Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines

Quantification of risk factors for postherpetic neuralgia in herpes zoster patients: A cohort study.

OBJECTIVE: To investigate risk factors for postherpetic neuralgia, the neuropathic pain that commonly follows herpes zoster. METHODS: Using primary care data from the Clinical Practice Research Datalink, we fitted multivariable logistic regression models to investigate potential risk factors for postherpetic neuralgia (defined as pain ≥90 days after zoster, based on diagnostic or prescription codes), including demographic characteristics, comorbidities, and characteristics of the acute zoster episode. We also assessed whether the effects were modified by antiviral use. RESULTS: Of 119,413 zoster patients, 6,956 (5.8%) developed postherpetic neuralgia. Postherpetic neuralgia risk rose steeply with age, most sharply between 50 and 79 years (adjusted odds ratio [OR] for a 10-year increase, 1.70, 99% confidence interval 1.63-1.78). Postherpetic neuralgia risk was higher in women (6.3% vs 5.1% in men: OR 1.19, 1.10-1.27) and those with severely immunosuppressive conditions, including leukemia (13.7%: 2.07, 1.08-3.96) and lymphoma (12.7%: 2.45, 1.53-3.92); autoimmune conditions, including rheumatoid arthritis (9.1%: 1.20, 0.99-1.46); and other comorbidities, including asthma and diabetes. Current and ex-smokers, as well as underweight and obese individuals, were at increased risk of postherpetic neuralgia. Antiviral use was not associated with postherpetic neuralgia (OR 1.04, 0.97-1.11). However, the increased risk associated with severe immunosuppression appeared less pronounced in patients given antivirals. CONCLUSIONS: Postherpetic neuralgia risk was increased for a number of patient characteristics and comorbidities, notably with age and among those with severe immunosuppression. As zoster vaccination is contraindicated for patients with severe immunosuppression, strategies to prevent zoster in these patients, which could include the new subunit zoster vaccine, are an increasing priority

Bacillary angiomatosis in HIV-infected patients - An epidemiological and clinical study

Background: No data were available on the epidemiological and clinical characteristics of bacillary angiomatosis (BA) in Germany. Objective:To determine epidemiological and clinical data on HIV-associated BA. Methods: A chart review of all BA cases between 1990 and 1998 was performed in 23 German AIDS treatment units. Results: A total of 21 cases of BA was diagnosed. During th is period, the participating HIV centers treated about 17,000 HIV-infected patients. As a result, a BA prevalence of 1.2 cases/1,000 patients can be assumed. 19 BA were localized in the skin; in 5 cases bones and in 4 cases the liver were involved. Out of 20 patients who received antibiotic therapy, 13 had complete remission. The median time of duration up to complete remission was 32 days (9-82), During the follow-up of the 20 patients, 7 relapses were observed, Conclusion: BA is a rare HIV-associated disease with a prevalence of 1,2 cases/1,000 patients in the presented study. Copyright (C) 2000 S. Karger AG, Basel

HIV/AIDS Clinical Manifestations and their Implication for Patient Clinical Staging in Resource Limited Settings in Tanzania

BACKGROUND: Tanzania HIV/AIDS management follows WHO clinical staging which requires CD4 counts as complement. Lacking CD4 counts facilities in rural health facilities remains a challenge. Simplified and sensitive clinical staging based on local clinical patterns is useful to ensure effective care without CD4 counts. OBJECTIVES: To assess whether local HIV clinical manifestations can be used to guide HIV management in settings with limited access to CD4 counts in Tanzania. METHODS: A Cross-sectional study conducted at Tumbi and Chalinze health facilities documented clinical manifestations and CD4 counts in 360 HIV/AIDS patients. Simplified management groups comprised of severe and moderate disease were formed based on clinical manifestations and CD4 counts results. Symptoms with high frequency were used to predict severe disease. RESULTS: A Weight loss (48.3%) and chronic cough (40.8 %) were the most reported manifestations in the study population. More than 50% of patients presented with CD4>/=200. Most symptoms were found to be highly sensitive (71% to 93%) in predicting severe immunosuppression using CD4>200 cut-off point as a 'Gold standard'. Chronic diarrhoea presented in 10.6%, and predicted well severe immunosuppression either alone (OR 1.95, 95%CI, 0.95-4.22) or in combination (OR 4.21, 95%CI 0.92-19.33) with other symptoms. Basing strictly on WHO clinical staging 30.8% of patients were detected to be severely immunosuppressed (Stage 4). While using our proposed management categories of severe and moderate immunosuppression 70% of patients were put into the severe immunosuppression group, consistent with CD4 cut-off count of>/=350. CONCLUSIONS: HIV/AIDS clinics managing large cohorts should develop validated site specific guidelines based on local experiences. Simplified guidelines are useful for resource constrained settings without CD4 counting facilitie

VALGANCICLOVIR INDUCED THROMBOCYTOPENIA: A CASE REPORT

Triple immunosuppression is very pivotal in maintaining the graft in case of renal transplantation. But because of severe immunosuppression, always there is chance of severe adverse effects. Hematological toxicity is usually very common but dreaded in case of renal transplant patients. Here, we report a case of valganciclovir-induced drop in platelet counts in a postrenal transplant patient

Acute Cytomegalovirus Colitis Presenting during Primary HIV Infection: an Unusual Case of an Immune Reconstitution Inflammatory Syndrom

