Impact of baseline NNRTI pretreatment resistance mutations on risk of virologic failure of RPV-based dual therapies
BACKGROUND: Study aim: to assess durability and rate of virologic failure of rilpivirine (RPV)-based dual therapy (RPV plus boosted-darunavir [DRV/b] or dolutegravir [DTG]) among NNRTI-experienced people living with HIV (PLWH) with known NNRTI-drug resistance mutations (DRM).
METHODS: Observational, retrospective study on Antiviral Resistance Cohort Analysis (ARCA) database including all PLWH on ART who switched to a dual regimen containing RPV+DTG or DRV/b with available genotypic resistance test (GRT) at baseline. Virological failure was defined as the first of two consecutive episodes with HIV-RNA >50 copies/ml or the first HIV-RNA >200 copies/ml.
RESULTS: 382 PLWH were included. DTG+RPV was the most represented group (223 PLWH), compared to DRV/b+RPV (159) as shown in Figure 1. The DTG+RPV group had a higher rate of pretreatment drug resistant mutations (PDRMs) (88%) compared to DRV/b+RPV (48%). There were 22 (one occurred in DRV/b group within 1 week from ART-switch and excluded from further analysis) virologic failures (1.4 failures per 100 person-years follow up) [DTG+RPV= 1.3 viral failures per 100 person-years follow-up (95%CI= 0.7 - 2.4); DRV/boosted + RPV= 1.6 viral failures per 100 person-years follow-up (95%CI= 0.8 - 3.0)]. Independent predictors of virologic failure were failure at ART switch [adjusted Hazard Ratio (aHR)= 9.08, 95% confidence interval (CI)= 3.76 - 21.90, p<.001] and at least one PDRMs for non-nucleos(t)ide reverse-transcriptase inhibitors (NNRTI) at baseline (aHR= 4.34, 95%CI= 1.78 ' 10.55, p=.001). Virologic failure at ART switch and at least one PDRMs for NNRTI at baseline were significantly associated with risk of failure (log rank p<.001) by Kaplan-Meier analysis.
CONCLUSIONS: RPV-based dual therapies were effective simplification strategies in this cohort. Detectable HIV-RNA and the presence of any NNRTI PDRMs at the time of switch were significantly associated with virologic failure.
D.F. Bavaro * (1), A. Lazzaro (2), P. Laghetti (1), A. Emilliozzi (3), A. Rizzo (4), F. Bassani (5), F. Conti (6), L. Pezzati (7), A. Bezenchek (8), A. Shallvari (9), F. Incardona (10), M. Zazzi (11), S. Rusconi (6)
(1) Clinic of Infectious Diseases, University Hospital of Bari, Bari, Italy, (2) Ospedale Amedeo di Savoia - Università degli Studi di Torino, Torino, Italy, (3) Azienda Ospedaliera Universitaria Senese, Siena, Italy, (4) Laboratorio di Microbiologia, Virologia e Diagnostica Bioemergenze - Ospedale Sacco, Milano, Italy, (5) Università degli Studi di Milano, Milano, Italy, (6) Divisione Malattie Infettive, DIBIC Luigi Sacco, Università degli Studi di Milano, Milano, Italy, (7) Universitá degli Studi di Milano - Ospedale Sacco, Milano, Italy, (8) InformaPRO s.r.l., ' EuResist Network GEIE, Roma, Italy, (9) InformaPRO s.r.l., Roma, Italy, (10) InformaPRO s.r.l. ' EuResist Network GEIE, Roma, Italy, (11) Department of Molecular Biology, University of Siena, Siena, Italy