PubMed Health⌕ Search

Biomedical subjects

J P Viard

Publications and source records attributed to J P Viard.

At least 19 recordsLinked to original sources
PubMed2004

Time to virological failure of 3 classes of antiretrovirals after initiation of highly active antiretroviral therapy: results from the EuroSIDA study group.

OBJECTIVE: The purpose of the present study was to determine the prevalence and incidence of virological triple drug-class failure (TCF) and to summarize the clinical outcome for patients who started receiving highly active antiretroviral therapy (HAART). METHODS: The present study is an observational longitudinal study of 3496 treatment-experienced (TE) and treatment-naive (TN) patients monitored from the time they started receiving HAART (baseline) until TCF occurred (as determined on the basis of viral loads), until AIDS was newly diagnosed, or until death. RESULTS: Four hundred forty-five patients (12.7%) had TCF; 370 (16.6%) of 2230 patients were TE, and 75 (5.9%) of 1266 patients were TN. At 6 years after starting HAART, 21.4% of TE and 11.2% of TN patients had TCF (P<.0001). The prevalence of TCF at or after 2002 was 15.5% in TE patients and 4.8% in TN patients. TN patients had a 32% annual increase in the incidence of TCF (95% confidence interval [CI], 14%-54%; P<.0001); at 5 years after starting HAART, the rate was comparable for TE and TN patients (3.3 and 3.4 cases/100 person-years of follow-up [PYFU], respectively). The incidence of new cases of AIDS or death was 2.7 cases/100 PYFU in patients who did not experience TCF and 5.0 cases/100 PYFU in patients who did experience TCF, an estimated 36% increase with each category of TCF (95% CI, 19%-56%; P<.0001). CONCLUSION: The prevalence of TCF was low after patients started receiving HAART, particularly among TN patients. Despite the influx of patients who had started receiving HAART more recently, the prevalence of TCF increased over calendar time. Patients with TCF had a higher incidence of newly diagnosed AIDS or death. Treatment of patients with TCF deserves further investigation.

Acquired Immunodeficiency Syndrome↗
PubMed2004

[Therapeutic strategies for HIV infection: tolerance to boost antiproteases].

As tolerance not only depends on protease inhibitors (PI) dosing but also on their trough concentrations, the enhanced exposure associated with PI boosting goes together with a reduced tolerance, especially at the biological level. Moreover, the toxicity associated with the low doses ritonavir used in boosting seems to compromise, at least partly, the favourable metabolic profile of certain PI. Eventually, boosted lopinavir tolerance is similar to that of other PI. Even if the advantage/risk ratio of lopinavir or other boosted PI globally seems favourable, the final choice belongs to the physician in charge of evaluating the individual risk of a lesser, especially metabolic tolerance, for his or her patient.

Drug Therapy, Combination↗
PubMed2002

[Castleman's disease in patients infected with HIV].

PURPOSE: Castleman's disease is a polyclonal lymphoplasmacytic and vascular proliferation prominant in lymphoid tissues. It is associated with lymph node enlargement, hepatosplenomegaly and fever. This manifestations could be secondary to hyperproduction of interleukin 6. The prognosis is poor. The opportunistic infections which are characteristic of severe HIV infection worsen the prognosis. Prolonged monochemotherapy with vinblastine or etoposide can control Castleman's disease. CURRENT KNOWLEDGE AND KEY POINTS: Recent advances in human herpesvirus 8 (HHV8) knowledge and its predominance in the forms which are linked to the HIV seropositivity have partly explained the clinical manifestations of Castleman's disease. Indeed, HHV8 produce an homologous interleukin 6, the vIL-6, responsible for lymphoplasmacytic proliferation. The presence of other homologues of human cytokines produced by HHV8 could contribute to lymphoplasmacytosis and to endothelial proliferation. FUTURE AND PROSPECTS: Taking into account this viral origin, alpha interferon could be an alternative in forms which are less progressive. However, antiviral therapy against HHV8 or HIV and the immunitary restoration do not have any influence on the evolution of Castleman's disease, contrary to opportunistic infections.

Castleman Disease↗
PubMed2002

Immunological and virological features of HIV-infected patients with increasing CD4 cell numbers despite virological failure during protease inhibitor-based therapy.

