Is there a massive glacial-Holocene flora continuity in Central Europe?

The prevailing paradigm about the Quaternary ecological and evolutionary history of Central European ecosystems is that they were repeatedly impoverished by regional extinctions of most species during the glacial periods, followed by massive recolonizations from southern and eastern refugia during interglacial periods. Recent literature partially contradicts this view and provides evidence to re-evaluate this Postglacial Recolonization Hypothesis and develop an alternative one. We examined the long-term history of the flora of the Carpathian (Pannonian) Basin by synthesising recent advances in ecological, phylogeographical, palaeoecological and palaeoclimatological research, and analysing the cold tolerance of the native flora of a test area (Hungary, the central part of the Carpathian Basin).

Preserving for the future the - once widespread but now vanishing - knowledge on traditional pig grazing in forests and marshes (Sava-Bosut floodplain, Serbia).

Background: Traditional knowledge is key for sustainability, but it is rapidly disappearing. Pig keeping in forests and marshes is an ancient, once widespread, now vanishing practice, with a major economic and ecological potential. The knowledge of pig keepers and the foraging activity of pigs are hardly documented.

Controlling invasive alien shrub species, enhancing biodiversity and mitigating flood risk: A win-win-win situation in grazed floodplain plantations.

The high nature conservation value of floodplain ecosystems is severely threatened by invasive alien species. Besides adversely affecting native biodiversity, these species also pose a major threat from a wider socio-ecological perspective (e.g.

Prohibited, but still present: local and traditional knowledge about the practice and impact of forest grazing by domestic livestock in Hungary.

Background: Forests have been grazed for millennia. Around the world, forest grazing by livestock became a controversial management practice, gradually restricted in many countries over the past 250 years. This was also the case in most Central and Eastern European countries, including Hungary, where forest grazing was a legally prohibited activity between 1961 and 2017.

Reviewing historical traditional knowledge for innovative conservation management: A re-evaluation of wetland grazing.

Wetlands are fragile, dynamic systems, transient at larger temporal scales and strongly affected by long-term human activities. Sustaining at least some aspects of human management, particularly traditional grazing, would be especially important as a way of maintaining the "necessary" disturbances for many endangered species. Traditional ecological knowledge represents an important source of information for erstwhile management practices.

Combination antiretroviral treatment for women previously treated only in pregnancy: week 24 results of AIDS clinical trials group protocol a5227.

Background: Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF).

Methods: Nonpregnant women with plasma HIV-1 RNA of ≥500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for ≥24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks.

Declining diversity in abandoned grasslands of the carpathian mountains: do dominant species matter?

Traditional haymaking has created exceptionally high levels of plant species diversity in semi-natural grasslands of the Carpathian Mountains (Romania), the maintenance of which is jeopardized by recent abandonment and subsequent vegetation succession. We tested the hypothesis that the different life history strategies of dominant grasses cause different patterns of diversity loss after abandonment of traditional haymaking in two types of meadow. Although diversity loss rate was not significantly different, the mechanism of loss depended on the life history of dominant species.

Discordant associations between SLCO1B1 521T→C and plasma levels of ritonavir-boosted protease inhibitors in AIDS clinical trials group study A5146.

Objective: Among HIV-positive patients prescribed ritonavir-boosted lopinavir, SLCO1B1 521T→C (rs4149056) is associated with increased plasma lopinavir exposure. Protease inhibitors (PIs) are also substrates for cytochrome P450 (CYP) 3A and ABCB1, which are induced by NR1I2. We characterized relationships between ABCB1, CYP3A4, CYP3A5, NR1I2, and SLCO1B1 polymorphisms and trough PI concentrations among AIDS Clinical Trials Group study A5146 participants.

A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in antiretroviral-experienced HIV-infected individuals: week 48 results of the A5146 study.

Background: We devised an open-label, randomized trial to evaluate whether therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and dose escalation based upon a normalized inhibitory quotient (NIQ), which integrates PI trough concentration and drug resistance, could improve virologic outcome in PI-experienced patients with treatment failure. Secondary analyses through 48 weeks are presented.

Methods: Eligible HIV-infected subjects with a screening viral load of ≥ 1000 copies/mL initiated a new PI-based regimen at entry and had NIQ performed at week 2.

Nonnucleoside reverse transcriptase inhibitor-resistant HIV is stimulated by efavirenz during early stages of infection.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent and commonly prescribed antiviral agents used in combination therapy (CART) of human immunodeficiency virus type 1 (HIV-1) infection. The development of drug resistance is a major limitation of CART. Reverse transcriptase (RT) genotypes with the NNRTI resistance mutations K101E+G190S are highly resistant to efavirenz (EFV) and can develop during failure of EFV-containing regimens in patients.

Augmented HIV-specific interferon-gamma responses, but impaired lymphoproliferation during interruption of antiretroviral treatment initiated in primary HIV infection.

Background: Antiretroviral therapy (ART) introduced during primary HIV infection followed by treatment interruption (TI) is postulated to enhance virologic control through induction of HIV-specific CD4 T cells, which foster virus-specific CD8+ T cells that suppress virus replication. This hypothesis was evaluated in 21 subjects enrolled in AIDS Clinical Trials Group 709, a substudy of AIDS Clinical Trials Group 371, which prospectively evaluated subjects who received ≥1 year of ART initiated in acute or recent HIV infection followed by TI.

