Response-guided therapy for chronic hepatitis C virus infection in patients coinfected with HIV: a pilot trial.

BACKGROUND: To study the feasibility of a response-guided therapy for chronic hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus (HIV) in a tertiary care hospital. METHODS: Treatment duration was individualized on the basis of week 4 and week 12 virologic response. Sixty patients were enrolled and received pegylated interferon alfa-2b (1.5 microg/kg per week) plus weight-based ribavirin (800-1400 mg/day). Patients who achieved a rapid virologic response, defined as viral load <50 IU/mL at treatment week 4, completed 24 weeks of therapy. Patients who did not achieve a rapid virologic response were reassessed at treatment week 12. Patients with a complete early virologic response, defined as an HCV RNA level <600 IU/mL, were treated for 48 weeks. Patients with a partial response, defined as a decrease in the viral load > or = 2 log10 and an HCV RNA level > or = 600 IU/mL, who attained an undetectable viral load at week 24 were treated for 60 weeks. The primary efficacy end point was sustained virologic response, defined as HCV RNA <50 IU/mL, 24 weeks after the end of treatment. RESULTS: Overall, 33 (55%) of 60 patients achieved a sustained virologic response: 11 (44%) of 25 patients with HCV genotype 1, 3 (27%) of 11 patients with genotype 4, and 19 (79%) of 24 patients with genotype 3. One-third of patients showed a rapid virologic response. Of patients with genotype 1, there was a rapid virologic response in 4 (16%) of 25; with genotype 4, in 1 (9%) of 11; and with genotype 3, in 14 (58%) of 24. Of the 19 patients with a rapid virologic response, 17 (89.5%) eradicated the virus after 24 weeks of therapy. The rate of sustained virologic response was significantly higher among patients with genotype 3 and low pretreatment HCV RNA levels. A high relapse rate (46%) after 48 weeks of therapy occurred among patients infected with genotypes 1 or 4 who first achieved undetectable viral load at treatment week 12. CONCLUSION: A response-guide therapy is feasible and may be useful to optimize the individual outcome of HCV treatment in patients coinfected with HIV.

Early monitoring of ribavirin serum concentration is not useful to optimize hepatitis C virus treatment in HIV-coinfected patients.

BACKGROUND: Emerging data suggest that higher ribavirin (RBV) exposure could improve early hepatitis C virus (HCV) response. Furthermore, interindividual RBV bioavailability shows high variation, and dose-limiting haemolytic anaemia is a common adverse event. Therefore, it has been suggested that monitoring RBV serum levels could be used to drive dose modification and to optimize management of HCV-infected patients receiving combination treatment. METHODS: To assess the effect of RBV serum levels on HCV RNA clearance at week 4 and 12 of treatment, and to determine the correlation between RBV serum concentration and haemoglobin decrease, RBV trough levels were measured by HPLC in stored serum samples obtained from 94 HCV-HIV-coinfected patients at week 4 and 12 of treatment with peginterferon-alpha2b (1.5 microg/kg/weekly) pIus ribavirin (800-1,200 mg/day). RESULTS: The median RBV levels increased from 1.70 microg/ml at week 4 to 1.97 microg/ml at week 12 of treatment (P = 0.001) and were independently predicted by weight-adjusted dose of RBV and co-administration of tenofovir. Haemoglobin drop was higher among patients who received zidovudine and weakly correlated with RBV level. Although RBV concentration was lower in genotype 1 or 4 HCV-infected patients who cleared the virus at treatment week 4, the ability of this parameter to discriminate between responders and non-responders at treatment week 4 and 12 was poor. CONCLUSION: Intracellular RBV accumulation early in treatment might improve the kinetics of HCV response in difficult to treat patients. Although this hypothesis and the potential interaction between RBV and tenofovir warrant further research, our data do not support RBV serum monitoring as a tool to optimize treatment in HCV-HIV-coinfected patients.

Tropical diseases screening in immigrant patients with human immunodeficiency virus infection in Spain.

Latent parasitic infections can reactivate because of immunosuppression. We conducted a prospective observational study of all human immunodeficiency virus (HIV)-infected immigrants who visited the Infectious Diseases Department of the Hospital Universitari Vall d'Hebron, Barcelona, Spain, during June 2010-May 2011. Screening of the most prevalent tropical diseases (intestinal parasitosis, Chagas disease, leishmaniasis, malaria, schistosomiasis, and strongyloidiasis) was performed according to geographic origin. A total of 190 patients were included: 141 (74.2%) from Latin America, 41 (21.6%) from sub-Saharan Africa, and 8 (4.2%) from northern Africa. Overall, 36.8% (70 of 190) of the patients had at least one positive result for any parasitic disease: 5 patients with positive Trypanosoma cruzi serology, 11 patients with positive Schistosoma mansoni serology, 35 patients with positive Strongyloides stercoralis serology, 7 patients with positive Leishmania infantum serology, intestinal parasitosis were detected in 37 patients, malaria was diagnosed in one symptomatic patient. We propose a screening and management strategy of latent parasitic infections in immigrant patients infected with HIV.