PubMed Health⌕ Search

Biomedical subjects

V Calvez

Publications and source records attributed to V Calvez.

At least 19 recordsLinked to original sources
PubMed2007

Constant mitochondrial DNA levels in blood leukocytes of patients enrolled in a NRTI-free therapeutic trial (BIKS-2 study).

OBJECTIVES: Determine if a nucleoside reverse transcriptase inhibitors (NRTI)-free regimen affected mitochondrial DNA (mtDNA) levels in peripheral blood mononuclear cells (PBMCs) of patients enrolled in BIKS-2 trial. METHODS: Antiretroviral (ARV) naïve (N=13) and NRTI experienced (N=7) patients, received lopinavir/ritonavir, a boosted protease inhibitor, and efavirenz, a non-nucleoside reverse transcriptase inhibitor from Month (M) 0 to M12 (1-year BIKS trial) and from M12 to M36 (2-year BIKS-2 trial). MtDNA was quantified at M12, M24 and M36 via real-time PCR assay. RESULTS: From M12 to M36, the 20 patients have maintained undetectable plasma HIV-1 RNA, gained CD4 cells and had no side effects attributable to these drugs. Median mtDNA contents were constant: 478.6 at M12, 478.6 at M24 and 324.4 copies/cell at M36 (pM12-M36=0.5). Because M0 data is missing, these results were compared to those of two groups of age matched individuals: healthy donors and HIV-infected patients before and after exposure to NRTIs. Healthy donors have higher contents (871), followed by patients never treated (602), than by BIKS patients where 7 had toxic NRTIs (478.6) and at last by patients exposed for six months to the most toxic combination (ddI-d4T) (85 copies/cell). CONCLUSION: Lopinavir/ritonavir+efavirenz did not affect mtDNA contents in PBMCs.

CD4 Lymphocyte Count↗
PubMed2007

KSHV after an organ transplant: should we screen?

The incidence of Kaposi sarcoma (KS) related to Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8) after organ transplantation is 500-1000 times greater than in the general population, and its occurrence is associated with immunosuppressive therapy. The reported incidence of posttransplant KS ranges from 0.5% to 5%, depending on the patient's country of origin and the type of organ received, mainly after renal transplantation. Posttransplant KS is caused by two possible mechanisms: KSHV reactivation in patients who were infected before the graft and KSHV contamination from the infected organ's donor to the recipient. KSHV reactivation appears to play a greater role in the risk of KS than incident infections. However, some studies, with findings based not only on serological data but also on molecular tracing of the viral infection, have shown that organ-related transmission of KSHV could be more common than previously thought and associated in some cases with severe KSHV-related disease. Precise estimates of KSHV seroprevalence in the organ donor and recipient populations in different countries are lacking. However, studies have reported seroprevalences among donors and recipients that are similar to those among the general population of the country considered. Many studies have suggested the potential utility of screening of KSHV antibodies among organ donors and recipients. However, to date the results of these studies have argued in favor of KSHV screening, even in low-KSHV infection prevalence countries, not to exclude the graft but to have the KSHV status information in order to have the opportunity to monitor, clinically and biologically, patients at risk for KSHV-related disease development. The detection of KSHV antibodies could be done in the days after the transplantation and the results transmitted to the physicians retrospectively. In conclusion, the question of screening donors and recipients for KSHV, even in low-KSHV infection prevalence countries, is still debated, and prospective studies are needed to evaluate the benefit of pre- and posttransplantation strategies.

Animals↗
PubMed2005

Persistent low viral load on antiretroviral therapy is associated with T cell-mediated control of HIV replication.

