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Biomedical subjects

C A Sabin

Publications and source records attributed to C A Sabin.

At least 19 recordsLinked to original sources
PubMed2006

Effects of highly active antiretroviral therapy on paediatric metabolite levels.

OBJECTIVES: Highly active antiretroviral therapy (HAART) has extended survival of HIV-infected children into adulthood, raising concerns about long-term metabolic changes in childhood. METHODS: A longitudinal study of metabolite levels in paediatric HIV-infected patients before and after starting HAART (January 2000 to June 2003). The effects of HAART on nonfasting blood levels of total (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, cholesterol ratio and lactate were analysed using mixed-effects regression. RESULTS: A total of 146 children attended 1208 appointments (median 6.7/child). Of these, 99 (68%) were African. At baseline, 75 (51%) were on HAART and had higher TC (4.19 vs 3.49 mmol/L, P<0.0001), HDL (1.03 vs 0.82 mmol/L, P<0.0001), and LDL (2.54 vs 2.11 mmol/L, P=0.0003) than those not on HAART. Metabolites increased with time on HAART exposure and then stabilized. At 2 years, TC had increased by 0.93 mmol/L (P<0.0001), with 29 children (20%) having repeated TC levels above the 95th centile. LDL and HDL had increased by 0.69 and 0.31 mmol/L at 2 years, respectively (both P<0.0001). Lactates declined with increasing age (-0.06 mmol/L/year, P=0.0001). CONCLUSIONS: This is the first cohort study to demonstrate significant elevations of HDL as well as LDL in children on HAART. This rise in cardio-protective HDL may represent a positive effect of treatment.

Adolescent↗
PubMed2006

The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study.

BACKGROUND: The D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) Study, a prospective observational study on a cohort of 23 468 patients with HIV infection, indicated that the incidence of myocardial infarction (MI) increased by 26% per year of exposure to combination antiretroviral treatment (CART). However, it remains unclear whether the observed increase in the rate of MI in this population can be attributed to changes in conventional cardiovascular risk factors. OBJECTIVE: To compare the number of MIs observed among participants in the D:A:D Study with the number predicted by assuming that conventional cardiovascular risk equations apply to patients with HIV infection. METHODS: The Framingham equation, a conventional cardiovascular risk algorithm, was applied to individual patient data in the D:A:D Study to predict rates of MI by duration of CART. A series of sensitivity analyses were performed to assess the effect of model and data assumptions. Predictions were extrapolated to provide 10-year risk estimates, and various scenarios were modelled to assess the expected effect of different interventions. RESULTS: In patients receiving CART, the observed numbers of MIs during D:A:D follow up were similar to or somewhat higher than predicted numbers: 9 observed vs 5.5 events predicted, 14 vs 9.8, 22 vs 14.9, 31 vs 23.2 and 47 vs 37.0 for<1 year, 1-2 years, 2-3 years, 3-4 years and >4 years CART exposure, respectively. In patients who had not received CART, the observed number of MIs was fewer than predicted (3 observed vs 7.6 predicted). Nine per cent of the study population have a predicted 10-year risk of MI above 10%, a level usually associated with initiation of intervention on risk factors. CONCLUSIONS: A consistent feature of all analyses was that observed and predicted rates of MI increased in a parallel fashion with increased CART duration, suggesting that the observed increase in risk of MI may at least in part be explained by CART-induced changes in conventional risk factors. These findings provide guidance in terms of choosing lifestyle or therapeutic interventions to decrease those risk factors in much the same way as in persons without HIV infection.

Adult↗
PubMed2005

Relationship between serum ferritin, hepatic iron staining, diabetes mellitus and fibrosis progression in patients with chronic hepatitis C.

