Pre-existent NRTI and NNRTI resistance impacts on maintenance of virological suppression in HIV-1-infected patients who switch to a tenofovir/emtricitabine/rilpivirine single-tablet regimen

• Published in: Journal of antimicrobial chemotherapy 2017-03, Vol.72 (3), p.855-865
• Main Authors: Armenia, D, Di Carlo, D, Calcagno, A, Vendemiati, G, Forbici, F, Bertoli, A, Berno, G, Carta, S, Continenza, F, Fedele, V, Bellagamba, R, Cicalini, S, Ammassari, A, Libertone, R, Zaccarelli, M, Ghisetti, V, Andreoni, M, Ceccherini-Silberstein, F, Bonora, S, Di Perri, G, Antinori, A, Perno, C F, Santoro, M M
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - therapeutic use; Deoxycytidine - therapeutic use; Drug Combinations; Emtricitabine - administration & dosage; Emtricitabine - therapeutic use; Female; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Humans; Male; Middle Aged; Reverse Transcriptase Inhibitors - therapeutic use; Rilpivirine - administration & dosage; Rilpivirine - therapeutic use; RNA, Viral - blood; Tablets; Tenofovir - administration & dosage; Tenofovir - therapeutic use; Viral Load - drug effects
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkw512

To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, by considering pre-existent resistance (pRes). pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated. Three hundred and nine patients were analysed; 5.8% of them showed resistance to both NRTIs and NNRTIs, while 12.6% showed resistance to only one of these drug classes. By 72 weeks, the probability of VR was 11.3%. A higher probability of VR was found in the following groups: (i) patients with NRTI + NNRTI pRes compared with those harbouring NRTI or NNRTI pRes and with those without reverse transcriptase inhibitor pRes (39.2% versus 11.5% versus 9.4%, P  <   0.0001); (ii) patients with a virus with full/intermediate resistance to both tenofovir/emtricitabine and rilpivirine compared with those having a virus with full/intermediate resistance to tenofovir/emtricitabine or rilpivirine and those having a virus fully susceptible to TDF/FTC/RPV (36.4% versus 17.8% versus 9.7%, P  <   0.001); and (iii) patients with pre-therapy viraemia >500 000 copies/mL compared with those with lower viraemia levels (>500 000: 16.0%; 100 000-500 000: 9.3%; 500 000 copies/mL were independent predictors of VR by multivariable Cox regression. TDF/FTC/RPV as a treatment simplification strategy shows a very high rate of VS maintenance. The presence of pRes to both NRTIs and NNRTIs and a pre-therapy viraemia >500 000 copies/mL are associated with an increased risk of VR, highlighting the need for an accurate selection of patients before simplification.