Efficacy, adherence and tolerability of once daily tenofovir DF-containing antiretroviral therapy in former injecting drug users with HIV-1 receiving opiate treatment: results of a 48-week open-label study.

Objective: To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF) 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU).

Methods: European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naive, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment.

Mutations in the C-terminal region of the HIV-1 reverse transcriptase and their correlation with drug resistance associated mutations and antiviral treatment.

Objective: replication of HIV-1 after cell entry is essentially dependent on the reverse transcriptase (RT). Antiretroviral drugs impairing the function of the RT currently aim at the polymerase subunit. One reason for failure of antiretroviral treatment is the evolvement of resistance-associated mutations in the viral genome.

Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease.

There are conflicting data about the frequency and role of regulatory T cells (Tregs) during the course of HIV infection. Peripheral blood of a large cohort of HIV-infected patients (n = 131) at different stages of disease, including 15 long-term nonprogressors and 21 elite controllers, was analyzed to determine the frequency and phenotype of Tregs, defined as CD4(+), CD25(high), CD127(low), FoxP3(high) cells. A significantly increased relative frequency of Tregs within the CD4(+) compartment of HIV(+) patients compared to that of healthy controls (P < 0.

Human immunodeficiency virus type-1 group M quasispecies evolution: diversity and divergence in patients co-infected with active tuberculosis.

The evolution of intra-host human immunodeficiency virus type 1 (HIV-1) quasispecies prior and after treating active tuberculosis (TB) with chemotherapy in HIV-1/TB patients was assessed. Two time points HIV-1 quasispecies were evaluated by comparing HIV-1-infected patients with active tuberculosis (HIV-1/TB) and HIV-1-infected patients without tuberculosis (HIV-1/non-TB). Plasma samples were obtained from the Frankfurt HIV cohort, and HIV-1 RNA was isolated.

Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R.

Objectives: The reverse transcriptase (RT)-mutation K65R limits further therapeutic options and has been selected by unfavorable RT-combinations, e.g. tenofovir in combination with abacavir and/or didanosine.

Prevalence- and gender-specific immune response to opportunistic infections in HIV-infected patients in Lesotho.

Background: The objective of this study was to assess the seroprevalence of coinfecting viruses and Treponema pallidum (T. pallidum) in a cohort of 205 antiretrovirally treated HIV-infected individuals (152 females and 53 males, aged: 19-71 years) in rural Lesotho. Furthermore agent-specific immune responses were investigated by analyzing antibody titers against herpes simplex virus type 2 (HSV-2) and against T.

Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial.

Background: Current conventional vaccination approaches do not induce potent CD8 T-cell responses for fighting mostly variable viral diseases such as influenza, avian influenza viruses or HIV. Following our recent study on vaccine penetration by targeting of vaccine to human hair follicular ducts surrounded by Langerhans cells, we tested in the first randomized Phase-Ia trial based on hair follicle penetration (namely transcutaneous route) the induction of virus-specific CD8 T cell responses.

Methods And Findings: We chose the inactivated influenza vaccine - a conventional licensed tetanus/influenza (TETAGRIP) vaccine - to compare the safety and immunogenicity of transcutaneous (TC) versus IM immunization in two randomized controlled, multi-center Phase I trials including 24 healthy-volunteers and 12 HIV-infected patients.

The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive Individuals.

Objective: This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated.

Methods: Multicenter, partially randomized, controlled clinical trial.

Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years.

Background: Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades.

Methods: We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards.

Mortality of HIV-infected patients starting potent antiretroviral therapy: comparison with the general population in nine industrialized countries.

Background: Mortality in HIV-infected patients has declined substantially with combination antiretroviral therapy (ART), but it is unclear whether it has reached that of the general population. We compared mortality in patients starting ART in nine countries of Europe and North America with the corresponding general population, taking into account their response to ART.

Methods: Eligible patients were enrolled in prospective cohort studies participating in the ART Cohort Collaboration.

Activity, pharmacokinetics and safety of lersivirine (UK-453,061), a next-generation nonnucleoside reverse transcriptase inhibitor, during 7-day monotherapy in HIV-1-infected patients.

Objective: To investigate the effects on viral load and assess dose-response relationships, pharmacokinetics, safety and tolerability of lersivirine (UK-453,061), a next-generation nonnucleoside reverse transcriptase inhibitor, in asymptomatic HIV-1-infected patients.

Design: Randomized, double-blind, placebo-controlled, parallel group, multicenter phase IIa clinical study.

Methods: Forty-eight HIV-1-infected patients were enrolled for the study of once-daily or twice-daily lersivirine at total daily doses ranging from 20 to 1000 mg.

Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression.

Background: Achieving virologic suppression is a clear therapeutic goal for patients receiving combination antiretroviral therapy (cART). However, the effects of immunologic responses, whether measured as CD4 count changes from baseline or CD4 counts at follow-up, in patients with virologic suppression, have not been clearly established.

