Immune reconstitution inflammatory syndrome (IRIS) due to Bacille Calmette Guerin (BCG) in an HIV-positive child.

We describe the development of a localized Mycobacterium bovis-BCG infection in association with insertion of HAART in an 18-month-old HIV-infected and BCG-vaccinated child.

Evaluation of safety and efficacy of rosiglitazone in the treatment of HIV-associated lipodystrophy syndrome.

BACKGROUND: HIV-associated lipodystrophy syndrome (LDS) as a long-term side effect of HAART is becoming increasingly important and negatively affects adherence to medication. Currently, an effective therapy is not available. There is some evidence that the drug class of thiazolidindiones might be effective in the treatment of LDS. PATIENTS AND METHODS: Prospective open-label study with 20 HIV-infected patients suffering from severe LDS. Patients received 4 mg rosiglitazone once daily for a 24-week study period. Efficacy was assessed by measurement of metabolic and anthropometric parameters, total body DXA scan, CT scan of the abdomen, photo documentation and self-assessment. RESULTS: Rosiglitazone treatment was well tolerated. DXA scans demonstrated a highly significant increase in adipose tissue of the limbs (2644 +/- 1334 g vs 3380 +/- 1614 g, p < or = 0.001) without any change in total fat mass. Abdominal CT-scans revealed a significant increase in subcutaneous adipose tissue (113.7 +/- 82.4 cm(2) vs 125.3 +/- 83.7 cm(2), p = 0.04). Abdominal circumference decreased significantly (94.7 +/- 8.7 cm vs 92.2 +/- 8.45 cm, p = 0.03) without any relevant change of body weight or BMI. We observed an increase in serum cholesterol (248 vs 281 mg/dl, p = 0.006) and serum triglycerides (301 vs 351 mg/dl, p = 0.1). Furthermore, no side effects of clinical relevance were observed. The insulin sensitivity index improved without reaching statistical significance. Thirteen patients (65%) reported general improvement of LDS symptoms. Evaluation of photo documentation by five HIV-experts revealed poor concordance and no relevant change of LDS. CONCLUSIONS: The results of this study suggest that rosiglitazone is safe in the treatment of HAART-associated lipodystrophy and has moderate clinical efficacy. We found a trend towards improved insulin sensitivity and as a possible limiting factor an unfavorable increase in serum cholesterol and triglycerides.

Impact of rosiglitazone treatment on the bioavailability of antiretroviral compounds in HIV-positive patients.

OBJECTIVES: The insulin-sensitizer rosiglitazone is under investigation for therapy of HIV-associated lipodystrophy syndrome (LDS). Little is known about pharmacological interactions with antiretroviral (ARV) drugs. METHODS: Therapeutic drug monitoring (TDM) of ARV drugs was performed in a prospective study before and at day 28 after start of treatment with 4 mg of rosiglitazone for combined LDS. Drug levels were measured in the morning fasting, and 0.5, 1, 2, 4, 6 and 8 h after standardized drug intake. Values were log-transformed for analysis. RESULTS: Twelve males and six females were assessed; mean age was 50.7 years and mean CD4 cell count was 496 cells/mm(3). All patients had a viral load below 50 copies/mL, and backbone ARV therapy consisted of two or three nucleoside reverse transcriptase inhibitors in all cases. After administration of rosiglitazone, no significant differences in Cmax, Cmin and AUC were found in cases treated with efavirenz (n = 10) and lopinavir (n = 4). Mean Cmax of nevirapine (n = 4) was reduced significantly [-0.44; 95% confidence interval (CI) -0.86 to -0.01]. Furthermore, there was a consistent trend to a reduction in the geometric mean ratio (GMR) of Cmax, Cmin and AUC (GMR of Cmax 0.95; 95% CI 0.9-1.0; GMR of Cmin 0.89; 95% CI 0.65-1.13; GMR of AUC 0.96; 95% CI 0.91-1.01). CONCLUSIONS: Treatment with 4 mg of rosiglitazone for HIV-associated LDS is likely to reduce the bioavailability of nevirapine. Thus, routine TDM is recommended for patients treated with rosiglitazone and nevirapine. A therapy consisting of efavirenz or lopinavir seems to be without negative impact. Further studies on the interaction of rosiglitazone with ARV drugs are necessary.

Atazanavir for treatment of HIV infection in clinical routine: efficacy, pharmacokinetics and safety.

INTRODUCTION: Atazanavir (ATV) is a novel protease inhibitor that has been recently introduced into therapy of HIV infection. Currently there is little data on ATV therapy from daily practice. METHODS: In this retrospective study, we report on ATV efficacy and safety in clinical routine. Drug monitoring was performed consisting of unscheduled single measurements and a 4-hour-profile. Trough concentration of >80 ng/ml and peak concentration of 2000-6000 ng/ml were regarded as sufficient. RESULTS: Between May 2003 and April 2004, ATV treatment was started in 42 patients, mean observation time was 32 weeks (6-53). Mean age was 45.6 years, 38% had prior AIDS, viral load was undetectable in 73%. Important side effects were minor or moderate diarrhea (27%) and fatigue (15%). ATV was discontinued in 10% due to side effects or malignant diseases. No significant influence on mean values of cholesterol, triglycerides, liver enzymes, CD4-cell-count, and HI-viral load was seen. Virologic failure occurred in 13% of patients, all of them were PI-experienced. Pharmacokinetic data are available for 32 patients, all patients had sufficient trough levels. 30% with unboosted ATV and 21% with boosted ATV had peak plasma concentrations below the level defined as sufficient. Mean trough levels, plasma profile and AUC did not differ significantly between groups with non-boosted versus boosted ATV regimes but showed a wide inter-patient variability. CONCLUSIONS: ATV treatment of HIV-infected patients with or without a RTV booster was safe and effective in clinical routine. Drug levels were sufficient in the majority of cases. The variability of pharmacokinetic results in our sample supports therapeutic drug monitoring in patients treated with ATV.

