CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

cases, these mutations occurred in the absence of TAMs, suggesting that there may be a role for these silent mutations independent of TAMs. K65K and K66K conferred a fitness advantage of 2.01 ± 0.11% and 2.41 ± 0.41% respectively to MDR HIV-1 variants in the absence of drug pressure (n=3 for each). Conclusions: K65K and K66K confer a fitness advantage in the context of MDR virus, even in the absence of drug. An unexpected tripling in prevalence of these mutations in drug- naïve individuals over the past 20 years was observed. Approximately one in three individuals with subtype B virus now harbor these mutations, suggesting that their potential impact should not be ignored.

484 No Effect of HIV-1 Subtype C on Virological Failure RateWith First-Line TDF Regimens EllenWhite 1 ; Erasmus Smit 2 ; Duncan Churchill 3 ; Simon Collins 4 ; Clare Booth 5 ; AnnaTostevin 1 ; Caroline Sabin 6 ; Deenan Pillay 7 ; David Dunn 1 ; for the UK HIV Drug Resistance Database and the UK Collaborative HIV Cohort 1 Med Rsr Council Clinical Trials Unit at Univ Coll London, London, UK; 2 Birmingham Heartlands Hosp, Birmingham, UK; 3 Brighton and Sussex Hosps NHS Trust, Brighton, UK; 4 HIV i-Base, London, UK; 5 Royal Free London NHS Fndn Trust, London, UK; 6 Univ Coll London, London, UK; 7 Africa Cntr for Hlth and Pop Studies, Mtubatuba, South Africa Background: In vitro and clinical studies have shown that subtype C viruses have a greater propensity to develop a K65R mutation due to polymorphisms at codons 64-66. This has potentially important public health implications given that subtype C infection accounts for around 50% of HIV infections worldwide and with the expanded use of tenofovir (TDF) as per WHO 2013 recommendations. We have exploited the wide diversity of viral subtypes within the UK to examine whether viral subtype influences the rate of virological failure (VF) on first-line TDF-containing regimens. Methods: Patients were included if HIV care was received at a participating clinic in the UK CHIC study; their first-line regimen was TDF+(XTC)+(EFV, NVP, LPV/r, DRV/r or ATV/r); and ≥2 viral loads (VLs) measured after 6 months following ART initiation. Subtypes were defined according to Rega-3, based on resistance tests conducted pre-therapy or at treatment failure. Time to VF (2 consecutive VLs >200 copies/ml after 6 months of ART) was analysed using Cox models, adjusting for demographic factors, baseline CD4 and VL, ART regimen, and year of initiation. Follow-up was censored at last VL or discontinuation of TDF. Multiple imputation was used to include patients with missing subtypes, taking advantage of the strong association with demographic factors. Results: 8746 patients were included and followed for a median of 3.3 years; 5465 (4123 observed, 1342 average of imputed) were subtype B, 1455 (823, 632) subtype C, and 1826 (1203, 623) non-B/non-C. Subtype B patients were mostly white (83%) and MSM (85%) while subtype C mostly black (70%) and heterosexual (79%). Subtype non-B/non-C patients were demographically more mixed (35%white, 53% black; 26%MSM, 63% heterosexual). Risk of VF for subtype non-B/non-C (173, 9.5%) was similar to subtype C (142, 9.8%) (aHR=1.1, 95% CI 0.8-1.4). In unadjusted analyses, patients with subtype B infection had a much lower risk of VF (309, 5.7%) than subtype C (HR=0.5, 95% CI 0.4-0.7). However this difference was markedly reduced in adjusted analyses (aHR=0.9, 95% CI 0.6-1.2, P=0.41), largely mediated by the effects of exposure group and ethnicity. Conclusions: Patients infected with subtype C virus on a first-line TDF containing regimen appear not to experience a higher rate of VF with differences observed explained by demographic factors rather than a subtype effect. This is a reassuring finding for expanded use of TDF in southern Africa, India, and other areas where subtype C virus predominates.

Poster Abstracts

485 National Molecular Surveillance of Recently Acquired HIV Infections, Germany 2013-14 Andrea Hauser 1 ; Alexandra Hofmann 1 ; Kirsten Hanke 1 ;Viviane Bremer 1 ; Barbara Bartmeyer 1 ; Claudia Kucherer 2 ; Norbert Bannert 2 1 Robert Koch Inst, Berlin, Germany; 2 Robert Koch-Inst, Berlin, Germany

Background: Continuous molecular HIV surveillance provides valuable public health information concerning the transmission of drug resistant viruses and the dynamics of currently circulating variants. To enable an up-to-date molecular analysis of HIV-genotypes circulating in Germany, the Robert Koch Institute (RKI) has established a surveillance

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CROI 2016

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