Corinne Amiel1, Veronique Schneider2, Sabine Guessant3, Mohammed Hamidi4, Khadijah Kherallah2, Marie-Gisele Lebrette4, Julie Chas4, Catherine Lependeven2, Gilles Pialoux5. 1. UPMC Univ Paris 06, Centre d'Immunologie et de Maladies Infectieuses (CIMI) UMRS CR7, Persistent Viral Infection (PVI) Team, Inserm U1135, 75013 Paris, France AP-HP, Groupe Hospitalier Paris Est, Virology Laboratory, Tenon Hospital, 75020 Paris, France corinne.amiel@tnn.aphp.fr. 2. AP-HP, Groupe Hospitalier Paris Est, Virology Laboratory, Tenon Hospital, 75020 Paris, France. 3. AP-HP Groupe Hospitalier Paris Est, Pharmacy, Tenon Hospital, 75020 Paris, France. 4. AP-HP Groupe Hospitalier Paris Est, Infectious Disease Department, Tenon Hospital, 75020 Paris, France. 5. UPMC Univ Paris 06, Centre d'Immunologie et de Maladies Infectieuses (CIMI) UMRS CR7, Persistent Viral Infection (PVI) Team, Inserm U1135, 75013 Paris, France AP-HP Groupe Hospitalier Paris Est, Infectious Disease Department, Tenon Hospital, 75020 Paris, France.
Abstract
OBJECTIVES: To study the single-tablet regimen (STR) combination rilpivirine/tenofovir/emtricitabine (RPV/TDF/FTC) as soon as it became available. We describe a 14 month follow-up in a real clinical setting with a focus on resistance to RPV/TDF/FTC and polymorphisms associated with these drugs. METHODS: We estimated drug resistance at STR baseline by combining all available resistance tests, resulting in a cumulative virtual genotype. Physicians were advised of current or archived resistance mutations for the three drugs. Virological response was analysed according to resistance genotype at baseline. RESULTS: Three hundred and sixty-three patients received RPV/TDF/FTC; 79% had received previous treatment and RPV/TDF/FTC was the result of a switch of one drug to rilpivirine in two-thirds of cases. The cumulative genotype showed 4% of rilpivirine resistance mutations at baseline and 16% of polymorphisms concerning non-nucleoside reverse transcriptase inhibitors (NNRTIs). With a median duration of STR of 8 months, 78% of patients with these polymorphisms were virologically suppressed compared with 96% with wild-type genotypes. Five genotypes were determined during the follow-up, revealing three rilpivirine resistance-associated mutations: E138Q/Y181I, M230L and K101P (potentially with a K101Q intermediate). CONCLUSIONS: This observational study reflects routine clinical practice and the relevance of virological advice. It also confirms the efficacy of this STR (RPV/TDF/FTC) for naive and virologically suppressed pretreated patients with a low prevalence of virological failure and resistance if the cumulative baseline genotype is free of resistance to NNRTIs and/or polymorphisms associated with NNRTIs.
OBJECTIVES: To study the single-tablet regimen (STR) combination rilpivirine/tenofovir/emtricitabine (RPV/TDF/FTC) as soon as it became available. We describe a 14 month follow-up in a real clinical setting with a focus on resistance to RPV/TDF/FTC and polymorphisms associated with these drugs. METHODS: We estimated drug resistance at STR baseline by combining all available resistance tests, resulting in a cumulative virtual genotype. Physicians were advised of current or archived resistance mutations for the three drugs. Virological response was analysed according to resistance genotype at baseline. RESULTS: Three hundred and sixty-three patients received RPV/TDF/FTC; 79% had received previous treatment and RPV/TDF/FTC was the result of a switch of one drug to rilpivirine in two-thirds of cases. The cumulative genotype showed 4% of rilpivirine resistance mutations at baseline and 16% of polymorphisms concerning non-nucleoside reverse transcriptase inhibitors (NNRTIs). With a median duration of STR of 8 months, 78% of patients with these polymorphisms were virologically suppressed compared with 96% with wild-type genotypes. Five genotypes were determined during the follow-up, revealing three rilpivirine resistance-associated mutations: E138Q/Y181I, M230L and K101P (potentially with a K101Q intermediate). CONCLUSIONS: This observational study reflects routine clinical practice and the relevance of virological advice. It also confirms the efficacy of this STR (RPV/TDF/FTC) for naive and virologically suppressed pretreated patients with a low prevalence of virological failure and resistance if the cumulative baseline genotype is free of resistance to NNRTIs and/or polymorphisms associated with NNRTIs.
Authors: William T Gray; Kathleen M Frey; Sarah B Laskey; Andrea C Mislak; Krasimir A Spasov; Won-Gil Lee; Mariela Bollini; Robert F Siliciano; William L Jorgensen; Karen S Anderson Journal: ACS Med Chem Lett Date: 2015-08-31 Impact factor: 4.345
Authors: Nadia Galizzi; Laura Galli; Andrea Poli; Nicola Gianotti; Elisabetta Carini; Alba Bigoloni; Giuseppe Tambussi; Silvia Nozza; Adriano Lazzarin; Antonella Castagna; Daniela Mancusi; Roberta Termini Journal: PLoS One Date: 2018-02-16 Impact factor: 3.240