Treatment of acute hepatitis C infection in HIV-infected patients: a retrospective analysis of eleven cases.

Studies on hepatitis C virus (HCV) monoinfected patients suggest high sustained treatment response rates of up to 98% when interferon monotherapy is administered during the acute phase of HCV-infection. To clarify whether early treatment of acute hepatitis C is similarly efficient in human immunodeficiency virus (HIV) positive patients, we conducted a retrospective survey of HIV-positive patients with acute HCV infection. Eleven HIV-positive patients who had been treated with interferon or interferon/ribavirin were identified at eight HIV-specialty outpatient clinics. The patients had been treated over a median 25 weeks with standard interferon (two patients), pegylated interferon (four patients) and pegylated interferon in combination with ribavirin (five patients). A post-treatment response (negative serum HCV-RNA at the end of treatment) was seen in 10 of 11 patients and HCV-RNA remained undetectable 24 weeks after the end of treatment in all the 10 responders. Alanine aminotransferase (ALT) normalized in eight patients while two virological responders and one nonresponder showed persistent mild ALT elevations. In conclusion, early treatment of acute hepatitis C seems to achieve high sustained virological treatment response rates also in patients with HIV-infection.

Haemodynamic crisis and reversible multiorgan failure caused by HIV post-exposure prophylaxis after needle-stick injury in a health care worker.

We report the case of a 59-year-old nurse from our HIV ward who developed a severe haemodynamic crisis with concomitant acute multiorgan failure after initiation of a post-exposure prophylaxis (PEP) with zidovudine/lamivudine (CombivirTM) and lopinavir/ritonavir (KaletraTM) after a needle-stick injury with an HIV-contaminated needle. Although serious and life-threatening adverse effects of post-exposure prophylaxis have been documented in several cases, this is the first report of a severe acute cardiovascular incident following PEP initiation.

[SARS--the facts. Transmission, diagnosis and managing suspected cases]. / SARS--die Fakten. Ubertragungswege, Diagnostik und Umgang mit Verdachtsfällen.

Severe Acute Respiratory Syndrome (SARS) is a new infectious disease that, in the short period between 1 February and 24 April 2003, has been diagnosed in more than 4000 patients. Its origin was traced to Guandong, a province in southeast China. The culprit organism was identified as a new coronavirus. The clinical presentation is unspecific and includes fever, respiratory symptoms, lymphopenia and pulmonary infiltrates on X-ray. Essential steps to prevent further dissemination of the virus are rapid identification, and treatment in an isolation unit. Despite all the international efforts and the rapid progress in the investigation of SARS coordinated by the World Health Organization (WHO), the epidemic has not yet been brought under control.

Immunotherapy of B-cell lymphoma with CD3x19 bispecific antibodies: costimulation via CD28 prevents "veto" apoptosis of antibody-targeted cytotoxic T cells.

Bispecific antibodies (CD3x19) against the CD3epsilon-chain of the T-cell-receptor/CD3 complex and the CD19 antigen on B cells can target polyclonal, nontumor-specific T cells to B lymphoma cells. This induces T-cell activation, and generation of cytotoxic T cells (CTLs). These polyclonal CTLs, targeted by the CD3x19 bispecific antibodies, can lyse CD19(+) B-lymphoma cells. In a xenotransplant model in severe combined immunodeficiency deficient (SCID) mice, we and others observed that CD28 triggering is required for efficient elimination of B-lymphoma cells and cure from the tumor in addition to CD3x19 administration. We also showed that the activation and targeting of CTLs to the target cell by signal one alone, ie, the CD3x19 mab, induces T-cell death by apoptosis. In blocking experiments we showed that this "veto" apoptosis is mediated by the CD95/Fas ligand. Addition of anti-CD28 (signal 2) renders the T cells resistant for veto apoptosis both in vitro and in vivo. We therefore conclude that the role of costimulation in immunotherapy with bispecific antibodies or other T-cell-based immune strategies is not only to facilitate T-cell activation but also to prevent T-cell deletion by apoptosis.

Costimulatory signals through B7.1/CD28 prevent T cell apoptosis during target cell lysis.

Expression of B7 on tumor cells can circumvent T cell tolerance and lead to the generation of tumor cell-specific T cell immunity. The effect of B7 expression on the generation of protective antitumor immunity has been attributed primarily to 1) more efficient T cell activation and 2) better generation of tumor-specific killer T cells. We have investigated the role of costimulation through B7.1 and its receptor, the CD28 molecule, in the generation of allogeneic human CTLs against MCF-7 breast cancer cells. In this setting, we describe how activated CTLs undergo activation-induced cell death upon killing the target cell. Instead of proliferation and clonal expansion, the majority of the CTLs underwent apoptotic cell death. CTL apoptosis could be blocked by 50% when binding of the Fas ligand to its receptor, the CD95 (APO-1/Fas) molecule, was prevented. Fas ligand was detected in the activated T cells, but not in MCF-7 or a panel of other breast cancer cell lines. This excludes an active role for MCF-7 during CTL death and indicates that the CTL apoptosis is due to an autocrine production of the Fas ligand by CTLs. Costimulation of CTLs by retrovirally B7.1-transfected MCF-7 drastically reduced the sensitivity of the CTLs to apoptosis during target contact. Thus, in tumor cell vaccination, B7.1 might play a major role in preventing T cell death by altering T cell susceptibility for apoptosis.