Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy.

Objectives: To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients.

Methods: Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals.

Effects of once-daily darunavir/ritonavir versus lopinavir/ritonavir on metabolic parameters in treatment-naive HIV-1-infected patients at week 96: ARTEMIS.

In the ARTEMIS trial, 689 treatment-naïve, HIV-1-infected adults received darunavir/ritonavir (DRV/r) 800/100 mg every day or lopinavir/ritonavir (LPV/r) 800/200 mg total daily dose plus fixed-dose tenofovir/emtricitabine. Week 96 metabolic parameters are reported. Adverse events (AEs) classed as metabolism/nutrition disorders were observed in 14% of DRV/r and 22% of LPV/r patients.

Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid.

Objectives: To determine HIV-1 RNA in cerebrospinal fluid (CSF) of successfully treated patients and to evaluate if combination antiretroviral treatments with higher central nervous system penetration-effectiveness (CPE) achieve better CSF viral suppression.

Methods: Viral loads (VLs) and drug concentrations of lopinavir, atazanavir, and efavirenz were measured in plasma and CSF. The CPE was calculated using 2 different methods.

The dose-response relationship of peginterferon alfa-2a and ribavirin in the treatment of patients coinfected with HIV-HCV.

Purpose: The relationship between peginterferon/ribavirin exposure and the probability of achieving a sustained virologic response (SVR) in HIV-HCV coinfected patients is not well described. We conducted a retrospective analysis of HIV-HCV coinfected patients randomized to 48 weeks of treatment with peginterferon alfa-2a (40 kD) 180 µg/week and ribavirin 800 mg/day in the multinational APRICOT study to define optimal exposure thresholds.

Method: Actual drug exposure was estimated in 287 patients, taking into consideration dose reductions for adverse events or laboratory abnormalities.

Nevirapine versus atazanavir/ritonavir, each combined with tenofovir disoproxil fumarate/emtricitabine, in antiretroviral-naive HIV-1 patients: the ARTEN Trial.

Background: Selection of first-line antiretroviral therapy requires consideration of efficacy as well as effects on lipids given the increased concern about cardiovascular risk in HIV-1 patients.

Methods: ARTEN is a randomized, open-label, non-inferiority trial that compares nevirapine (NVP) 200 mg twice daily or 400 mg once daily to atazanavir/ritonavir (ATZ/r) 300 mg/100 mg once daily, each combined with fixed-dose tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg once daily, in antiretroviral-naive HIV-1 patients with CD4(+) T-cell counts <400 (men) and <250 cells/mm(3) (women). The primary end point was plasma HIV RNA<50 copies/ml at two consecutive visits prior to week 48.

Efficacy, tolerability and risk factors for virological failure of darunavir-based therapy for treatment-experienced HIV-infected patients: the Swiss HIV Cohort Study.

Objectives: Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice.

Methods: We included all patients in the Swiss HIV Cohort Study starting darunavir after recording a viral load above 1000 HIV-1 RNA copies/mL given prior exposure to both PIs and nonnucleoside reverse transcriptase inhibitors.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study.

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks.

Diffusion-weighted MR imaging of intramedullary spinal cord abscess.

Early diagnosis and prompt initiation of adequate treatment are essential for clinical outcome in ISCA. We report a case in which DWI provided a more specific diagnosis than conventional MR imaging and allowed differentiation of a ring-enhancing lesion from intramedullary tumor. Diagnosis was proved by PCR from CSF (Streptococcus intermedius).

Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007.

Background: Combination antiretroviral treatment (cART) has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort.

Methods: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence.

Implementation of raltegravir in routine clinical practice: selection criteria for choosing this drug, virologic response rates, and characteristics of failures.

Background: Raltegravir (RAL) achieved remarkable virologic suppression rates in randomized-clinical trials, but today efficacy data and factors for treatment failures in a routine clinical care setting are limited.

Methods: First, factors associated with a switch to RAL were identified with a logistic regression including patients from the Swiss HIV Cohort Study with a history of 3 class failure (n = 423). Second, predictors for virologic outcome were identified in an intent-to-treat analysis including all patients who received RAL.

