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N Clumeck

Publications and source records attributed to N Clumeck.

At least 55 records · Page 3Linked to original sources
PubMed1997

Survival of European patients with Kaposi's sarcoma as AIDS-defining condition during the first decade of AIDS. AIDS in Europe Study Group.

OBJECTIVES: To determine whether the survival of patients with Kaposi's sarcoma as first manifestation of AIDS has changed between 1979 and 1989; and to define whether prognosis factors could be identified. PATIENTS AND METHODS: This is a multicentric retrospective cohort study from 52 centers in 17 European countries involving adults AIDS patients diagnosed between 1979 and 1989. Variables such as age, sex, geographical regions, transmission groups, date of Kaposi's sarcoma diagnosis, zidovudine use, CD4+ cell count and concomitant opportunistic infections or AIDS-related malignancies were evaluated by using uni- and multivariable proportional hazard models. Log-rank tests were used to determine which variables were associated with survival. RESULTS: From the 6,546 AIDS patients recruited in the database of the AIDS in Europe Study Group, 1,394 were diagnosed with Kaposi's sarcoma at the time of AIDS diagnosis, from 1979 and 1989. A total of 1,047 Kaposi's sarcoma patients died during the follow-up period. By Kaplan-Meier analyses, the median and mean survival for these Kaposi's sarcoma patients were 17 and 25 months, respectively, with no change over time. However, age, sex (female), geographic region, low CD4+ cell count (< 150 x 10(6)/l) and some opportunistic infections and non-Hodgkin's lymphoma were associated with a poorer prognosis. Zidovudine use, year of diagnosis and risk factor for HIV-1 infection brought no additional information as predictor of mortality. CONCLUSIONS: This study suggests that the survival of patients with Kaposi's sarcoma as first manifestation of AIDS has remained poor during the last decade in contrast with the overall AIDS survival which had significantly improved from a median of 13-18 months during the same period of observation. There is a need for further prospective information to explain the worse prognosis in women and the geographical variations.

AIDS-Related Opportunistic Infections↗
PubMed1997

Cytomegalovirus retinitis in patients with AIDS in Europe. AIDS in Europe Study Group.

The incidence of cytomegalovirus (CMV) retinitis and risk factors associated with the condition were studied in patients with the acquired immune deficiency syndrome (AIDS) in a multicenter retrospective cohort study of 6458 patients from 52 centers in 17 countries in Europe. Cytomegalovirus retinitis was diagnosed in 154 patients (2.4%) at the time of AIDS diagnosis, the probability of this diagnosis being significantly higher for those with CD4+ cell counts of < 100/mm3 (3.4%) than with counts of 100-200/mm3 (1.3%) or > 200/mm3 (0.8%). The rate of developing CMV retinitis after AIDS diagnosis was 9.4 per 100 patient years of follow-up. Multivariate analysis showed that risk behavior was significantly associated with the risk of developing CMV retinitis: lower for intravenous drug users [relative risk (RR) 0.47] and those engaged in "other risk behavior" (RR 0.58) than for homosexual men. The risk of developing CMV retinitis after AIDS diagnosis was significantly associated with CD4+ cell count at the time of AIDS diagnosis: for counts < 100/mm3 (RR 2.90) and from 100 to 200/mm3 (RR 2.13), there was a higher risk than for counts > 200/mm3. Patients with Pneumocystis carinii pneumonia, toxoplasmosis, or extraocular CMV infection at time of AIDS diagnosis exhibited an increased risk of developing CMV retinitis. Patients treated with zidovudine exhibited an increased rate of CMV retinitis: RR was 1.75 during and 2.87 after the second year of treatment as compared to those who had not received zidovudine. Median survival after CMV retinitis at time of AIDS diagnosis was eight months.

AIDS-Related Opportunistic Infections↗
PubMed1997

A controlled trial of dapsone versus pyrimethamine-sulfadoxine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with AIDS.

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic human immunodeficiency virus (HIV)-related infection, occurring in 85% of HIV infected patients without prophylaxis. Preventive treatment is required when CD4 cell count falls below 200 cells per cubic millimeter. Cotrimoxazole has been shown to be highly effective but alternative drug regimens are often necessary because of the frequent drug hypersensitivity exhibited by HIV infected patients. The aim of this prospective, open, randomized, one-site study, involving HIV-infected patients with a CD4 cell count below 200/mm3, or a percentage under 20%, randomly assigned to receive either dapsone 50 mg daily or Fansidar one tablet weekly, was to compare the efficacy and safety of these drugs in the primary prophylaxis of PCP. Both dapsone and Fansidar appear to be safe and effective alternative agents for the prevention of PCP. Their role in Toxoplasma gondii prophylaxis requires further evaluation.