Methods: Treatment-naive individuals aged > or =16 years, who initiated cART between 1998 and 2005 in participating cohorts of the ART Cohort Collaboration and achieved viral load < or =400 copies per milliliter 6 months after cART initiation, were included.

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.

Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies.

Background: The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. In the absence of randomised trials, we examined this question in prospective cohort studies.

Methods: We analysed data from 18 cohort studies of patients with HIV.

Switching from a toxicity-causing antiretroviral to enfuvirtide in patients with HIV: the SWITCH TOX study.

Purpose: Treatment-related toxicities frequently limit antiretroviral therapy for patients with HIV-1 infection. This study evaluated the changes in treatment-limiting toxicities when the primary toxicity-causing agent was replaced with enfuvirtide.

Method: Adult patients with HIV-1 infection (N = 91) with antiretroviral treatment-limiting toxicities were enrolled in this multicenter, open-label, single-arm, 24-week study.

Pharmacokinetics, safety and efficacy of saquinavir/ ritonavir 1,000/100 mg twice daily as HIV type-1 therapy and transmission prophylaxis in pregnancy.

Background: A saquinavir/ritonavir-containing regimen is one option for the prevention of mother-to-child transmission of HIV during pregnancy. We evaluated the pharmacokinetics, efficacy and safety of saquinavir/ritonavir 1,000/100 mg twice daily plus nucleos(t)ide reverse transcriptase inhibitors in 13 women during late pregnancy and compared the results to those of 15 non-pregnant women.

Methods: Protease inhibitor plasma concentration profiles were assessed at 12 h using a standardized therapeutic drug monitoring procedure and measured by LC-MS/MS.

Determinants of virological failure after successful viral load suppression in first-line highly active antiretroviral therapy.

Background: We aimed to investigate the long-term virological outcomes of a cohort initially showing good responses to first-line highly active antiretroviral therapy (HAART) with no evidence ofvirological failure during the first year after achieving viral load (VL) undetectability (<50 copies/ml).

Methods: Virological failure was defined as a confirmed VL >400 copies/ml or a single VL >400 copies/ml followed by a treatment change or end of follow-up. Risk factors for low-level VL rebound (50-400 copies/ml) in the first year after achieving undetectability and for virological failure during subsequent follow-up were investigated by logistic and Poisson regression.

Short communication: Different mutation patterns in subtype CRF06_cpx after mother-to-child transmission.

Abstract Development of drug resistance mutation patterns (DRMP) in HIV after treatment failure depends on the drugs used in the failing regimen. However, selected patterns may not be unique; there is evidence that selection of DRMP for nelfinavir is dependent on subtype and/or background polymorphisms. Here we describe the selection of DRMP in a mother and son infected with subtype CRF06_cpx by mother-to-child transmission.

Factors associated with viral rebound among highly treatment-experienced HIV-positive patients who have achieved viral suppression.

Objective: More and more highly treatment-experienced patients are achieving viral suppression. However, the durability of suppression remains unclear.

Methods: Patients from Royal Free Hospital (London, UK) and JW Goethe University Hospital (Frankfurt, Germany) who had failed > or = 1 antiretroviral (ARV) regimen in all three main drug classes and > or = 3 previous ARV regimens and subsequently achieved viral load < 50 HIV-1 RNA copies/mL were included.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

Objective: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART.

Design: Observational cohort study of patients initiating ART between January 2000 and December 2005.

Setting: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States.

Comparing QuantiFERON-tuberculosis gold, T-SPOT tuberculosis and tuberculin skin test in HIV-infected individuals from a low prevalence tuberculosis country.

Objective: To evaluate the interferon-gamma-releasing assays QuantiFERON-tuberculosis (TB) Gold and T-SPOT.TB in addition to tuberculin skin test (TST) for diagnosis of latent tuberculosis infection in HIV patients.

Design, Setting And Participants: Prospective cross-sectional study for asymptomatic HIV-infected outpatients from a large University hospital.

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.

Greater viral rebound and reduced time to resume antiretroviral therapy after therapeutic immunization with the ALVAC-HIV vaccine (vCP1452).

Objective: Evaluate immunogenicity and clinical efficacy of two immunization strategies with the ALVAC-HIV-recombinant canarypox vaccine (vCP1452) in treated HIV-infected patients.

Design: Randomized, double-blind, placebo-controlled, phase II study of vCP1452 immunization in chronically HIV-infected patients on therapy with CD4 T-cell count more than 350 cells/microl, CD4 nadir less than 400 cells/microl and pHIV-RNA less than 400 copies/ml. Patients were equally randomized to four injections at weeks 0, 4, 8, 20; three injections at weeks 4, 8, 20; and placebo.