BACKGROUND: Chronic infection with the hepatitis C virus affects over 170 million individuals worldwide and 20% of patients develop cirrhosis after 20 years. Increased iron stores and hepatic iron content have been suggested to be important in fibrosis progression. The increased prevalence of diabetes mellitus has been associated with increased iron deposits in patients with chronic hepatitis C. AIM: To assess the potential relationship between serum ferritin and hepatic iron staining and liver fibrosis in patients with chronic hepatitis C virus infection and whether these factors are increased in diabetic patients with hepatitis C virus. METHODS: This was a cross-sectional, multi-centre study involving hospitals in the north-east of London between 1992 and 2003. Chronic hepatitis C patients with a liver biopsy and data concerning age, sex, basal metabolic index, diabetes mellitus or impaired glucose tolerance, alcohol intake, serum ferritin level and ethnicity were enrolled. Each biopsy was scored for fibrosis and stained for hepatic iron. RESULTS: Three hundred and thirty nine patients (200 Caucasian; 139 Asian) were enrolled. Fifty three patients had no fibrosis, 131 had mild fibrosis (stage one to two Modified Ishak), 68 moderate fibrosis (stage three to four) and 87 cirrhosis (stage five to six). 4.4% of patients had elevations in serum ferritin, whilst 11% had increased hepatic iron staining. The serum ferritin and hepatic iron staining were unrelated to the degree of fibrosis. Serum ferritin was significantly higher in patients with diabetes or impaired glucose tolerance compared to non-diabetics. No association was seen between diabetes and hepatic iron staining. CONCLUSIONS: Many patients with chronic hepatitis C virus infection may have elevated serum ferritin and/or iron deposition within the liver. However, both played no significant role in the progression of hepatitis C virus related liver injury. The association between chronic hepatitis C virus infection and type II diabetes mellitus exists, however the biological mechanism of this association still remains to be elucidated.

Adult↗
PubMed2005

An unusual form of autoimmune hepatitis in young Somalian men.

BACKGROUND: Significant diversity in disease severity has been identified for autoimmune disorders among different ethnic groups. Current knowledge of both the natural history and management of autoimmune hepatitis (AIH) has been derived from European or Japanese patients, and there is limited information about the disease in patients from other ethnic groups. AIMS: To assess the clinical, histological and immunological features of AIH in patients from Somalia and to determine their response to therapy. METHODS: Retrospective review of a cohort of young Somalian men with atypical AIH compared with a control group of European patients. RESULTS: The six Somalian men were younger at presentation (median age 37 (range 24-59) years) than the seven female and three male European controls (55 (34-54) years, P = 0.06). The Somalians had slightly more severe disease at presentation-median modified Ishak stage of 2.5 compared with 2 in Europeans (P = 0.61) and four (66%) had features of cholestasis compared with only one (10%) European patient (P = 0.04). Therapy with prednisolone and azathioprine was completely effective for eight of 10 Europeans but only one of seven Somalians (P = 0.04). Analysis of human leucocyte antigen types revealed differences between the Somalian and European patients, although these differences did not reach statistical significance. CONCLUSIONS: Somalian men with AIH present with cholestatic features and respond poorly to standard immunosuppressive regimes.

Adult↗
PubMed2005

Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy.

OBJECTIVES: To assess whether insulin resistance is associated with liver fibrosis in a group of patients with chronic hepatitis C virus (HCV) infection and whether there were any differences in insulin resistance between Asians and the indigenous Caucasian population. Secondly, to assess whether insulin resistance is associated with sustained virological response to antiviral therapy. METHODS: We determined insulin resistance in 59 (30 Caucasians; 29 Asians) consecutive patients with HCV prior to starting antiviral therapy. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship between insulin resistance and biochemical, virological, and histological data together with response to antiviral therapy was assessed. RESULTS: In multivariable analyses, insulin resistance as measured using the HOMA-IR model correlated positively with the stage of fibrosis, with higher degrees of insulin resistance in those with greater degrees of fibrosis (p < 0.001). This significant relationship remained even after excluding cirrhotic patients, or after adjusting for other factors associated with fibrosis in univariable analyses. Insulin resistance was significantly higher in Asians than Caucasians (p= 0.004). Around half (55.6%) of patients completing a course of antiviral treatment had a sustained virological response. Multivariable logistic regression identified HCV genotype 3, lower fasting glucose levels, and lower aspartate transaminase (AST) levels as being associated with a higher odds of a sustained virological response. After adjusting for these variables, Asian ethnicity, higher fasting insulin levels, and higher HOMA-IR levels were all associated with a poorer virological response to therapy. CONCLUSIONS: Insulin resistance contributes to liver fibrosis in chronic HCV infection; this relationship is not genotypic specific. Asian patients had higher insulin resistance than Caucasians. Insulin resistance is also an important predictor of sustained response to antiviral therapy.

Adult↗
PubMed2004

Cardio- and cerebrovascular events in HIV-infected persons.