Methods: Lymphoproliferation was assessed by [methyl-H] thymidine incorporation and HIV-specific CD8+ T-cell interferon-gamma responses by enzyme-linked immunospot-forming assays.

A randomized, placebo-controlled trial of abacavir intensification in HIV-1-infected adults with virologic suppression on a protease inhibitor-containing regimen.

Background And Objective: Maximizing the durability of viral suppression is a key goal of antiretroviral therapy. The objective of AIDS Clinical Trials Group Study 372A was to determine whether the intensification strategy of adding abacavir to an effective indinavir-dual nucleoside regimen would delay the time to virologic failure.

Methods: Zidovudine-experienced subjects (n=229) on therapy with indinavir + zidovudine + lamivudine with plasma HIV-1 RNA levels<500 copies/mL were randomized to abacavir 300 mg twice daily or placebo.

Sequences in the U3 region of human immunodeficiency virus 1 improve efficiency of minus strand transfer in infected cells.

A tRNA gene-like sequence has been identified near the 3' end of HIV-1. Two segments of this sequence (motif 9 and segment 1) promoted minus strand transfer in vitro. The segments are complementary to the tRNA(3)(Lys) primer, and apparently act by binding the tRNA, thereby bringing the 3' and 5' ends of viral RNA into proximity for strand transfer.

Human immunodeficiency virus type 1 protease inhibitor drug-resistant mutants give discordant results when compared in single-cycle and multiple-cycle fitness assays.

The replication fitness of HIV-1 drug-resistant mutants has been measured using either multiple-cycle or single-cycle assays (MCAs or SCAs); these assays have not been systematically compared. We developed an MCA and an SCA that utilized either intact or env-deleted recombinant viral vectors, respectively, in which virus-infected cells were detected by flow cytometry of a reporter gene product. Fitness was measured using each assay for 11 protease mutants, 9 reverse transcriptase mutants, and two mutants with mutations in gag p6, which is important for the release of virus particles from the cell membrane.

HIV-1 reverse transcriptase connection domain mutations: dynamics of emergence and implications for success of combination antiretroviral therapy.

Background: Factors promoting the emergence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) connection domain mutations and their effect on antiretroviral therapy (ART) are still largely undetermined. We investigated this matter by analyzing genotypic resistance tests covering 400 amino acid positions in the RT of HIV-1 subtype B viruses and corresponding treatment histories and laboratory measurements.

Methods: The emergence of connection domain mutations was studied in 334 patients receiving monotherapy or dual therapy with thymidine analogues at the time of the genotypic resistance test.

Quality assessment for therapeutic drug monitoring in AIDS Clinical Trials Group (ACTG 5146): a multicenter clinical trial.

In a randomized trial, AIDS Clinical Trials Group (ACTG) protocol 5146 (A5146) investigated the use of therapeutic drug monitoring (TDM) to adjust doses of HIV-1 protease inhibitors (PIs) in patients with prior virologic failure on PI-based therapy who were starting a new PI-based regimen. The overall percentage of "PI trough repeats" such as rescheduled visits or redrawn PI trough specimens increased from 2% to 5% to 10% as the process progressed from the clinical sites, the pharmacology specialty laboratory, and the study team, respectively. Cumulatively, this represents a 17% rate of failure to obtain adequate PI trough sample.

Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions.

Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of multidrug therapy for HIV-1. Understanding the effect of NNRTI-resistant mutants on virus replication and reverse transcriptase (RT) function is valuable for the development of extended-spectrum NNRTIs. We measured the fitness of six NNRTI-resistant mutants, the K103N, V106A, Y181C, G190A, G190S, and P236L viruses, using a flow cytometry-based cell culture assay.

vFitness: a web-based computing tool for improving estimation of in vitro HIV-1 fitness experiments.

Background: The replication rate (or fitness) between viral variants has been investigated in vivo and in vitro for human immunodeficiency virus (HIV). HIV fitness plays an important role in the development and persistence of drug resistance. The accurate estimation of viral fitness relies on complicated computations based on statistical methods.

The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations.

We measured the effects of non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutations K101E+G190S, on replication fitness and EFV-resistance of HIV(NL4-3). K101E+G190S reduced fitness in the absence of EFV and increased EFV resistance, compared to either single mutant. Unexpectedly, K101E+G190S also replicated more efficiently in the presence of EFV than in its absence.

Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase.

Background: The connection domain mutation N348I confers resistance to zidovudine (AZT) and is associated with the lamivudine (3TC) mutation M184V. We explored the biochemical and virological influence of N348I in the context of M184V.

Methods: Genotypic resistance data for patients receiving monotherapy or dual therapy with AZT, lamivudine (3TC), or AZT/3TC were analyzed.

No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy.

Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks.

Antiretroviral therapy in acute and recent HIV infection: a prospective multicenter stratified trial of intentionally interrupted treatment.

Background: Antiretroviral therapy in early HIV infection may enhance outcome and viral control may be better in acute versus recent infection 24 weeks after treatment interruption.

Methods: A prospective trial of treatment stratified by acute versus recent HIV-1 infection. If HIV viral load <50 copies/ml after at least 52 weeks, treatment was interrupted.