BACKGROUND: It is unclear how stable low-level viral replication and CD4 cell numbers can be maintained under highly active antiretroviral therapy (HAART). This study was designed to analyse whether HIV-specific responses in stable partially controlled patients during antiretroviral therapy (ART) differ from those observed in complete HAART failure and whether they contribute to the control of viral load (VL). METHODS: Three groups of patients were selected according to plasma HIV RNA levels during 18 months of ART: persistently low VL (LoVL; HIV RNA <10,000 copies/ml; n = 28), undetectable VL (UnVL; HIV RNA <200 copies/ml; n = 29) and high VL (HiVL; HIV RNA >10,000 copies/ml; n = 14). T-cell responses were studied using lymphoproliferative and interferon (IFN)-gamma-ELISpot assays against HIV-p24, -gp160, recall antigens, and 15 pools of HIV-(Gag + RT) peptides. RESULTS: Frequencies of IFN-gamma-producing CD4 T cells against HIV-p24 were higher in LoVL than in UnVL or HiVL groups [median, 131, 47 and 23 spot-forming cells (SFC)/1 x 10 peripheral blood mononuclear cells (PBMC), respectively; P = 0.012 and P = 0.047]. Lymphoproliferative responses to HIV-p24 and recall antigens were similar in LoVL and UnVL groups but lower in HiVL (P = 0.004). Frequencies of HIV-specific CD8 T cells were higher in LoVL than in UnVL (1340 versus 410 SFC/1 x 10 PBMC; P = 0.001). They correlated negatively with VL in the LoVL and HiVL (r, -0.393, P = 0.039 and r, -0.643, P = 0.024, respectively) and positively correlated with anti-HIV CD4 cell frequencies in the LoVL group only (r, 0.420; P = 0.026). CONCLUSION: Persistently low viral replication (<10,000 copies/ml) during ART stimulates high frequencies of HIV-specific CD4 and CD8 T cells compared to full virus suppression or complete ART failure. The association of high anti-HIV activity with large numbers of HIV-specific CD8 T cells contribute to the control of viral replication.

Adult↗
PubMed2004

Cluster formation for multi-strain infections with cross-immunity.

Many infectious diseases exist in several pathogenic variants, or strains, which interact via cross-immunity. It is observed that strains tend to self-organise into groups, or clusters. The aim of this paper is to investigate cluster formation. Computations demonstrate that clustering is independent of the model used, and is an intrinsic feature of the strain system itself. We observe that an ordered strain system, if it is sufficiently complex, admits several cluster structures of different types. Appearance of a particular cluster structure depends on levels of cross-immunity and, in some cases, on initial conditions. Clusters, once formed, are stable, and behave remarkably regularly (in contrast to the generally chaotic behaviour of the strains themselves). In general, clustering is a type of self-organisation having many features in common with pattern formation.

Animals↗
PubMed2004

[Therapeutic strategies for HIV infection: virology approach].

Among antiretroviral therapies available for the treatment of human immunodeficiency virus infection, protease inhibitors (PI) are the most promising molecules. Yet they are likely to induce the emergence of resistance mutations in viral strains, which as a consequence can affect their efficacy. Boosting has improved PI's efficacy by increasing their half-life and trough concentration. Boosted PI are hence, especially relevant for the treatment of patients with virological failure. Moreover, using boosted PI as first line treatment could avoid the appearance of viral mutations in case of virological failure. Indeed, boosted PI are more rapidly cleared from blood circulation than unboosted PI. Their concentrations rapidly drop and cross the range of sub-inhibitory drug concentrations i.e. the zone of highest selective pressure, thus limiting the risk of viral mutations.

HIV↗
PubMed2004

GENOPHAR: a randomized study of plasma drug measurements in association with genotypic resistance testing and expert advice to optimize therapy in patients failing antiretroviral therapy.

OBJECTIVES: To evaluate the benefits of therapeutic drug monitoring (TDM) in association with genotypic resistance testing and expert advice to optimize therapy in multiexperienced patients infected with HIV-1. METHODS: Patients with a viral load>1000 HIV-1 RNA copies/mL and an unchanged antiretroviral therapy regimen over the last 3 months were randomized into two groups: a genotypic group (G) and a geno-pharmacological group (GP). Treatment was selected by an expert committee according to genotypic resistance testing (the G and GP groups) and TDM (the GP group) at week 4. Treatment could be modified at each visit according to toxicity, poor virological response and TDM. Results of TDM were withheld from the G group until week 12. The primary endpoint of the study was the percentage of patients with viral load<200 copies/mL at week 12. RESULTS: A total of 134 patients were randomized in the study, with 67 in each group, and included in the intent-to-treat (ITT) analysis. At baseline, median values were as follows: viral load (log(10) copies/mL): G=4.1, GP=4.0; CD4 cell count (cells/microL): G=292, GP=294; and number of prior drugs: G=7, GP=8. The median number of resistance mutations was five in the G group [nucleoside reverse transcriptase inhibitors (NRTIs)=three; non-nucleoside reverse transcriptase inhibitors (NNRTIs)=one; protease inhibitors (PI)=one] and seven in the GP group (NRTI=four; NNRTI=two; PI=one). At week 8, treatment was adjusted according to the TDM in 13 of the 67 patients in the GP group (19%). By ITT missing equal failure analysis at week 12, and after only one intervention according to plasma concentration results, a viral load<200 copies/mL was achieved in 30 of the 67 patients (45%) in the G group and in 29 of the 67 patients (43%) in the GP group (not significant). In the multivariate analysis, only prior exposure to at least two PIs at baseline gave a poor response to subsequent antiretroviral therapy. At week 24, a viral load<200 copies/mL was achieved in 35 of the 67 patients (52%) in the G group and in 40 of the 67 patients (60%) in the GP group. CONCLUSIONS: A statistically significant benefit of using TDM was not found in this short-term study where patients appeared to be adherent. However, combining genotypic resistance testing with the use of an expert committee to monitor subsequent therapy individually in patients with multiple resistance mutations was associated with high antiviral efficacy.