OBJECTIVE: Recent results from the D:A:D Study indicated that the incidence of myocardial infarction (MI) increased by 26% per year of exposure to combination antiretroviral treatment (CART). The present study was performed to investigate whether this risk was similar when including other cardio- and cerebro-vascular disease events (CCVE). DESIGN: D:A:D is an international collaboration of 11 cohorts, following 23 468 HIV-infected patients prospectively at 188 clinics in 21 countries situated in Europe, USA and Australia. METHODS: The end-point was the occurrence of a first CCVE during prospective follow-up, defined as the first of: acute MI, invasive cardiovascular procedures, stroke, or death from other cardiovascular disease. Relative rates (RR) for CCVE from Poisson regression models and 95% confidence intervals (CI) are reported. All models are adjusted for other risk factors for CCVE, including age, gender, ethnicity, family history, body mass index, and smoking status as well as cohort and HIV transmission group. RESULTS: Over 36 145 person-years of follow-up, 207 patients experienced at least one CCVE (23.7% fatal). The first event was MI in 126 patients, invasive cardiovascular procedure in 39 patients, stroke in 38 patients, and death from other cardiovascular disease in four patients. The incidence of first CCVE was 5.7 per 1000 person-years [95% confidence interval (CI) 5.0-6.5] and increased with longer exposure to CART (RR per year of exposure, 1.26; 95% CI, 1.14-1.38; P < 0.0001). CONCLUSION: CART increases the risk of CCVD, and this increase is comparable with how CART affects the risk of MI. This finding is consistent with the hypothesis that atherosclerosis is a side-effect of CART.

Anti-Retroviral Agents↗
PubMed2004

Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles?

Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC : HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC : HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC : HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine.

Adult↗
PubMed2004

Cardiovascular disease risk factors and antiretroviral therapy in an HIV-positive UK population.

AIM: Although the benefits of antiretroviral therapy (ART) have been dramatic, studies have started to report a variety of drug-related side effects and toxicities. We sought to characterize the risk factors for cardiovascular disease present in an HIV-positive population. METHODS: A total of 394 HIV-positive ambulant patients attending the Royal Free Hospital, London, were asked to complete a questionnaire. Questions focused on smoking habits and general health. RESULTS: In total, 38% of patients were aged >40 years, 37% had a family history of heart disease, 3% had diabetes, 14% suffered from raised blood pressure, 20% had a body mass index (BMI)>26 kg/m3, 7% had an alcohol consumption above the recommended UK limit, and 18% had total cholesterol levels >6.3 mmol/L [corrected]. The rate of smoking observed (45%) was much higher than that observed amongst the general population in the British Health Survey for England (34%). There were significant differences between those receiving and not receiving ART. Those on ART tended to be younger (P<0.0001) and less likely to smoke cigarettes (P=0.06) or have an alcohol consumption above the recommended limit (P=0.08), but were more likely to have diabetes (P=0.05). More patients receiving ART reported, and so perceived themselves to have, raised blood fats (P<0.0001). This was confirmed when considering blood lipid levels, where those on ART had significantly raised total cholesterol levels compared to those not currently receiving ART (P<0.0001). CONCLUSION: We have demonstrated an excess of cardiovascular risk factors in this cohort. These issues must be addressed if we wish to maintain the benefit of treating HIV infection.

Adult↗
PubMed2003

Findings from the first national clinical audit of treatment for people with HIV.

OBJECTIVES: We reviewed the impact of and assessed adherence to British HIV Association (BHIVA) guidelines in routine clinical practice. Feedback has been provided to clinical centres to facilitate any necessary change. METHODS: We used a questionnaire to gauge clinicians' views on the guidelines and availability of antiretroviral therapy (ART) drugs and specialized tests. A case note review of 2044 patients was conducted to assess adherence to guideline recommendations plus patterns of use of HIV resistance testing. RESULTS: Most clinicians (74.1%) report that BHIVA guidelines have influenced care at their centres. A significant minority report problems with access to specialized tests. Most patients who started ART did so at CD4 counts lower than guidelines recommend but in most cases this reflected the CD4 count at diagnosis of HIV. Of patients on ART, an overwhelming majority (97.6%) were receiving three or more drugs. Of those on three or more drugs, 58.9% had latest viral load (VL) below 50 HIV-1 RNA copies/mL and a further 18.1% below 500 copies/mL. Only 19.3% of patients had been tested for HIV resistance, of whom more than half showed resistance to more than one class of drugs. CONCLUSIONS: This clinical audit provides encouraging evidence of the quality of care offered to people with diagnosed HIV in the UK. However late diagnosis means most people start ART at a more advanced stage than guidelines recommend.