AIDS-Related Opportunistic Infections↗
PubMed1997

A dose comparison study of a new triazole antifungal (D0870) in HIV-positive patients with oral candidiasis.

OBJECTIVE: This multicentre study evaluated the clinical efficacy and tolerability of D0870 in treating oropharyngeal candidiasis in HIV-positive patients who had no history of clinical resistance to fluconazole. METHODS: Three regimens were evaluated in two phases. In phase I a 50 mg initial dose was followed by 10 mg for 4 days (Group 1). In phase II a 100 mg initial dose was followed by 25 mg for 4 days (Group 2), or 10 mg for 5 days (Group 3). RESULTS: Clinical cure was obtained in 27 patients of a total of 35 (77%) and six other patients improved (17%). Two patients at the lowest dose failed and both had very low plasma concentration of D0870. No association was found between clinical outcome; minimum inhibitory concentration of D0870 pre-therapy for Candida albicans, maximum recorded plasma D0870 concentration, cfu of culture or CD4 cell count at entry. Overall, 37% of the patients experienced relapse during the 2 weeks post therapy. Tolerance was excellent. Mild adverse events possibly related to the study drug were recorded in five patients. CONCLUSION: D0870 demonstrates excellent efficacy at low doses in the treatment of HIV-related OPC and exhibits a favourable safety profile.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Manifestations, diagnosis and treatment of non-tuberculous mycobacterial infections in patients with HIV infection].

The most frequent bacterial infections in patients infected with HIV and suffering from AIDS are non-tuberculous mycobacterial infections. Their incidence is increasing all the more as the survival of profoundly immunocompromised patients is prolonged. There are unknown factors as regards the precise origin of these infections and as to the exact epidemiology of atypical mycobacteria. It is known that 95 per cent of atypical mycobacterial infections are due to M. avium. If the pathophysiology of the infection (involving the intervention of cytokines and also factors in relation to the virulence of the germ) is imperfectly understood, the atypical mycobacteria are an independent cause of mortality in advanced stages of the disease. The clinical picture is that of a low grade fever with weight loss and a deterioration in the general physical state. There are subtle physical signs such as a fall in the functional capacity accompanied by weight loss and an unexplained anaemia these should also suggest a diagnosis. More rarely the infection will be localised. The clinical diagnosis will be confirmed by bacteriology which has been aided by recent progress in molecular biology. With the arrival of the newer macrolides it has been shown that treatment prolongs survival in a significant manner. Current recommendations consist of a treatment with a combined regime including a minimum of Clarithyromycin and Ethambutol. The place for polychemotherapy remains to be determined in particular the role for Rifabutine and Amikacine. Immunomodulation by interferon-gamma or GCSF are also under review. The duration of treatment and the necessity of long term suppressive treatment is the object of randomised studies. Prophylaxis is currently recommended for patients with CD4 < 75/mm3. The role of Rifabutine and the new macrolides remains to be determined. Finally, in a large European study the objective is to compare prophylaxis to systematic bacteriological surveillance both as regards efficacy, tolerance, and in terms of pharmaco-economics.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Impact of anti-retroviral treatment with protease inhibitors on the evolution of cytomegalovirus retinitis in the patient carrying acquired immunodeficiency syndrome].

Up to now cytomegalovirus retinitis (CMVR) recurrence in AIDS patients was considered to be very high, even on maintenance therapy. Protease inhibitors (PI) are antiretroviral molecules which, with more efficacity than reverse transcriptase inhibitors, decrease viral charge and increase CD4's count aswell as survival. We analysed the impact of PI on CMVR evolution in a retrospective review of 18 patients with CMVR on maintenance therapy and PI treatment. In a first group, 13 patients started PI some time after CMVR diagnosis (median CD4 = 9/mm3). A second group of 5 patients developed CMVR (median CD4 = 63/mm3) after initiation of PI. In the first group, incidence of CMVR recurrences/1000 patients days was 6,45 (2323 patients days of follow-up (PDFU) before starting PI and 3,44 (4066 PDFU) after starting PI. In this group, during the follow-up's period of CD4's count inferior to 75/mm3, incidence of CMVR is 6,84/1000 patients days and becomes 0,86/1000 patients days during the follow-up's period of CD4's count superior to 75/mm3. In the second group, incidence of CMVR was 0/1000 patients days (1972 PDFU). In summary, incidence of CMVR decreases with PI's treatment. Interruption of CMVR maintenance therapy could be considered in patients with CD4's count higher than 75/mm3.

