P056
Reasons for choosing darunavir/ritonavir 600/100 mg BID
versus 800/100 mg QD in ART-na
€ıve patients
A Tavelli1; M Palma2; S Lo Caputo3; G Madeddu4; P Bonfanti5; B Menzaghi6; S Nozza7; A Antinori8; R Termini2; A
d’Arminio Monforte9; on behalf of Icona Foundation Study Group
1Icona Foundation, Milan, Italy.2Janssen-Cilag SpA, Cologno Monzese,
Italy.3Clinic of Infectious Diseases, Policlinic of Bari, Bari, Italy.4Unit
of Infectious Diseases, University of Sassari, Sassari, Italy.5Unit of
Infectious Diseases, A Manzoni Hospital, Lecco, Italy.6Unit of
Infec-tious Diseases, ASST della Valle Olona, Busto Arsizio, Italy.7Clinic of
Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.8HIV/
AIDS Unit, INMI L. Spallanzani IRCCS, Rome, Italy.9Clinic of Infectious and Tropical Diseases, ASST Santi Paolo e Carlo University of Milan, Milan, Italy
Background: Ritonavir-boosted darunavir (DRV/r) is recommended in ART-na€ıve, specifically in those with perceived low adherence and before results of resistance test. DRV/r 600/100 mg twice daily (BID) is licensed for ART-experienced, while 800/100 mg once daily formu-lation (QD) is recommended in first-line and in experienced patient without DRV RAMs. In clinical practice, however, a non-negligible pro-portion of ART-na€ıve subjects started with DRV/r BID. The aim of this study is to identify patterns of prescription of DRV/r BID in ART-naive, analysing predictors of DRV/r BID start versus QD.
Materials and methods: All patients from Icona cohort that started a DRV/r-based regimen from ART-na€ıve in 2008 to 2017 were included. A cross-sectional analysis was performed comparing demographics, clinical and lifestyle factors at the time of starting DRV/r in BID or QD, using chi-square and Wilcoxon test as appropriate. Univariable and multivariable logistic regression models were used to identify pre-dictors of DRV/r BID start.
Results: One thousand five hundred and three ART-naive patients were included: 1297 started DRV/r QD (86%) and 206 DRV/r BID (14%). Eighty-two percent male, median age 40 years, 80% Italian, 80% in triple therapy, 6% in two-drug regimen and 14% in combina-tion with>3 ARV drugs (69% with raltegravir and 13% with maravi-roc). Median HIV-RNA in DRV/r QD and BID groups were 5.1 and 5.3 log10 copies/mL (p= 0.02), with 31% DRV/r BID with HIV-RNA
>500,000 copies/mL (vs. 22% QD; p < 0.01); median CD4 counts were 260 cells/mm3 for DRV/r QD and 215 cells/mm3 for BID
(p= 0.07); 48% of DRV/r BID patients had CD4 < 200/mm3(vs. 40%
QD; p= 0.04). Fitting a logistic regression model, after controlling for potential confounders, older patients (>40 years: adjusted OR [aOR] 1.44; p= 0.019), subjects with CD4 < 200 cells/mm3 (aOR 1.48;
p= 0.019), patients given >3 ARV drugs (aOR 2.11; p = 0.001), cen-tres from southern Italy (aOR 2.57; p< 0.001), patients starting first cART in 2012 to 2013 (aOR 2.46; p= 0.001) showed a significantly higher probability of starting DRV/r BID. A decreased probability of DRV/r BID start was observed in AIDS presenters (aOR 0.63; p= 0.037). There was evidence that the use of regimens with >3 ARV was greater in people with HIV-RNA >500,000 than in those with HIV-RNA≤500,000 (OR 5.9; p < 0.001).
Conclusions: Italian clinicians allocate DRV/r BID as first-line regimen in several scenarios: elderly, severely immune-suppressed and highly viraemic patients, with more than three ARV drugs and with a peak of use in 2012 to 2013. Subjects with AIDS are mostly given DRV/r QD probably due to the the pill burden of concomitant medications for opportunistic infections.
P057
Network meta-analysis of
darunavir/cobicistat/emtric-itabine/tenofovir-alafenamide and elvitegravir/cobicistat/
emtricitabine/tenofovir-alafenamide in treatment-naive
patients with HIV-1 infection
S Van Sanden1; B Schweikert2; C Moecklinghoff3and K Tronczynski4
1Health Economics Market Access and Reimbursement, Janssen
EMEA, Beerse, Belgium.2RWESA, ICON, Munich, Germany.3Janssen,
Medical Affairs, Neuss, Germany.4Health Economics Market Access
and Reimbursement, Janssen, Warsaw, Poland
Background: In recent years, several single-tablet regimens (STRs) have been developed for HIV, with the aim of simplifying treatment and improving adherence whilst maintaining safety and efficacy. Two recently approved STR treatment options combine the boosting agent cobicistat and the common nucleotide/nucleoside reverse transcrip-tase inhibitors (NRTI) backbone F/TAF with the third agent darunavir (D/C/F/TAF) or elvitegravir (E/C/F/TAF). In absence of comparative head-to-head trials, we performed an indirect treatment comparison to compare the efficacy and safety between D/C/F/TAF and E/C/F/ TAF.
Methods: A systematic literature review (SLR) was conducted to identify RCTs including EVG or DRV in combination with two NRTIs. Bayesian fixed and random effect network meta-analyses (NMA) were performed to compare virological suppression (HIV-RNA suppression to<50 copies/mL according to FDA Snapshot algorithm) and discon-tinuation due to the adverse events (DAE), both at Week 48 in treat-ment-na€ıve HIV-1 infected population. In addition to the SLR, 48-week results of the AMBER study comparing D/C/F/TAF versus darunavir-boosted cobicistat (DRV/c) plus emtricitabine and tenofovir disoproxil (TDF/TAF) in a treatment-na€ıve population were included in the net-work by, for the base case, assuming equality between DRV/c and darunavir-boosted ritonavir (DRV/r). Several sensitivity analyses were performed to assess the impact of alternative definitions of the viro-logical suppression endpoint, inclusion/exclusion of trials related to dif-ferent patient populations or backbone used or an alternative way to connect the AMBER study to the network.
Results: Twenty-two RCTs were identified by the SLR and selected for inclusion in at least one network. Based on the deviance informa-tion criterion (DIC), the fixed effects model was considered as the base case for both endpoints and random effects models were per-formed as sensitivity analyses. In the base case analysis, no substantial differences in virological suppression were found between D/C/F/TAF and E/C/F/TAF: OR [95% CI] was 1.06 [0.48 to 2.33], with a probabil-ity (p) of 55% of D/C/F/TAF to be better than E/C/F/TAF. The OR for the DAE was 0.43 [0.08 to 2.39] in the base case analysis, with a probability of 83% of D/C/F/TAF to be better than E/C/F/TAF. Results of the NMA were stable across sensitivity analyses, supporting the robustness of the base case analysis findings.
Conclusions: These NMA results suggest similar efficacy between D/ C/F/TAF and E/C/F/TAF while for DAE the results suggest that the number of patients who discontinue D/C/F/TAF treatment due to adverse events may be lower or at least similar compared to E/C/F/ TAF.
Abstract Supplement HIV Glasgow 2018
Journal of the International AIDS Society 2018, 21(S8):e25187
