Boosted protease inhibitor monotherapy in HIVinfected adults: outputs from a pan-European expert panel meeting

While the introduction of combination highly active antiretroviral therapy (HAART) regimens represents an important advance in the management of human immunodeficiency virus (HIV)-infected patients, tolerability can be an issue and the use of several different agents may produce problems. The switch of combination HAART to ritonavir-boosted protease inhibitor (PI) monotherapy may offer the opportunity to maintain antiviral efficacy while reducing treatment complexity and the risks of toxicity. Current European AIDS Clinical Society (EACS) guidelines recognise ritonavir-boosted PI monotherapy with twice-daily lopinavir/ritonavir or once-daily darunavir/ritonavir as a possible option in patients who have intolerance to nucleoside reverse transcriptase inhibitors, or for treatment simplification. Clinical trials data for PI boosted monotherapy are encouraging, showing substantial efficacy in the majority of patients; however, further data are required before this approach can be recommended as a routine treatment. Available data indicate that the most suitable candidates for the use of boosted PI monotherapy are long-term virologically suppressed patients who have demonstrated good adherence to antiretroviral therapy, who do not have chronic hepatitis B, have no history of treatment failure on PIs and are able to tolerate low-dose ritonavir

The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients

<p>Abstract</p> <p>Background</p> <p>This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the <it>env </it>C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2–4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity</p> <p>Results</p> <p>The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%), increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites.</p> <p>Conclusion</p> <p>The evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size limiting the number of virus escape mutants. The C3 region seems to be a target for IgA antibodies and increasing N-linked glycosylation may prevent HIV-2 envelope recognition by these antibodies. Our results provide new insights into the biology of HIV-2 and its relation with the human host and may have important implications for vaccine design.</p

Custos diretos com tratamento do VIH/SIDA em Portugal

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Bulk cytokine production versus frequency of cytokine-producing cells in HIV1 infection before and during HAART

Copyright © 2000, ElsevierCytokine imbalances play a major role in HIV immunopathogenesis. This study analyzes simultaneously the frequency of cytokine-producing cells at the single cell level by flow cytometry and the disturbances in cytokine secretion assessed by ELISA in a cohort of asymptomatic HIV1 patients in different stages of CD4 depletion and during antiretroviral therapy (HAART). Early in the disease, there is an increased frequency of IFN-γ lymphocytes and bulk IFN-γ+ production, in parallel with a reduced proportion of IL4+ cells and IL4 secreted. The two IL4 measurements are significantly correlated. No such correlation was found for IFN-γ, which is consistent with a large variation in the amount of IFN-γ released per individual cell. Moreover, HAART was associated with a reduction to normal levels in the bulk IFN-γ secretion concomitant with a persistency of the overexpanded IFN-γ+ cell subset in the peripheral blood. This study emphasizes the importance of using a conjoint approach to assess the cytokine network in trials of antiretroviral and/or immune-based therapies to avoid missing significant effects which are possibly relevant in the clinical setting.This work was supported by grants from “Ministério da Ciência e Tecnologia–Praxis XXI” and from “Comissão Nacional de Luta Contra a SIDA–Ministério da Saúde” to RMMV. AES received a scholarship from Praxis and AFC received a scholarship from CNLCS

C2V3C3-specific IgG response is associated with disease progression

Objective: To examine the unspecific and envelope-specific IgA and IgG responses in acute and chronic HIV-2 infection. Methods: Twenty-eight chronically infected adults and two children with perinatal infection were studied. Total plasma concentrations of. - Fundacao para a Ciencia e Tecnologia [POCTI/ESP/48045]. - The present work was supported by Fundacao para a Ciencia e Tecnologia (project POCTI/ESP/48045). Jose Marcelino is the recipient of a PhD scholarship from Fundacao para a Ciencia e Tecnologia (FCT), Portugal. The Instituto Portugues do Sangue (IPS), Por

Direct treatment costs of HIV/AIDS in Portugal

OBJECTIVE: To analyze the direct medical costs of HIV/AIDS in Portugal from the perspective of the National Health Service. METHODS: A retrospective analysis of medical records was conducted for 150 patients from five specialized centers in Portugal in 2008. Data on utilization of medical resources during 12 months and patients' characteristics were collected. A unit cost was applied to each care component using official sources and accounting data from National Health Service hospitals. RESULTS: The average cost of treatment was 14,277 €/patient/year. The main cost-driver was antiretroviral treatment (€ 9,598), followed by hospitalization costs (€ 1,323). Treatment costs increased with the severity of disease from € 11,901 (> 500 CD4 cells/µl) to € 23,351 (CD4 count ≤ 50 cells/ µl). Cost progression was mainly due to the increase in hospitalization costs, while antiretroviral treatment costs remained stable over disease stages. CONCLUSIONS: The high burden related to antiretroviral treatment is counterbalanced by relatively low hospitalization costs, which, however, increase with severity of disease. The relatively modest progression of total costs highlights that alternative public health strategies that do not affect transmission of disease may only have a limited impact on expenditure, since treatment costs are largely dominated by constant antiretroviral treatment costs

Baseline susceptibility of primary HIV-2 to entry inhibitors

Background The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. Methods The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC50), 90% inhibitory concentration (IC90) and dose–response curve slopes were determined for each drug. Results ENF and T-1249 were significantly less active on HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC50 and IC90 values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC90 values (42.7 versus 9.7 nM; P<0.0001) and lower slope values (0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants derived from AIDS patients were significantly less sensitive to MVC than variants from asymptomatic patients, this being inversely correlated with the absolute number of CD4+ T-cells. Conclusions T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage.This work was supported by Fundação para a Ciência e Tecnologia (grant number PTDCSAU-FCF6767/2006), Portugal, and by the Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN), from the European Union. PB, RC, IB and CR are supported by PhD grants from Fundação para a Ciência e Tecnologia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: bicyclam JM-2987 (hydrobromide salt of AMD-3100), pNL4-3 from Malcolm Martin, pSG3.1 from Sajal Ghosh, T-20 (ENF, fusion inhibitor) from Roche, TAK-779 from Takeda Chemical Industries, TZM-bl from John C Kappes, Xiaoyun Wu, and Tranzyme, Inc. pROD10 plasmid was a kind gift from Keith Peden. Trimeris Inc (NC, USA) and Pfizer Inc (NY, USA) provided T-1249 and MVC, respectively.info:eu-repo/semantics/publishedVersio

Multi-centre International Study of the Efficacy and Tolerability of Eviplera (EVA) in Routine Clinical Settings

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Uptake of Tenofovir-based Combination Antiretroviral Therapy (cART) among HIV/HBV Co-infected Patients in the EuroSIDA Study

For EuroSIDA in EuroCoordinfo:eu-repo/semantics/nonPublishe