Adult↗
PubMed1996

Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group.

OBJECTIVE: To compare safety and efficacy of lamivudine-zidovudine combination therapy with zidovudine monotherapy in treating human immunodeficiency virus type 1 (HIV-1)-infected, antiretroviral therapy-naive patients. DESIGN: Double-blind, randomized, multicenter, comparative trial of 129 patients throughout 24 weeks followed by 24 weeks of open-label lamivudine in combination with zidovudine. SETTING: Outpatients from 14 hospitals in Belgium, France, Germany, Spain, and the United Kingdom were enrolled within 6 months. PATIENTS: HIV-1-positive, antiretroviral-naive ( < or = 4 weeks prior zidovudine use) patients aged atleast 18 years with CD4+ cell counts between 0.10 x 10(9)/L and 0.40 x 10(9)/L (100-400/microL). INTERVENTION: Patients received either 300 mg of lamivudine every 12 hours in combination with 200 mg of zidovudine every 8 hours for 24 weeks or zidovudine monotherapy for 24 weeks. All patients were then allowed to receive zidovudine in combination with open-label lamivudine (300 mg every 12 hours). MAIN OUTCOME MEASURES: Efficacy was assessed by changes in CD4+ cell counts beta 2-microglobulin, neopterin, HIV-1 immune-complex dissociated (ICD) p24 antigenemia, and HIV-1 viral load. Safety was assessed by incidence of adverse clinical events and defined laboratory-measured toxic effects. RESULTS: Combination therapy showed superior treatment effects compared with monotherapy during the first 24 weeks as documented by changes in CD4+ cell counts (increase of 0.08 x 10(9)/L vs 0.02 x 10(9)/L; P < .001), ICDp24 (-88% vs -49%; P = .04), cellular viremia (-1.27 vs -0.20 log10 median tissue-culture infected dose [TCID50] per 10(6) peripheral blood mononuclear cells; P = .001), and viral load measured by HIV-1 RNA polymerase chain reaction using a Roche method (-1.33 vs -0.57 log10 copies/mL; P = .001) or an immune-capture method (-0.6 vs -0.14log10 copies/mL; P = .008). Observed changes were sustained to 48 weeks for patients continuing to receive combination therapy. Patients switching to receive combination therapy at week 24 showed improvements in CD4+ cell count and viral load to week 48. Mutation results suggested that mutations associated with zidovudine resistance may have developed more slowly over the first 24 weeks in patients receiving combination therapy. In contrast, mutations associated with lamivudine resistance appeared to develop rapidly, despite sustained antiviral treatment effect. However, the number of patients evaluated for genotypic changes was small, and confirmation of these results is needed in larger studies. No statistically significant differences in incidence or severity of clinically manifested or laboratory-measured toxic effects were noted between treatment groups. CONCLUSIONS: The combination of lamivudine and zidovudine results in a potent and sustained antiviral effect in antiretroviral-naive patients that is superior to that observed with zidovudine monotherapy.

Adult↗
PubMed1996

Factors associated with the CD4+ lymphocyte count at diagnosis of acquired immunodeficiency syndrome. The AIDS IN EUROPE Study Group.

To assess which factors are associated with the CD4+ lymphocyte count at the time of AIDS diagnosis we studied 3046 patients in the AIDS IN EUROPE study who were diagnosed with AIDS in 1 of 17 European countries between 1979 and 1989 and for whom the CD4 count at AIDS diagnosis was known. Data were extracted retrospectively from patient case notes, using a standardized form. There was a wide range of average CD4+ lymphocyte counts at AID diagnosis, according to which diseases were present at diagnosis. The highest geometric mean CD4+ lymphocyte counts at AIDS diagnosis were associated with the diagnosis of extrapulmonary tuberculosis, Kaposi's sarcoma, and non-Hodgkin's lymphoma while the lowest counts were found when histoplasmosis and cytomegalovirus (CMV) retinitis were present. There were no appreciable differences between CD4+ lymphocyte counts at AIDS in patients according to the three major transmission route categories (sex, age, or region of diagnosis) but there was a marked trend (p < 0.005) toward lower CD4+ lymphocyte counts at AIDS diagnosis in more recent years. These associations remained largely unchanged after adjustment for other factors.

AIDS-Related Opportunistic Infections↗
PubMed1996

Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS.

