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: 3.79x106 IU/ml; HIV RNA: 65x103 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&lt;0.0001), higher CD4+ T-cell count (530 cells/|il versus 430 cells/|il; P&lt;0.0001), lower HIV RNA levels (18x103 copies/ml versus 47x103 copies/ml; P=0.0008) and higher alanine aminotransferase (ALT; 113 IU/ml versus 75 IU/ml; P&lt;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&lt;0.0001) and CD4+ T-cell count ( P&lt;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 modifable reasons. </jats:sec

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence. </jats:p

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence