Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure?

OBJECTIVE: To investigate whether HIV-infected patients on a stable and fully suppressive combination antiretroviral therapy (cART) regimen could safely be monitored less often than the current recommendations of every 3 months. DESIGN: Two thousand two hundred and forty patients from the EuroSIDA study who maintained a stable and fully suppressed cART regimen for 1 year were included in the analysis. METHODS: Risk of treatment failure, defined by viral rebound, fall in CD4 cell count, development of new AIDS-defining illness, serious opportunistic infection or death, in the 12 months following a year of a stable and fully suppressed regimen was assessed. RESULTS: One hundred thirty-one (6%) patients experienced treatment failure in the 12 months following a year of stable therapy, viral rebound occurred in 99 (4.6%) patients. After 3, 6 and 12 months, patients had a 0.3% [95% confidence interval (CI) 0.1-0.5], 2.2% (95% CI 1.6-2.8) and 6.0% (95% CI 5.0-7.0) risk of treatment failure, respectively. Patients who spent more than 80% of their time on cART with fully suppressed viraemia prior to baseline had a 38% reduced risk of treatment failure, hazard ratio 0.62 (95% CI 0.42-0.90, P = 0.01). CONCLUSION: Patients who have responded well to cART and are on a well tolerated and durably fully suppressive cART regimen have a low chance of experiencing treatment failure in the next 3-6 months. Therefore, in this subgroup of otherwise healthy patients, it maybe reasonable to extend visit intervals to 6 months, with cost and time savings to both the treating clinics and the patients.

Fungal infection as a risk factor for HIV disease progression among patients with a CD4 count above 200/microl in the era of cART.

The identification of clinical risk factors for AIDS in patients with preserved immune function is of significant interest. We examined whether patients with fungal infection (FI) and CD4 cell count >or=200/microl were at higher risk of disease progression in the era of cART. 11,009 EuroSIDA patients were followed from their first CD4 cell count >or=200/microl after 1 January 1997 until progression to any non-azoles/amphotericin B susceptible (AAS) AIDS disease, last visit or death. Initiation of antimycotic therapy (AMT) was used as a marker of FI and was modelled as a time-updated covariate using Poisson regression. After adjustment for current CD4 cell count, HIV-RNA, starting cART and diagnosis of AAS-AIDS, AMT was significantly associated with an increased incidence of non-AAS-AIDS (IRR=1.55, 95% CI 1.17-2.06, p=0.0024). Despite low incidence of AIDS in the cART era, FI in patients with a CD4 cell count >or=200/microl is associated with a 55% higher risk of non-AAS-AIDS (95% confidence interval 1.17-2.06, p=0.0024). These data suggest that patients with FI are more immune compromized than would be expected from their CD4 cell count alone. FI can be used as a clinical marker for disease progression and indirect indicator for initiation/changing cART in settings where laboratory facilities are limited.

Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe.

BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. RESULTS: Of 1940 HCV Ab-positive patients, 1496 (77%) were serum HCV RNA positive. Injection drug users (IDUs) were less likely to have spontaneously cleared HCV than were homosexual men (20% vs. 39%; adjusted odds ratio [aOR], 0.36 [95% confidence interval {CI}, 0.24-0.53]), whereas patients positive for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4, respectively. A greater HCV RNA level was associated with a greater chance of being infected with HCV genotype 1 (aOR, 1.60 per 1 log higher [95% CI, 1.36-1.88]). CONCLUSIONS: More than three-quarters of the HIV- and HCV Ab-positive patients in EuroSIDA showed active HCV replication. Viremia was more frequent in IDUs and, conversely, was less common in HBsAg-positive patients. Of the patients with HCV viremia analyzed, 53% were found to carry HCV genotype 1, and this genotype was associated with greater serum HCV RNA levels.

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

Atlas sive Cosmographicae meditationes de fabrica mundi et fabricati figura / [Gerardo Mercatore Rupelmundano]

[Duisburgi] : [Clivorum], [1595]

Michael Agricola Christiano Salutem

Porvoo : Werner Söderström osakeyhtiö 1907 : Porvoo

Increased risk of cardiovascular disease (CVD) with age in HIV-positive men : a comparison of the D:A:D CVD risk equation and general population CVD risk equations

OBJECTIVES: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. RESULTS: A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.

Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.

Background In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]). We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis. Methods and Findings Stored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and prothrombin fragment 1þ2. Two studies were conducted: (1) a nested case-control study for studying biomarker associations with mortality, and (2) a study to compare DC and VS participants for biomarker changes. For (1), markers were determined at study entry and before death (latest level) for 85 deaths and for two controls (n¼170) matched on country, age, sex, and date of randomization. Odds ratios (ORs) were estimated with logistic regression. For each biomarker, each of the three upper quartiles was compared to the lowest quartile. For (2), the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following randomization. Higher levels of hsCRP, IL-6, and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality. Unadjusted ORs (highest versus lowest quartile) were 2.0 (95% confidence interval [CI], 1.0-4.1; p¼0.05), 8.3 (95% CI, 3.3-20.8; p , 0.0001), and 12.4 (95% CI, 4.2-37.0; p , 0.0001), respectively. Associations were significant after adjustment, when the DC and VS groups were analyzed separately, and when latest levels were assessed. IL-6 and D-dimer increased at 1 mo by 30% and 16% in the DC group and by 0% and 5% in the VS group (p , 0.0001 for treatment difference for both biomarkers); increases in the DC group were related to HIV-RNA levels at 1 mo (p , 0.0001). In an expanded case-control analysis (four controls per case), the OR (DC/VS) for mortality was reduced from 1.8 (95% CI, 1.1-3.1; p¼0.02) to 1.5 (95% CI, 0.8-2.8) and 1.4 (95% CI, 0.8-2.5) after adjustment for latest levels of IL-6 and D-dimer, respectively. Conclusions IL-6 and D-dimer were strongly related to all-cause mortality. Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels. Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation.