OBJECTIVES: To investigate the extent of functional T cell recovery and to characterize plasma virus and virus producing cells in patients with increasing CD4 cell counts despite virological failure during protease inhibitor (PI) based therapy. METHODS: The study group included 13 patients who were treated for at least 12 months with a PI based regimen and were selected on the basis of a sustained immunological response (increase of > 70 CD4 cells/microL) despite virological failure (< 1 log10 copies/mL decrease in HIV-1 RNA plasma levels). RESULTS: Compared to a historical series of 11 complete responders with less advanced disease, the proportion of memory CD4 T cells was significantly higher (67.8+/-17.8 vs. 52.8+/-11.0; P=0.045) and the proportion of naive CD4 T cells significantly lower (30.5+/-14.8 vs. 45.0+/-10.4, P=0.021) in patients who were immunological responders/virological nonresponders. In those patients, ongoing viral replication was associated with a strong activation of circulating CD8 T lymphocytes; interleukin-2 production remained decreased. CD4 T cell reactivity to cytomegalovirus proteins was observed in nine of 11 patients tested. In the study group, the proportion of infectious virus present in plasma as well as the levels of intracellular viral replication were similar to those measured in untreated patients. Virological failure in this group of patients probably resulted from pre-existing mutations in the reverse transcriptase gene. CONCLUSIONS: This study of patients with increasing CD4 cell numbers despite virological failure shows the persistence of immune activation and partial immune restoration with no evidence of specific viral dynamics in vivo.

Adult↗
PubMed2001

Immunological and virological effects of long term IL-2 therapy in HIV-1-infected patients.

We report the long-term outcome of 27 HIV-infected patients treated for over 3 years with IL-2 and binucleoside analogues. These patients experienced a sustained increase in CD4 cells and a decrease of proviral DNA with infrequent IL-2 cycles. In three cases, virus could not be isolated from activated peripheral cells. A high frequency of HIV-1-specific memory CD4 T cells was found in the patients studied. IL-2 maintains specific effector cells and reduces the pool of infected cells in patients, albeit treated only with binucleosides.

Anti-HIV Agents↗
PubMed2001

Lipodystrophic syndromes and hyperlipidemia in a cohort of HIV-1-infected patients receiving triple combination antiretroviral therapy with a protease inhibitor.

OBJECTIVES: To assess the frequency and features of lipodystrophic syndromes in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) with a protease inhibitor (PI), and examine whether clinical and biologic abnormalities are always associated in these conditions. METHODS: Retrospective-prospective single-center observational study of 175 patients. Comparisons for continuous variables by t-test and paired t-test, and Kaplan-Meier analysis of time to onset of lipodystrophy were performed. RESULTS: In all, 51 patients (29%) had morphologic changes, after a mean HAART duration of 20.0 +/- 6.1 months, and were categorized into pure lipoatrophy (n = 16), mixed syndrome (truncal fat accumulation and face or limb lipoatrophy) (n = 30) or pure truncal fat accumulation (n = 5). Because of the small number, the latter group was not analyzed statistically. No differences were found among patients with lipoatrophy, mixed syndrome, or no lipodystrophy, in terms of gender, CD4 count, and HIV RNA plasma load at time of HAART initiation, nor in response to treatment. Patients with a mixed syndrome were older. Patients with lipoatrophy had longer duration of HIV disease, pre-HAART exposure to nucleoside analog therapy, and HAART. Baseline and pre-HAART fasting triglyceride levels were higher in patients who developed lipoatrophy, whereas weight and fasting cholesterol were higher in patients who developed a mixed syndrome. After 12 and 24 months on HAART, triglycerides and cholesterol rose significantly in all patients, independently of lipodystrophy, whereas these parameters were not increased during nucleoside analog therapy. CONCLUSIONS: Nucleoside analog exposure appears as a risk factor for lipoatrophy. Age and nutritional status (reflected by baseline weight, triglycerides and cholesterol) may influence the evolution to lipoatrophy or a mixed syndrome. Hyperlipidemia is observed in the absence of lipodystrophy and depends on PI exposure.