Adolescent↗
PubMed2003

Modelling the 3-year risk of myocardial infarction among participants in the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study.

OBJECTIVES: To estimate the 3-year risk of myocardial infarction (MI) among participants in the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study. METHODS: Conventional cardiovascular risk equations were applied to baseline data from the DAD study to estimate the 3-year risk of MI. Best estimates were obtained by simply applying the risk equations, with upper and lower limits based on worst case and optimistic case scenarios. Three-year risks of AIDS or death were also estimated based on a prognostic scoring system for patients receiving antiretroviral (ARV) treatment, and on estimated AIDS rates in untreated people with HIV for those patients not on ARVs or if they were to cease ARVs. RESULTS: Analyses were based on 17 600 patients (24.3% female) recruited into the DAD study with baseline data and no previous MI. The overall 3-year risk of MI was estimated to be 0.72% (lower limit 0.35, upper limit 1.12%), corresponding to a total predicted 127 (65-197) MIs over a 3-year follow-up period. The risk was much greater for men than women (0.92% vs. 0.07%), with only three (2-8) MIs predicted in women. The 3-year risk of MI was estimated to increase from 0.30% (0.20-0.38%) in ARV naive patients to 1.07% (0.43-1.77%) in patients receiving ARVs from all three drug classes. The estimated 3-year risk of AIDS or death was in the range 6.2% to 11.1% in patients receiving ARVs if they continued treatment, and 22.5% to 29.4% if they ceased ARVs. DISCUSSION: These models suggest that although the increase in relative risk of MI as a result of ARV treatment may be as high as threefold in a worst case scenario, the absolute risk is modest with a best estimate of 3-year risk less than or equal to 1% in all groups of patients, and is outweighed by the benefits of ARV treatment in terms of reduced risk of AIDS and death in most patients. As estimates are based on models not validated for people receiving ARV drugs, all estimates should be interpreted cautiously.

Adult↗
PubMed2003

An audit of antiretroviral treatment use in HIV-infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use.

OBJECTIVE: To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines. METHODS: All patients under follow-up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow-up, were used to identify which patients should be receiving HAART according to the guidelines. RESULTS: One thousand two hundred and sixty-four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/ micro L and over 80% had previously had a viral load above 4 log10 HIV-1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty-five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it. CONCLUSION: Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.

Adult↗
PubMed2002

DDAVP nasal spray for treatment of menorrhagia in women with inherited bleeding disorders: a randomized placebo-controlled crossover study.

To assess DDAVP (1-deamino-8-d-arginine vasopressin; desmopressin) nasal spray in the management of menorrhagia in patients with inherited bleeding disorders, 39 women (aged 18-50 years) with menorrhagia were recruited and were randomized to start 2 months' therapy with placebo or DDAVP (300 micro g) spray in a double-blind crossover study. Twenty-eight and 24 completed first and second period of treatment, respectively. Menstrual loss was assessed using the pictorial blood assessment chart (PBAC) during each treatment period. The main outcome measure was comparison of PBAC scores following DDAVP and placebo treatments. The safety of DDAVP spray was also assessed by monitoring side-effects. Overall, PBAC scores were significantly lower in the second treatment period than the first (P = 0.01). After adjusting for this differences, mean PBAC scores were slightly lower (mean difference 8; 95% confidence interval of - 15.5 to 31.6) in women receiving DDAVP than when receiving placebo, although this difference was not statistically significant (P = 0.51). In conclusion, although there was an indication that menstrual bleeding was less heavy when women received DDAVP than when receiving placebo, the small sample size meant that this difference was not significant.

Administration, Intranasal↗
PubMed2002

A randomized, controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis.

