Viral rebound after switch to maraviroc/raltegravir dual therapy in highly experienced and virologically suppressed patients with HIV-1 infection
Author(s) -
Silvia Nozza,
Alba Bigoloni,
Andrea Calcagno,
Laura Galli,
A. R. Pignataro,
Antonio D’Avolio,
Alessia Carbone,
Marco Ripa,
Stefano Bonora,
Adriano Lazzarin,
Antonella Castagna
Publication year - 2014
Publication title -
journal of antimicrobial chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.124
H-Index - 194
eISSN - 1460-2091
pISSN - 0305-7453
DOI - 10.1093/jac/dkt530
Subject(s) - raltegravir , maraviroc , ccr5 receptor antagonist , medicine , human immunodeficiency virus (hiv) , antiretroviral therapy , virology , viral load , integrase inhibitor , pharmacology , immunology , inflammation , chemokine , chemokine receptor
+ 800 mg of ribavirin daily + telaprevir (750 mg/ 8 h) she achieved undetectable HCV-RNA at weeks 4 and 12. Treatment was complicated by severe anaemia, requiring pegy-lated interferon and ribavirin dose reduction and blood transfusion. HCV-RNA remained ,15 IU/L, and she continued on pegylated interferon + ribavirin treatment. HIV-RNA remained undetectable at treatment weeks 4, 8 and 12. Darunavir and telaprevir PK data are shown in Table 1. There were decreases in all darunavir PK parameters when administered with telaprevir for both patients, except for unbound trough concentration in Patient 2. These decreases, ranging from 58% to 97%, were even higher than those previously described in healthy volunteers. 2,3 However, darunavir/ritonavir doses were different in both cases (800/100 mg once daily in our patients and 600/ 100 mg twice daily in healthy volunteers). 2 We also observed decreases in unbound darunavir concentrations in both patients (except for the aforementioned increase in unbound C trough in Patient 2), although the free fraction decreased less than total drug (ranging from 46% to 93%). There are scarce data on daru-navir PK in HIV/HCV-coinfected patients: in a Spanish cohort, dar-unavir once-daily concentrations (total and unbound) were higher than those observed in our two patients, even before telaprevir co-administration. 5 We could not evaluate the impact of darunavir on telaprevir concentrations, as antiretroviral therapy was maintained. However, telaprevir concentrations in our patients were much higher than previously reported in healthy volunteers or HCV-monoinfected patients. 2,3,6 These high telaprevir concentrations in our coinfected patients with advanced fibrosis could partially explain the marked reduction in darunavir levels, although an association between telaprevir exposure and extent of drug interaction with antiretrovirals has not been previously described. Despite the impact of telaprevir co-administration on daruna-vir concentrations (total darunavir C trough was below wild-type virus IC 50 in one patient), HIV-RNA remained undetectable during the 12 weeks of telaprevir therapy. Prolonged HIV suppression prior to starting anti-HCV therapy, preserved antiviral potency of the darunavir-based regimen and interferon anti-HIV effect 7 could have played a role in keeping HIV-RNA undetectable. Having only two patients, we must take into account all the potential confounding factors and the inter-and intra-individual variability , which hamper generalization of our results. However, our results are concordant between both patients. Besides, as PK parameters can be modified with hepatic impairment, it is very important to have data on interaction between telaprevir and darunavir/ ritonavir in …
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