Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe.

OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan-Meier and multivariable Cox models were used to compare risks of failure by PI/r-based regimen. The main analysis was performed with intention-to-treat (ITT) ignoring treatment switches. RESULTS: The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART. CONCLUSIONS: Although confounding by indication and calendar year cannot be completely ruled out, in ART-experienced subjects the long-term effectiveness of DRV/r-containing regimens appears to be greater than that of ATZ/r and LPV/r.

A comparison of estimated glomerular filtration rates using Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration estimating equations in HIV infection.

OBJECTIVES: The aim of this study was to determine whether the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)- or Cockcroft-Gault (CG)-based estimated glomerular filtration rates (eGFRs) performs better in the cohort setting for predicting moderate/advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). METHODS: A total of 9521 persons in the EuroSIDA study contributed 133 873 eGFRs. Poisson regression was used to model the incidence of moderate and advanced CKD (confirmed eGFR < 60 and < 30 mL/min/1.73 m(2) , respectively) or ESRD (fatal/nonfatal) using CG and CKD-EPI eGFRs. RESULTS: Of 133 873 eGFR values, the ratio of CG to CKD-EPI was ≥ 1.1 in 22 092 (16.5%) and the difference between them (CG minus CKD-EPI) was ≥ 10 mL/min/1.73 m(2) in 20 867 (15.6%). Differences between CKD-EPI and CG were much greater when CG was not standardized for body surface area (BSA). A total of 403 persons developed moderate CKD using CG [incidence 8.9/1000 person-years of follow-up (PYFU); 95% confidence interval (CI) 8.0-9.8] and 364 using CKD-EPI (incidence 7.3/1000 PYFU; 95% CI 6.5-8.0). CG-derived eGFRs were equal to CKD-EPI-derived eGFRs at predicting ESRD (n = 36) and death (n = 565), as measured by the Akaike information criterion. CG-based moderate and advanced CKDs were associated with ESRD [adjusted incidence rate ratio (aIRR) 7.17; 95% CI 2.65-19.36 and aIRR 23.46; 95% CI 8.54-64.48, respectively], as were CKD-EPI-based moderate and advanced CKDs (aIRR 12.41; 95% CI 4.74-32.51 and aIRR 12.44; 95% CI 4.83-32.03, respectively). CONCLUSIONS: Differences between eGFRs using CG adjusted for BSA or CKD-EPI were modest. In the absence of a gold standard, the two formulae predicted clinical outcomes with equal precision and can be used to estimate GFR in HIV-positive persons.

Temporal changes and regional differences in treatment uptake of hepatitis C therapy in EuroSIDA.

OBJECTIVES: All HIV/hepatitis C virus (HCV)-coinfected patients with chronic HCV infection and ≥ F2 fibrosis should be considered for HCV therapy. This study aimed to determine the rate of HCV treatment uptake among coinfected patients in Europe. METHODS: EuroSIDA patients with viraemic HCV infection were included in the study. Poisson regression was used to identify temporal changes and regional differences in HCV treatment uptake. RESULTS: A total of 1984 patients were included in the study, with a median follow-up time of 168 months [interquartile range (IQR) 121-204 months]. To date, 501 (25.3%) HIV/HCV-coinfected patients have received HCV therapy. Treatment incidence rose from 0.33 [95% confidence interval (CI) 0.16-0.50] per 100 person-years of follow-up (PYFU) in 1998 to 5.93 (95% CI 4.49-7.38) in 2007, falling to 3.78 (95% CI 2.50-5.07) in 2009. After adjustment, CD4 cell count > 350 cells/µL [incidence rate ratio (IRR) 1.33 (95% CI 1.06-1.67) vs. CD4 count 200-350 cells/µL] and ≥F2 liver fibrosis [IRR 1.60 (95% CI 1.14-2.25; P = 0.0065) vs. < F2 fibrosis] were predictors of anti-HCV treatment initiation. However, 22% of patients who remain untreated for HCV, with fibrosis data available, had ≥F2 fibrosis and should have been considered for treatment, while only 36% of treated patients had ≥F2 fibrosis. CONCLUSIONS: Although treatment incidence for HCV has increased, there remain a large proportion of patients indicated for treatment who have yet to be treated.

Severe bacterial non-aids infections in HIV-positive persons: incidence rates and risk factors.

