CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

217 HIV Transmission Hotspot Detection Combining Sexual and Phylogenetic Network Analysis Dana K. Pasquale 1 ; Irene A. Doherty 2 ; Lynne A. Sampson 3 ; Peter A. Leone 4 ; Joseph Sebastian 5 ; Sue L. Ledford 6 ;WilliamMiller 7 ; Joseph J. Eron 7 ; Ann M. Dennis

1 Univ of North Carolina at Chapel Hill Sch of Global PH, Chapel Hill, NC, USA; 2 RTI, Research Triangle Park, NC, USA; 3 North Carolina Division of PH, Raleigh, NC, USA; 4 Univ of North Carolina at Chapel Hill Sch of Med, Chapel Hill, NC, USA; 5 Lab Corporation of America, Research Triangle Park, NC, USA; 6 Wake County Human Services, Raleigh, NC, USA; 7 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Studying local HIV transmission using molecular approaches may provide new avenues to supplement routine contact tracing. We investigated the overlap between phylogenetic transmission clusters and sexual networks involving new HIV cases in metropolitan Wake County, NC in the context of the statewide epidemic. Methods: Sexual networks were constructed using partner contact tracing data for index cases newly diagnosed with HIV from 2012-2013 (N=280) and their HIV+ and HIV- partners. HIV pol sequences (n=15,247; one per individual), from genotypes performed by the largest reference lab in NC from 1997-2014, were matched to HIV+ study cases with the remainder used as background references. Maximum-likelihood phylogenies were constructed. Transmission clusters (TC) were defined as clades with short branch lengths and high support (≥0.90) and confirmed with Bayesian methods. “Study” TCs were clusters including ≥2 persons from the traced Wake County network. Results: Of 280 index cases, 80%were interviewed by the health department and reported 854 sex partners and 34 social contacts; 446 (50%) were traceable. The resultant sexual network included 663 unique persons in 137 network components including 411 HIV+ cases. Most persons were Black (64%), MSM (59%), and between ages 25-45 years. 230 cases (53% index and 63% HIV+ partners) had a pol sequence. Of these, 171 (74%) were identified in 118 TCs (range 2-36 members; 804 total sequences); 87 (38%) were in 34 study TCs. However, only 48% (42/87) in a study TC were also in the same network component as at least one other study person in their TC. Both partners were in the same study TC in every heterosexual pair where each had a sequence. TC members were more likely to be men (77% vs. 57%women), men reporting male contacts vs. no named partners, and younger (median age 29 vs. 37 years). The four largest TC (range 6-36 members) involved 14 index and 5 partner cases distributed in 11 components (Figure). Three large TCs had growth after 2012 (75% sequences were sampled 2012-2014) indicating significant ongoing transmission. Conclusions: Phylogenetic analysis offers considerable promise to identify transmission in high risk populations that is not detected through contact tracing. Overlapping sexual networks with phylogenetic clusters provides novel methods for understanding HIV transmission dynamics and identifying transmission hotspots where interventions can be intensified, particularly among young MSM.

218 Metamorphosis of the Montreal MSM Epidemic: Large Cluster Viruses Fuel Transmission

Poster Abstracts

Bluma G. Brenner 1 ; Maureen oliveira 1 ; Ruxandra Ilinca Ibanescu 1 ; Olga Golubkov 1 ; Isabelle Hardy 2 ; Michel Roger 2 ; Mark A.Wainberg 3 1 Lady Davis Inst, Montreal, QC, Canada; 2 Cntr Hospier Univ de Montréal, Montreal, QC, Canada; 3 McGill Univ AIDS Cntr, Montreal, QC, Canada

Background: The 25-50% decline in HIV transmissions with antiretroviral therapy has raised optimism that Treatment-as-Prevention (TasP) may control the global pandemic by 2030. Paradoxically, transmissions among MSM have not declined, raising concerns that early-stage infection, frequently undiagnosed, may offset the benefit of TasP. Phylogenetics ascribe the growth of the Montreal MSM epidemic to large cluster outbreaks, averaging 43 linked transmissions/cluster. This study characterized the distinct genotypic and phenotypic features of large cluster viral variants favoring their selection advantage. Methods: Phylogenetic analysis was performed on RT/protease sequences from all newly infected MSM (n=4319, 2002-2014), assessing clustering dynamics (frequency, size, periodicity). Nucleotide mixed base calls estimated recency of infection, using a 0.44% cut-off for primary HIV infection (PHI). PHI cohort data evaluated the natural history (viral load, quasispecies diversity) in subjects belonging to large clusters vs. solitary transmission groups. Viruses were amplified from both cluster groups to ascertain infectivity, tropism, drug susceptibility and emergent resistance to integrase inhibitors. Results: There has been a significant rise in the relative contribution of X-large clusters representing 29%, 34%, and 46% of new infections over the 2002-2005, 2006-2009 and 2010-2013 periods. Overall, 40 viral lineages led to 1235 transmissions as compared to 1375 solitary “dead-end” transmissions (n=1375). Primary infections (0-0.44% genetic diversity) accounted for 57% and 26% of transmissions in large cluster and solitary transmission groups, respectively. PHI cohort data revealed viruses belonging to large clusters showed prolonged high viremia for 2 years as compared to unique transmissions where viremia declined to set points by 6 months. Amplified viruses from representative large clusters harbored X4/R5 dual tropic viruses (n=5/7) as compared to dominant R5 tropism in the unique transmission group (0/6). Large cluster variants developed drug resistance mutations under dolutegravir and elvitegravir pressure in 6-12 weeks as compared to solitary transmission variants that retained wild-type genotype at 26 weeks. Conclusions: Failure to control early stage transmission is leading to worrisome trends towards the selection of super-viruses showing prolonged viremia, dual tropism, rapid tropism shift, and/or facilitated escape from drug pressure. 219 Assessing HIV Transmission Networks in a Thai Cohort With Acute HIV Infection Eugène Kroon 1 ; Mark de Souza 1 ; Frits van Griensven 2 ; Donn Colby 1 ; Peter P. Pham 3 ; Sunee Sirivichayakul 4 ; Nelson L. Michael 5 ; Nittaya Phanuphak 1 ; Jintanat Ananworanich 6 ; Sodsai P. Tovanabutra 7 ; for the RV254/SEARCH010 StudyTeam and MHRPViral Sequencing Core 1 SEARCH, Bangkok, Thailand; 2 Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand; 3 Military HIV Rsr Prog, Silver Spring, MD, USA; 4 Chulalongkorn Univ, Bangkok, Thailand; 5 US Military HIV Rsr Prog, Bethesda, MD, USA; 6 Military HIV Rsr Prog, Bethesda, MD, USA; 7 US Military HIV Rsr Prog, Silver Spring, MD, USA Background: Bangkok has an ongoing HIV epidemic in MSM but phylogenetic support as to whether this occurs within networks or at random is lacking. Studies from other metropolitan areas suggest local transmission among networks of MSM with certain characteristics, which might allow for targeted interventions. The RV254 study enrolls subjects in the earliest stages of HIV infection. Baseline drug resistance genotyping allows for inventory of subtypes and clustering in this cohort.

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CROI 2016