This European multicenter study compares the efficacy and tolerance of the combination of pyrimethamine-clindamycin (Pyr-Cm) with the standard therapy pyrimethamine-sulfadiazine (Pyr-Sdz) for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. Two hundred ninety-nine human immunodeficiency virus-infected patients with TE were randomly assigned to receive 50 mg of pyrimethamine daily combined with either 2,400 mg of clindamycin or 4 g of sulfadiazine for 6 weeks followed by maintenance therapy with 25 mg of pyrimethamine daily with either 1,200 mg of clindamycin or 2 g of sulfadiazine. An intent-to-treat analysis showed that Pyr-Cm was less effective than Pyr-Sdz; the overall risk of progression of TE was 1.84 times higher for patients receiving Pyr-Cm therapy. There was no statistically significant difference in efficacy during acute therapy, although the rate of crossover motivated by a lack of response was higher among Pyr-Cm recipients. The difference in efficacy was evidenced during the maintenance phase of treatment; the relapse rate was twice as high among patients in the Pyr-Cm group (P = .02). The rate of side effects due to both regimens was similar, although the toxic effects of Pyr-Cm led to fewer discontinuations of therapy than did those of Pyr-Sdz (11% vs. 30%, respectively; P = .001). Pyr-Sdz appears to be the most effective treatment of TE. Pyr-Cm is a valuable alternative but is less effective for long-term prevention of relapses.

AIDS-Related Opportunistic Infections↗
PubMed1996

Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. G-CSF 92105 Study Group.

BACKGROUND: Patients with HIV infection frequently experience disease or treatment-related myelosuppression leading to neutropenia. Neutropenia often leads to dose-reduction or discontinuation of important myelosuppressive therapy. OBJECTIVE: To examine the efficacy and safety of filgrastim for reversing neutropenia and determine the effect of this on use of myelosuppressive medications. DESIGN: Open-label, non-comparative, multicentre study in 200 HIV-positive patients with neutropenia [absolute neutrophil count (ANC) < 1.0 x 10(9)/l]. Filgrastim was started at 1 microgram/kg/day subcutaneously for 28 days. This initial treatment phase was followed by a maintenance phase, using 300 micrograms on 1-7 days/week. In both phases the dose of filgrastim was adjusted to achieve an ANC of 2-5 x 10(9)/l. RESULTS: Filgrastim reversed neutropenia in 98% of patients (ANC > or = 2 x 10(9)/l), with a median time to reversal of 2 days (range 1-16) and a median dose of 1 microgram/kg/day (range 0.5-10). Most patients (96%) achieved reversal of neutropenia with a filgrastim dose of < or = 300 micrograms/day (< or = 1 vial/day). Normal ANCs were then maintained with a median of 1 microgram/kg/day (range 0.22-10.6) during the treatment phase and 3 x 300 micrograms vials/week (range 1-7) during the maintenance phase. Ganciclovir, zidovudine, co-trimoxazole and pyrimethamine were the drugs most frequently considered to be causing neutropenia, and 83% of patients received one or more of these in the study. Filgrastim allowed > 80% of patients to increase or maintain dose-levels of these four medications or add them to their therapy. The number of these four medications received per patient increased by > 20% during filgrastim therapy. Filgrastim was well tolerated. CD4, CD8 and total lymphocyte counts all increased slightly, and there was no difference in HIV-1 p24 antigen levels. CONCLUSION: Filgrastim rapidly reverses neutropenia and maintains normal ANC in patients with HIV infection. This allows greater use of myelosuppressive medications without the potentially life-threatening complications of neutropenia.

Adolescent↗
PubMed1996

Comparative evaluation of NASBA HIV-1 RNA QT, AMPLICOR-HIV monitor, and QUANTIPLEX HIV RNA assay, three methods for quantification of human immunodeficiency virus type 1 RNA in plasma.

Three commercial assays for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated. The assays differed in their sample volumes, the means of preparing samples, and methods of amplification and detection. Plasma samples were obtained from 36 HIV-1-infected patients representing all stages of HIV-1 infection and were analyzed as coded specimens. Measurement of HIV-1 RNA baseline levels revealed no significant difference in sensitivity between the three assays. The assays were also applied to the quantitation of HIV-1 RNA levels in the plasma of patients who were changing their antiretroviral therapy. The changes measured in HIV-1 RNA levels in plasma in response to therapy were comparable by the three assays. No close correlation was found between the amount of HIV-1 RNA and the CD4 T-cell count; HIV-1 RNA assays were more sensitive than p24 antigen assays as an indicator of plasma viremia. Overall, the study demonstrates that all three quantitative assays for HIV-1 RNA can be used to measure the HIV-1 RNA copy number representing the HIV-1 viremia status in patients with HIV-1 infection. Since this copy number is likely to be useful in monitoring the effectiveness of antiviral therapy, these quantitative assays for HIV-1 RNA are ready to be built into clinical trials.