Adolescent↗
PubMed2003

Markov modelling of changes in HIV-specific cytotoxic T-lymphocyte responses with time in untreated HIV-1 infected patients.

HIV-specific cytotoxic CD8(+) T-lymphocytes (CTL) appear to be the cornerstone of the immune response to HIV infection. Recent studies show that CTL activity reflects patients' anti-HIV immune status and slows disease progression. However, the dynamics of the diversity of this response also appears as a key parameter for immune control but the dynamics of this diversity is largely undocumented. We modelled changes in CTL responses against the seven principal HIV proteins over time. We also studied the influence of plasma viral load on temporal changes in HIV protein recognition by memory CTL. The generic model we developed is based on a continuous time homogeneous Markov process with reversible states. Those states are defined by the number of proteins recognized by memory CTL in a given patient at a given time. This approach was developed within a Bayesian framework. Full Bayesian inference is implemented using Markov chain Monte Carlo simulations (MCMC). The Gibbs sampling algorithm was used to estimate the marginal posterior distributions of the transition intensities between stages of CTL responses. We applied our model to data of 152 HIV-infected patients included in the IMMUNOCO cohort. The model suggested that the diversity of HIV protein recognition by memory CTL in treatment-naive patients decreases as the disease progresses. Namely, the loss of T cytotoxic responses is globally faster than their acquisition. Indeed, these patients' T cytotoxic responses were characterized by marked individual turnover and a gradual loss of multiple protein recognition over time, this loss accelerating as viral load increased.

Adult↗
PubMed2003

P-glycoprotein in blood CD4 cells of HIV-1-infected patients treated with protease inhibitors.

OBJECTIVE: Many factors are involved in the virological failure of antiretroviral treatments such as low pharmacological plasma levels of drugs, poor adherence to therapy and emergence of viral resistance. P-glycoprotein (P-gp) has been demonstrated to play a role in multidrug resistance in the therapy of solid tumours, haematological malignancies and Plasmodium falciparum infection. HIV-1 protease inhibitors (PIs) have been described to be substrates of P-gp. In vitro and in vivo studies performed in mice have demonstrated that P-gp may affect the oral bioavailability and intracellular accumulation of PIs. P-gps have been detected on peripheral CD4 blood cells in HIV-1-infected, but antiretroviral-naive patients. METHOD: We quantified P-gp expression and performed functional tests of P-gp activity in the CD4 cells in HIV-1-infected patients, with and without virological failure, treated with PIs, and in healthy patients (control group). RESULT: Out of the 18 HIV-infected patients studied, P-gp expression and function were found in the CD4 cells of six patients (four of 10 without, and two of eight with virological failure). Out of the 43 healthy patients studied, P-gp expression and function were found in the CD4 cells of 11 patients (26%). We found P-gp in peripheral CD4 cells of patients treated with PIs, with and without virological failure, within the same frequency than in antiretroviral naive patients or than in non HIV-infected patients. CONCLUSIONS: P-gp expression in peripheral CD4 blood cells does not seem to be enhanced by PI treatment and does not seem to be linked particularly to virological failures. These facts do not preclude of the role of P-gp on PI absorption or efficacy in other compartments of the body such as gut, lymph nodes or brain in HIV-1 PI-treated patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Quantitative analysis of human mitochondrial DNA using a real-time PCR assay.