OBJECTIVES: This study aimed to determine incidence rates (IR) and identify risk factors for severe bacterial non-AIDS infections (SBnAI) requiring hospital admission. METHODS: Data from the prospective EuroSIDA cohort were utilized to determine IRs of first diagnosis of the following SBnAI requiring hospital admission: bacteremia, endocarditis, meningitis, peritonitis, pneumonia, osteitis, and pyolonephritis. Incidence rate-ratios (IRRs) and risk factors were assessed by Poisson regression. RESULTS: During 35,839 person-years of follow-up (PYFU), 275 patients were diagnosed with SBnAI (IR = 7.67 per 1000 PYFU, 95% confidence interval: 6.79-8.64). The most frequent infections were pneumonia (IR = 5.36, 4.63-6.17), bacteremia (IR = 1.14, 0.82-1.55), and pyelonephritis (IR = 0.67, 0.43-1.00). A strong risk factor for SBnAI was reduced estimated glomerular filtration rate [eGFR] (adjusted IRR = 5.07, 2.12-12.1 and IRR = 2.73, 1.63-4.56 for eGFR ≤ 60 and 60.1-90 compared to eGFR > 90, respectively). No current combined antiretroviral therapy (cART) compared with current cART use increased the risk of SBnAI (adjusted IRR = 2.96, 2.03-4.32). Other risk factors for SBnAI included current CD4+ count <350 cells/µL, female gender, age, infection with HIV through IDU, prior AIDS diagnosis, and anaemia. CONCLUSIONS: Enhanced attention directed towards people with comorbidity is warranted to limit the burden of these infections.

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change.

OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies. METHODS: A total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional demographic variables. Baseline was defined as the date of starting new antiretrovirals. RESULTS: Four hundred and fifty-one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI) 6.7-8.0]. After adjustment, patients who had rebounded in the year prior to baseline had a 2.4-times higher rate of virological failure after baseline (95% CI 1.77-3.26; P<.0001), while there was no increased incidence in patients whose last viral rebound was >3 years prior to baseline [Incidence rate ratio (IRR) 1.06; 95% CI 0.75-1.50; P=0.73] compared with patients who had never virally rebounded. Patients had an 86% (95% CI 1.36-2.55; P<.0001), 53% (95% CI 1.06-2.04; P=0.02) and 5% (95% CI 0.80-1.38; P=0.72) higher virological failure rate after baseline if they were virally suppressed <50%, 50-70% and 70-90% of the time they were on cART prior to baseline, respectively, compared with those virally suppressed >90% of the time. DISCUSSION: Intensive monitoring after a treatment switch is required in patients who have rebounded recently or have a low percentage of time suppressed while on cART. Consideration should be given to increasing the provision of adherence counselling.

Opportunistic infections and other AIDS-defining illnesses in Poland in 2000-2002.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) led to a decreased incidence of the most severe opportunistic infections (OIs) in HIV-infected patients. In Poland, HAART became widely used in 1998. MATERIALS AND METHODS: This study was based on data from medical records data collected in the years 2000-2002 from medical centers for HIV-infected patients in Poland. The aim of the study was to determine the incidence of opportunistic infections (OIs) and other AIDS defining illnesses (ADIs). The chi(2) test was used to determine any significant trends. RESULTS: The incidence of ADIs was 6.8, 6.5 and 4.8/100 persons/year in 2000-2002, respectively. The most common diagnosed OIs were: fungal infections, tuberculosis, recurrent pneumonia, PCP and toxoplasmosis. In patients receiving HAART (HAART+) the incidence of ADIs was significantly lower than in non-ARV-treated as well as in all HIV+ (p < 0.02, p < 0.001, p < 0.001, respectively). A significant decrease in the incidence of ADIs in HAART+ patients between 2000 and 2002 (p < 0.0001) was observed. From 25% to 30% of ADIs among HAART+ patients were diagnosed within the first 3 months of antiretroviral therapy. In HAART+ patients the most common ADIs were fungal infections and tuberculosis. The diagnosis of ADIs resulted in the recognition of HIV status in 8.7-8.9% of patients. CONCLUSIONS: Five years after the introduction of HAART the incidence of ADIs had declined. Fungal infections and tuberculosis were the most common OIs in HIV+ patients in Poland.

TGF-beta1 mRNA expression in liver biopsy specimens and TGF-beta1 serum levels in patients with chronic hepatitis C before and after antiviral therapy.

