CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: MVC intensification of cART in immunological non-responders slightly increases CCR5-ligand expression, NF- κ B regulated gene expression and HIV RNA expression. This is in line with our in vitro observation of MVC induced HIV production. Together, these data indicate that MVC induces HIV production, potentially via upregulation of the NF-kB pathway which warrants further investigation into the potential consequences of this observation for the use of MVC as a pre-exposure prophylaxis. 550 Consistency of Dolutegravir Treatment Difference in HIV+ Treatment Naives at Week 96 Catherine M. Granier 1 ; Robert Cuffe 2 ; Louise Martin-Carpenter 3 ; KimberlyY. Smith 3 ; Clare Brennan 4 ; Keith Pappa 4 ; BrianWynne 4 ; Steve Almond 5 ; Naomi Givens 1 ; Michael Aboud 2 1 GlaxoSmithKline, Uxbridge, United Kingdom; 2 ViiV Healthcare, London, United Kingdom; 3 ViiV Healthcare, Research Triangle Park, NC, US; 4 GlaxoSmithKline, Research Triangle Park, NC, US; 5 GlaxoSmithKline, Mississauga, Canada Background: DTG 50mg QD plus two N(t)RTIs has been compared to 3 preferred regimens in pivotal studies up to 96 weeks (SPRING2 and FLAMINGO) or 144 weeks (SINGLE) in treatment naïve patients. Consistency of the treatment difference was explored within key subgroups. Methods: SPRING-2 randomized participants to DTG 50mg QD or RAL 400 mg BID, FLAMINGO randomized participants to DTG 50mg or DRV/r QD. In both studies, investigator selected NRTIs (TDF/FTC or ABC/3TC). SINGLE randomized participants to DTG 50 mg + ABC/3TC QD or TDF/FTC/EFV QD. Snapshot response rates were analyzed by NRTI backbone, baseline viral load and baseline CD4. Also, time to efficacy related failure, where withdrawals unrelated to efficacy are censored, were used for the week 96 pooled analyses and were summarised by NRTI backbone and baseline viral load. Results: The three studies randomized and treated a total of 2139 subjects. Overall, there was no evidence of compromised efficacy in individuals on DTG with high viral load or low CD4s. Subgroup analysis of the Week 96 snapshot suggested that, in individuals with high viral load, there were similar response rates to DTG and EFV in SINGLE however, DTG had a higher response rate vs DRV/r in FLAMINGO. These apparent interactions were not consistent across studies or timepoints. In the SINGLE study, at Weeks 48 and 144, the response rate for patients with high VL at baseline receiving DTG was 7-8 percentage points higher than for those on EFV. Exploratory analyses examining time-to-efficacy related failure showed no difference in response rates between the background NRTIs pooled across the studies irrespective of baseline viral load. Additionally, there was no suggestion of a difference in efficacy related failures between DTG vs comparator agents at high or low viral load.

Poster Abstracts

Conclusions: In three large treatment-naïve studies, DTG was effective up to week 96 with both ABC/3TC and TDF/FTC, in subjects with high and low viral load and across CD4 strata. DTG is a once daily, unboosted INI that can be used effectively with either TDF/FTC or ABC/3TC backbone in treatment-naive, HIV-infected individuals. 551 Predictors of HIV RNA Suppression on Darunavir/Ritonavir Monotherapy in the MONET and PROTEA Trials Diego Ripamonti 2 ; Ralph DeMasi 3 ; AndrewM. Hill 1 ; Ceyhun Bicer 4 ; Christiane Moecklinghoff 5 1 Chelsea and Westminster Hospital, London, United Kingdom; 2 A.O. Papa Giovanni XXIII, Bergamo, Italy; 3 Janssen Pharmaceuticals, Inc., Titusville, NJ, US; 4 Janssen Pharmaceuticals, Inc., Beerse, Belgium; 5 Janssen Pharmaceuticals, Inc., Neuss, Germany Background: In previous studies of protease inhibitor (PI) monotherapy, patients with higher nadir CD4 counts, no HCV co-infection, higher adherence to treatment, or lower baseline levels of HIV RNA or DNA have been the most likely to show sustained HIV RNA suppression <50 copies/mL. Methods: In the MONET and PROTEA trials, 529 patients with HIV RNA <50 copies/mL at screening switched to DRV/r 800/100 mg once daily, either as monotherapy (n=264) or as triple therapy with 2NRTIs (n=265). Patients with CD4 nadir <100 cells/ m L were excluded from these studies. At the screening visit, patients were taking either 2NRTIs plus either NNRTI- based or non-NNRTI based treatment (typically 2NRTI/PI or 2NRTI/Integrase). At Week 48, treatment failure was defined as HIV RNA>50 copies/mL or discontinuation of study drugs (FDA Snapshot method). Multivariate logistic regression was used to identify factors predictive of treatment failure in the two combined clinical trials by Week 48: baseline HIV RNA (target not detected), age, gender, race, HCV co-infection, nadir CD4 count, duration of diagnosis, time to ARV use, treatment group, baseline CD4 count and prior treatment. Results: In the two trials, there were 224/264 patients on DRV/r monotherapy (85%) with HIV RNA <50 copies/mL at Week 48, versus 240/265 (91%) on triple therapy. In the multivariate logistic regression analysis, the two significant predictors of higher response rates at Week 48 were CD4 nadir ≥ 200 cells/ m L and no prior use of NNRTI-based treatment before baseline. The efficacy of DRV/r monotherapy ranged from 69% for those with CD4 nadir <200 cells/ m L and prior NNRTI treatment, to 91% for those with CD4 nadir >200 m L and no prior NNRTI treatment (Table). There was no further improvement in efficacy for patients on DRV/r monotherapy with CD4 nadir categories above 200 cells/ uL,

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CROI 2015