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Biomedical subjects

Vincent Calvez

Publications and source records attributed to Vincent Calvez.

68 records · Page 4Linked to original sources
PubMed2002

Prospective study of the effects of antiretroviral therapy on Kaposi sarcoma--associated herpesvirus infection in patients with and without Kaposi sarcoma.

OBJECTIVE: To investigate the effect of highly active antiretroviral therapy (HAART) on circulating Kaposi sarcoma (KS)-associated herpesvirus (KSHV) load in HIV-infected individuals with and without KS. DESIGN: Twenty-nine HIV-infected subjects (21 with KS and 8 without KS) were recruited for the study; they were prospectively studied before and at regular intervals during HAART. METHODS: Patients with KS were clinically assessed using Adult Clinical Trials Group (ACTG) criteria, and sequential blood samples were obtained from all patients for determination of plasma HIV-1 load, CD4 cell count, titer of antibody to KSHV, and KSHV load. RESULTS: Ten of 21 patients with KS had a favorable KS response (complete response, 6; partial response, 4) with HAART alone. Of the 20 subjects with detectable KSHV viremia prior to HAART, over one half (12 [60%]) had an undetectable KSHV load with antiretroviral therapy. There was no significant difference between subjects receiving protease inhibitor- or nonnucleoside reverse transcriptase inhibitor-based treatment combinations. Achieving undetectable KSHV viremia is associated with a better clinical outcome in patients with KS. CONCLUSIONS: To our knowledge, we demonstrate for the first time that both protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based antiretroviral treatment combinations may lead to an undetectable KSHV load and confirm that an undetectable KSHV load is associated with KS regression. There was no clear association between CD4 cell count response and KS response to HAART, but there was a significant relationship between HIV load response to HAART and clinical improvement of KS.

Adult↗
PubMed2002

Interleukin-2 accelerates CD4 cell reconstitution in HIV-infected patients with severe immunosuppression despite highly active antiretroviral therapy: the ILSTIM study--ANRS 082.

BACKGROUND: Despite effective highly active antiretroviral therapy (HAART), some patients infected with HIV have persistently low CD4 cell counts with risk of HIV disease progression. The addition of interleukin-2, a cytokine that stimulates CD4 T lymphocyte helper cells, may benefit patients with discordant responses. METHODS: A total of 72 HIV-infected patients with CD4 cell counts of 25-200 x 10(6) cells/l (median 145) and plasma HIV RNA < 1000 copies/ml were randomized in a multicentre study to receive open-label 4.5 x 10(6) IU interleukin-2 subcutaneously twice daily for 5 days every 6 weeks plus their ongoing HAART or were maintained on HAART alone (control group). After 24 weeks, all patients received interleukin-2 therapy plus HAART up to week 80. Primary end-point was the CD4 T cell area under the curve minus baseline up to week 24. RESULTS: After four cycles of interleukin-2, in an intent-to-treat analysis, the respective median CD4 cell area under the curve minus baseline values were +51 and +11 cells in the interleukin-2 (n = 34) and the control group (n = 36) (P < 0.0001). The percentage of patients in the two groups with CD4 cell counts > 200 x 10(6) cells/l was 81% and 33%, respectively (P < 0.0001). At week 80, the median CD4 cell counts in the two groups were 380 and 270 x 10(6) cells/l, respectively. Interleukin-2 treatment was reasonably well tolerated and did not result in sustained increases in plasma HIV RNA levels. CONCLUSIONS: Administration of interleukin-2 produces significant and sustained increase in CD4 cell counts in HAART-treated patients with persistent CD4 cell counts < 200 x 10(6) cells/l.

Adult↗
PubMed2002

Final analysis of the Trilège induction-maintenance trial: results at 18 months.

BACKGROUND: First results of Trilège demonstrated that the strategy of less intensive antiviral therapy is less effective than continuation of triple-drug therapy. OBJECTIVE: To compare the final number of failures at month 18 and to study viral dynamics in patients experiencing a virological failure. DESIGN: Longitudinal follow-up from a randomized controlled trial. SETTING: Forty-three AIDS clinical-trial units. PATIENTS: A total of 279 HIV-1 infected adults randomized in Trilège. MEASUREMENTS: Analysis of recurrent values of HIV RNA > 500 copies/ml beyond time to virologic failure. RESULTS: A total of 83 patients experienced virological failure by month 18; 10 in the zidovudine (ZDV) + lamivudine (3TC) + indinavir (IDV) arm, 46 in the ZDV + 3TC arm, and 27 in the ZDV + IDV arm, confirming previous results. Whatever the treatment ultimately received, 87% of patients had an HIV RNA < 500 copies/ml at month 18 with no statistical difference between randomized arms. Patients experiencing a failure in the triple-drug regimen had a greater tendency to maintain HIV RNA > 500 copies/ml beyond the time of virological failure than patients in both less intensive treatment groups who experienced failure. Lower levels of HIV RNA at failure and reinitiating of either the original triple-drug regimen or a new combination of nucleoside analogue reverse transcriptase inhibitors and protease inhibitors were associated with lower hazard ratios for developing recurrent HIV RNA > 500 copies/ml. CONCLUSION: Results confirmed the failure of a less intensive regimen to maintain patients with a viral suppression (HIV RNA < 500 copies/ml). Although there is a lower incidence of failure in the triple-drug regimen, randomization to a less intensive regimen of ZDV + 3TC or ZDV + IDV was not detrimental, as treatment modification, either to the original triple regimen, or a different regimen was successful.