Adult↗
PubMed2001

Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.

OBJECTIVE: To compare the clinical response among patients who initiate protease inhibitor therapies with different virological potency. DESIGN: We analysed patients who started indinavir, ritonavir or saquinavir hard gel capsule (hgc) as part of at least triple therapy during prospective follow-up within the EuroSIDA study. METHODS: Changes in plasma viral load (pVL) and CD4 cell count from baseline were compared between treatment groups. Time to new AIDS-defining events and death were compared in Kaplan--Meier models, and Cox models were established to further assess differences in clinical progression (new AIDS/death). Adjustment was made for differences in baseline parameters, in particular pVL, CD4 cell count, and region of Europe. RESULTS: A total of 2708 patients (median follow-up: 30 months) were included, of which 556 started ritonavir (21%), 1342 indinavir (50%), and 810 saquinavir hgc (30%). The three groups were fairly evenly balanced at baseline regarding CD4 count, previous diagnosis of AIDS and pVL, After 12 months, the median changes in CD4 cell count were 90, 96 and 74 x 10(6) cells/l, respectively;P < 0.001, the proportions of patients with pVL < 500 copies/ml were 47, 54 and 41%; P < 0.001, and the proportions with clinical progression were 11.9, 9.2 and 11.9%, respectively; P = 0.20 (log-rank test). In multivariate models the relative risk of clinical progression for indinavir compared with saquinavir hgc was: 0.77 (0.60--0.99); P = 0.043, and for ritonavir 0.83 (0.62--1.11); P = 0.20. CONCLUSIONS: Saquinavir hgc was associated with an inferior long-term clinical response relative to indinavir, which was consistent with the observed differences in virological and immunological responses.

Administration, Oral↗
PubMed2001

Influence of age on CD4 cell recovery in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy: evidence from the EuroSIDA study.

Influence of age on the CD4 cell response to highly active antiretroviral therapy (HAART) was examined in 1956 patients (median age, 37.2 years) in the EuroSIDA study. Median initial CD4 cell count was 192x106 cells/L, follow-up was 31 months, and time to maximum CD4 cell response was 20 months. Age groups were not different for baseline CD4 cell count, baseline human immunodeficiency virus RNA load, or treatment history. CD4 cell increase, stratified by age quartiles, differed during months 3-36 of HAART (P=.023). Maximum CD4 cell increase from start of HAART differed by age group (P=.0003), as did maximum CD4 cell count (P<10-4). Multivariate analysis confirmed the inverse relationship between age and maximum CD4 cell response (P=.023). Time to a CD4 increase of >200x106 cells/L was shorter for patients in the younger age groups (P=.0026), as confirmed by multivariate analysis (P<10-4). Younger age may favor CD4 cell restoration because of preserved thymic function.

Adult↗
PubMed2000

Possible role of catheters in Saccharomyces boulardii fungemia.

Four cases of Saccharomyces boulardii fungemia, a very rare side effect of Saccharomyces boulardii therapy, are reported. The clinical impact of Saccharomyces boulardii infection appeared to be moderate. However, even though organ involvement was never demonstrated, septic shock with no other etiology was observed in one of our patients. All patients had an indwelling vascular catheter. Contamination of the air, environmental surfaces, and hands following the opening of a packet suggests that catheter contamination may have been a source of infection. To prevent catheter contamination it is recommended that packets or capsules of Saccharomyces boulardii be opened with gloves, outside the patient's room.

Adult↗
PubMed2000

Sequential occurrence of thyroid autoantibodies and Graves' disease after immune restoration in severely immunocompromised human immunodeficiency virus-1-infected patients.

