bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fat distribution is altered in HIV‐infected men without clinical evidence of the HIV lipodystrophy syndrome
Authors: Kosmiski L , Kuritzkes D , Hamilton J , Sharp T , Lichtenstien K , Hill J , Eckel R 
Published: July 2003

ObjectiveTo determine if fat distribution is altered in HIV‐infected men without clinical evidence of lipodystrophy.MethodsIn a cross‐sectional design, 14 protease inhibitor (PI)‐treated men with lipodystrophy and 12 PI‐treated and five PI‐naive men without clinical evidence of lipodystrophy underwent body composition and fat distribution analysis by dual‐energy X‐ray absorptiometry and computed tomography. Their fat distribution was compared to 43 uninfected male controls matched for age and BMI.ResultsThe percent of body fat in the trunk of men with HIV lipodystrophy was significantly greater compared to both HIV‐infected and healthy controls. The percentage of body fat in the extremities was significantly lower in men with HIV lipodystrophy compared to both HIV‐infected and healthy controls. HIV‐infected men without clinical evidence of lipodystrophy also had a significantly greater percentage of total body fat in the trunk and a significantly lower percent of body fat in the extremities compared to healthy controls. Among the HIV‐infected men, age was an independent predictor of truncal and extremity adiposity.ConclusionThis study suggests that a continuum of change is present in the adipose organ of HIV‐infected men on antiretroviral therapy. Physical examination alone can miss significant changes in body fat distribution in HIV‐infected patients.
HIV/HBV and HIV/HCV coinfection, and outcomes following highly active antiretroviral therapy
Authors: Lincoln D , Petoumenos K , Dore GJ ,   on behalf of the Australian HIV Observational Database
Published: July 2003

ObjectivesTo assess the prevalence and risk factors for HBV and HCV coinfection in the Australia HIV Observational Database (AHOD), and examine outcomes of HIV disease following initiation of highly active antiretroviral therapy (HAART).MethodsAnalyses were based on 2086 participants recruited to AHOD by September 2002. Of these, 1605 (77%) had been tested for HBV surface antigen, 1704 (82%) for anti‐HCV antibody and 1453 (70%) for both. Demographic and clinical predictors of HBV and HCV coinfection were examined. The impact of HBV and HCV coinfection on HIV disease progression was assessed by Kaplan‐Meier survival curves and Cox proportional hazard model of time to AIDS events and death.ResultsAmong those tested, prevalence of HBV surface antigen and HCV antibody were 6.3% and 13.1%, respectively (4.8% and 10.7%, respectively, among the entire cohort). In multivariate analyses, the only independent risk factor for HIV/HBV coinfection was coinfection with HCV. Independent risk factors for HIV/HCV coinfection were HIV exposure category (with people who reported injecting drug use [MSM & IDU, IDU only] or receipt of blood or blood products at markedly increased risk) and HBV coinfection. HIV disease outcomes following first initiation of a HAART regimen were similar for HIV/HBV and HIV/HCV coinfected patients compared with HIV‐only patients in terms of AIDS‐free survival and detectable HIV virus during the first 12 months. However, patients coinfected with HIV/HCV appeared to have a poorer response to HAART in terms of CD4 count changes, with a CD4 count increase of 32 cells/μL (95% CI 1–67) less than HIV‐only patients.ConclusionsCoinfection with HBV or HCV is relatively common among HIV‐infected participants in AHOD. HIV disease outcomes following HAART do not appear to be adversely affected by HBV/HCV coinfection, except for slightly poorer CD4 count responses in HIV/HCV coinfected patients.
Low‐dose indinavir in combination with low‐dose ritonavir: steady‐state pharmacokinetics and long‐term clinical outcome follow‐up
Authors: Justesen US , Levring AM , Thomsen A , Lindberg JA , Pedersen C , Tauris P 
Published: July 2003