BACKGROUND AND OBJECTIVE: Transforming growth factor (TGF)-beta1 is the best-characterized profibrogenic cytokine. TGF-beta1 increases the production of extracellular matrix proteins and their receptors and inhibits the synthesis of matrix degrading proteolytic enzymes. We undertook this study to simultaneously evaluate the effect of interferon alpha 2b plus ribavirin therapy on TGF-beta1 daily serum levels and on mRNA TGF-beta1 expression in liver biopsy specimens from 60 patients with chronic hepatitis C. METHODS: Serum levels of TGF-beta1 were measured by ELISA. The levels of the RNAs in liver biopsy specimens were measured by quantitative reverse transcriptase polymerase chain reaction. After treatment, patients were divided into two groups: 34 responders [undetectable hepatitis C virus (HCV)-RNA, normal ALT levels, decrease in histology activity index compared with pretreatment liver biopsy] and 26 non-responders (detectable HCV-RNA, elevated ALT levels, no decrease in the histology activity index). RESULTS AND DISCUSSION: In patients with hepatitis C, the 'responders' to the antiviral treatment showed significant decreases in both mean daily serum TGF-beta1 levels and mRNA TGF-beta1 expression in the liver biopsy specimens. The 'non-responders' serum TGF-beta1 concentrations did not change significantly, but the mRNA TGF-beta1 expression did. CONCLUSION: Both serum TGF-beta1 concentration and mRNA TGF-beta1 expression in liver biopsy specimens may be useful as prognostic markers in patients with hepatitis C undergoing antiviral therapy.

Prednisolone does not prevent hypersensitivity reactions in antiretroviral drug regimens containing abacavir with or without nevirapine.

OBJECTIVES: To determine the effect of adjuvant prednisolone use on the development of abacavir (ABC)- and nevirapine (NVP)-associated hypersensitivity reactions (HSR). METHODS: Randomized open-label study in antiretroviral-naive adult HIV-1 infected patients using a factorial design in which NVP and/or hydroxyurea (HU) and/or prednisolone are added to a regimen of ABC, zidovudine and lamivudine. Prednisolone (40 mg once daily) was added for the first 2 weeks of treatment. As it was difficult to distinguish ABC-associated HSR from NVP-associated HSR, these events were treated as a composite endpoint. The odds ratio (OR) of developing HSR for prednisolone-use was calculated with and without stratification by NVP and/or HU. Logistic regression was performed to identify risk factors for developing HSR. RESULTS: Of the 229 patients 115 were randomized to prednisolone and 114 to no-prednisolone; 19 (17%) and 11 (10%) patients, respectively, developed HSR. The expected prevention of HSR by prednisolone use was not observed. In fact use of prednisolone showed an increased risk for HSR although this did not reach statistical significance [OR, 1.82; 95% confidence interval (CI), 0.82-4.03]. There was a higher incidence of HSR in the NVP group than in the non-NVP group (20% versus 6%; P = 0.002). An additional risk factor identified in a multivariate logistic model was a high baseline CD4 cell count (OR, 1.26 per 100 x 10(6) cells/l increase; 95% CI, 1.06-1.51). CONCLUSIONS: The simultaneous start of ABC and NVP in first-line antiretroviral regimens should be avoided because of a high (20%) incidence of HSR. Short-term therapy with prednisolone did not prevent HSR in patients using ABC with or without NVP.

[The estimation of Pneumocystis carinii in HIV-infected patients occurrence based on three different methods]. / Ocena wystepowania Pneumocystis carinii u chorych zakazonych wirusem HIV w oparciu o wyniki trzech metod diagnostycznych.

The frequency of Pneumocystis carinii occurrence in BAL of 38 HIV-infected patients was determined with three different method. BAL sediments were stained with Giemsa method, silvered according to Gomori-Grocott method and studied with indirect immunofluorescence assay. Using Giemsa method staining Pneumocystis carinii was diagnosed in 81.6% of patients, in Gomori-Grocott method--in 31.6% of patients, but results of indirect immunofluorescence assay were positive only in 23.,7%. In our study staining BAL sediments with Giemsa method allowed to detect Pneumocystis carinii in the highest percentage of examined patients.

[Rare case of endogenous hepatic coma in a patient during the course of viral hepatitis A with a good outcome after arterialization of portal blood]. / Rzadki przypadek endogennej spiaczki watrobowej u chorej w przebiegu ostrego wirusowego zapalenia watroby typu A leczonej z dobrym wynikiem arterializacja krwi wrotnej.

A case of endogenous hepatic coma during acute virus hepatitis A is reported. Arterialization of portal blood gave a good result.

[Endogenic hepatic coma in the course of acute hepatitis treated with arterialization of portal blood]. / Endogenna spiaczka watrobowa w przebiegu wirusowego zapalenia watroby leczona arterializacja krwi wrotnej.

Symptoms of endogenic hepatic coma were observed in the course of acute hepatitis in 17 patients admitted to the I Clinic of Infectious Diseases of Silesian Medical School between 1987 and 1992. Five of them were treated with the arterialization of portal blood. At least one exchange transfusion preceded the arterialization in four cases. Recovery was obtained in 3 patients. Two patients died because of complications which occurred during the twenty-four hours after the intervention. In the first case the reason of the death was the extensive myocardial infarction, in the second one-DIC and ARDS. As it has been observed, the prothrombin rate should not be lower than 30% in these patients who are to undergo the arterialization of portal blood. This value of the prothrombin rate is provided by at least one exchange transfusion.