E Poveda1, J Hernández-Quero2, M J Pérez-Elías3, M A Ribas4, O J Martínez-Madrid5, J Flores6, J Navarro7, F Gutiérrez8, M García-Deltoro9, A Imaz10, A Ocampo11, A Artero12, F Blanco13, E Bernal14, J Pasquau15, C Mínguez-Gallego16, N Pérez17, A Aiestaran17, F García2, R Paredes18. 1. Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complejo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain. 2. Hospital Universitario San Cecilio, Granada, Spain. 3. Hospital Ramón y Cajal, Madrid, Spain. 4. Hospital Son Espases, Palma de Mallorca, Spain. 5. Hospital General Universitario Santa Lucía, Cartagena, Spain. 6. Hospital Arnau de Vilanova, Valencia, Spain. 7. Hospital Universitari Vall d'Hebron, Barcelona, Spain. 8. Hospital Universitario de Elche, Elche, Spain. 9. Hospital General Universitario de Valencia, Valencia, Spain. 10. Hospital Universitari de Bellvitge, Barcelona, Spain. 11. Hospital Xeral de Vigo, Vigo, Spain. 12. Hospital Universitario Dr. Peset, Valencia. 13. Hospital Carlos III, Madrid, Spain. 14. Hospital Reina Sofía, Murcia, Spain. 15. Hospital Virgen de la Nieves, Granada, Spain. 16. Hospital General de Castelló, Castelló, Spain. 17. Universitat Politécnica de Catalunya, Barcelona, Spain. 18. HIV Unit and irsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Abstract
OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.
OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infectedpatients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.
Authors: Ian McGowan; Timothy Wilkin; Raphael J Landovitz; Chunyuan Wu; Ying Chen; Mark A Marzinke; Craig W Hendrix; Paul Richardson; Susan H Eshleman; Adriana Andrade; Wairimu Chege; Peter L Anderson; Marybeth McCauley; Jason Farley; Kenneth H Mayer; Peter Anton; Rhonda M Brand; Ross D Cranston; Roy Gulick Journal: AIDS Date: 2019-02-01 Impact factor: 4.177