Adult↗
PubMed2002

Kaposi's sarcoma herpesvirus and HIV-1 seroprevalences in prostitutes in Djibouti.

Kaposi's sarcoma herpesvirus (KSHV) is linked causally to Kaposi's sarcoma. Epidemiological studies have shown that KSHV transmission can occur during sex among homosexual men, but heterosexual transmission seems to be very rare in KSHV low prevalence countries. A seroepidemiological study was conducted to determine whether KSHV is transmitted sexually between heterosexuals in an endemic country. Sera from 282 subjects of African origin living in Djibouti were tested for antibodies to KSHV and HIV-1. Among the 282 individuals, 43 were female prostitutes working in the streets (group 1), 123 were female prostitutes working in luxury bars (group 2), 41 were non-prostitute females (group 3), and 75 were non-prostitute males (group 4). KSHV seroprevalence was 26, 20, 17, and 36% in groups 1, 2, 3, and 4, respectively. The seroprevalence of KSHV is not different between street or bar prostitutes and non-prostitute females (OR = 1.67; P = 0.34 and OR = 1.18; P = 0.73). These results suggest that in this endemic country commercial sex work does not seem to be a risk factor for KSHV infection and provides evidence against heterosexual transmission of KSHV in the female population studied.

Adolescent↗
PubMed2002

Human immunodeficiency virus (HIV) Type 1 reverse transcriptase resistance mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV chronic infection once daily with 10 milligrams of adefovir dipivoxil combined with lamivudine.

Adefovir dipivoxil (ADV) at a suboptimal concentration for human immunodeficiency virus type 1 (HIV-1) (10 mg once daily) can be used to treat hepatitis B virus (HBV) infection in HIV-1-HBV-coinfected patients and does not, even in the case of uncontrolled HIV-1 replication, select for either ADV mutations at codons 65 and 70 or any other particular HIV-1 reverse transcriptase resistance profile.

Adenine↗
PubMed2002

Kaposi's sarcoma associated with previous human herpesvirus 8 infection in heart transplant recipients.

The aim of this study was to evaluate the seroprevalence of human herpesvirus 8 (HHV-8) in a group of 150 patients awaiting heart transplants and to detect HHV-8 seroconversion after transplantation. Four patients were HHV-8 seropositive before transplantation, and one of them developed Kaposi's sarcoma. One patient converted to seropositive HHV-8 status after transplantation.

Antibodies, Viral↗
PubMed2002

Identification of Kaposi's sarcoma-associated herpesvirus (KSHV)-specific cytotoxic T-lymphocyte epitopes and evaluation of reconstitution of KSHV-specific responses in human immunodeficiency virus type 1-Infected patients receiving highly active antiretroviral therapy.

Following the introduction of highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) has significantly declined in human immunodeficiency virus type 1 (HIV-1)-positive (HIV-1(+)) individuals and clinical remission is often observed. We hypothesize that these effects are partly due to anti-KS-associated herpesvirus (KSHV) immune restoration. Here, 15-mer overlapping peptides from proteins K12 and K8.1 were used to identify novel KSHV-specific cytotoxic T-lymphocyte epitopes. Three immunogenic peptides, two lytic and one latent, were subsequently used to monitor the anti-KSHV CD8(+) T-cell responses in a cohort of 19 HIV-1(+) KSHV(+/-) KS(+/-) individuals during 52 weeks of HAART. KSHV and HIV-1 loads, KSHV antibody titers, and both CD4(+) and CD8(+) T-lymphocyte counts were enumerated. Prior to HAART, the total number of spot-forming cells (SFC) for all three peptides correlated with both CD4(+) and CD8(+) T-lymphocyte counts (P < or = 0.05) in the KSHV-positive KS-positive cohort (n = 11). Following 52 weeks of HAART, significant decreases in HIV-1 and KSHV loads were associated with significant increases in CD4(+) T-lymphocyte counts and number of SFC for the three KSHV-specific peptides. Although these increases were modest in comparison to the number of SFC observed with the HIV-1 gag peptide SLYNTVATL, they represented a fourfold increase from the baseline, continuing an upward trend to week 52.

AIDS-Related Opportunistic Infections↗
PubMed2002

Impact of stavudine phenotype and thymidine analogues mutations on viral response to stavudine plus lamivudine in ALTIS 2 ANRS trial.

