Table of Contents
The conference included very encouraging results from the first studies of telaprevir (tradename Incivek, Vertex) and boceprevir (tradename Victrelis, Merck) in people with HIV/HCV coinfection.
Both studies generally showed similar response rates in HIV/HCV coinfection to those seen in HCV monoinfection. Sustained virological response (SVR) results at 12 weeks are highly predictive of SVR at week 24.
SVR results at 12 weeks after treatment, from a double-blind, placebo controlled Phase 2 study telaprevir in combination with pegylated interferon (peg-IFN) + ribavirin (RBV) in 60 patients with HIV and HCV genotype-1 coinfection were presented by Douglas Dieterich. 
Patients were randomised to either telaprevir (750 mg every 8 hours) or placebo, plus PEG-IFN alpha-2a (Pegysys) + RBV, (800 mg/day) for 12 weeks followed by 36 weeks of peg-IFN+RBV. This was a two-part study depending on whether patients were using ART (Part B, n=47) or not (Part A, n=13). In the ART arm atazanavir/ritonavir (n=23) or efavirenz (n=24) based regimens were allowed (with an increased telaprevir dose for efavirenz patients).
Baseline characteristics included: mean age of 46 years; 88% male; 27% African American; 68% with subtype 1a and 3% had cirrhosis. HCV RNA was >800,000 IU/mL in 92% and 81% of no-ART and ART groups respectively; median CD4 counts were approximately 500-600 cells/mm3 (range 300 - >1,100).
Undetectable HCV RNA in the combined active vs placebo groups were achieved by 68 vs 4.5%, 82% vs 32%, 63 vs 4.5% and 74% vs 55% at week 4, 12, weeks 4 and 12, and week 24 respectively, see Table1). ART use did not affect response rates. Outcomes by baseline HCV RNA were not presented.
Both safety and tolerability of telaprevir in combination with peg-IFN+RBV was comparable to that previously observed in HCV-mono-infected patients. No severe rashes were reported.
|N (%)||No ART||No ART||EFV/TDF/FTC||EFV/TDF/FTC||ATZ/r/TDF/FTC||ATZ/r/TDF/FTC|
|Week 4 (RVR)||5 (71)||0||12 (75)||1 (12)||9 (60)||0|
|Week 12 (oRVR)||6 (66)||2 (33)||14 (80)||2 (25)||11 (73)||3 (38)|
|Week 4 and 12 (eRVR)||4 (57)||0||12 (75)||1 (12)||8 (53)||0|
|Week 24||6 (86)||2 (33)||12 (75)||4 (50)||10 (67)||6 (75)|
T: telaprevir; P: peg-IFN; R: ribavirin. BLQ: undetectable: lower limit of quantification: 25 IUlmL; limit of detection 10-15 IU/mL.
Interaction data between telaprevir and HIV drugs was also included in the same presentation. Telaprevir concentrations were similar with efavirenz and atazanavir to reference concentrations with mean (90%CI) Cmin, Cavg and Cmax of 93 ng/mL (56, 156), 97 ng/mL (64, 146) and 101 ng/mL (72, 143) with efavirenz and 131 ng/mL (77, 222), 107 ng/mL (70, 165) and 98 ng/mL (69, 140) with atazanavir, respectively.
The mean concentration ratios to reference levels were also close to 100% for levels of efavirenz and atavanavir, indicating the higher efavirenz dose is sufficient to overcome this interaction.
Telaprevir can only be used with boosted atazanavir, efavirenz (with a higher dose of telaprevir -- 1125 mg tid vs. 750 mg tid) or raltegravir. Background nucleosides are tenofovir plus FTC or 3TC.
No comments have been made.
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