ObjectivesTo evaluate the long‐term efficacy and pharmacokinetics of indinavir (IDV)/ritonavir (RTV) 400/100 mg twice a day in combination with two nucleoside reverse transcriptase inhibitors.MethodsThe study was retrospective with a prospective pharmacokinetic study at a single centre. All HIV‐1‐infected patients who started the regimen in the period from January 1999 to February 2001 were included in the study. Plasma HIV RNA and CD4 cell counts were recorded from baseline to week 120. Results were evaluated as intention‐to‐treat and on‐treatment analyses with separate analyses for protease inhibitor naive and experienced patients. Patients who were still on the regimen by August 2001 were asked to participate in a pharmacokinetic evaluation.ResultsTwenty‐one patients started treatment with the regimen (median follow‐up: 116 weeks). The percentage of patients with below 20 HIV‐1 RNA copies/mL was 70.0% at week 120 and the median CD4 cell count increased from 320 to 607 cells/μL (P=0.062). The median IDV morning and evening Cmin were 434 ng/mL and 220 ng/mL, respectively.ConclusionsTreatment with the IDV/RTV 400/100 mg regimen appears to be efficacious for up to 2 years. However, rather low IDV Cmin suggests that the regimen should be evaluated further before its widespread use and that the regimen probably should be guided by pharmacokinetic evaluation.
Characterization of viro‐immunological responses in a closely followed cohort of heavily pretreated patients: evidence from the GenPheRex Study
Authors: Torti C , Quiros‐Roldan E , Scudeller L , Lo Caputo S , Tomasoni L , Castelli F , Poggio A , Delle Foglie P , Chirianni A , Sighinolfi L , Mazzotta F , Carosi G ,   for the GenPheRex Group of the Ma.S.Te.R. Cohort
Published: July 2003

Objectives To assess prevalence and predictive factors of viro‐immunological discordant trends in a cohort of heavily pretreated patients.Methods Factors associated with viro‐immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV‐positive patients from a multicentre prospective study of real‐ vs. virtual‐phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow‐up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow‐up considering CD4 and plasma viral load (pVL) as continuous measures.Results Among 58 virological responder patients (≥1 log10 HIV‐1 RNA copies/mL decrease) and 101 virologically non‐responders, immunological discordances (increase in CD4 count of<or ≥100 cells/μL) were observed in 58.6% and 38.6%, respectively. Baseline CD4 count was associated with discordant responses in both groups. Multivariable linear regression over the entire 48 weeks' follow‐up demonstrated significant correlation between absolute decrease in pVL and increase in CD4 count (HR 28.06, 95%CI 35.32–20.79; P<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45–57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27–64.01; P<0.001) correlated with highly significant immune recovery.Conclusions These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard‐to‐reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.
Depressive disorders and unprotected casual anal sex among Australian homosexually active men in primary care
Authors: Rogers G , Curry M , Oddy J , Pratt N , Beilby J , Wilkinson D 
Published: July 2003

ObjectiveTo examine the relationship between depressive disorders and unprotected anal intercourse with casual partners, among homosexually active men attending for primary care.MethodsThe first 460 homosexually active men enrolling in an Australian integrated primary care programme were screened for current depressive disorders using the Primary Care Evaluation of Mental Disorders (PRIME‐MD) and completed questionnaires on their sexual behaviour in the prior 6 months. One hundred and sixty‐two (35%) were HIV positive, 283 (62%) were HIV negative and 15 (3%) were untested.ResultsThe prevalence of major depressive episode (MDE), as measured by the PRIME‐MD, on enrolment was 28% (129/460), while the prevalence of dysthymic disorder (DD) was 26% (121/460). These include 84 men (18%) who met the criteria for both disorders (‘double depression’). Neither disorder was associated with HIV status. Men with MDE were less likely to have been sexually active than the remainder of the cohort (90/129 [70%] vs. 291/331 [88%]; OR: 0.32 [95% CI: 0.19–0.52]; P<0.0001). Men with DD alone, however, were significantly more likely than men with neither disorder to report having had unprotected anal intercourse with a casual partner (11/38 [29%] vs. 43/292 [15%]; OR: 2.36 [95%CI: 1.09–5.10]; P=0.035).ConclusionsDepressive disorders were highly prevalent in this cohort and independent of HIV status. MDE was associated with reduced sexual activity. Among men without MDE, the presence of DD was independently associated with an increased likelihood of reporting unsafe anal sex with a casual partner in the prior 6 months.
Factors associated with a reduced CD4 lymphocyte count response to HAART despite full viral suppression in the EuroSIDA study
Authors: Florence E , Lundgren J , Dreezen C , Fisher M , Kirk O , Blaxhult A , Panos G , Katlama C , Vella S , Phillips A ,   for the EuroSIDA Study Group
Published: July 2003

