Telaprevir-Based Triple Therapy for HIV/HCV Coinfection
Telaprevir-Based Triple Therapy for HIV/HCV Coinfection
This study was a medical record review of patients who began TVR in combination with pegIFN and RBV before December 2011 at the Icahn School of Medicine at Mount Sinai (MSSM), New York, NY and Johns Hopkins University (JHU), Baltimore, MD. Seventeen coinfected patients and 116 monoinfected patients were treated at MSSM and 16 coinfected patients were treated at JHU. None of the patients had previously received a liver transplant and none was treated for more than 48 weeks. All patients were treated with weight-based RBV dosing. TVR was administered at a dose of 750 mg three times a day, except when co-administered with efavirenz, where a dose of 1125 mg three times a day was used. Monoinfected patients who were naïve to HCV treatment or who previously relapsed after treatment with pegIFN/RBV, who were not cirrhotic and who had undetectable levels of HCV RNA at weeks 4 and 12 were eligible for a shortened treatment course of 24 weeks [response-guided therapy (RGT)]. For this subset of patients, week-24 data were carried forward for the week-48 analysis (EOT). Coinfected patients were not considered for RGT.
Data were collected at baseline, at weeks 4, 12, 24 and 48, and at 12 weeks post-EOT. Data recorded included demographics, baseline medical conditions and medications, previous HCV treatment history, laboratory values and adverse events including rash, rectal symptoms, emergency room visits and hospitalizations. To evaluate the workload associated with treatment planning, pretreatment medical visits were counted. The education visit for injection learning was not counted, as it is standard of care for all patients. HCV and HIV viral loads were measured by real-time–polymerase chain reaction (RT-PCR) (Roche Cobas Ampliprep Cobas Taqman version 2.0, Roche Molecular Systems Inc., Branchburg, NJ, USA). An HCV viral load below the lower limit of detection (18 IU/mL) was recorded as 'undetectable'. HCV virological failure was defined as a viral load > 1000 IU/mL at week 4 or 12 or a detectable HCV viral load after week 24. Patients were considered to have advanced fibrosis or cirrhosis if they had a Fib-4 score ≥ 3.25. Anaemia was defined as haemoglobin < 135 g/L in men and < 120 g/L in women. Based on the Division of AIDS (DAIDS) criteria, severe anaemia was defined as haemoglobin ≤ 89 g/L and/or a decrease of ≥ 45 g/L. Institutional Review Board approval was received from each institution.
χ or Fisher exact tests were used for discrete variables and Student's t-tests or Mann–Whitney U-tests were used for continuous variables. Baseline characteristics of the HIV/HCV-coinfected patients from MSSM and JHU were compared to each other and were combined because no statistically significant differences were found. Treatment outcomes were evaluated on an intention-to-treat basis. Patients lost to follow-up were considered to have a virological failure.
Data for coinfected and monoinfected patients were included in a multivariable logistic regression analysis of factors independently associated with sustained virological response at week 12 post-end-of-treatment (SVR12). Factors known to influence SVR during dual therapy were included: age, sex, race (African American or not), previous treatment response [favourable (naïve or relapser) vs. not favourable (nonresponder or treatment-intolerant)], body mass index (BMI), logarithm of the HCV viral load, fibrosis stage (Fib-4 score below vs. above 3.25) and HIV infection status. To confirm the comparability of the patients, the treatment site was also evaluated. The multivariable model was built using forward and backward likelihood ratios. Entry and exit P-values were both fixed at 0.10 and factors with P-values < 0.05 in the final model were retained. Data were analysed in spss version 20 (SPSS, Chicago, IL). A P-value < 0.05 was considered statistically significant.
Methods
Study Design and Patients
This study was a medical record review of patients who began TVR in combination with pegIFN and RBV before December 2011 at the Icahn School of Medicine at Mount Sinai (MSSM), New York, NY and Johns Hopkins University (JHU), Baltimore, MD. Seventeen coinfected patients and 116 monoinfected patients were treated at MSSM and 16 coinfected patients were treated at JHU. None of the patients had previously received a liver transplant and none was treated for more than 48 weeks. All patients were treated with weight-based RBV dosing. TVR was administered at a dose of 750 mg three times a day, except when co-administered with efavirenz, where a dose of 1125 mg three times a day was used. Monoinfected patients who were naïve to HCV treatment or who previously relapsed after treatment with pegIFN/RBV, who were not cirrhotic and who had undetectable levels of HCV RNA at weeks 4 and 12 were eligible for a shortened treatment course of 24 weeks [response-guided therapy (RGT)]. For this subset of patients, week-24 data were carried forward for the week-48 analysis (EOT). Coinfected patients were not considered for RGT.
Data were collected at baseline, at weeks 4, 12, 24 and 48, and at 12 weeks post-EOT. Data recorded included demographics, baseline medical conditions and medications, previous HCV treatment history, laboratory values and adverse events including rash, rectal symptoms, emergency room visits and hospitalizations. To evaluate the workload associated with treatment planning, pretreatment medical visits were counted. The education visit for injection learning was not counted, as it is standard of care for all patients. HCV and HIV viral loads were measured by real-time–polymerase chain reaction (RT-PCR) (Roche Cobas Ampliprep Cobas Taqman version 2.0, Roche Molecular Systems Inc., Branchburg, NJ, USA). An HCV viral load below the lower limit of detection (18 IU/mL) was recorded as 'undetectable'. HCV virological failure was defined as a viral load > 1000 IU/mL at week 4 or 12 or a detectable HCV viral load after week 24. Patients were considered to have advanced fibrosis or cirrhosis if they had a Fib-4 score ≥ 3.25. Anaemia was defined as haemoglobin < 135 g/L in men and < 120 g/L in women. Based on the Division of AIDS (DAIDS) criteria, severe anaemia was defined as haemoglobin ≤ 89 g/L and/or a decrease of ≥ 45 g/L. Institutional Review Board approval was received from each institution.
Statistical Analysis
χ or Fisher exact tests were used for discrete variables and Student's t-tests or Mann–Whitney U-tests were used for continuous variables. Baseline characteristics of the HIV/HCV-coinfected patients from MSSM and JHU were compared to each other and were combined because no statistically significant differences were found. Treatment outcomes were evaluated on an intention-to-treat basis. Patients lost to follow-up were considered to have a virological failure.
Data for coinfected and monoinfected patients were included in a multivariable logistic regression analysis of factors independently associated with sustained virological response at week 12 post-end-of-treatment (SVR12). Factors known to influence SVR during dual therapy were included: age, sex, race (African American or not), previous treatment response [favourable (naïve or relapser) vs. not favourable (nonresponder or treatment-intolerant)], body mass index (BMI), logarithm of the HCV viral load, fibrosis stage (Fib-4 score below vs. above 3.25) and HIV infection status. To confirm the comparability of the patients, the treatment site was also evaluated. The multivariable model was built using forward and backward likelihood ratios. Entry and exit P-values were both fixed at 0.10 and factors with P-values < 0.05 in the final model were retained. Data were analysed in spss version 20 (SPSS, Chicago, IL). A P-value < 0.05 was considered statistically significant.
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