CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

M184V at VF. Exclusion mutations were also detected at low frequencies in 7 control patients (BL VL >100,000 c/mL: K65R, E138K n=2 each; Y181C, E138G n=1 each; BL VL ≤ 100,000 c/mL: E138G n=1). Six were virologic successes at Week 96; 1 patient with 1.08% K65R discontinued at Week 32 with HIV-1 RNA 64 c/mL. Additional NRTI- or NNRTI- associated mutations not detected by population sequencing at VF were detected in 41% (9/22) of RAP VF isolates with deep sequencing data. Conclusions: The presence of low-frequency NRTI- and NNRTI-associated mutations at baseline was not predictive for VF or resistance development for RPV/FTC/TDF-treated patients in the STaR study. Deep sequencing results were generally consistent with population sequencing but detected additional low-frequency resistance mutations at VF. 606 High Rates of Early Virologic Failure in a Cohort of Tanzanian HIV-Infected Adults Claudia A. Hawkins 1 ; Nzovu Ulenga 2 ; Enju Liu 3 ; Said Aboud 4 ; Ferdinand Mugusi 4 ; Guerino Chalamilla 2 ; David Sando 2 ; Eric Aris 2 ;Wafaie Fawzi 3 1 Northwestern University, Feinberg School of Medicine, Chicago, IL, US; 2 Management and Development for Health, Dar es Salaam, United Republic of Tanzania; 3 Harvard School of Public Health, Boston, MA, US; 4 Muhimbili University of Health and Allied Sciences, Dar es Salaam, United Republic of Tanzania Background: There are few data on antiretroviral treatment (ART) failure and HIV drug resistance in Tanzania where there are a wide diversity of non-B HIV subtypes. We assessed rates and risk factors associated with virologic failure (VF) in a cohort of Tanzanian HIV-infected adults on first line antiretroviral therapy (ART) and describe resistance patterns in a subset of patients. Methods: Non-pregnant, ART naïve, HIV-1 infected adults who were enrolled in a randomized controlled multivitamins trial between November 2006 -2008, and on at least 24 weeks first-line NNRTI-containing ART were included in the analysis. Population-based genotyping (GT) of HIV-1 protease and reverse transcriptase was performed on plasma samples from patients with VF, defined as a viral load (VL) >1000 copies/mL at >24 weeks of ART, where available. Log-binomial regression models were used to examine predictors of virologic failure. Results: 2,403 HIV-infected adults (median age 37 (IQR 32,43); 70% female) were included in the study. Median baseline CD4+ T cell count was 128 (IQR 62,190) cells/mm 3 and 76%were WHO stage III or IV. The combination of d4T, 3TC and NVP or AZT, 3TC and EFV was used in 82%. Median time on ART was 10.3 (IQR 7.5,11.9) months. Subtype distribution (n=64) was A (17, 27%), B (1,2%), C (24, 37%), CRF01_AE (4, 6%), and D (18, 28%). The overall rate of VF was 14.9% (IQR 13.2%, 16.1%). In multivariate analyses, significant predictors of VF were lower CD4+ T cell counts, [RRs 1.4 (95%CI 0.9-1.9), 1.6 (1.1-2.2), 1.2 (0.8-1.6) for patients with CD4<50, 50-<100, 100-<200 cells/mm 3 vs. CD4>200 cells/ mm 3 respectively, (p for trend=0.01)], and visit non-adherence [RR 1.5 (1.1, 1.9), p<0.01]. GT was performed on 115 samples from 106 patients with VF. Drug resistance mutations (DRMs) were present in 87/115 (75.7%). The most common drug resistance mutations (DRMs) were M184V/I (60/115, 52%), K103N (40/115, 35%), Y181C/I (29/115, 25%), G190A/S (20/115,17%). At least one Thymidine Analog Mutation (TAM) was present in 6/115 (5%). DRMs (>1) conferring potential resistance to etravirine were present in 6%. K65R was present in 2 patients. Conclusions: High levels of early ART failure and DRMs were observed in this Tanzanian cohort of HIV-1 infected patients enrolled in a well-monitored study setting, reinforcing the importance of routine VL testing. Early initiation of ART and optimal adherence early on in therapy is crucial for the success of commonly used first line therapies in sub-Saharan Africa. 607 HIV Drug Resistance Surveillance in Honduras After 10 Years of Widespread ART Claudia Garcia-Morales 1 ; Santiago Avila-Rios 1 ; DanielaTapia-Trejo 1 ; Rita Meza 2 ; Sandra Nuñez-Rubio 2 ; Norma Flores 5 ;Wendy Murillo 3 ; Ivette Lorenzana 3 ; Elsa Palou 4 ; Gustavo Reyes-Terán 1 1 National Institute of Respiratory Diseases, Mexico City, Mexico; 2 Honduran HIV National Program and National Laboratory, Tegucigalpa, Honduras; 3 Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras; 4 Hospital Escuela Universitario, Tegucigalpa, Honduras; 5 Instituto Nacional Cardiopulmonar, Tegucigalpa, Honduras Background: HIV drug resistance (DR) surveillance is key to maximizing the long-term effectiveness of antiretroviral treatment (ART) regimens and to ensure the sustainability of ART programs. We present results from a national study to assess the prevalence and trends of HIVDR in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART. Methods: 294 HIV-infected, ART-naïve, and 316 ART-experienced Honduran individuals were enrolled in 5 reference centers in Tegucigalpa, San Pedro Sula, Choluteca and La Ceiba, between April 2013 and July 2014. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIV transmitted DR (TDR) surveillance mutation list and the Stanford algorithm (v7.0). Recently infected (RI) individuals were identified using a multiassay algorithm using incidence tests, in order to assess TDR. Results: PDR to any ARV drug was 9.9%. NNRTI PDR prevalence (6.5%) was higher than NRTI (2.0%) and PI (2.0%, p<0.0001). A decrease in NNRTI PDR was observed comparing 2013 and 2014 (p=0.0234). This observation was confirmed using a moving average approach (p=0.0028), and was consistent with lower, although not significant, NNRTI TDR in RI individuals (4.8%). The most prevalent PDR mutations were M46IL (1.7%) to PI, T215X (0.7%) to NRTI, and K103NS (4.4%) to NNRTI. E138X mutations, conferring DR to rilpivirine were also highly prevalent (4.4%), causing higher PDR estimations when using the Stanford DR definition (15.6% to any ARV drug). The overall ADR prevalence for individuals with <48 months on ART was 88.0% and for the ≥ 48 months on ART group 79.8%. In both cases, PI ADR was lower, compared with NRTI and NNRTI (p<0.0001). ADR to two drug families was 71.1% and 67.0% and ADR to three drug families 1.2 and 9.9% respectively, with an increase in PI ADR in individuals with longer time on ART. M184V (67.0%), and K103N (40.3%) were highly frequent. PDR mutation frequency correlated with ADR mutation frequency both in individuals with <48 and ≥ 48 months on ART for PI and NNRTI (p<0.0005 in all cases), but not for NRTI.

Poster Abstracts

383

CROI 2015