ObjectivesTo describe the prevalence and risk factors of poor CD4 count rise despite a good virological response on highly active antiretroviral treatment (HAART).MethodsThe patients from the EuroSIDA study who started HAART with a baseline CD4 count of <350 cells/μL and where all viral load (pVL) measures remained below 500 HIV‐1 RNA copies/mL between 6 and 12 months after the start of HAART were included. The risk factors for poor CD4 count rise were analyzed by multiple regression.ResultsSeven hundred and eighty patients were included. A low CD4 count response was observed in 225 patients (29%). The risk factors for this condition were older age, lower CD4 count at baseline, higher increase from the nadir to baseline CD4 count and lower pVL at baseline. Patients taking ≥one drug from each of the three antiviral classes were more likely to have a good CD4 response but a minority of the study participants was taking this treatment regimen (3.1%) and the confidence interval was large.ConclusionsA poor immune reconstitution despite a good virological control is frequent after initiation of HAART among patients with a baseline CD4 count of <350 cells/μL. The underlying mechanisms leading to this condition seems mainly driven by the age and the baseline immunological and virological status of the patients.
Quality of generalist vs. speciality care for people with HIV on antiretroviral treatment: a prospective cohort study
Authors: Page J , Weber R , Somaini B , Nöstlinger C , Donath K , Jaccard R ,   for the SESAM Study Group
Published: July 2003

ObjectivesTo describe health‐care use by persons with HIV in an urban area of Switzerland (Zurich). Further, to compare the different health‐care settings.DesignA 1‐year prospective cohort study recruiting 60 patients at general practices and 60 patients at a specialized university outpatient clinic.MethodsPatients and their treating physicians were interviewed or answered questionnaires, respectively, at baseline, month 6 and 12.ResultsDuring the study period, five patient groups were identified among the 106 enrolled patients, of whom (i) 42% saw a general practitioner exclusively, (ii) 31% were treated at the specialized outpatient clinic, (iii) 8% were in shared care, (iv) 10% changed health‐care model, and (v) 9% were lost to follow‐up. Baseline demographic, psychosocial and clinical data were similar among patient groups. At study end, the proportion of patients with HIV‐1 RNA < 400 copies/mL was 72%, 74%, 88%, 55% among groups (i) to (iv), respectively (ns), and 22% at month 6 among those lost to follow‐up. Indicators for quality of care were similarly good among all patient groups.ConclusionsA well‐working system offers high‐quality healthcare to persons living with HIV, where existing teams of speciality and primary health‐care professionals efficiently and effectively co‐operate.
Quantitative analysis of human mitochondrial DNA using a real‐time PCR assay
Authors: Gourlain K , Amellal B , Ait Arkoub Z , Dupin N , Katlama C , Calvez V 
Published: July 2003

ObjectivesKnown for their ability to inhibit the human DNA polymerase‐γ, nucleoside analogues induce toxic effects on mitochondria ranging from increased serum lactate levels to fatal lactic acidosis. DNA polymerase‐γ ensures the mitochondrial DNA (mtDNA) replication and, thus, its inhibition leads to the decrease of the mtDNA. We describe a real‐time PCR assay for mtDNA quantification associating DNA extraction procedures applied on peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissues and to study the antiretroviral effect on mitochondria.MethodsTotal DNA was extracted from PBMCs and subcutaneous adipose tissues. Nuclear and mitochondrial genes were amplified to determine the number of copies of mtDNA per cell using a cyt‐b recombinant plasmid as standard control. We analysed eight HIV‐infected asymptomatic patients never treated, four patients who had been treated for 6 months with highly active antiretroviral therapy (HAART) and six non‐infected donors.ResultsThe mtDNA quantification gave rise to reproducible results as the mean coefficients of variation were 1.09% for replicates of samples undertaken 10 times within the same run, and 5.78% and 3.7% for replicates tested in five different runs at 1:100 and 1:1000 dilutions, respectively. Median levels of mtDNA in PBMCs of healthy donors, naive and treated HIV‐infected patients were 2.94, 2.78 and 1.93 log HIV‐1 RNA copies/mL, respectively. Whereas DNA from PBMCs was shown to be devoid of inhibitors, subcutaneous adipose tissues needed an extra treatment as they were found to be highly inhibited.ConclusionsThe method generated consistent and reproducible results and was successfully applied to DNAs extracted from PBMCs and subcutaneous adipose tissues with adapted extraction. The mtDNA changes in PBMCs were found to be fast as they fall off after 6 months' therapy, decreasing from 2.78 to 1.93 log copies/mL.
HIV lipodystrophy: prevalence, severity and correlates of risk in Australia
Authors: Miller J , Carr A , Emery S , Law M , Mallal S , Baker D , Smith D , Kaldor J , Cooper DA 
Published: July 2003

ObjectiveTo establish the prevalence, severity and factors associated with the HIV lipodystrophy syndrome.MethodsCross‐sectional study of lipodystrophy conducted in high HIV caseload primary care sites and HIV outpatient clinics. A subset of patients was examined using dual energy X‐ray absorptiometry (DEXA) and single cut abdominal computerized tomography (CT) at the L4 vertebral level to quantify regional and total body fat. Factors associated with lipodystrophy, lipoatrophy and lipohypertrophy were assessed using multiple logistic regression based on assignment of cases and non‐cases.ResultsOne thousand, three hundred and forty‐eight patients (95% male) were surveyed, 20% had AIDS, the mean CD4 lymphocyte count was 486 cells/μL, and 55% had <500 HIV‐1 RNA copies/mL. Most participants (87%) had previously received or were currently receiving combination antiretroviral therapy, 73% with at least one protease inhibitor (PI) and 14% a non‐PI‐containing regimen. Lipodystrophy prevalence was 53% and of these, 55% reported both peripheral lipoatrophy and central lipohypertrophy, 31% experienced peripheral lipoatrophy only and 14% had central lipohypertrophy only. The prevalence of any body habitus change was 62% in PI‐experienced patients, 33% in PI‐naive patients and 21% in antiretroviral‐naive patients. Lipodystrophy severity was less in antiretroviral‐naive patients and most severe in PI‐experienced patients. Increasing severity of lipodystrophy was both positively and significantly correlated with elevated liver enzymes, decreased testosterone levels, decreased skin‐fold thickness, lower levels of total and peripheral fat (DEXA) and higher levels of visceral fat (CT). Lipodystrophy was also significantly associated with increasing age, symptomatic HIV disease, effective viral suppression, and increasing duration of therapy with both nucleoside reverse transcriptase inhibitors and PIs.ConclusionsThe prevalence and severity of lipodystrophy reflects both length and type of treatment with antiretroviral therapy and is associated with decreased testosterone, increases in liver enzymes and greater suppression of HIV RNA. The reports of lipodystrophy in a small percentage of antiretroviral‐naive patients suggests that factors other than antiretroviral therapy may be involved in the aetiology of this syndrome or that some conditions, such as wasting or age‐associated obesity, may mimic lipoatrophy and lipohypertrophy, respectively.
Recurrence of post‐traumatic stress disorder symptoms after initiation of antiretrovirals including efavirenz: a report of two cases
Authors: Moreno A , Labelle C , Samet JH 
Published: July 2003

BackgroundSome antiretrovirals has been reported to cause a wide range of psychiatric symptoms. However, reappearance of post‐traumatic stress disorder (PTSD) symptoms has not been described in relation to these medications.DesignCase report.SettingsThe Boston Medical Center, a tertiary care academic centre.FindingsTwo HIV‐infected refugees re‐experienced symptoms of PTSD after starting therapy with efavirenz (EFV) and zidovudine (ZDV). The two patients had no typical factors present to account for the PTSD exacerbation. In both patients, the symptoms of PTSD gradually subsided to baseline within the first 4 weeks of antiretroviral treatment.ConclusionsWe believe that EFV, a non‐nucleoside reverse transcriptase inhibitor, with ZDV, may be mani‐festing its known neuropsychiatric toxicities in a heretofore unreported presentation of PTSD exacerbation.
Methylenetetrahydrofolate Reductase (MTHFR) Allele Frequencies in Amerindians
Authors: Monsalve M. V. , Salzano F. M. , Rupert J. L. , Hutz M. H. , Hill K. , Hurtado A. M. , Hochachka P. W. , Devine D. V. 
Published: July 2003

