CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

HIV RNA<50 copies/mL at Week 48, PROTEA/MONET trials Conclusions: In the combined MONET and PROTEA trials, patients with CD4 nadir above 200 cells/uL and no prior NNRTI-based treatment were most likely to show sustained HIV RNA suppression on DRV/r monotherapy at Week 48 (91%). CD4 nadir may be an indirect marker of prior disease severity. 552 Second-Line Treatment in Sub-Saharan Africa: Week 144 Follow-up of the EARNEST Trial James G. Hakim 1 ; JenniferThompson 2 ; Cissy M. Kityo 3 ; SarahWalker 2 ; Joep van Oosterhout 4 ; Anne Hoppe 2 ; Andrew D. Kambugu 5 ; Peter Mugyenyi 3 ; Nicholas Paton 6 On behalf of the EARNESTTrialTeam 1 University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe; 2 University College London, London, United Kingdom; 3 Joint Clinical Research Centre, Kampala, Uganda; 4 Dignitas, Zomba, Zomba, Malawi; 5 Infectious Disease Institute, Kampala, Uganda; 6 National University of Singapore, Singapore, Singapore; 7 MRC Clinical Trials Unit at University College London, London, United Kingdom Background: Trials to date have not shown any clear short-term benefit to replacing NRTIs with raltegravir in PI-based second-line therapy. However, longer-term efficacy and safety outcome data are needed to fully assess the potential value of this new combination for ART rollout programme settings. Methods: 1277 patients aged ≥ 12 years who met WHO-defined treatment failure criteria after >12 months on NNRTI-based first-line ART were randomised in an open-label trial in 14 sub-Saharan African sites to receive bPI + 2/3 clinician-selected NRTIs (PI/NRTI group), bPI plus RAL (400mg bd) (PI/RAL group); or bPI monotherapy (+RAL induction for first 12 weeks; by DMC recommendation, treatment was re-intensified after week 96 (at median week 124), adding NRTIs only in 94% or by other treatment switch in 6%)(PI-mono group). bPI was standardised to lopinavir/ritonavir, 400mg/100mg bd. Treatment was monitored clinically and by open CD4 count; VL and resistance testing were done annually blinded, reviewed by the DMC. The primary (composite) endpoint, good disease control, was defined as no newWHO stage 4 events (or death) after randomisation, and CD4 count >250 cells/mm3 and VL < 10,000 copies/ml (or >10,000 copies/ml without major/minor PI resistance mutations) at week 96. Here we report final trial outcomes at week 144. Results: Patients were 58% female, median baseline CD4=71 cells/mm 3 , VL=69,782 copies/ml; 2%were withdrawn/lost to follow-up by week 144. There was no evidence of benefit of PI/RAL over PI/NRTI on any efficacy or safety outcome at week 144 (Table 1). In both PI/RAL and PI/NRTI intermediate-high level resistance to lopinavir was low; in PI/ NRTI, NRTI resistance was also low (<3.5%); 6.7% of PI/RAL were estimated to have intermediate-high level raltegravir resistance. In PI-mono, clinical and CD4 outcomes were similar to other groups, and VL suppression recovered substantially at week 144 (up from 61.3%<400 c/ml at week 96 to 77.8% at week 144). A substantial proportion of patients in all groups still had not achieved a CD4 >250 cells/mm 3 after 144 weeks on second-line therapy.

Poster Abstracts

Table: Efficacy and Safety Outcomes at Week 144 Conclusions: PI/RAL was not superior to PI/NRTI at week 144. NRTI re-initiation led to good re-suppression in PI-mono. PI with 2NRTIs remains the optimal regimen for rollout programme settings. 553 Withdrawing Inactive NRTIs in Subjects With Suppressed Viremia: A Randomized Trial Josep M. Llibre 1 ; Hortensia Alvarez 8 ; Antonio Antela 2 ; JessicaToro 1 ; Juan González-Moreno 3 ; M Jesús Perez-Elias 4 ; Arkaitz Imaz 5 ; Mar Masià 6 ; Manel Crespo 7 ; Bonaventura Clotet 1 1 Univ Hosp Germans Trias, Badalona, Spain; 2 Hospital Clínico Universitario, Santiago de Compostela, Spain; 3 Hospital Son Llàtzer, Mallorca, Spain; 4 Hospital Ramón y Cajal, IRYCIS, Madrid, Spain; 5 Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain; 6 Hospital Universitario de Elche, Elche, Spain; 7 Hospital Universitari Vell d’Hebró, Barcelona, Spain; 8 Complejo Universitario de Ferrol, A Coruña, Spain Background: Extensively pretreated subjects with virologic failure (VF) may receive salvage regimens containing NRTIs with only residual activity. Once virologic suppression is achieved, their contribution remains elusive. Withdrawing NRTIs with intermediate to complete genotypic resistance (Spanish RIS Resistance Score) when viral load (VL) <50 c/mL could have non-inferior efficacy to their maintenance, with lower potential toxicity and cost. Methods: Multicenter, randomized, prospective, open study. Subjects with ≥ 1 prior VF, VL<50 c/mL for ≥ 6 months, any CD4 count, without hep B, receiving ≥ 2 active drugs (one of them an active boosted PI), and ≥ 1 NRTI without complete activity, were randomly allocated to stop NRTIs without complete activity (one or both, Exp arm) or to maintain the treatment (Ctrol). No drug changes allowed during last 6 months or at screening. Main endpoint VL<50 c/mL at 48 weeks (Snapshot analysis), non-inferiority margin at -12. EudraCT: 2012-000198-21. Results: 92 subjects were screened and 90 randomized (Exp, n=45, Ctrol, n=45). Median age 50y old, 80%male, 37% stage C3, 40% chronic hep C, CD4 488 (IQR 355-712) cells, 17 median years on ART. Had received a median of 9 lines of ART, 4 PIs, and a median of 3 (1-4) prior VF. The baseline regimen contained 4 drugs in 46 (51%) subjects, and 3 in 37 (41%). 74 subjects (82%) harbored M184V/I, and the median of TAMs was 3 (2-4; D67X and T215X the most frequent). 32 (71%) subjects removed 1 NRTI (12 TDF, 9 FTC, 8 3TC, 2 ABC, 1 ddI)

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CROI 2015