Adult↗
PubMed1996

Epidemiology of AIDS-related Kaposi's sarcoma in Europe over 10 years. AIDS in Europe Study Group.

OBJECTIVES: To determine the incidence and risk factors associated with Kaposi's sarcoma (KS) occurrence as an AIDS-defining condition or after the diagnosis of AIDS. DESIGN: Multicentre retrospective cohort study of AIDS in Europe database from 52 clinical centres in 17 European countries. METHODS: Patients' charts (n = 6546) were reviewed and collected in the database of the AIDS in Europe Study Group from 1979 to 1989. At the time of AIDS diagnosis 1394 patients had KS, whereas an additional 525 others developed KS after AIDS diagnosis. Univariate analysis and development of multivariate models determined factors associated with KS occurrence. RESULTS: Frequency of KS as an AIDS-defining condition significantly declined over time (P < 0.0001). In our cohort of patients, homo-/bisexual men from central Europe with CD4 cell counts > 150 x 10(6)/l were statistically more likely to develop KS at the time of AIDS diagnosis (P < 0.0001). For patients with an AIDS diagnosis other than KS, the probability of developing KS during the follow-up was 10 and 24% after 12 and 36 months, respectively. Variables significantly associated with a further KS development were transmission group, central European residence, previous herpes simplex infection other than ulcers, and low CD4 cells (< 150 x 10(6)/l). Previous zidovudine therapy had no influence on KS appearance. For patients who developed KS subsequent to AIDS diagnosis, there was no significant decline of the incidence over the 10-year time period. CONCLUSIONS: This large cohort study clearly shows that demographic data such as sex, transmission group and region of Europe have a major influence on KS development. It also suggests that KS as an AIDS-defining disease occurs earlier in the course of the chronic HIV infection than other opportunistic diseases. Reasons for geographical variations and its declining frequency as an initial AIDS diagnosis remain undetermined.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Human immunodeficiency virus infection: physiopathological approach to specific therapeutic strategies].

Our understanding of the physiopathology of HIV infection has considerably improved: the determination of HIV viral load, the impact of new antiretroviral agents (the protease inhibitors) and the discovery of various patterns of immune response (type T-helperl - T-helper2; Th1/Th2) have contributed to a comprehensive view of HIV infection from the seroconversion to the latest stage of AIDS. This new understanding allows to set up new therapeutical goals such as the rapid reduction of viral load during seroconversion or the reconstitution of Th1 pattern during clinical latency. This global individualised therapeutical strategy is now feasible. HIV infection has become a chronic disease which is presently treatable.

CD4 Lymphocyte Count↗
PubMed1995

A controlled trial of zidovudine in primary human immunodeficiency virus infection.

BACKGROUND: It is possible that antiretroviral treatment given early during primary infection with the human immunodeficiency virus (HIV) may reduce acute symptoms, help preserve immune function, and improve the long-term prognosis. METHODS: To assess the effect of early antiviral treatment, we conducted a multicenter, double-blind, placebo-controlled trial in which 77 patients with primary HIV infection were randomly assigned to receive either zidovudine (250 mg twice daily; n = 39) or placebo (n = 38) for six months. RESULTS: The mean time from the onset of symptoms until enrollment in the study was 25.1 days. Among the 43 patients who were still symptomatic at the time of enrollment, there was no appreciable difference in the mean (+/- SE) duration of the retroviral syndrome between the zidovudine group (15.0 +/- 4.1 days) and the placebo group (15.8 +/- 3.6 days). During a mean follow-up period of 15 months, minor opportunistic infections developed in eight patients: oral candidiasis in four, herpes zoster in two, and oral hairy leukoplakia in two. Disease progression was significantly less frequent in the zidovudine group (one opportunistic infection) than in the placebo group (seven opportunistic infections; P = 0.009 by the log-rank test). After adjustment for the base-line CD4 cell count, the patients treated with zidovudine had an average gain of 8.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, -1.4 to 19.1) during the first six months of the study, whereas those receiving placebo had an average loss of 12.0 CD4 cells per cubic millimeter per month (95 percent confidence interval, 5.2 to 18.7), for a between-group difference of 20.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, 8.5 to 33.2; P = 0.001). CONCLUSIONS: Antiretroviral therapy administered during primary HIV infection may improve the subsequent clinical course and increase the CD4 cell count.

AIDS-Related Opportunistic Infections↗