We analyzed the kinetics of CD4 cells, human immunodeficiency virus (HIV) viral load, and autoantibodies in acquired immune deficiency syndrome patients with Graves' disease (GD) after immune restoration on highly active antiretroviral therapy (HAART; retrospective study). Five patients (median age, 41 yr) were diagnosed with GD after 20 (range, 14-22) months on HAART on the basis of clinical and biological hyperthyroidism, diffuse hyperfixation of thyroid scan, and the presence of anti-TSH receptor (anti-TSHR) antibodies (Ab). GD was diagnosed several months after the plasma HIV ribonucleic acid load became undetectable, when the CD4+ cell count had risen from 14 (range, 0-62) to 340 (range, 163-460) x 10(6) cells/L. Antithyroid peroxidase (anti-TPO) and anti-TSHRAb appeared 14 (range, 9-18) and 14 (range, 11-20) months after starting HAART and 12 (range, 6-15) and 11 (range, 9-17) months after the increase in CD4+ cells. In 3 patients, TPOAb preceded TSHRAb by 3-10 months. No other autoantibodies were detected. Thyroid antibodies were absent in a group of 55 HIV-1-positive patients with comparable response to HAART and no symptoms of hyperthyroidism (cross-sectional study). Thyroid-specific autoimmunity can occur upon immune restoration with HAART. Our observations suggest a relationship between thymus-dependent immune reconstitution after immunosuppression and autoimmunity and may provide insight into the pathophysiology of GD.

Adult↗
PubMed2000

Interruption of prophylaxis for major opportunistic infections in HIV-infected patients receiving triple combination antiretroviral therapy.

UNLABELLED: Interruption of prophylaxis for major opportunistic infections in HIV-infected patients receiving triple combination antiretroviral therapy. OBJECTIVE: To determine whether HIV-infected patients receiving highly active antiretroviral therapy (HAART) and recovering a CD4 cell number above 200x10(6)/l may safely discontinue primary and secondary prophylaxes for major opportunistic infections. DESIGN: Retrospective study of a single-center, prospectively constituted cohort of 223 patients receiving HAART with a protease inhibitor, of whom 137 received at least one prophylaxis. METHODS: Exhaustive informations on prophylaxis use, clinical and laboratory data were used to produce descriptive statistics on infectious events, duration of HIV infection, time on HAART, time to prophylaxis interruption, length of follow-up and biological values at relevant time points. RESULTS: Fifty-one patients with a history of severe immunodepression (median CD4 nadir: 62x10(6)/l), including 16 patients with CDC stage C infection, discontinued at least one prophylaxis. Primary or secondary P. carinii pneumonia prophylaxis was discontinued in 43 patients: 1 first episode of PCP occurred after 2 months but no other episode was recorded after a median follow-up of 16 months. Toxoplasmosis primary or secondary prophylaxis, secondary cytomegalovirus prophylaxis and primary or secondary M. avium complex prophylaxes were discontinued in respectively 37, 5 and 5 patients, and no event was recorded after respective follow-ups of 16, 7 and 15 months. Nine secondary and 2 primary acyclovir prophylaxes were discontinued, and two events were observed after 1 and 19 months; no other event was noted after a follow-up of 22 months. CONCLUSION: Prophylaxis for opportunistic infections could be safely interrupted in most of these severely immunodeficient patients recovering a CD4 cell count above 200x10(6)/l on HAART. This confirms the efficiency of immune restoration and is beneficial to patients but, since 3 infectious events were recorded, caution should be taken before making a decision based on immunological and virological considerations.

AIDS-Related Opportunistic Infections↗
PubMed1999

A comparison of exposure groups in the EuroSIDA study: starting highly active antiretroviral therapy (HAART), response to HAART, and survival.

BACKGROUND: Concerns have been raised that intravenous drug users may be less likely to start highly active antiretroviral therapy (HAART) and that adherence to therapy may be poor among this group of patients. Given the decreased mortality and incidence of AIDS-defining illnesses among patients with HIV who start HAART, this may lead to a poorer prognosis among intravenous drug users. PURPOSE: To compare homosexual men, intravenous drug users, and heterosexuals in EuroSIDA, a prospective European cohort of 7331 patients with HIV in terms of starting a HAART treatment regimen, immunologic and virologic response to therapy, and survival. METHODS: 6645 patients were included in this analysis. Logistic regression and Cox proportional hazards models were used to investigate the factors associated with use of HAART regimens and survival following recruitment to the EuroSIDA study. RESULTS: In a multivariate logistic regression model, intravenous drug users were significantly less likely to be receiving HAART at recruitment to EuroSIDA (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.37-0.62; p<.0001) when compared with homosexual men. Similarly, during follow-up, intravenous drug users were at a 27% reduced risk of starting HAART, after adjustment for other factors related to starting HAART (relative hazard [RH], 0.73; 95% CI, 0.64-0.82; p<.0001). There were no differences between heterosexual and homosexual patients, and similar results were found within regions of Europe (South, Central and Northern). Among those patients who started HAART, there were no significant differences between exposure groups in CD4 lymphocyte count response to HAART or virologic response to HAART. After adjustment for factors related to survival, intravenous drug users were at a small, but nonsignificant increased risk of death compared with homosexuals (RH 1.16; 95% CI, 0.99-1.38; p = .074). CONCLUSIONS: Intravenous drug users were significantly less likely to start HAART, but among those who did, response to therapy was similar to that of other exposure groups. There were no differences in risk of death. If intravenous drug users continue to use HAART less commonly than other exposure groups, it may result in a poorer prognosis, a different spectrum of AIDS-defining illnesses, and differential long-term clinical needs.