SummaryNeural tube defects (NTDs) have been associated with abnormalities of folate metabolism. Methylenetetrahydrofolate reductase (MTHFR) is the regulatory enzyme for the conversion of homocysteine to methionine. The C677T mutation in the MTHFR gene affects folate distribution, and homozygosity for the T allele may be associated with an increased risk of NTDs. A second mutation, an A1298C transversion in this same gene, is also associated with an increased risk for NTDs but only in conjunction with the 677T allele. A low incidence of NTDs has been observed in high‐altitude populations; however, these studies did not provide information about the allele distribution of genes involved in folate metabolism. This investigation compares allele frequencies of the C677T and A1298C polymorphisms between Quechua people living at 3200–4200 m in the Peruvian Central Andes and an Aché group living at low altitude. Allele frequencies at both loci were not significantly different between the two populations. The absence of the 677T/677T genotypes and of the 677T/1298C arrangement in both groups may indicate a genetic contribution to reduced risk for NTDs; however, factors other than altitude are likely responsible for the low variant allele frequencies in these populations.
Genetic Differentiation of the Cabo Verde Archipelago Population Analysed by STR Polymorphisms
Authors: Fernandes A. T. , Velosa R. , Jesus J. , Carracedo A. , Brehm A. 
Published: July 2003

SummaryAllele frequencies for 17 STR loci were analyzed in a sample of unrelated males from the Cabo Verde Archipelago. The samples were gathered in such a way that the origin of the subjects was perfectly identified, and they could be included in one of the leeward or windward groups of islands. This study reveals that there are significant differences between both groups of islands, and between Cabo Verdeans and other populations from sub‐Sahara Africa including the Guineans, the most probable source population for Cabo Verdeans. This study confirms mtDNA data and, together with HLA and Y chromosome data already published, shows that the Cabo Verde population is sub‐structured and atypical, diverging substantially from mainland sub‐Saharan populations. Overall these differences are most probably due to admixture between sub‐Saharan slaves brought into the islands and other settlers of European origin. In the absence of a clear indication of a different ethnic composition of the first sub‐Saharan settlers of Cabo Verde, the differentiation exhibited in both groups of islands can be most probably be attributed to genetic drift.
Assessing Optimal Neural Network Architecture for Identifying Disease‐associated Multi‐marker Genotypes using a Permutation Test, and Application to Calpain 10 Polymorphisms Associated with Diabetes
Authors: North B. V. , Curtis D. , Cassell P. G. , Hitman G. A. , Sham P. C. 
Published: July 2003

SummaryBiallelic markers, such as single nucleotide polymorphisms (SNPs), provide greater information for localising disease loci when treated as multilocus haplotypes, but often haplotypes are not immediately available from multilocus genotypes in case‐control studies. An artificial neural network allows investigation of association between disease phenotype and tightly linked markers without requiring haplotype phase and without modelling any evolutionary history for the disease‐related haplotypes. The network assesses whether marker haplotypes differ between cases and controls to the extent that classification of disease status based on multi‐marker genotypes is achievable. The network is “trained” to “recognise” affection status based on supplied marker genotypes, and then for each multi‐marker genotype it produces outputs which aim to approximate the associated affection status. Next, the genotypes are permuted relative to affection status to produce many random datasets and the process of training and recording of outputs is repeated. The extent to which the ability to predict affection for the real dataset exceeds that for the random datasets measures the statistical significance of the association between multi‐marker genotype and affection. This permutation test performs well with simulated case‐control datasets, particularly when major gene effects are present. We have explored the effects of systematically varying different network parameters in order to identify their optimal values. We have applied the permutation test to 4 SNPs of the calpain 10 (CAPN10) gene typed in a case‐control sample of subjects with type 2 diabetes, impaired glucose tolerance, and controls. We show that the neural network produces more highly significant evidence for association than do single marker tests corrected for the number of markers genotyped. The use of a permutation test could potentially allow conditional analyses which could incorporate known risk factors alongside marker genotypes. Permuting only the marker genotypes relative to affection status and these risk factors would allow the contribution of the markers to disease risk to be independently assessed.