CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

years [0.8-5.1]). The subtype difference in K65R prevalence was observed irrespective of NRTI exposure, and K65R was frequently selected by ABC, ddI, and d4T in patients with no previous exposure to TDF (Figure). Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (odds ratio 1.95, 95% CI: 1.51-2.51, P<0.001).

Conclusions: These clinical data complement experimental evidence that K65R is more likely to be detected at VF for subtype C viruses compared with subtype B viruses. 597 Viral Failure and High K65R in Kenyan Patients on Tenofovir-Based First-Line Therapy Katherine C. Brooks 2 ; Lameck Diero 1 ; Allison Delong 2 ; Maya Balamane 2 ; Marissa Reitsma 2 ; Emmanuel Kemboi 3 ; Millicent Orido 3 ; Mia Coetzer 2 ; Joseph Hogan 2 ; Rami Kantor 2 1 Moi University, Eldoret, Kenya; 2 Brown University, Providence, RI, US; 3 Academic Model Providing Access to Healthcare, Eldoret, Kenya Background: Tenofovir (TDF)-based 1 st -line antiretroviral therapy (ART) is globally recommended by the World Health Organization (WHO). Effects of switching from prior non-TDF to TDF-based regimens on ART success are unknown. High rates of the TDF-associated K65R mutation in HIV-1 subtype C, but not B, are reported, associated with a poly-A template in reverse transcriptase (RT) positions 64-66. Such mechanisms in other HIV-1 subtypes are not well-defined. Methods: We examined treatment failure and resistance in Kenyan patients on ≥ 6 months of TDF-based 1 st -line ART at the academic model providing access to healthcare (AMPATH). We compared these outcomes among patients with (Prior-ART Group) and without (TDF-Only Group) prior non-TDF-based 1 st -line ART. Pol sequences of patients with detectable VL (>40 copies/mL) were interpreted with Stanford Database tools using Fisher exact and Wilcoxon tests. Results: Among 332 enrolled patients (55% female, median age 41 years, 63% XTC/TDF/nevirapine; 37% XTC/TDF/efavirenz; median CD4 336 cells/ μ L), detectable VL was in 17%, and VL>1,000 copies/mL (WHO cutoff) in 10%. Of those, 216 were in the TDF-Only Group (median 20 months on ART), and 116 in the Prior-ART Group (median 24 months on TDF-based ART and 47 months on prior ART). Detectable VL was in 23% of the TDF-Only Group and 7% of the Prior-ART Group (p<.001 ) . TDF-only failing patients had lower CD4 values (p<.001) and higher WHO stage (p=.03). VL>1,000 copies/mL was seen in 15% of the TDF-Only Group and 1% of the Prior-ART Group ( p<.001). In 35 available genotypes from the TDF-Only Group 69%were subtype A, 11% D, 12% C and 9% AD. RT resistance was in 89%, 89% to NNRTIs, 83% to NRTIs and 83% dual-class. K65R occurred in 69% (24/35) of patients ; subtype C 100% (4/4), subtype A 71% (17/24) and subtype D 50% (2/4) (p=.22). Patients with K65R had lower CD4 values (p<.02), higher WHO stage (p=.004) and more RT resistance mutations (p<0.001). Examination of RT positions 64-66 from subtype A infected ART-naïve persons from the same Kenya clinic (n=32) and from the Stanford Database (n=3,903), demonstrated similarity to subtype B, without the poly-A chain that promotes K65R in subtype C. Conclusions: In this Kenyan cohort, switching from non-TDF to TDF-based 1 st line ART was successful. Higher failure rates were seen in patients with only TDF-based ART compared to those with prior 1 st -line ART exposure. High observed K65R rates in subtype A were not explained by the poly-A template, suggesting alternative mechanisms. 2:30 pm– 4:00 pm Transmitted HIV Drug Resistance: Assessing the Threat 598 Large NNRTI-Resistant Transmission Cluster in Injection Drug Users From Saskatchewan Alexander Wong 1 ; Jaspreet Kambo 1 ; Richard Harrigan 2 ; Art F. Poon 2 ; Jeffrey B. Joy 2 1 University of Saskatchewan, Regina, Canada; 2 BC Centre for Excellence in HIV/AIDS, Vancouver, Canada Background: Saskatchewan, a Canadian Prairie province, is currently experiencing a unique HIV epidemic characterized by high rates of transmission through injection drug use. Aboriginal peoples are disproportionately affected. Methods: We reviewed the epidemiologic and clinical characteristics of all HIV-positive individuals who attend the Regina Qu’Appelle Health Region Infectious Diseases Clinic, which serves the southern half of Saskatchewan and represents 25% of the province’s HIV burden. Molecular phylogenies were inferred from anonymized bulk HIV-1 pol sequences from pre-therapy resistance genotyping of all patients for whom testing was available. Short tip-to-tip distances (patristic distance < 0.02) between sequences from different individuals on the phylogeny were used to define clusters. Resistance data was super-imposed on phylogenetic trees to identify clusters of primary transmitted drug resistance. Results: 415 individuals were included in the analysis. 227/415 (54.6%) were Aboriginal, 246/415 (59.2%) had injection drug use as their primary risk factor for HIV acquisition, and 243/415 (58.5%) were positive for hepatitis C antibody. Through phylogenetic analysis, a large transmission cluster of 81 individuals (19.5% of clinic) was identified in which 76 individuals were harbouring a G190A mutation in the reverse transcriptase gene, conferring NNRTI resistance. Compared to the overall clinic population, individuals with a G190A mutation in this cluster were more likely to be Aboriginal (58/76 [76.3%], RR 1.5, P < 0.01), have injection drug use as their primary risk for acquisition of HIV (63/76 [82.9%], RR 1.5, P < 0.01), and be co-infected with hepatitis C (64/76 [84.2%], RR 1.6, P < 0.01). 10 other clusters were identified but were of smaller size ( ≤ 18), and none were associated with transmitted drug resistance. THURSDAY, FEBRUARY 26, 2015 Session P-L3 Poster Session Poster Hall

Poster Abstracts

379

CROI 2015