OBJECTIVES: Known for their ability to inhibit the human DNA polymerase-gamma, nucleoside analogues induce toxic effects on mitochondria ranging from increased serum lactate levels to fatal lactic acidosis. DNA polymerase-gamma ensures the mitochondrial DNA (mtDNA) replication and, thus, its inhibition leads to the decrease of the mtDNA. We describe a real-time PCR assay for mtDNA quantification associating DNA extraction procedures applied on peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissues and to study the antiretroviral effect on mitochondria. METHODS: Total DNA was extracted from PBMCs and subcutaneous adipose tissues. Nuclear and mitochondrial genes were amplified to determine the number of copies of mtDNA per cell using a cyt-b recombinant plasmid as standard control. We analysed eight HIV-infected asymptomatic patients never treated, four patients who had been treated for 6 months with highly active antiretroviral therapy (HAART) and six non-infected donors. RESULTS: The mtDNA quantification gave rise to reproducible results as the mean coefficients of variation were 1.09% for replicates of samples undertaken 10 times within the same run, and 5.78% and 3.7% for replicates tested in five different runs at 1:100 and 1:1000 dilutions, respectively. Median levels of mtDNA in PBMCs of healthy donors, naive and treated HIV-infected patients were 2.94, 2.78 and 1.93 log HIV-1 RNA copies/mL, respectively. Whereas DNA from PBMCs was shown to be devoid of inhibitors, subcutaneous adipose tissues needed an extra treatment as they were found to be highly inhibited. CONCLUSIONS: The method generated consistent and reproducible results and was successfully applied to DNAs extracted from PBMCs and subcutaneous adipose tissues with adapted extraction. The mtDNA changes in PBMCs were found to be fast as they fall off after 6 months' therapy, decreasing from 2.78 to 1.93 log copies/mL.

Adipose Tissue↗
PubMed2001

Effects of cyclosporine and hydrocortisone on Kaposi's sarcoma-associated herpesvirus genome replication and cell apoptosis induction.

BACKGROUND: Iatrogenic immunosuppressed patients are at increased risk for development of various cancers that comprise Kaposi's sarcoma (KS). METHODS: To investigate the direct impact of immunosuppressive agents on Kaposi's sarcoma-associated herpesvirus (KSHV) and KS development, we quantified the effects of cyclosporine (CsA) and hydrocortisone (HC) on KSHV genome replication and the consequences on the cell survival. RESULTS: In the presence of phorbol ester 12-O-tetradecanoyl phorbol-13-acetate, we observed an increase of intracellular and extracellular KSHV DNA concomitantly with an increase of gp (glycoprotein) K8.1 expression, indicating KSHV genome replication. This replication was accompanied by cell apoptosis. In comparison, in the presence of CsA, HC, or both, we did not observe any effect on KSHV replication or gp K8.1 expression. CONCLUSION: Our results suggest that immunosuppressive agents such as HC and CsA do not activate the lytic cycle of KSHV and do not modify the cell survival thus promoting cancer progression by a direct cellular effect.

Apoptosis↗
PubMed2001

Re-occurrence of HIV-1 drug mutations after treatment re-initiation following interruption in patients with multiple treatment failure.

Antiretroviral treatment interruption in 20 extensively pre-treated HIV-1 patients with treatment failure led to genotype viral reversion of at least one class of drug-mutation resistance in half of the patients. The only predictive factor of reversion was found to be the duration of interruption. The outgrowth of residual wild-type virus seems not to be a true genetic reversion because drug mutations are detected rapidly at salvage therapy re-initiation.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Human herpesvirus-8 seroconversions after renal transplantation.

BACKGROUND: Human herpesvirus-8 (HHV-8) is a new human herpesvirus that is clearly associated with Kaposi's sarcoma (KS). A previous study has reported that the prevalence of KS in a cohort of renal transplant recipients with previous HHV-8 infection was 28% and two other studies have shown that KS can be linked to HHV-8 seroconversion after graft. The aim of this study was to evaluate the HHV-8 seroconversion rate in a cohort of renal allograft recipients in Paris. METHODS: Two hundred eighty-seven patients who were HHV-8 seronegative before renal transplantation were tested for HHV-8 antibodies by an immunofluorescence assay 12 months after transplantation. RESULTS: Of the 287 patients, 6 (2.09%) seroconverted after renal transplantation. None of these 6 patients developed KS within 3 years of the first HHV-8 positive serum. None of the clinical manifestations that could be associated with HHV-8 primary infection were observed during the seroconversion. CONCLUSIONS: Our results demonstrated that HHV-8 seroconversion can be observed even in a low HHV-8 prevalence area and confirmed the need to perform systematic screening for HHV-8 antibodies in renal graft donors and recipients.

Adult↗
PubMed2001

Prevalence of resistance mutations in antiretroviral-naive chronically HIV-infected patients in 1998: a French nationwide study.

