (ART) Centre in Tumkur district of Karnataka State, India. There is no published information about pre-ART loss to follow-up from India. Objective: To assess the proportion lost to follow-up (defined as not visiting the ART Centre within 1 year of registration) and associated socio-demographic and immunological variables. Design: Retrospective cohort study involving a review of medical records of adult HIV-infected persons (aged ⩾15 years) registered in pre-ART care during January 2010–June 2012. Results: Of 3238 patients registered, 2519 (78%) were eligible for ART, while 719 (22%) were not. Four of the latter were transferred out; the remaining 715 individuals were enrolled in pre-ART care, of whom 290 (41%) were lost to follow-up. Factors associated with loss to follow-up on multivariate analysis included age group ⩾45 years, low educational level, not being married, World Health Organization Stage III or IV and rural residence. Conclusion: About four in 10 individuals in pre-ART care were lost to follow-up within 1 year of registration. This needs urgent attention. Routine cohort analysis in the national programme should include those in pre-ART care to enable improved review, monitoring and supervision. Further qualitative research to ascertain reasons for loss to follow-up is required to design future interventions

Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs

Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability

HIV/AIDS-tuberculosis (pulmonary and extra pulmonary) co-infection: CD4 correlation

Background: AIDS is the leading cause of death among people 15-59 years old in low income countries. Worldwide, approximately one-third of all AIDS-related deaths are associated with TB. TB is the primary cause of death for 10-15% of patients with HIV infection. So the present study was conducted to find the correlation between sputum positivity and CD4 cell count in patients with HIV/AIDS-Tuberculosis co-infection.Methods: The present study was a retrospective hospital based study of patients with HIV/AIDS-Tuberculosis co-infection, attending ART centre, department of medicine, Osmania general hospital, Hyderabad, Telangana, India between November 2014 to September 2015. Data included clinical profile, complete blood picture, renal and liver function tests, sputum microscopy and C/S and chest X-Ray and others as and when required.Results: We included 180 HIV/AIDS infected patients on ART with tuberculosis (TB) co-infection. Out of 180 patients, 132 were males and 48 were females. Among male’s ≥40 (51.51%) year’s age group and among females 30-39 (56.25%) year’s age group was the most commonly affected. Out of 180 cases 60 were sputum positive. 60 sputum negative pulmonary tuberculosis and 60 were extra pulmonary TB. CD4 cell count was <200/mm3 in 36 (60%) of sputum positive TB, 43 (71.7%) of sputum negative pulmonary TB & 39 (65%) of extra pulmonary TB patients. CD4 cell count was 200-400/mm3 in 16(26.7%) of sputum positive pulmonary TB, 13 (21.7%) of sputum negative TB and 19 (31.7%) of extra pulmonary TB patients. CD4 cell count was >400/mm3 in 8 (13.3%) of sputum positive pulmonary TB, 4 (6.6%) of sputum negative pulmonary TB and 2 (3.3%) of extra pulmonary TB patients.Conclusions: Present study concludes that male sex and age group >30 years were the commonly affected population. All forms of tuberculosis were common when CD4 count was <200 cells/mm3. The sputum negativity was higher with lower CD4 counts.

Control of sexually transmitted infections and global elimination targets, south-east asia region