Prior therapy influences the efficacy of lamivudine monotherapy in patients with lamivudine-resistant HIV-1 infection.

Background: The M184V mutation decreases the replication capacity of HIV-1. This prospective study aimed to characterize the virologic and immunologic changes during monotherapy with lamivudine (3TC) in patients with limited options for a fully suppressive new therapy.

Methods: Clinically stable patients with CD4 cells greater than 300/microL, previous virologic failure, and a M184V mutation were treated with 3TC 300 mg once daily during 48 weeks.

Cost-effectiveness of raltegravir in antiretroviral treatment-experienced HIV-1-infected patients in Switzerland.

Objectives: Raltegravir, a novel integrase inhibitor, has shown great efficacy in reducing HIV viral load among treatment-experienced patients. A cohort state-transition model was used to assess the long-term effect of raltegravir treatment on costs and quality-adjusted life expectancy from a Swiss perspective.

Methods: Patients were stratified into health states according to opportunistic infection status, HIV RNA level, and CD4 count, with each group assigned a treatment cost and utility (quality of life) score.

Tenofovir use is associated with an increase in serum alkaline phosphatase in the Swiss HIV Cohort Study.

Background: Tenofovir (TDF) use has been associated with proximal renal tubulopathy, reduced calculated glomerular filtration rates (cGFR) and losses in bone mineral density. Bone resorption could result in a compensatory osteoblast activation indicated by an increase in serum alkaline phosphatase (sAP). A few small studies have reported a positive correlation between renal phosphate losses, increased bone turnover and sAP.

Refining abacavir hypersensitivity diagnoses using a structured clinical assessment and genetic testing in the Swiss HIV Cohort Study.

Background: We aimed to assess the value of a structured clinical assessment and genetic testing for refining the diagnosis of abacavir hypersensitivity reactions (ABC-HSRs) in a routine clinical setting.

Methods: We performed a diagnostic reassessment using a structured patient chart review in individuals who had stopped ABC because of suspected HSR. Two HIV physicians blinded to the human leukocyte antigen (HLA) typing results independently classified these individuals on a scale between 3 (ABC-HSR highly likely) and -3 (ABC-HSR highly unlikely).

Natural history of HIV-associated pulmonary arterial hypertension: trends in the HAART era.

Pulmonary arterial hypertension (PAH) is an infrequent but nevertheless serious life-threatening severe complication of HIV infection. As a result of its non-specific presentation, PAH tends to be recognized at a late stage of the disease, and patients have generally been in New York Heart Association functional class III or IV by the time of diagnosis. The widespread use of HAART has improved overall survival in HIV-infected individuals, but its effect on the incidence and severity of PAH in particular has been controversial.

Effect of baseline viral susceptibility on response to darunavir/ritonavir versus control protease inhibitors in treatment-experienced HIV type 1-infected patients: POWER 1 and 2.

Data from two Phase IIb trials, POWER 1 and 2 (TMC114-C213 and C202), were pooled to examine the effect of baseline viral susceptibility on response to control protease inhibitors [CPI(s)] compared with response to darunavir (TMC114) given with low-dose ritonavir (darunavir/r) in treatment-experienced HIV patients. POWER 1 and 2 were randomized, controlled Phase IIb trials with a similar design. Patients with one or more primary PI mutations and HIV-1 RNA >1000 copies/ml were randomized to receive an optimized background regimen plus darunavir/r or CPI(s).

CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy.

Background: In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain.

Methods: During January 1996 through December 2004 [corrected] all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4(+) T cell counts and HIV-1 RNA values (n = 3293). For follow-up, we used the Swiss HIV Cohort Study database update of May 2007 [corrected] The mean (+/-SD) duration of follow-up was 26.

Phase II study of vicriviroc versus efavirenz (both with zidovudine/lamivudine) in treatment-naive subjects with HIV-1 infection.