OBJECTIVE: To estimate the prevalence of resistance-conferring mutations to antiretroviral drugs in previously untreated patients with chronic HIV-1 infection as a basis for French recommendations on viral genotyping before antiretroviral treatment initiation. DESIGN: Resistance mutations were sought in samples from 404 patients seen in 23 specialized centres throughout metropolitan France in 1998. METHODS: The protease and reverse transcriptase (RT) genes of plasma virions were sequenced. Primary and secondary protease and RT gene mutations were identified from the International AIDS Society resistance testing - USA panel. RESULTS: The prevalence of patients with primary and secondary mutations were 3.7% (95% CI 1.7-5.7) and 50.3% (95% CI 45.0-55.6), respectively. The prevalence of patients with mutations associated with resistance to nucleoside RT inhibitors (NRTI) and non-nucleoside RT inhibitors was 3.3% (95% CI 1.5-5.1) and 0.8% (95% CI 0.0-1.7), respectively. The prevalence of patients with NRTI primary mutations differed according to whether seropositivity had been diagnosed more or less than one year previously (0.2 versus 2.2% P = 0.023). Primary mutations associated with protease inhibitor resistance occurred at a prevalence of 1.9% (95% CI 0.5-3.4) with no difference according to the duration of known seropositivity. CONCLUSION: In France, in 1998, the prevalence of patients with primary mutations associated with resistance to antiretroviral drugs was low. Genotyping before the initiation of therapy was not recommended in chronically HIV-1-infected naive patients. A national sentinel survey of resistance in this clinical setting is performed regularly to update the recommendations for resistance testing.

Adult↗
PubMed2001

Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study.

BACKGROUND: Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients. METHODS: 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. FINDINGS: Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44-48). Mean decreases in serum HBV DNA concentrations from baseline (log 8.64 copies/mL [SE log 0.08]) were 2log 3.40 copies/mL [log 0.12] at week 24 (n=31) and 2log 4.01 copies/mL [log 0.17] at week 48 (n=29; p<0.0001). Two patients underwent hepatitis B e antigen seroconversion-one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. INTERPRETATION: These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.

Adenine↗
PubMed2001

A long-term follow-up of an HIV type 1-infected patient reveals a coincidence of Nef-directed cytotoxic T lymphocyte effectors and high incidence of epitope-deleted variants.

Cytotoxic T lymphocytes (CTL) play a critical role in controlling human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) infections. However, in spite of developing a strong CTL response most HIV-1-infected patients eventually progress to AIDS. Amino acid changes in CTL epitope have been previously described and may permit HIV to escape from CTL immune responses. The importance of CTL selection pressure in controlling the course of viral evolution in HIV-infected patient remains debatable. For over a 10-year period, we longitudinally followed a patient for bulk unstimulated effector (eCTL) and stimulated memory CTL responses (mCTL) against the viral proteins Gag, Pol, and Nef. The patient showed a strong CTL response against Nef in unstimulated peripheral blood mononuclear cells with a peak during Month 40 of the follow-up. The mCTL response was also higher against Nef than Gag and Pol. PCR amplification and nucleotide sequencing of the plasma viral variants showed a viral variant with the epitope deletion that was detected early during the follow-up and essentially replaced the wild-type virus during the peak eCTL response. These studies support the importance of Nef epitope deletion as a mechanism for HIV-1 escape from CTL immune pressure.

Amino Acid Sequence↗
PubMed2001

[Management of therapeutic failure in HIV-infected patients].

A COMMON SITUATION: Among HIV-infected patients treated with antiretroviral regimens, 20% to 50% escape therapeutic control. The principal factors predictive of treatment failure are low CD4 counts and high viral load prior to institution of the antiretroviral treatment. Several virological and pharmacological mechanisms are implicated. GENOTYPING AND PHENOTYPING: Genotyping is particularly useful to optimize treatment in HIV-infected patients who escape therapeutic control, irrespective of the therapeutic strategy. A committee of experts has developed a scheme for adapting treatment to the very complex results of genotyping tests. The benefit of phenotyping remains to be established. MANAGEMENT: Serum concentrations of antiretroviral agents should be determined and adapted in order to maximize the treatment effect. However, to manage therapeutic escape, the only method with a proven impact is genotyping. The possible usefulness of regular drug assays for adjusting treatment doses in case of therapeutic escape remains to be assessed in prospective trials.

Algorithms↗
PubMed2001

Clinical and spectroscopic improvement in HIV-associated cognitive impairment.

To assess the impact of highly active antiretroviral therapy (HAART) on AIDS-associated cognitive impairment, 22 patients with AIDS with (n = 11) and without (n = 11) cognitive deficit were evaluated clinically and by MRS every 3 months for 9 months. Nineteen patients were on HAART at study entry, 21 after 2 months. Cognitively impaired patients presented with a subcorticofrontal deficit and decreased N-acetyl-aspartate in frontal white matter. These clinical and metabolic abnormalities reversed partially on HAART, whereas they remained within normal limits in cognitively unimpaired patients.

AIDS Dementia Complex↗