The World Health Organization (WHO) set targets for a 90% reduction in the incidence of syphilis and gonorrhoea between 2018 and 2030. We review trends in sexually transmitted infections in the WHO South-East Asia Region to assess the feasibility of reaching these targets. Myanmar, Sri Lanka and Thailand reported 90% or greater reductions in the incidence or prevalence of syphilis and/or gonorrhoea between 1975 and 2005. Evidence suggests that smaller, more recent reductions in trends in sexually transmitted infections in India have driven regional declines. In other countries, sexually transmitted infections remain high or are increasing or data are not reliable enough to measure change. Sri Lanka and Thailand have strong control programmes for sexually transmitted infections that ensure universal access to services for these infections and targeted interventions in key populations. India and Myanmar have implemented targeted control efforts on a large scale. Other countries of the region have prioritized control of human immunodeficiency virus, and limited resources are available for other sexually transmitted infections. At national and subnational levels, data show rapid declines in sexually transmitted infections when targeted promotion of condom use and sexually transmitted infection services are scaled up to reach large numbers of sex workers. In contrast, recent outbreaks of sexually transmitted infections in underserved populations of men who have sex with men have been linked to rising trends in sexually transmitted infections in the region. A renewed and focused response to sexually transmitted infections in the region is needed to meet global elimination targets.</p

Linking HIV-Infected TB Patients to Cotrimoxazole Prophylaxis and Antiretroviral Treatment in India

BACKGROUND:HIV-infected persons suffering from tuberculosis experience high mortality. No programmatic studies from India have documented the delivery of mortality-reducing interventions, such as cotrimoxazole prophylactic treatment (CPT) and antiretroviral treatment (ART). To guide TB-HIV policy in India we studied the effectiveness of delivering CPT and ART to HIV-infected persons treated for tuberculosis in three districts in Andhra Pradesh, India, and evaluated factors associated with death. METHODS AND FINDINGS:We retrospectively abstracted data for all HIV-infected tuberculosis patients diagnosed from March 2007 through August 2007 using standard treatment outcome definitions. 734 HIV-infected tuberculosis patients were identified; 493 (67%) were males and 569 (80%) were between the ages of 24-44 years. 710 (97%) initiated CPT, and 351 (50%) collected >60% of their monthly cotrimoxazole pouches provided throughout TB treatment. Access to ART was documented in 380 (51%) patients. Overall 130 (17%) patients died during TB treatment. Patients receiving ART were less likely to die (adjusted hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.3-0.6), while males and those with pulmonary TB were more likely to die (HR 1.7, 95% CI 1.1-2.7, and HR 1.9, 95% CI 1.1-3.2 respectively). CONCLUSIONS:Among HIV-infected TB patients in India death was common despite the availability of free cotrimoxazole locally and ART from referral centres. Death was strongly associated with the absence of ART during TB treatment. To minimize death, programmes should promote high levels of ART uptake and closely monitor progress in implementation

Effectiveness of symptom screening and incidence of tuberculosis among adults and children living with HIV infection in India.

BACKGROUND WHO recommends the use of a simplified symptom-based algorithm for screening for tuberculosis (TB) among people living with HIV (PLHIV). We assessed the feasibility and effectiveness of this algorithm and determined the prevalence and incidence of TB among PLHIV attending antiretroviral treatment (ART) centres in India. METHODS We did a prospective multicentric implementation research study in four states of India. To rule out TB, we administered the WHO symptom-screen algorithm to all PLHIV every month for 6 months. If they were found to be symptomatic any time during this period, they were referred for investigations for TB. A case of TB diagnosed during the first month of screening was taken as a prevalent case while those detected TB in the subsequent 5 months were considered cases of incident TB. We calculated the incidence rate using the person-years method. Results . Between May 2012 and October 2013, a total of 6099 adults and 1662 children living with HIV were screened for TB at the ART centres of four states. Of the 6099 adult PLHIV, 1815 (30%) had at least one symptom suggestive of TB, of whom only 634 (35%) were referred for investigations of TB. Of those referred, 97 (15%) PLHIV were diagnosed with TB. Overall, the prevalence of undiagnosed TB was 0.84 person-years and in the subsequent period, the incidence of TB was 2.4/100 person-years (95% CI 1.90-3.10). Among 1662 children, 434 (26%) had at least one symptom suggestive of TB. But only 57 (13%) children were referred for investigations of TB and 13 (23%) of them were diagnosed with TB. The prevalence of TB among children was 0.5% and its incidence among them was 2.7/100 person-years (95% CI 1.60-4.30). CONCLUSION Prevalence and incidence of TB is high among PLHIV attending ART centres. This emphasizes the need to strengthen regular screening for symptoms of TB and further referral of those symptomatic for diagnosis of TB

Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes

BCCIP is a BRCA2- and CDKN1A(p21)-interacting protein that has been implicated in the maintenance of genomic integrity. To understand the in vivo functions of BCCIP, we generated a conditional BCCIP knockdown transgenic mouse model using Cre-LoxP mediated RNA interference. The BCCIP knockdown embryos displayed impaired cellular proliferation and apoptosis at day E7.5. Consistent with these results, the in vitro proliferation of blastocysts and mouse embryonic fibroblasts (MEFs) of BCCIP knockdown mice were impaired considerably. The BCCIP deficient mouse embryos die before E11.5 day. Deletion of the p53 gene could not rescue the embryonic lethality due to BCCIP deficiency, but partially rescues the growth delay of mouse embryonic fibroblasts in vitro. To further understand the cause of development and proliferation defects in BCCIP-deficient mice, MEFs were subjected to chromosome stability analysis. The BCCIP-deficient MEFs displayed significant spontaneous chromosome structural alterations associated with replication stress, including a 3.5-fold induction of chromatid breaks. Remarkably, the BCCIP-deficient MEFs had a ∼20-fold increase in sister chromatid union (SCU), yet the induction of sister chromatid exchanges (SCE) was modestly at 1.5 fold. SCU is a unique type of chromatid aberration that may give rise to chromatin bridges between daughter nuclei in anaphase. In addition, the BCCIP-deficient MEFs have reduced repair of irradiation-induced DNA damage and reductions of Rad51 protein and nuclear foci. Our data suggest a unique function of BCCIP, not only in repair of DNA damage, but also in resolving stalled replication forks and prevention of replication stress. In addition, BCCIP deficiency causes excessive spontaneous chromatin bridges via the formation of SCU, which can subsequently impair chromosome segregations in mitosis and cell division

Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas

<p>Abstract</p> <p>Background</p> <p>Loss of heterozygosity of chromosome 10q26 has been shown to be associated with the aggressiveness of astrocytic tumors (or astrocytomas), but the responsible gene(s) residing in this region has not been fully identified. The <it>BCCIP </it>gene is located at chromosome 10q26. It encodes a BRCA2 and CDKN1A (p21) interacting protein. Previous studies have shown that down-regulation of BCCIP impairs recombinational DNA repair, G1/S cell cycle checkpoint, p53 trans-activation activity, cytokinesis, and chromosome stability, suggesting a potential role of <it>BCCIP </it>in cancer etiology. In this study, we investigated whether <it>BCCIP </it>is altered in astrocytomas.</p> <p>Methods</p> <p>Genomic DNA from 45 cases of grade IV astrocytic tumor (glioblastoma) tissues and 12 cases of normal tissues were analyzed by quantitative PCR. The BCCIP protein expression in 96 cases of grade II–IV astrocytic tumors was detected by immunohistochemistry (IHC). IHC staining of glial fibrillary acid protein (GFAP), a marker for astrocytic cells, was used to identify cells of the astrocytic lineage.</p> <p>Results</p> <p>We found that BCCIP protein is expressed in normal cells with positive staining of GFAP. However, BCCIP protein expression was not detectable in ~45% of all astrocytic tumors, and in > 60% in the grade IV glioblastoma. About 45% glioblastoma have significant (p < 0.01) reduction of <it>BCCIP </it>gene copy number when compared to normal DNA. Furthermore, the frequency of lacking BCCIP expression is associated with the aggressiveness of astrocytic tumors.</p> <p>Conclusion</p> <p>Our data implicate a role of BCCIP in astrocytic tumorigenesis, and lack of <it>BCCIP </it>may be used as a marker for astrocytomas.</p