Safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B and/or C virus coinfection.

OBJECTIVE: The aim was to examine the long-term safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B virus (HBV) and/or hepatitis C virus (HCV) coinfection in three double-blind, randomized, controlled Phase III studies. METHODS: In STARTMRK, treatment-naïve patients received raltegravir 400 mg twice a day (bid) or efavirenz 600 mg at bedtime, both with tenofovir/emtricitabine. In BENCHMRK-1 and -2, highly treatment-experienced patients with multi-drug resistant virus and prior treatment failure received raltegravir 400 mg bid or placebo, both with optimized background therapy. Patients with chronic HBV and/or HCV coinfection were enrolled if baseline liver function tests were ≤5 times the upper limit of normal. HBV infection was defined as HBV surface antigen positivity for all studies; HCV infection was defined as HCV RNA positivity for STARTMRK and HCV antibody positivity for BENCHMRK. RESULTS: Hepatitis coinfection was present in 6% (34 of 563) of treatment-naïve patients (4% HBV only, 2% HCV only and 0.2% HBV+HCV) and 16% (114 of 699) of treatment-experienced patients (6% HBV only, 9% HCV only and 1% HBV+HCV). The incidence of drug-related adverse events was similar in raltegravir recipients with and without hepatitis coinfection in both STARTMRK (50 vs. 47%) and BENCHMRK (34 vs. 38.5%). Grade 2-4 liver enzyme elevations were more frequent in coinfected vs. monoinfected patients, but were not different between the raltegravir and control groups. At week 96, the proportion of raltegravir recipients with HIV RNA <50 HIV-1 RNA copies/mL was similar between coinfected and monoinfected patients (93 vs. 90% in STARTMRK; 63 vs. 61% in BENCHMRK). CONCLUSION: Raltegravir was generally well tolerated and efficacious up to 96 weeks in HIV-infected patients with HBV/HCV coinfection.

Different distributions of hepatitis C virus genotypes among HIV-infected patients with acute and chronic hepatitis C according to interleukin-28B genotype.

OBJECTIVES: The C allele of the single nucleotide polymorphism rs12979860, located near the interleukin-28B (IL-28B) gene, has a strong impact on hepatitis C virus (HCV) treatment response, as well as on spontaneous viral clearance. In patients with chronic hepatitis C (CHC), genotype CC carriers harbour HCV genotype 3 more commonly than those with non-CC genotypes. The aim of this study was to compare the HCV genotype distributions, according to IL-28B genotype, in HIV-infected patients with CHC and those with acute hepatitis C (AHC). METHODS: The rs12979860 genotype was determined by polymerase chain reaction (PCR) in two subpopulations of HIV-infected patients. The first consisted of 80 German patients with AHC. The second consisted of 476 patients with CHC, belonging to one German and two Spanish cohorts. RESULTS: In the AHC group, 31 (81.6%) rs12979860 CC carriers were infected with HCV genotype 1 or 4 vs. 32 (76.2%) among non-CC carriers (P=0.948). In patients with CHC, among those with the CC genotype, 119 (54.6%) were infected with HCV genotype 1 or 4 and 99 (45.4%) with genotype 2 or 3, whereas in the subset with non-CC genotypes, 200 (77.5%) harboured HCV genotype 1 or 4 and 58 (22.5%) genotype 2 or 3 (P<0.001). CONCLUSIONS: Among HIV-infected patients with CHC, those bearing the IL-28B genotype CC were more commonly infected with genotype 3 than subjects with non-CC genotypes, whereas in HIV-infected subjects with AHC this finding was not obtained. These results strongly suggest that the protective effect of the CC genotype against evolution to CHC is mainly exerted in patients infected with HCV genotype 1 or 4.

Safety, efficacy and development of resistance under the new protease inhibitor lopinavir/ritonavir: 48-week results.

BACKGROUND: Within this open-label, uncontrolled prospective trial we evaluated safety, efficacy and development of genotypic resistance under the new protease inhibitor lopinavir/ritonavir (LPV/r) in antiretroviral (ARV) HIV patients. PATIENTS AND METHODS: 58 patients with virological failure under their current ARV therapy were started on a LPV/r containing regimen. Median baseline HIV RNA and CD4 count were 4.6 log(10) cps/ml (range 2.1-6.4) and 128 x 10(6)/l (0-767), respectively. CD4 count, HIV RNA and metabolic parameters were assessed at weeks 0, 4, 8, 12, 16, 24, 32, 40, 48. Genotypic resistance testing was performed at baseline and again at weeks 12, 24 and 48 in the event of virological failure. RESULTS: Until week 48, viral load (VL) decreased by a median of 1.9 log(10) cps/ml (-0.8-3.8). A VL below 80 cps/ml was found in 20/58 patients (34.5%) at week 48. In parallel, CD4 cells increased to a median of 332 x 10(6)/l (8-905). Nine patients discontinued study treatment. At 48 weeks, median triglyceride and cholesterol levels increased significantly. While the median number of overall protease mutations at baseline was four in all patients, it was six in patients virologically failing on LPV/r. The average number of mutations increased significantly to eight at week 48. Several mutations were detected considerably more often in the event of failure than in response to treatment, e. g. at amino acid positions 10, 24, 54, 71, 82, 84. CONCLUSION: LPV/r is effective in heavily pretreated patients. Discontinuation due to adverse events is infrequent. No individual mutation can be associated with failure on LPV/r. However, a greater number of protease mutations at baseline is associated with poorer treatment outcome and several mutations seem to be related to treatment failure.