HIV-1 replication in central nervous system increases over time on only protease inhibitor therapy.

There are concerns about central nervous system (CNS)-replication of HIV-1 in patients on boosted protease inhibitors. Purpose of this study was to compare HIV-1 viral loads (VLs) from patients treated with only boosted dual protease inhibitor (bdPI), versus combination antiretroviral therapy (cART group), containing two nucleoside analogue reverse transcriptase inhibitors (NRTI) and a third partner. All patients from a large German HIV-treatment cohort with available medication, clinical and demographic data, including results from simultaneous HIV-1 viral load (VL) assessments in cerebrospinal fluid (CSF) and blood plasma, were retrospectively evaluated as controlled cross-sectional study.

Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels.

Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance.

Evolution and function of the HCV NS3 protease in patients with acute hepatitis C and HIV coinfection.

Little is known about the importance of the hepatitis C virus (HCV) NS3 protease in acute hepatitis C. In this prospective study, 82 consecutive patients with acute hepatitis C and human immunodeficiency virus (HIV) coinfection were enrolled. Individuals were infected with highly related HCV strains and the baseline NS3 quasispecies diversity and complexity was higher compared to a chronic hepatitis C control group (P<0.

Improved virological and immunological efficacy of resistance-guided switch in antiretroviral therapy: a Frankfurt HIV cohort analysis.

To evaluate the treatment outcome of antiretroviral therapy, depending on the use and utility of a concept of resistance-guided switch, patients from the Frankfurt HIV cohort have been followed for 24 weeks. If available, prior resistance data have been evaluated and patients were grouped into their expected viral response. The data of 354 patients were thus analysed, taking into account the genotypic sensitivity score of the administered medication (> or ≤2).

Long-term effects of chemoradiotherapy for anal cancer in patients with HIV infection: oncological outcomes, immunological status, and the clinical course of the HIV disease.

Background: Despite the increasing evidence for chemoradiotherapy as standard treatment for anal cancer in patients with HIV infection, there is still some uncertainty regarding increased toxicity and adverse effects on the immune status.

Objective: We report the clinical outcome of 5-fluorouracil/mitomycin C-based concurrent chemoradiotherapy for anal carcinoma in patients with HIV infection with an emphasis on the long-term course of CD4 counts and the HIV-related morbidity during follow-up.

Design And Settings: A retrospective single-institution chart review was performed.

Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration.

Objectives: The renal elimination of tenofovir (TFV) may be subject to renal drug-drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug-drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells.

Methods: A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out.

End-stage renal disease and dialysis in HIV-positive patients: observations from a long-term cohort study with a follow-up of 22 years.

Objectives: Renal disease is a common and serious complication in HIV-infected patients.

Methods: A retrospective cohort analysis for the period 1989-2010 was carried out to determine the prevalence, incidence and risk factors for end-stage renal disease (ESRD). ESRD was defined as initiation of renal replacement therapy.

Impact of HIV-1 replication on immunological evolution during long-term dual-boosted protease inhibitor therapy.

To explore CD4-cell and viral evolution in relation to different levels of HIV-1 replication, as observed during protease inhibitor (PI)-based antiretroviral therapy. Adult HIV-1 infected cohort patients, receiving historical salvage therapy with daily doses of saquinavir (2,000 mg), ritonavir (200 mg) and either lopinavir (800 mg) or atazanavir (300 mg) for >36 weeks were retrospectively analysed for highest detectable viral load up to week 96 and assigned to groups according to the viral load level: always <50 copies/ml (1), 50-199 copies/ml (2), 200-499 copies/ml (3) and ≥500 copies/ml (4). A total of 126 patients were evaluated; at baseline, median CD4-cell count was 204/mm(3), HIV-1 RNA was 5.

Assessment of liver fibrosis and associated risk factors in HIV-infected individuals using transient elastography and serum biomarkers.

Background: Liver fibrosis in human immunodeficiency virus (HIV)-infected individuals is mostly attributable to co-infection with hepatitis B or C. The impact of other risk factors, including prolonged exposure to combined antiretroviral therapy (cART) is poorly understood. Our aim was to determine the prevalence of liver fibrosis and associated risk factors in HIV-infected individuals based on non-invasive fibrosis assessment using transient elastography (TE) and serum biomarkers (Fibrotest [FT]).

Comparison of drug resistance scores for tipranavir in protease inhibitor-naive patients infected with HIV-1 B and non-B subtypes.

Genotypes of samples from protease inhibitor-naïve patients in Frankfurt's HIV Cohort were analyzed with five tipranavir resistance prediction algorithms. Mean scores were higher in non-B than in B subtypes. The proportion of non-B subtypes increased with increasing scores, except in weighted algorithms.

Once-daily treatment with saquinavir mesylate (2000 mg) and ritonavir (100 mg) together with a fixed-dose combination of abacavir/lamivudine (600/300 mg) or tenofovir/emtricitabine (245/200 mg) in HIV-1-infected patients.

Objectives: To investigate the feasibility and pharmacokinetics of a once-daily regimen of 2000 mg saquinavir mesylate boosted with 100 mg ritonavir.

Patients And Methods: Patients successfully treated with 1000 mg saquinavir boosted with 100 mg ritonavir twice daily together with two nucleoside or nucleotide reverse transcriptase inhibitors [N(t)RTIs] who were switched to 2000 mg saquinavir with 100 mg ritonavir once daily with unchanged N(t)RTI therapy were analysed. CD4 cells, HIV-RNA PCR and metabolic parameters were compared between baseline and 3, 6, 9 and 12 months after the switch.

Treatment during primary HIV infection does not lower viral set point but improves CD4 lymphocytes in an observational cohort.

Objective: To investigate if early treatment of primary HIV-1 infection (PHI) reduces viral set point and/or increases CD4 lymphocytes.

Methods: Analysis of two prospective multi-centre PHI cohorts. HIV-1 RNA and CD4 lymphocytes in patients with transient treatment were compared to those in untreated patients.

Quadruple nucleos(t)ide reverse transcriptase inhibitors-only regimen of tenofovir plus zidovudine/lamivudine/abacavir in heavily pre-treated HIV-1 infected patients: salvage therapy or backbone only?

Background: We investigated the virologic and immunologic responses to a mono-class, nucleoside/nucleotide reverse transcriptase inhibitor - combination therapy consisting of tenofovir and zidovudine/lamivudine/abacavir in therapy experienced patients.

Methods: Retrospective study of 122 patients. Primary analysis was performed at 48 weeks.

Is transmission of HIV-1 in non-viraemic serodiscordant couples possible?

Several studies have shown that HIV-1 transmission in serodiscordant couples is significantly reduced when the plasma viral load (pVL) in the infected partner is low or undetectable. However, residual infectivity in the seminal compartment despite undetectable pVL has also been shown. Here we report HIV-1 transmission in a serodiscordant couple despite successful antiretroviral therapy of the HIV-infected partner.

Platelet-leucocyte adhesion markers before and after the initiation of antiretroviral therapy with HIV protease inhibitors.

Introduction: Thromboembolic complications under antiretroviral therapy (ART) have been described in the past. In particular, the influence of protease inhibitors (PIs) on platelet activation and coagulation is currently under discussion.

Methods: HIV-1-infected, PI-naive adults (n = 18) were investigated before and 4 weeks after the start of the ART, consisting either of boosted PI regimens (n = 13) plus reverse transcriptase inhibitors (RTIs) or a double PI regimen (n = 5) without RTI co-medication.

Significant effects of tipranavir on platelet aggregation and thromboxane B2 formation in vitro and in vivo.

Objectives: In the past, bleeding events have been described for patients with haemophilia taking HIV-1 protease inhibitors. Recently, the FDA published a warning concerning intracranial haemorrhage in patients taking the HIV-1 protease inhibitor tipranavir co-administered with ritonavir.

