Laurent Roudiere

Human Herpesvirus 8–Positive Castleman Disease in Human Immunodeficiency Virus–Infected Patients: The Impact of Highly Active Antiretroviral Therapy

We report the case histories of 7 human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) who had a diagnosis of Castleman disease. All 6 patients who were treated responded to chemotherapy; immune reconstitution was observed in 5 patients, but it did not prevent relapse of Castleman disease. However, the mean duration of survival observed in this series (48 months) was most probably due to immune reconstitution resulting from receipt of HAART, which reduced the mortality associated with HIV disease.

Risk factors for osteonecrosis in HIV-infected patients: impact of treatment with combination antiretroviral therapy.

Background:Osteonecrosis was increasingly associated with HIV infection in the 1990s. It is unclear whether its risk increases with the duration of HIV infection, the duration of combination antiretroviral therapy (cART) or both. Objective:To analyse factors associated with the rate of symptomatic osteonecrosis, particularly the relative impacts of the duration of HIV infection and the duration of cART, using the French Hospital Database on HIV, which comprises a large number of subjects with substantial follow-up. Methods:Poisson regression model was used to identify factors associated with the rate of osteonecrosis among patients enrolled in 1996–2002. Results:The study involved 56 393 subjects with a total follow-up of 229 031 person-years. Symptomatic osteonecrosis was diagnosed in 104 subjects with an incidence rate of 4.5/10 000 person-years. Multivariate analysis identified three factors associated with the rate of osteonecrosis: prior AIDS-defining illnesses [adjusted relative rate (RR), 3.1; 95% confidence interval (CI), 2.0–4.9], the CD4 cell nadir [RR, 1.6 (95% CI, 0.9–2.9) for CD4 cell count 50–199 cells/μl; RR, 1.8 (95% CI, 1.0–3.3) for CD4 cell count < 50 cells/μl; both relative to CD4 cell count ≥ 200 cells/μl] and exposure to cART. Compared with unexposed patients, the RR of osteonecrosis ranged from 2.6 (95% CI, 1.2–5.9) in patients treated with cART for < 12 months to 5.1 (95% CI, 2.1–12.6) in patients treated for ≥ 60 months. Conclusions:Osteonecrosis appears to be a complication of both HIV infection and cART.

Assessment of Cetirizine, an Antihistamine, to Prevent Cutaneous Reactions to Nevirapine Therapy: Results of the Viramune-Zyrtec Double-Blind, Placebo-Controlled Trial

We conducted a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of cetirizine to assess the ability of antihistamines to prevent nevirapine-associated rash in patients infected with human immunodeficiency virus type 1. Patients initiating treatment with nevirapine were randomized to receive either cetirizine, 10 mg q.d. (104 patients), or placebo (96 patients) during the first 6 weeks of therapy. Rash occurred in 22 (11%) of 200 patients; 10 (9.6%) were in the cetirizine group and 12 (12.5%) were in the placebo group (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.31-1.81; P=.5). Five of 22 rashes were cases of hypersensitivity syndrome. The rate of nevirapine discontinuation due to rash was similar in the 2 groups (7.7% and 6.25% in the cetirizine and placebo groups, respectively; P=.4). Multivariate analysis showed no treatment-group effect but indicated that age >40 years (OR, 3.83; 95% CI, 1.4-10.46; P=.008) was associated with an increased risk of rash. Cetirizine has no preventive effect on nevirapine-associated rash.

Pattern and impact of emerging resistance mutations in treatment experienced patients failing darunavir-containing regimen

Background:Ritonavir-boosted darunavir (DRV/r) has proven potent efficacy when used in heavily pretreated patients, harboring protease inhibitor-associated resistance mutations. Limited data are available on resistance pattern emerging in patients failing DRV/r and on subsequent remaining protease inhibitor options. Methods:Analysis of baseline and failure resistance genotypes were performed in patients experiencing virologic failure (>200 copies/ml) after at least 3 months on a DRV/r (600/100 mg twice daily)-containing regimen. Results:Twenty-five highly protease inhibitor-experienced patients were included. Baseline median human immunodeficiency virus type 1 RNA was 5 log10 copies/ml and number of total-protease inhibitor, major-protease inhibitor and DRV-associated-resistance mutations was 13, 4 and 3, respectively. Median viral replication duration on DRV/r selective pressure was 34 weeks. Emergence of DRV-associated-resistance mutations was observed in 72% (18/25) of patients, at codons L89I/M/V (32%), V32I (28%), V11I (20%), I47V/A (20%), I54L/M (20%), L33F/I (16%) and I50V (16%). A high risk of DRV resistance was observed in patients with 2 and 3 baseline DRV-associated-resistance mutations and in patients with more than 24 weeks of ongoing viral replication. According to 2007 ANRS algorithm, isolates classified as susceptible to ritonavir-boosted tipranavir decreased from baseline to failure from 76 to 60% and susceptible to DRV/r from 32 to 12%. Conclusion:Emerging mutations observed after DRV/r failure were those already described to impact the DRV efficacy. Our study provided recommendations to firstly, reconsider lowering the cutoff number of DRV mutations to two; secondly, avoid keeping patients on a DRV-failing regimen for more than 24 weeks and thirdly, to examine the efficacy of using tipranavir after DRV failure.

Prevalence of Mixed Cryoglobulins in Relation to CD4 Cell Count among Patients Coinfected with HIV and Hepatitis C Virus

Cryoglobulinemia was studied in human immunodeficiency virus-positive, hepatitis C virus (HCV)-positive patients in relation to their CD4 cell count. Cryoglobulinemia was found in 18 (31.6%) of 57 patients: 17 (44.7%) of 38 patients with a CD4 cell count of >or=200 cells/ micro L versus 1 (5.3%) of 19 patients with a CD4 cell count of <200 cells/ micro L (P=.0064). Cell-mediated immunity could, therefore, contribute to the production of HCV-associated cryoglobulins.

Recurrent Mycobacterium avium infection after seven years of latency in a HIV-infected patient receiving efficient antiretroviral therapy

We report the first case of Mycobacterium avium reactivation, after prolonged latency, in a HIV-infected patient receiving highly active antiretroviral therapy with undetectable viral replication and normal CD4 cell count. The patient presented with a painful swollen shoulder seven years after initial M. avium bacteriaemia. Articular puncture grew M. avium. The isolates of the first and second infection were identical using repetitive-sequence-based Polymerase Chain Reaction analyses.