CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: The degree of association between VCY and risk of clinical events varied across different AUC shapes, especially for AIDS/death. In particular, for a given difference in AUC, in people showing stable VL trajectories rather than periods of VL dips and spikes, VCY appear to better discriminate the risk. Strategies to maximize the chance of viral suppression should be considered for patients with suboptimal viral response even at low-level detectable viremia. 563 Monitoring and Switching of Antiretroviral Therapy in Sub-Saharan Africa Andreas D. Haas 1 ; Olivia Keiser 1 ; François Dabis 2 ; Mary-Ann Davies 3 ; Rosalind M. Parkes-Ratanshi 4 ; Steven J. Reynolds 5 ; KaraWools-Kaloustian 6 ; GillesWandeler 1 ; Matthias Egger 1 IeDEA East,West and Southern Africa 1 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; 2 Université Bordeaux, Bordeaux, France; 3 University of Cape Town, Cape Town, South Africa; 4 Makerere University College of Health Sciences, Makerere, Uganda; 5 National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, US; 6 Indiana University, Indianapolis, IN, US Background: Monitoring of antiretroviral combination therapy (ART) aims to maximize the durability of first-line ART regimens. Viral load monitoring is recommended but limited access to viral load tests in resource-limited settings means that decisions about switching to second-line ART are often based on clinical or immunological criteria. We examined monitoring of ART and switching to second-line regimens in sub-Saharan Africa. Methods: We included adult treatment naïve HIV-1 infected patients starting ART in sub-Saharan Africa. Monitoring strategies were defined as routine virologic monitoring (>75 viral load tests per 100 person-years), routine immunological monitoring (>75 CD4 cell counts per 100 person-years), or clinical monitoring. Switching to second-line ART was defined as changing from an NNRTI-based regimen to a PI-based regimen and changing at least one NRTI. We calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) from Cox regression models to identify predictors of switching. Results: 421,518 patients from 38 ART programmes in 17 countries were followed for a total of 885,135 person-years of follow-up; 11,075 patients switched. Rates of switching ranged from 0.0 to 1.7 per 100 person-years in nine programmes with clinical monitoring, from 0.0 to 4.6 per 100 person-years in 21 programmes with immunological monitoring and from 1.1 to 4.2 per 100 person-years in eight programmes with virologic monitoring. Compared to clinical monitoring, switching was twice as common with virologic monitoring (aHR 2.30; 95% CI 1.44-3.68), but similar with immunological monitoring (aHR 0.99; 95% CI 0.85-1.16). Switching increased with viral load testing (Figure 1), was higher in urban than in rural sites, and higher in regional and University hospitals than in district hospitals or health centres. Effects were not explained by differences in patient characteristics. Among the patients with a confirmed immunological or virologic failure (n=25,300) only relatively few (16%) switched within two years after failure. The proportion of patients switching to second-line ART was lowest in programmes with clinical monitoring (7.9%-23.7%), and highest in patients with viral loads >10,000 copies/ml in CD4 monitoring sites (71.8%).

Poster Abstracts

Figure 1: Bubble plot of rates of viral load testing and switching to second-line antiretroviral therapy according to monitoring strategy. Rates were calculated by calendar year and site. The size of the circles is proportional to the number of person-years in the respective year and site. Conclusions: Rates of switching to second line ART vary widely across treatment programmes in sub-Saharan Africa. Rates increase with viral load testing, but a sizable proportion of patients with documented virologic treatment failure are not switched to second-line ART. 564 Virological Factors AssociatedWith Outcome of Dual MVC/RAL Therapy (ANRS-157 Trial) Cathia Soulie 1 ; Lambert Assoumou 2 ; Melanie Darty 3 ; Christophe Rodriguez 3 ; Gilles Peytavin 4 ; Marc-AntoineValantin 5 ; Dominique Costagliola 2 ; Christine Katlama 5 ;Vincent Calvez 1 ; Anne-Genevieve Marcelin 1 1 Hôpital Pitié Salpêtrière, Paris, France; 2 INSERM/UPMC, Paris, France; 3 APHP Mondor, Creteil, France; 4 APHP Bichat, Paris, France; 5 Hôpital Saint-Louis, APHP, Université Paris Diderot, Paris, France Background: ROCnRAL ANRS-157 was a single-arm study designed to evaluate a switch to a maraviroc (MVC) 300 mg bid plus raltegravir (RAL) 400 mg bid regimen in virologically suppressed patients with lipohypertrophy, and R5-tropic B or CRF02_AG HIV-1 subtype determined on DNA by Sanger sequencing. In these long-term antiretroviral experienced patients (n=44), the combo MVC/RAL lacks virological robustness despite a good treatment adherence, adequate respective plasma pharmacokinetics and benefit in lipid profile: 7 patients failed MVC/RAL therapy with 5 virological failures (VF) defined as two consecutive plasma viral load (pVL) > 50 cp/mL and 2 treatment discontinuations due to serious adverse events. The aim of this work was to investigate the factors associated with VF. Methods: At baseline (BL), Ultra Deep Sequencing (UDS) of DNA gp120 V3 and integrase regions (454 Roche) and quantification of cellular HIV DNA were performed in PBMC. Viral tropismwas interpreted using Geno2pheno algorithm (samples harboring >2% non-R5 variants were classified non-R5 viruses). Genotypic resistance mutations were evaluated according to the ANRS and IAS mutations list. Quantification of pVL was measured using an ultrasensitive assay (1 cp/mL). Tropism, BL ultrasensitive HIV RNA pVL, BL HIV DNA VL, subtype, age, ethnicity, transmission group, AIDS status, nadir CD4 and BL CD4 cell count, time since HIV diagnosis, duration of antiretroviral treatment, duration of suppressed viremia, pVL zenith, CD4/CD8 ratio, BL CD8 cell count were investigated as potential factors associated with VF.

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CROI 2015