Severe ulcerous cytomegalovirus pancolitis developed during primary human immunodeficiency virus (HIV) infection in a patient who underwent early combination antiretroviral treatment. This massive inflammatory process led to acute colon perforation. Serological testing demonstrated cytomegalovirus reactivation. Severe immunosuppression caused by primary HIV infection resulted in cytomegalovirus colitis, and initiation of early combination antiretroviral therapy triggered an immune reconstitution inflammatory syndrome potentially leading to colonic perforatio

Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières

OBJECTIVES: To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. DESIGN/METHODS: We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression. RESULTS: Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl. CONCLUSION: The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment

Profile of HIV Infection in Children and Its Correlation with their CD4 Counts

Objectives: (i) To study the clinical profile of human immunodeficiency virus (HIV) infection in children. (ii) To establish the pattern of correlation of these clinical features with the CD4 counts. (iii) To evaluate the effect of highly active antiretroviral therapy (HAART) on CD4 count of children at 6 months of therapy. Material and methods: Sixty-eight children enrolled at our ART centre or admitted at our hospital were enrolled for the study. Their case papers were reviewed. Complete clinical profile was obtained and baseline investigations including CD4 counts done. Children were then followed up and repeat CD4 levels done 6 monthly. The children were managed as per current guidelines. Results: The mean age at presentation was 6.54 ± 2.69 years. Male-to-female ratio was 2.579:1. Vertical transmission accounted for 95.58% of cases. Prolonged fever and chronic diarrhea were the most common symptoms and hepatosplenomegaly and lymphadenopathy were the most common signs. There was strong correlation between clinical and immunological staging (p < 0.0001). Failure to thrive, recurrent skin infections and abscesses were signs and symptoms at lowest CD4 levels. Orphan-hood (p < 0.0001) and socioeconomic status (p = 0.0003) significantly affected schooling among these children. Malnutrition, anemia and stunting were features of severe immunosuppression. HAART significantly raised the CD4 count at 6 months of therapy (paired ‘t’ = 6.830, p < 0.0001) with best results at higher baseline CD4 levels. Gastritis was the most common (81.5%) adverse effect and the major cause of decreased compliance. Tuberculosis and candidiasis were the commonest opportunistic infections and pneumonia accounted for majority of hospitalizations (61.5%). Conclusions: Clinical and immunological staging have good correlation. The features of severe immunosuppression are failure to thrive, recurrent bacterial skin infections, abscesses, Pneumocystis jirovecii pneumonia, extrapulmonary tuberculosis, anemia and stunting. Orphan-hood and poor socioeconomic status affect schooling in these children. Early initiation of ART at higher baseline CD4 has best results. Gastritis is the major adverse effect causing decreased compliance.&nbsp

Development of colon cancer after liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis

Between February 26, 1981, and July 30, 1987, 36 patients underwent orthotopic liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Three of the 36 recipients died within 3 mo because of graft nonfunction or surgical complications. The other 33 (92%) lived for at least 1 yr. Two of the 33 died after 12 and 14 mo, respectively, of recurrent cholangiocarcinoma that was not diagnosed before transplantation. Four other patients died of recurrent liver failure (three cases) or immunoblastic sarcoma (one case) after 14, 21, 36 and 44 mo. Twenty‐seven (75%) of the patients are still alive 23 to 81 mo after transplantation. Two patients have been diagnosed as having colorectal cancer 11 and 21 mo respectively, after transplantation, for an overall incidence of 5.6% (2 of 36) and a corrected incidence of 6.5% (2 of 31) if the three early deaths and two later deaths caused by cholangiocarcinomas are excluded. It is not known whether colorectal malignancies were present but undetected at the time of transplantation or whether they developed afterward. It is clear that patients who undergo liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis should have careful follow‐up of the colon, including colonoscopy and multiple biopsies of the colorectal mucosa. Whether proctocolectomy should be considered prophylactically after liver transplantation is an unresolved issue.(HEPATOLOGY 1990;11:477–480.) Copyright © 1990 American Association for the Study of Liver Disease

Health outcomes following transition from paediatric to adult care among young people with HIV in the UK

With increasing numbers transferring from paediatric to adult HIV care, a limited number of studies have investigated the health outcomes of young people post-transfer, with inconsistent findings reported. This thesis aims to investigate the risk of disengagement from care and health outcomes of young people and the availability of youth-friendly services following transfer to adult care. In this thesis, data linkage algorithms were developed to link national paediatric cohort data from the Collaborative HIV Paediatric Study (CHIPS) to adult data from the UK Collaborative HIV (UK CHIC) study and two national HIV surveillances systems: Survey of Prevalent HIV Infections Diagnosed (SOPHID); and HIV and AIDS Reporting System (HARS). By five years post-transfer, one-in-eleven young people had experienced an AIDS event and/or died, one-in-twenty became loss-to-follow-up (LTFU) and a quarter had experienced severe immunosuppression or viral failure. Young people with poorer health outcomes in paediatric care were at higher risk of AIDS/mortality, poor immunological and virological outcomes in adult care, and provision of youth-friendly adult services had no association with improved health outcomes and engagement in adult care. The lack of association is likely attributable to the cross-sectional nature of the clinic-level data. Having measured cascade of care post-transfer to adult care, the majority of young people had completed a first adult visit, were engaged and on ART, while low levels were virally suppressed and with a good immune status. However, this group had significantly better cascade outcomes when compared to young people with behaviourally-acquired HIV (BHIV) in adult care. My findings highlight the need for additional resources for young people with pre-existing problems managing their HIV disease in paediatric care. As young people from paediatric care progressed considerably better across the adult care pathway compared to newly diagnosed young people with BHIV, HIV exposure-based interventions may be beneficial