Improved lipid profiles and maintenance of virologic control in heavily pretreated HIV-infected patients who switched from stavudine to tenofovir treatment.

A retrospective chart analysis of 66 human immunodeficiency virus type 1 (HIV-1)-infected patients whose treatment was switched from stavudine to tenofovir without any other treatment changes was conducted. The mean total cholesterol values decreased significantly within 3 months after the tenofovir substitution and remained significantly less than baseline values during 18 months of follow-up (mean decrease, 36 mg/dL; P = .002). Regimens containing tenofovir provided effective control of HIV-1 infection, with stable CD4+ cell counts and continued suppression of plasma HIV-1 level following the treatment switch from stavudine.

Successful therapy of hepatitis B with tenofovir in HIV-infected patients failing previous adefovir and lamivudine treatment.

Three HIV-infected patients with chronic hepatitis B (genotype A) were switched to adefovir therapy after unsuccessful lamivudine treatment. Surprisingly, adefovir therapy failed, although none of the virus isolates displayed mutations known to be associated with adefovir resistance (A181V, N236T). In two isolates we identified hepatitis B virus DNA polymerase mutation L217R, in one case we found multiple frameshifts in the same region. In all cases adefovir was replaced by tenofovir, resulting in a significant drop in the viral load.

Effects of interleukin-2 plus highly active antiretroviral therapy on HIV-1 replication and proviral DNA (COSMIC trial).

BACKGROUND: The effect of interleukin-2 (IL-2) in combination with antiretroviral therapy on HIV-1 replication and reservoirs was investigated. METHODS: In a prospective, open-label trial, 56 asymptomatic HIV-1-infected subjects (CD4 T cell count > 350 x 10(6) cells/l) were randomized to highly active antiretroviral therapy (HAART: stavudine, lamivudine, nelfinavir, saquinavir) with or without IL-2 (9 megaunits daily for 5 days in 6-weekly intervals for a total of eight cycles). Productive and latent infection were analysed in peripheral blood, and residual virus replication in the lymphoid tissue and in the cerebrospinal fluid. The influence of IL-2 on viral rebound after treatment discontinuation was studied. RESULTS: Virus replication was detected in 21 of 31 on-treatment lymph nodes despite undetectable plasma viraemia. Viral RNA was found in resting as well as in proliferating cells. RNA-negative patients tended towards more rapid proviral DNA elimination. Supplementary IL-2 led to a greater increase in CD4 T cell counts than HAART alone (P < 0.001), resulting in normalization in approximately 90% of IL-2-treated patients compared with approximately 50% HAART-only subjects. IL-2 had no beneficial effect on virus replication and on proviral DNA in peripheral blood. CONCLUSIONS: Viral persistence during HAART is partly a result of continued low-level replication, calling for more active regimens. IL-2 accelerates the normalization of CD4 T cell counts but does not impact on virus production or latency.

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.

Pegylated interferon alpha-2b plus ribavirin for the treatment of chronic hepatitis C in HIV-coinfected patients.

OBJECTIVES: HIV-coinfection accelerates the course of HCV-related liver disease. Since, highly active anti-retroviral therapy significantly improved survival of HIV-patients more coinfected patients develop end stage liver disease. Therefore, treatment options for chronic hepatitis C in HIV-coinfected patients need to be evaluated. METHODS: Efficacy and safety of pegylated interferon alpha-2b (peg IFN) plus ribavirin (RBV) was examined within this prospective, uncontrolled, multicentre trial. Patients received peg IFN (1.5 microg/kg) once weekly plus RBV 800 mg daily for 48 weeks for HCV genotypes (GT) 1/4 and 24 weeks for GT 2/3. RESULTS: One hundred and twenty-two patients were enrolled. Patients were predominantly male (68%) and former i.v. drug users (61%). Baseline characteristics (median) were as follows: age 39 years (range 23-58), CD4 count 494 cells/microl (range 150-1578/microl), HIV-RNA 2.3log copies/ml (range <1.7-5.4log copies/ml). 61% currently received anti-retroviral treatment. Fifty-six percent had HCV GT 1. EOT response was achieved by 52%. However, only 25% achieved sustained response (SR) due to a high relapse rate. SR rates were significantly higher among patients with GT 2/3 compared to those with GT 1/4 (44 vs. 18%). SR was observed in only one patient without early response (ER). Discontinuation rate was 30%, 21% discontinued due to adverse events. CONCLUSION: Peg IFN/RBV appears safe and effective in HIV/HCV-coinfected patients. GT 2/3 is associated with better SR. Lack of ER strongly predicts non-response. High relapse rates substantially reduce treatment success. In terms of toxicity neuro-psychiatric side effects frequently required treatment discontinuation.