Methods: We investigated (i) platelet aggregation in vivo in HIV-1-infected adult patients (n = 5) immediately before and 2 and 4 h after dosing of tipranavir/ritonavir 500/200 mg.

First case of successful allogeneic stem cell transplantation in an HIV-patient who acquired severe aplastic anemia.

We report on the first successful allogeneic stem cell transplantation (SCT) in an HIV-infected patient with severe aplastic anemia (SAA) per- formed at a tertiary care institution. Highly active antiretroviral therapy (HAART) was administered until transplantation and restarted 34 days later with sustained virological response. The patient did however develop a rapid rise in HIV load during the interruption of HAART associated with an acute febrile illness.

Consensus recommendation from a group of German experts for the use of enfuvirtide in heavily pretreated HIV patients.

Background: The EU approval of enfuvirtide (Fuzeon) was granted in May 2003 on the basis of the 48-week data from the TORO 1 and TORO 2 studies. Enfuvirtide is licensed for use in pretreated HIV patients experienced with three classes of drugs who exhibited treatment failure or who have shown intolerance to previous antiretroviral treatment regimens. Recent studies with the new protease inhibitors tipranavir and darunavir (RESIST and POWER studies) showed that a high proportion of heavily pretreated HIV patients achieve a viral load reduction to below the limit of detection when treated with enfuvirtide plus one of these new ritonavir-boosted protease inhibitors and an optimised background treatment regimen.

A comparison of the steady-state pharmacokinetics of nevirapine in men, nonpregnant women and women in late pregnancy.

Aims: To evaluate the pharmacokinetics of nevirapine and any possible influencing factors in pregnant women (n = 16), nonpregnant women (n = 13) and men (n = 14), who received nevirapine 200 mg twice daily together with nucleoside reverse transcriptase inhibitors.

Methods: Blood samples were taken for 12 h at steady state. Nevirapine concentrations were measured by liquid chromatography-tandem mass spectrometry.

The LOPSAQ study: 48 week analysis of a boosted double protease inhibitor regimen containing lopinavir/ritonavir plus saquinavir without additional antiretroviral therapy.

Objectives: To evaluate the virological, immunological and clinical responses to the boosted double protease inhibitor (PI) regimen combination of lopinavir/ritonavir and saquinavir ('LOPSAQ') without reverse transcriptase inhibitors (RTI) in HIV-positive patients who have few viable RTI treatment options.

Methods: Cohort study of 128 heavily pre-treated patients who were experiencing therapy failure on their current regimen due to RTI resistance and/or systemic toxicities. Patients with PI-resistance mutations or RTI toxicity underwent a structured treatment interruption (STI) (n=76) until virus reverted to wild-type or until resolution of toxicity symptoms.

Use of viral load measured after 4 weeks of highly active antiretroviral therapy to predict virologic outcome at 24 weeks for HIV-1-positive individuals.

Early prediction of suboptimal viral response to highly active antiretroviral therapy (HAART) is vital to prevent early development of drug resistance. We used logistic regression to predict the odds of achieving virologic suppression (<50 copies/mL) after 24 weeks of HAART in 656 antiretroviral-naive patients starting HAART at the J.W.

First-line ritonavir/indinavir 100/800 mg twice daily plus nucleoside reverse transcriptase inhibitors in a German multicentre study: 48-week results.

Objectives: To evaluate safety and efficacy of the protease inhibitor combination ritonavir/indinavir 100/800 mg twice daily plus 2-3 nucleoside reverse transcriptase inhibitors (NRTI) in antiretroviral-naive patients.

Methods: Within this open-label, uncontrolled multicentre trial, antiretroviral-naive patients (n = 57) with median baseline HIV-RNA of 308,000 copies/mL (range 170-3.01 million copies/mL) and median CD4 cell count of 50 cells/microL (range 0-853 cells/microL) were started on 2-3 NRTIs plus ritonavir/indinavir 100/800 mg twice daily.