BACKGROUND & AIMS: Patients who have had one variceal bleed are at high risk of rebleeding. Since its introduction, endoscopic variceal banding has been shown to be superior to needle sclerotherapy. Banding has not been compared with hepatic venous pressure-guided medical therapy (beta-blockers and nitrates). METHODS: One hundred two patients with cirrhosis and a recent esophageal variceal bleed were randomized to either endoscopic banding (51 patients) or medical therapy (51 patients). The hepatic venous pressure gradient was measured in all patients at baseline, at 3 months (drug therapy arm), and at yearly intervals (all patients). Primary end points were death or rebleeding. RESULTS: The 2 groups were well matched. Fifty-one percent were Pughs C, with a median Pughs score of 9.5. Nineteen patients rebled in the drug arm (median time, 24 days) and 27 patients in the banding arm (median time, 24 days). At 1 year, 43.7% of patients had bled in the drug arm compared with 53.8% in the banding arm (P = 0.25). Thirty-two percent of patients on medical therapy had died at 1 year, 22.5% on banding (P = 0.97). CONCLUSIONS: In the prevention of variceal rebleeding, beta-blockers +/- nitrates are as effective as endoscopic banding.

Adrenergic beta-Antagonists↗
PubMed2001

Penetration of efavirenz into the male genital tract: drug concentrations and antiviral activity in semen and blood of HIV-1-infected men.

Efavirenz is a potent non-nucleoside reverse transcriptase inhibitor, licensed for the treatment of HIV-1. Data on sanctuary site penetration are limited. Therefore, we measured efavirenz concentrations in the blood and semen of 19 HIV-1-positive men and found concentrations in seminal plasma averaged 10% of those in blood plasma. Furthermore, seminal plasma viral loads were suppressed by 24 weeks of therapy in all patients. These data suggest that efavirenz-containing regimens have antiviral activity within the male genital tract.

Alkynes↗
PubMed2001

Reduced bone mineral density in HIV-positive individuals.

A total of 105 HIV-positive patients underwent dual-energy X-ray absorbtiometry (DEXA) scan to assess bone mineral density (BMD). The prevalence of reduced BMD was found to be 71% and was higher in patients who had ever been treated with protease inhibitors (PI). Our results suggest a possible association between PI and reduced BMD, and further complicate the debate regarding when to commence treatment of HIV and with what agents to start.

Absorptiometry, Photon↗
PubMed2001

Relationships among the detection of p24 antigen, human immunodeficiency virus (HIV) RNA level, CD4 cell count, and disease progression in HIV-infected individuals with hemophilia.

The aim of this study was to assess the relationships among the detection of p24 antigen, human immunodeficiency virus (HIV) RNA level, CD4 cell count, and disease progression in 111 males with hemophilia who were infected with HIV for < or =20 years. Sixty-four individuals (58%) developed p24 antigenemia a median of 11.6 years after seroconversion. The time to first detection of p24 antigen was shorter among those who were older (P=.04) and those with a high initial HIV RNA level (P=.006). The median HIV RNA level and CD4 cell count at the time of the detection of p24 antigen were 4.95 log(10) copies/mL and 100 cells/mm(3), respectively. In univariate analyses, p24 antigenemia was associated with more-rapid progression to AIDS (relative hazard [RH], 5.50; P=.0001). The effect was reduced (RH, 1.85; P=.06) after adjusting for CD4 cell counts and HIV RNA levels during follow-up, age, and calendar year. A significant relationship between p24 antigenemia and death was nonsignificant after adjusting for CD4 cell count.

Adolescent↗
PubMed2001

The relationships between ethnicity, sex, risk group, and virus load in human immunodeficiency virus type 1 antiretroviral-naive patients.

This cross-sectional study examined the relationships between ethnicity, sex, risk group, and virus load in human immunodeficiency virus type 1 (HIV-1) antiretroviral-naive patients. HIV-1 RNA levels were measured in 322 patients attending St. Thomas' Hospital between May 1997 and February 1999. By univariate analyses, only clinical status and CD4(+) cell count were related to virus load. In multivariate analysis, variables independently related to virus load were CD4(+) cell count (P=.001), being black African (P=.001), having a nonsexual risk for HIV infection (P=.03), and having AIDS (P=.05). Neither sex nor age was a significant predictor of initial virus load after adjusting for other variables. For a given CD4(+) cell count, black Africans and people who contracted HIV nonsexually presented with a virus load lower than that of patients in other groups. Because virus loads may need to be interpreted differently according to ethnicity, this may affect decisions on when to initiate antiretroviral therapy and how to interpret clinical trial results.

CD4 Lymphocyte Count↗