Background: Vicriviroc (VCV) is a CCR5 antagonist with nanomolar activity against human immunodeficiency virus (HIV) replication in vitro and in vivo. We report the results of a phase II dose-finding study of VCV plus dual nucleoside reverse-transcriptase inhibitors (NRTIs) in the treatment-naive HIV-1-infected subjects.

Methods: This study was a randomized, double-blind, placebo-controlled trial that began with a 14-day comparison of 3 dosages of VCV with placebo in treatment-naive subjects infected with CCR5-using HIV-1.

Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study.

Background: A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in cGFR in a large observational HIV cohort.

Methods: We compared treatment-naive patients or patients with treatment interruptions > or = 12 months starting either a TDF-based combination antiretroviral therapy (cART) (n = 363) or a TDF-sparing regime (n = 715).

Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification.

Background: Antiretroviral therapy (ART) decreases morbidity and mortality in HIV-infected patients but is associated with considerable adverse events (AEs).

Methods: We examined the effect of AEs to ART on mortality, treatment modifications and drop-out in the Swiss HIV Cohort Study. A cross-sectional evaluation of prevalence of 13 clinical and 11 laboratory parameters was performed in 1999 in 1,078 patients on ART.

Lipodystrophy and weight changes: data from the Swiss HIV Cohort Study, 2000-2006.

Background And Objectives: Combination antiretroviral therapy (cART) is changing, and this may affect the type and occurrence of side effects. We examined the frequency of lipodystrophy (LD) and weight changes in relation to the use of specific drugs in the Swiss HIV Cohort Study (SHCS).

Methods: In the SHCS, patients are followed twice a year and scored by the treating physician as having 'fat accumulation', 'fat loss', or neither.

Effect of baseline CD4 cell count on the efficacy and safety of peginterferon Alfa-2a (40KD) plus ribavirin in patients with HIV/hepatitis C virus coinfection.

Objective: The impact of baseline CD4 status on hepatitis C virus (HCV) treatment response among patients with HIV/HCV coinfection was investigated using data from a randomized study of peginterferon alfa-2a (40KD) + ribavirin (Peg-IFN/RBV).

Methods: Of 860 patients treated with conventional interferon alfa-2a + ribavirin (IFN/RBV), peginterferon alfa-2a (40KD) + placebo (Peg-IFN), or Peg-IFN/RBV for 48 weeks, 857 patients had baseline CD4 data available and were included in the analysis. Efficacy and safety were analyzed according to baseline CD4 status as absolute cell count and proportion of total lymphocytes.

Predictors of optimal viral suppression in patients switched to abacavir, lamivudine, and zidovudine: the Swiss HIV Cohort Study.

Objective: To investigate predictors of continued HIV RNA viral load suppression in individuals switched to abacavir (ABC), lamivudine (3TC) and zidovudine (ZDV) after successful previous treatment with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy.

Design And Methods: An observational cohort study, which included individuals in the Swiss HIV Cohort Study switching to ABC/3TC/ZDV following successful suppression of viral load. The primary endpoint was time to treatment failure defined as the first of the following events: two consecutiveviral load measurements > 400 copies/ml under ABC/3TC/ZDV, one viral load measurement > 400 copies/ml and subsequent discontinuation of ABC/3TC/ZDV within 3 months, AIDS or death.

Is depression a risk factor for heart complaints? Longitudinal aspects in the Zurich study.

Background: The objective of this longitudinal study was to assess the association between major depression and heart complaints in a population of young and healthy adults.

Methods: Starting at the age 20/21, participants of the Zurich Study underwent 6 structured, psychological interviews during a span of 20 years. We evaluated longitudinal data from 277 persons who participated in all 6 interviews including questions about heart complaints.

Combined tipranavir and enfuvirtide use associated with higher plasma tipranavir concentrations but not with increased hepatotoxicity: sub-analysis from RESIST.

In RESIST, enfuvirtide co-administered with ritonavir-boosted tipranavir was associated with higher plasma tipranavir concentrations, which seldom rose above those associated with an increased risk of grade 3/4 transaminase elevations. Transaminase elevation rates (6.5%) and clinical hepatic event rates (5.