CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: Two years after its introduction in Switzerland, more than 50% of patients within the SHCS were switched to TAF, with the highest proportions among men, patients >50 years, as well as in those with renal impairment or on PI-based ART. However, we noted large differences in switching rates across centers, potentially driven by clinical and programmatic factors.

Poster Abstracts

507 SEVEN-YEAR TREATMENT RESPONSES IN SUBTYPE A1 VS D HIV-1 INFECTIONS IN MBARARA, UGANDA

Guinevere Q. Lee 1 , Nicholas Musinguzi 2 , David B. Gootenberg 1 , Suzanne McCluskey 3 , Yap Boum 2 , Bosco M. Bwana 2 , Conrad Muzoora 2 , Simone Kigozi 2 , Peter W. Hunt 4 , Jeffrey N. Martin 4 , David R. Bangsberg 5 , Jessica E. Haberer 3 , Mark J. Siedner 3 , P. Richard Harrigan 6 , Musie Ghebremichael 1 1 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 2 Mbarara University of Science and Technology, Mbarara, Uganda, 3 Massachusetts General Hospital, Boston, MA, USA, 4 University of California San Francisco, San Francisco, CA, USA, 5 Oregon Health and Sciences University, Portland, OR, USA, 6 University of British Columbia, Vancouver, BC, Canada Background: Subtype D HIV-1 has been associated with more rapid progression to AIDS in untreated infections. In a previous study, we found that subtype A1 and D infections did not differ in initial response to short term therapy: 86% of individuals achieved undetectable viremia within 6 months. Here, we compared long-term treatment responses and odds of detecting drug resistance between subtype A1 versus D HIV-1 infections. Methods: 500 chronically-infected individuals enrolled just prior to initiation of NNRTI based therapy between 2005-2010 were followed >7 years in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort. Pre-therapy plasma HIV-1 genotype was obtained by Sanger sequencing of HIV-1 pol and subtyped by RIP 3.0. Piecewise linear mixed-effects models were used for trajectory analyses. Definitions used were: viral load blips (>=1000 copies/mL), virologic suppression (<=400 copies/mL to accommodate older detection limits), adherence (Medication Event Monitoring System), loss to follow-up (lack of viral load measurements within 180 days before study cutoff on Jan-1-2013), post- therapy stool microbial community compositions (V3-V4 16S rRNA sequences processed with QIIME, R, and Phyloseq). Results: A total of n=198 subtype A1 and n=156 subtype D infections were detected. Pre-treatment, subtype D was associated with a marginally lower pre-therapy CD4 count (A1 versus D: median 141 vs 123, Mann-Whitney p=0.06) but baseline viral load did not differ (median 5.1 vs 5.1, Mann-Whitney p=0.8). Upon therapy initiation, 84% A1 and 88% D individuals achieved virologic suppression within 6 months. Over the >7 years follow up, neither viral load, CD4 trajectories nor adherence differed (piecewise linear mixed-effects models p=1.0 and p=0.6 Table1; mean adherence 91% vs 89%, unpaired t-test p=0.2). Infections by the two subtypes also did not differ in (i) percentage of individuals experiencing blips (10% vs 7%, Fisher’s 2-tailed p=0.4), (ii) odds of developing drug resistance over the span of 7 years (all Fisher’s 2-tailed p>0.4; 10% vs 9% of participants had drug resistance by year 5), (iii) loss to follow-up by year-7 (30% vs 32%, Fisher’s 2-tailed p=0.8), and (iv) stool microbial community compositions at year-7 (p=0.8, n=45 A1 and n=19 D, PERMANOVA of inter- community Jensen-Shannon Distance).

506 PREDICTORS OF SWITCHING FROM TDF TO TAF: REAL-WORLD DATA FROM A NATIONWIDE STUDY Bernard Surial 1 , Matthias Cavassini 2 , Alexandra Calmy 3 , Jan S. Fehr 4 , Marcel Stoeckle 5 , Enos Bernasconi 6 , Pietro L. Vernazza 7 , Christoph A. Fux 8 , Helen Kovari 4 , Hansjakob Furrer 1 , Andri Rauch 1 , Gilles Wandeler 1 , for the Swiss HIV Cohort Study 1 University Hospital of Bern, Bern, Switzerland, 2 Lausanne University Hospital, Lausanne, Switzerland, 3 University Hospitals of Geneva, Geneva, Switzerland, 4 University Hospital Zurich, Zurich, Switzerland, 5 University Hospital Basel, Basel, Switzerland, 6 Ospedale Regionale di Lugano, Lugano, Switzerland, 7 St. Gallen Cantonal Hospital, St Gallen, Switzerland, 8 Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Aarau, Switzerland Background: Since its availability in October 2016, tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in the antiretroviral therapy (ART) regimen of many HIV-infected persons. We used data of the Swiss HIV Cohort Study (SHCS) to explore individual predictors for being switched to TAF. Methods: We included all HIV-infected adults on TDF-containing ART in January 2016 with clinical follow-up thereafter. We determined the proportion of patients who switched to TAF and used multivariable logistic regression to explore related predictors. We repeated the analyses in patients with risk factors for TDF-related toxicity, namely osteoporosis or impaired renal function (estimated glomerular filtration rate [eGFR] <60ml/min and/or proteinuria ≥50mg/mmol). Results: Of 5’012 patients included, 3’645 (72.7%) were male, 789 (15.8%) were of black ethnicity and median age was 49 years (interquartile range [IQR] 41-56). The eGFR was <60 ml/min in 213 patients (4.2%), 407 patients (8.1%) had proteinuria, and osteoporosis was diagnosed in 261 patients (5.2%). Protease inhibitors (PI) were part of the ART regimen in 1’178 individuals (23.5%). As of 1st July 2018, 2’732 (54.5%) had TDF replaced by TAF. Men (adjusted odds ratio [aOR] 1.30, 95% confidence interval [CI] 1.08-1.56), patients >50 years (aOR 1.29, CI 1.09-1.51), and those with an eGFR <60ml/min (aOR 2.67, CI 1.75–4.06) or PI-based ART (aOR 3.10, CI 2.57-3.74) were most likely to switch. Individuals with a CD4 cell count <500/µl (aOR 0.83, CI 0.71-0.97) and those followed in non-tertiary centers (aOR 0.75, CI 0.64-0.87) were less likely to receive TAF (Figure). We observed large differences in switching rates across centers, ranging from 32.6% to 65.3% (p<0.001). Of 795 patients with at least one risk factor for TDF-toxicity, 533 (67.1%) switched to TAF, with an increased probability in those with an eGFR <60 ml/min (aOR 2.17, CI 1.24-3.78) or a PI-based regimen (2.83, CI 1.66-4.81). Of patients remaining on TDF despite the presence of risk factors, the most common regimens were fixed-dose combinations including rilpivirine (35.9%) or efavirenz (29.2%).

CROI 2019 189