Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial.

BACKGROUND: TMC125 (etravirine) is a non-nucleoside reverse-transcriptase inhibitor (NNRTI) with activity against NNRTI-resistant HIV-1 in phase IIb trials. The aim of DUET-2 is to examine the efficacy, tolerability, and safety of TMC125 in treatment-experienced patients. METHODS: In this continuing randomised, double-blind, placebo-controlled, phase III trial, HIV-1-infected patients on failing antiretroviral therapy with evidence of resistance to currently available NNRTIs and at least three primary protease inhibitor mutations were eligible for enrolment if on stable (8 weeks unchanged) antiretroviral therapy with plasma HIV-1 RNA greater than 5000 copies per mL. Patients were randomly assigned to receive either TMC125 (200 mg) or placebo, each given twice daily with darunavir-ritonavir, investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors, and optional enfuvirtide. The primary endpoint was the proportion of patients with confirmed viral load below 50 copies per mL at week 24 (FDA time-to-loss of virological response algorithm). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00255099. FINDINGS: 591 patients were randomised and treated (295 patients in the TMC125 group and 296 in the placebo group). By week 24, 51 (17%) patients in the TMC125 group and 73 (25%) in the placebo group had discontinued, mainly because of virological failure. 183 (62%) patients in the TMC125 group and 129 (44%) in the placebo group achieved confirmed viral load below 50 copies per mL at week 24 (difference 18%, 95% CI 11-26; p=0.0003). The type and frequency of adverse events were much the same in the two groups. INTERPRETATION: In treatment-experienced patients, treatment with TMC125 led to better virological suppression at week 24 than did placebo. The safety and tolerability profile of TMC125 was generally comparable with placebo.

HIV and cancer in Germany.

BACKGROUND: Cancer is now the leading cause of death in persons with HIV. In this study, we gathered current epidemiological data on Aids-defining (AD) and non-Aids-defining (NAD) malignancies among HIV-positive patients in Germany. METHODS: From 2000 to 2007, all 35 specialized HIV outpatient clinics and 189 HIV ambulatory care centers in Germany were contacted and asked to fill out a structured questionnaire on the incidence of malignancies in HIV-positive patients during multiple periods of observation. RESULTS: 552 evaluable data sets were reported. 253 (45.8%) of the reported malignancies were AD. Among the 299 cases (54.2%) of NAD malignancies, there were 214 solid tumors, including 71 anal carcinomas (23.7% of all NAD malignancies), and 85 hematopoietic malignancies, including 29 cases of Hodgkin`s lymphoma (9.7% of all NAD malignancies). The high percentage of NAD malignancy remained constant throughout the entire period of the study. Only a single case of primary cerebral lymphoma was reported after 2001. The number of patients with Hodgkin`s lymphoma rose steadily from 2000 to 2007. CONCLUSION: The spectrum of HIV-associated malignancies has changed since the early days of the HIV epidemic. In Germany, NAD malignancies have become more common than AD malignancies. In particular, anal carcinoma and Hodgkin's lymphoma are much more common among persons with HIV than in the general population. Persons with HIV need more intensive preventive care for cancer than non-infected persons do.

Considerable under-treatment of chronic HCV infection in HIV patients despite acceptable sustained virological response rates in a real-life setting.

BACKGROUND: According to guidelines, treatment of HCV infection should be considered a priority in HIV-HCV-coinfected patients. METHODS: This multicentre study includes HIV-HCV-coinfected patients diagnosed since 2001 in 14 participating centres in Austria and Germany. Demographic and virological data were recorded. Factors associated with non-initiation of HCV treatment were identified. RESULTS: Among 9,524 HIV patients screened, 1,033 HIV-HCV-coinfected patients were identified (male/female: 760/273; age: 43±9 years; weight: 71±12 kg; CD4(+) T-cell nadir: 255±189 cells/µl; HCV RNA: 3.79×10(6) IU/ml; HIV RNA: 65×10(3) copies/ml). HCV genotype (GT) was predominantly GT-1 (62%). A total of 416 (40%) patients received HCV treatment, whereas 617 (60%) patients remained untreated. The main reasons for deferral of HCV treatment were patient refusal (20%), adherence/compliance (18%), active intravenous drug abuse (14%) and advanced immunodeficiency/AIDS (9%). Patients starting HCV treatment had significantly lower fibrosis stage (F2 versus F4; P<0.0001), higher CD4(+) T-cell count (530 cells/µl versus 430 cells/µl; P<0.0001), lower HIV RNA levels (18×10(3) copies/ml versus 47×10(3) copies/ml; P=0.0008) and higher alanine aminotransferase (ALT; 113 IU/ml versus 75 IU/ml; P<0.0001) than patients without initiation of HCV treatment. Age, HCV GTs, HCV RNA, haemoglobin levels, platelet count and white blood cell count were similar in patients receiving and in patients not receiving antiviral therapy. Multivariate analysis identified ALT levels (P<0.0001) and CD4(+) T-cell count (P<0.0001) as independent predictors of treatment uptake. The overall sustained virological response (SVR) was 41% (155/416), with GT-1 and non-GT1 patients achieving SVR rates of 29% and 48%, respectively. CONCLUSIONS: This large cohort study provides evidence for considerable under-treatment of chronic HCV infection in HIV patients. Despite acceptable treatment success in this real-life setting, HCV remains untreated in the majority of patients and often owing to potentially modifiable reasons.