CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

and presence of archived 3TC mutations detected by NGS. 144-week study extension of our trial is ongoing

487 CLINICAL OUTCOMES OF 2-DRUG REGIMENS (2DRS) VS 3-DRUG REGIMENS (3DRS) IN HIV

Lauren Greenberg 1 , for the RESPOND: The International Cohort Consortium of Infectious Diseases 1 University College London, London, UK Background: While 2DRs have shown good efficacy in clinical trials, there are limited data comparing longer term clinical outcomes to 3DRs. Methods: Antiretroviral treatment (ART) experienced persons in RESPOND starting a new 2DR or 3DR from 1/1/12-1/1/18 were included (figure). Poisson regression compared prospectively collected AIDS and non-AIDS events (non- AIDS-defining cancer, cardiovascular disease, end stage liver/renal disease, diabetes, chronic kidney disease [CKD], fractures, non-AIDS related death) between 2DRs vs 3DRs. Results: Of 5211 persons included, 967 (18.6%) started 2DRs and 4244 (81.4%) started 3DRs. The most common 2DRs were dolutegravir plus lamivudine (18.7%) and boosted darunavir plus raltegravir (18.5%). The main reason for discontinuing the previous regimen before starting a 2DR/3DR was toxicity (33.3% and 36.3% 2DRs vs 3DRs respectively; p=0.14). Persons on 2DRs were older (median 52 years [interquartile range 46-59] 2DRs vs 46 [39-53] 3DRs), had been on ART longer (14 years [6-18] vs 9 [4-15]), had higher CD4 counts (611 cells/µL [394-822] vs 590 [411-797]), and a lower CD4 nadir (170 [68-282] vs 205 [96-310]). A similar proportion had ≥1 comorbidity (63.1% vs 60.7%) and were virally supressed at baseline (86.6% vs 84.5%). Overall, there were 99 AIDS and 548 non-AIDS events during 12717 person years of follow-up [PYFU] (1813 2DR, 10904 3DR). The most common events were diabetes (crude incidence rate [IR] 1.2/100 PYFU [95% CI 1.0-1.4]) and CKD (0.9 [0.7-1.1]; figure). In unadjusted analyses, there was a lower IR of AIDS events on 2DRs (0.4 [0.2-0.9] 2DRs vs 0.8 [0.7-1.0] 3DRs) and a higher IR of non-AIDS events (6.1 [5.1-7.4] vs 4.0 [3.7-4.4]). After adjustment there was no significant difference between 2DRs and 3DRs for non-AIDS events (IR ratio 1.19 [0.94-1.50], p=0.15). The small number of AIDS events precluded adjusted analyses. Sensitivity analyses excluding diabetes, CKD, and fractures showed similar results. Conclusion: This is the first large, international cohort to assess clinical outcomes on 2DRs. After accounting for demographic and clinical characteristics, there was a similar incidence of non-AIDS events on 2DRs and 3DRs, however confounding by indication cannot be excluded. With a median follow-up of 1.7 years, 2DRs appear to be a viable treatment option with regard to clinical outcomes, although further research on long-term durability and potential toxicities of 2DRs is needed.

486 EFFECT OF PAST VIROLOGICAL FAILURE ON

DOLUTEGRAVIR+LAMIVUDINE AS MAINTENANCE REGIMEN Roberta Gagliardini 1 , Patrizia Lorenzini 1 , Alessandro Cozzi-Lepri 2 , Alessandro Tavelli 3 , Vanni Borghi 4 , Laura Galli 5 , Gianmarco Tagliaferri 3 , Franco Maggiolo 6 , Cristina Mussini 4 , Antonella Castagna 5 , Antonella D'Arminio Monforte 3 , Andrea Antinori 1 , for the Icona Foundation Study Group 1 IRCCS Lazzaro Spallanzani, Rome, Italy, 2 University College London, London, UK, 3 Azienda Ospedaliera San Paolo, Milan, Italy, 4 Azienda Ospedaliera Universitaria Policlinico di Modena, Modena, Italy, 5 San Raffaele Vita-Salute University, Milan, Italy, 6 Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy Background: Dolutegravir (DTG)+lamivudine (3TC) was shown to be as effective as triple therapy in RCT on patients (pts) switching during virological suppression, but limited data are available about the use of this regimen in pts with previous virological failures (VF), since RCT excluded these pts. Methods: The analysis included data of HIV+ pts with HIV-RNA<=50 c/ ml enrolled in a retrospective multi-cohort study across Italian infectious disease clinics switching for the first time to DTG+3TC from any other regimen (baseline). Primary endpoint was viral rebound (VR, confirmed HIV-RNA >=50 c/mL). Kaplan-Meier curves were used to estimate probabilities of VR according to history of previous VF (single HIV-RNA >=1000 or confirmed HIV-RNA >=50 c/mL). Weighted Cox regression model was fitted to estimate causal HR of VR, after controlling for confounding variables (time of viral suppression and nadir CD4). A further analysis with a different definition [Def 2] of previous VF (only at NRTI or INSTI regimens) and of VR (that included also a single HIV-RNA>=50 c/ml followed by change of therapy) and a sensitivity analysis excluding pts with incomplete history of viral load data (>1 year gap in measurements) were performed. Results: 966 pts included: 74%males, median age 51 (IQR 44-57), 15% CDC-C stage, nadir CD4 246 (99-372), years of viral suppression 7 (3-12), 80%without previous VF, 12%with one previous VF, 8%with >=2 previous VF. VR was detected in 11 pts over 1555 person-year-follow-up (PYFU): total incidence ratio (IR) was 0.7 x 100 PYFU (95% CI 0.4-1.3), 0.5 x 100 PYFU (0.2-1.1) in pts without previous failures and 1.4 x 100 PYFU (0.6-3.4) in pts with >=1 previous VF, with an estimated 1-year probability of 0.4% (0.1-1.4) and 1.3% (0.3-5.3) respectively (log-rank p=0.071). With Def 2, VR was detected in 18 pts, IR 1.2 x 100 PYFU (0.7-1.9), 1.9 x 100 PYFU (0.6-1.8) in pts without previous failures and 1.9 x 100 PYFU (0.8-4.2) in pts with >=1 previous VF. By multivariate analysis, pts with 1 previous VF had higher risk of VR but not statistically significant throughout all the analyses (table), while having >=1 previous VF resulted to be associated to VR in the two sensitivity analyses. Conclusion: Despite the increased risk of VR in pts with previous VF, especially in those with >=1 VF, the 1-year VR was very low. Although longer follow-up is needed to confirm this observation, current data suggest that DTG+3TC should be cautiously used in pts with current viral suppression but a history of VF

Poster Abstracts

CROI 2020 172