ANALYSE DISCURSIVE DE L’IDENTITE ET DU VOILE ISLAMIQUE. Étude de cas des étudiantes musulmanes de Montréal

Tässä pro gradu -tutkielmassa keskitytään Montrealissa asuvien muslimiopiskelijoiden identiteetin tutkimiseen islamilaisen hunnun kautta. Montrealin suurkaupunkia on vuosien varrella rikastuttanut ja muokannut suuret maahanmuuttajien virrat. Kulttuurien kohdatessa länsimaalaisten nuorten keskuudessa ilmenee usein uusia uskonnollisuuden muotoja. Siksi on olennaista perehtyä nuorten asenteisiin itseä sekä toiseutta kohtaan monikulttuurisessa ympäristössä. Työssä tutkitaankin muslimiopiskelijoiden omakuvan sekä identiteetin rakentumista kielen kautta suhteessa toiseuteen ja jumalaan. Työn teoreettisena lähtökohtana toimii näkökulma identiteetin syntymisestä kielessä sekä vastavuoroisuuden kontekstissa. Tämän diskursiivisen näkökulman mukaan identiteetti ei ole olemassa ihmisessä itsessään, vaan se on kontekstisidonnainen ilmiö, joka muodostuu diskurssissa sekä suhteessa toiseuteen. Lisäksi tutkimuksessa käytetään psykokognitiivista teoriaa representaatioista, sillä se korostaa uskonnollisten representaatioiden erityispiirteitä muihin representaaitoihin nähden. Tutkimus on laadullinen ja sen aineisto koostuu viidestä hunnuttautuvan naispuolisen muslimiopiskelijan haastattelusta. Analyysimetodina työssä käytetään diskurssianalyysia, jonka puitteessa identiteetin muodostumista analysoidaan kielen subjektiivisten elementtien sekä muslimiopiskelijoiden diskurssiin tuomien toiseuden ja jumalan äänen kautta. Tutkielman tulokset osoittavat kuinka länsimaalaiset individualistiset arvot, islamin usko sekä jumalan auktoriteettinen asema esiintyvät toisiaan täydentävinä, ei ristiriitaisina ilmiöinä muslimiopiskelijoiden diskurssissa. Auktoriteettinen jumala antaa jokaiselle yksilölle vapaan tahdon päättää ja toimia haluamallaan tavalla. Siksi huivin käytön taustalta löytyy usein henkilökohtaisia motiiveja, joita vahvistamaan haastateltavat lainaavat niin muiden ihmisten kuin jumalan puhetta. Huivin käyttöönottoa on edeltänyt pitkä itsetutkiskeluprosessi – uskon intellektualisointi. Täten korkeakoulussa opiskelevien musliminaisten usko eroaa pitkälti ”automaattisesta” uskosta, sillä se sisältää kyseenalaistamista, harkintaa sekä voimakkaita tunteellisia kokemuksia. Työn tulokset edesauttavat ymmärtämään kulttuurien välistä kommunikaatiota ja toiseutta. Mielekästä olisikin tutkia tarkemmin huivin käytön taustalta löytyviä motivaatioita sekä eihunnuttautuvien musliminaisten asenteita islamilaista huivia kohtaan tietyssä ympäristössä, kuten työpaikoilla tai yliopistolla.

Avaliação semanal dos efeitos da radioterapia externa convencional pela contagem dos leucócitos e plaquetas de pacientes portadores de câncer nas áreas de cabeça e pescoço, tórax e pelve

OBJETIVO: Avaliar a necessidade de monitoração semanal, pela contagem de leucócitos e plaquetas, dos pacientes portadores de câncer das áreas de cabeça e pescoço, tórax e pelve submetidos a radioterapia externa convencional. MATERIAIS E MÉTODOS: Cento e um adultos, portadores de câncer das áreas de cabeça e pescoço (11 pacientes), tórax (35 pacientes) e pelve (55 pacientes), submetidos a radioterapia, avaliados semanalmente com leucograma e contagem de plaquetas, comparando-se as contagens das células antes do início do tratamento com as obtidas nas semanas ao longo do tratamento, área tratada, sexo e faixa etária. RESULTADOS: A maior queda dos leucócitos e plaquetas ocorreu na quarta semana, quando linfócitos, leucócitos totais, neutrófilos, monócitos e plaquetas apresentaram diminuição de 53,5%, 26,8%, 19,4%, 22,2% e 14,6%, respectivamente, ao serem comparados aos valores do início do tratamento. Durante o tratamento, as médias geométricas da pelve foram estatisticamente menores do que as de tórax e cabeça e pescoço. Os linfócitos foram os mais sensíveis à irradiação. Não houve alteração da contagem de leucócitos e plaquetas relacionadas ao sexo ou à faixa etária. CONCLUSÃO: A partir dos resultados obtidos não parece ser necessária a contagem semanal de leucócitos e plaquetas para pacientes submetidos a radioterapia externa convencional em campos localizados.