LETTER TO THE EDITOR Safe Coadministration of Raltegravir-Based HAART in HIV-Infected Patients With HCV- Cirrhosis Receiving Triple Therapy With Telaprevir or Boceprevir To the Editors: Boceprevir (BOC) and telaprevir (TPV), inhibitors of the hepatitis C virus (HCV) NS3/4A serine protease signifi- cantly increase rates of sustained viro- logical response in patients with HCV genotype 1, commencing the routine use of direct-acting antivirals in HCV ther- apy. 1–4 To date, however, there are lim- ited data on their safety and efficacy in HIV/HCV-coinfected patients. More- over, in the 2 small phase 2 studies of BOC and TPV in previously nontreated HIV/HCV-coinfected subjects, the pro- portion of cirrhotics was less than 5%. 5,6 Raltegravir (RAL), the first approved HIV-1 integrase inhibitor, combines rapid and potent antiretroviral activity with a lack of interference with the hepatic cytochrome P450-3A4. 7,8 We have previously reported the absence of safety issues in HIV/HCV patients with Child–Pugh grade C cirrhosis receiving RAL 9 and the safe coadministration of RAL plus peg-IFN/ RBV in HCV subjects with severe liver damage. 10 The aim of the present report is to describe for the first time the safe coadministration of RAL-based highly active antiretroviral therapy (HAART) in 11 consecutive cirrhotic patients after at least 12 weeks of TPV (N = 9) or BOC (n = 2) in the clinical setting. From January 2012, early access (n = 13) or compassionate use (n = 7) allowed triple therapy with HCV- protease inhibitors (90% TPV) in 20 con- secutive cirrhotic patients at our center. Sixteen (80%) received HAART with RAL, and we report data in 11 that have completed the first 12 weeks of therapy (the whole duration of triple therapy for those on TPV). Table 1 summarizes the most relevant HIV-related features of the cohort. Mean age was 48 6 5 years, 73% were male (n = 8), and prior AIDS was reported in 3 (27%). Ten subjects (91%) were on PI-based HAART (70% on rito- navir-boosted PI monotherapy). Only P7 was already on a RAL-based HAART (94 weeks) at the time she started HCV- therapy, whereas in all the remaining change to RAL was performed to avoid drug interactions. The most frequent combination was RAL plus fixed dose lamivudine 300 mg/abacavir 600 mg (KI- VEXA) (n = 7). The median baseline CD4 count was 556 (382–843) cells/ mL, and all subjects had HIV-RNA below 1.57 log 10 copies/mL. During the 12 weeks of triple therapy, there was only one confirmed HIV-RNA rebound (P9), due to nonadherence, but resistance testing showed no integrase or NRTI- associated mutations. Only one subject was naive to HCV-therapy (P9). Among pretreated subjects (mean 2 cycles), patterns of prior response were as follows: partial response (at least 2 log 10 IU/mL decrease within the first 12 weeks) in 4 (40%), null response in 4 (40%), and relapse in 2. All subjects had compensated cirrhosis (Child–Pugh score #6 in 82%); median Model for End-stage Liver Disease 10 (7– 15). Six patients were infected with HCV genotype 1b (54%), 4 with HCV geno- type 1a (36%), and P11 had a mixture of both 1a and 1b (P11). IL28B was avail- able in all: 7 subjects were CT (64%), 2 patients each were TT or CC respectively. Peg-IFN-a2a was used in 8 (73%), and all subjects started weight adjusted RBV (median, 15.6 mg/kg per day; range, 12– 25 mg/kg per day), with an initial dose of 1200 mg/day in 8 (73%). Median baseline HCV-RNA was 6.4 log 10 IU/mL (4.75– 6.87). Only P11 prematurely discontinued BOC at week 8 because of severe anemia despite RBV adjustment and human recombinant erythropoietin use. P6 and P8 stopped TPV-peg-INF/RBV following futility rules after 8 and 12 weeks, respec- tively, and P1 has already completed 24 weeks on BOC. Eight patients (73%) achieved negative HCV-RNA, with no cases of breakthrough during triple ther- apy or recurrence during follow-up. Peg- IFN and RBV dose adjustments were needed in 3 subjects each (27%); P7 had to adjust both peg-IFN and RBV doses. None of the subjects received G-CSF, but human recombinant erythro- poietin was used in 3 (27%). Our data support the safety of RAL-based HAART in patients with HCV-cirrhosis receiving triple therapy with BOC or TPV added to full-dose peg-IFN/RBV. According to metabolism and pharmacokinetic data, 11 TPV in com- bination with ritonavir-boosted PI other than atazanavir could reduce exposure of the antiretroviral agents or TPV, and they are not recommended for use in combination. To our knowledge, our data are the first available on the safety of RAL plus TPV in HIV/HCV-subjects, for patients in the small phase 2 clinical trial only received EFV or r/atazanavir, 5 and available pharmacokinetic data come from healthy volunteers. 12 On the other hand, although 84% of subjects in the phase 2a study of BOC were on r/PI, and BOC is a primary substrate of aldoke- toreductase (IC2 and IC3), more extensive pharmacokinetic studies in healthy volun- teers have identified concerning interac- tions with ritonavir-boosted HIV-protease inhibitors and, therefore, coadministration is currently not recommended. 11 In con- trast to TPV, in the BOC clinical trial, a small proportion of the patients (less than 20%) were on RAL-based HAART, and it did not affect safety or efficacy. 6 Although available data support the coadministration of TPV with r/atazanavir or efavirenz, 5 increases in bilirubin levels leading to higher Model for End-stage Liver Disease scores in patients with cirrhosis 13 and enhanced costs due to the need of higher doses of TPV (1125 mg every 8 hours), respectively, make more attractive the use of RAL in this setting. This advantageous pharmacoki- netic profile of RAL in HIV/HCV- coinfected patients receiving drugs metabolized by the liver P450 system has been already observed in the setting of liver transplantation, 14,15 and reinforces its role as the backbone of HAART The authors have no funding or conflicts of interest to disclose. J Acquir Immune Defic Syndr  Volume 61, Number 3, November 1, 2012 www.jaids.com | e47