OBJECTIVE: Stavudine-based antiretroviral combinations are less effective in zidovudine-experienced patients than in naive subjects and recently, mutations have been described to be associated to the use of both stavudine and zidovudine. In the ALTIS 2 trial, it was shown that a combination of stavudine and lamivudine is less effective in zidovudine-experienced patients than in naive patients. We conducted a retrospective genotypic and phenotypic resistance study (expressed as stavudine phenotypic index, calculated by dividing the inhibitory concentrations 50% [IC50] by the mean value of the sensitive viruses) to evaluate the factors associated with decrease in plasma HIV-1 RNA. DESIGN: Associations with continuous variables were studied using non-parametric Spearman correlation coefficients. Associations with categorical variables were studied using non-parametric Mann-Whitney tests. Multivariate stepwise regression analyses were used to determine independent prognostic factors of the virological response. RESULTS: At baseline, most of the subjects harboured zidovudine-associated mutations in plasma and peripheral blood mononuclear cells. Zidovudine and stavudine IC50 and IC50 were strongly associated with response. It appears that a cut-off of stavudine phenotypic index of 1.8-fold of IC50, much lower than the usually used value, could be clinically significant for response to stavudine. In the multivariate analysis, the stepwise model with the higher multiple correlation coefficient (R2 = 0.742) included the presence of a 215 Y/F mutation, the number of previously used nucleoside analogues and a resistant stavudine phenotype. CONCLUSION: These results argue for a phenotypic and genotypic cross resistance between stavudine and zidovudine. Modest increases of IC50 and IC50 for stavudine had an important impact on the virological response during the trial and plead for a new definition of the threshold value for stavudine phenotypic index.

Adult↗
PubMed1996

Novel human herpesviruses (human herpesviruses 6, 7 and 8).

The number of members in the family Herpesviridae has increased in the last 10 years due to the description of three novel human herpesviruses: human herpesvirus 6 (HHV-6) in 1986, human herpesvirus 7 (HHV-7) in 1990, and human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), in 1994. HHV-6 and HHV-7 were first isolated from blood lymphocyte cultures, while HHV-8 was identified following a specific molecular biology approach in the search for the etiologic agent of Kaposi's sarcoma. The three viruses are lymphotropic, T-cells being the targets of HHV-6 and HHV-7, and B-cells being probably those of HHV-8. The ability to be propagated in cell cultures in vitro differs according to the virus concerned: this can be done readily with HHV-6, with more difficulties in the case of HHV-7, and has not yet been achieved in the case of HHV-8. Human infection with HHV-6 and HHV-7 is ubiquitous, widespread and acquired early in life. HHV-8 epidemiology is still unclear, and there are two hypotheses: a restricted dissemination in the general population like herpes simplex virus type 2, or a widespread infection like all other human herpesviruses. The polymerase chain reaction is the common method for the detection of infection using specific primers and probes for HHV-6, HHV-7 and HHV-8 respectively. Serologic assays are only available for HHV-6 and HHV-7, with limitations being due, in particular, to possible cross-reactions with cytomegalovirus. HHV-6 is the causative agent of exanthem subitum (sixth disease). Its role as an opportunistic agent and immune dysfunction inducer is debated and currently under investigation. The pathogenic role of HHV-7 seems to be modest, with one case of exanthem subitum reported so far. HHV-8 is strongly associated with three diseases: Kaposi's sarcoma, Castleman's disease and body-cavity-based lymphomas. The therapy against these novel viruses has to be considered in the future.

Journal Article↗
PubMedDate not supplied

Predictors of virologic response to ritonavir-boosted protease inhibitors.

The primary mechanism of resistance to protease inhibitors involves the stepwise accumulation of mutations that alter and block the substrate binding site of HIV protease. The large degree of cross-resistance among the different protease inhibitors is a source of considerable concern for the management of patients after treatment failure. Although the output of HIV-resistance tests has been based on therapeutically arbitrary criteria, there is now an ongoing move towards correlating test interpretation with virologic outcomes on treatment. This approach is undeniably superior, in principle, for tests intended to guide drug choices. However, the predictive accuracy of a given stratagem that links genotype or phenotype to drug response is strongly influenced by the study design, data capture and the analytical methodology used to derive it. There is no definitively superior methodology for generating a genotype-response association for use in interpreting a resistance test, and the various approaches used to date all have their strengths and weaknesses. Combining the information of therapeutic drug monitoring and resistance tests is likely to be of greatest clinical utility in antiretroviral-experienced patients harboring HIV strains with reduced susceptibility. The combination of pharmacologic and virologic parameters as a predictor of the virologic response has been merged into the parameter known as "inhibitory quotient". This article discusses the potential interest of the use of inhibitory quotients as an approach for enhancing the potency and durability of boosted protease inhibitors against protease inhibitor-resistant viruses.

Anti-HIV Agents↗