Adult↗
PubMed1999

Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group.

BACKGROUND: Intermittent interleukin-2 therapy for HIV-1 by continuous intravenous infusion leads to sustained increase of CD4 T cells. This method of administration is, however, inconvenient and has limiting toxic effects. We did a randomised study to compare safety and efficacy of antiviral treatment alone or combined with various interleukin-2 regimens in HIV-1-infected patients. METHODS: 94 symptom-free patients, naïve to antiretroviral treatment, with CD4-T-cell counts of 250-550 cells/microL at baseline were randomly assigned zidovudine and didanosine alone (n=26) or combined with interleukin-2 administered intravenously (12 million IU/day, n=22) or subcutaneously (3 million IU/m2 twice daily, n=24) for 5 days, or were given polyethylene-glycol-modified (PEG) interleukin-2 (2 million IU/m2 intravenous bolus, n=22) administered every 2 months from week 2 to week 50 (seven cycles). Safety and immunological and virological results were monitored until week 56. FINDINGS: CD4-T-cell count increased to higher than baseline by a mean of 564 cells/microL (subcutaneous group), 676 cells/microL (intravenous group), 105 cells/microL (PEG group), and 55 cells/microL (antiretroviral-therapy group, p=0.0001). 68% and 77% of patients in the subcutaneous and intravenous groups, respectively, achieved an 80% increase of CD4 T cells (p<0.001). In these two groups, 50% of patients restored a CD4/CD8-T-cell ratio of more than 1. The groups did not differ significantly for changes in plasma HIV-1 RNA loads throughout the study. The duration of common side-effects of interleukin-2 was shorter in the subcutaneous group, which enabled outpatient treatment. Naïve and memory CD4 T cells, CD28 expression on CD4 and CD8 T cells, and restoration of in-vitro proliferative response to mitogens and recall antigens increased in the intravenous and subcutaneous groups. INTERPRETATION: Subcutaneous interleukin-2 is a convenient regimen that, as well as intravenous therapy, improves immunological function in HIV-1-infected patients receiving two nucleosides. Larger studies are needed to show whether immunological improvements translate into clinical benefit.

Adult↗
PubMed1999

The influence of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma.

To assess the clinical and biological benefit of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma (KS), 13 patients with AIDS-associated Kaposi's sarcoma (five pulmonary KS and eight cutaneous KS) were prospectively followed for a mean duration of 12 months. Six patients were treated with specific anti-KS chemotherapy before or simultaneously with the introduction of antiretroviral therapy. Clinical response was assessed according to the AIDS Clinical Trial Group (ACTG) criteria. CD4 cell counts, plasma HIV-1 RNA and human herpesvirus 8 (HHV-8) viraemia were measured at baseline and at different points. Among patients with pulmonary KS, we observed three complete responses (CR), one partial response (PR) and one progression. The median survival time after the diagnosis of pulmonary KS was 15 months with a median duration of the response after the discontinuation of specific chemotherapy for KS of 8 months. Among patients with cutaneous KS, we observed four CR, three PR and one stable response. A complete response was significantly associated with a reversal in HHV-8 viraemia (five of six vs. one of six; P = 0.02, Mann-Whitney test).

Acquired Immunodeficiency Syndrome↗