CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

525 IMPACT OF TRANSMITTED RESISTANCE ON CLINICAL OUTCOMES IN THE VMVN TRIAL IN VIETNAM Vu P. Thao 1 , Cuong D. Do Duy 2 , Thanh Thuy Pham Thi 2 , Duong T. Hao 3 , Bui T. That 1 , Donn Colby 4 , Todd Pollack 3 , Thuy Le 1 1 Oxford University Clinical Research Unit in Vietnam, Ho Chi Minh, Vietnam, 2 Bach Mai Hospital, Hanoi, Vietnam, 3 Beth Israel Deaconess Medical Center, Boston, MA, USA, 4 SEARCH, Bangkok, Thailand Background: Transmitted drug resistance (TDR) has been shown to impair treatment outcomes. Baseline drug resistance testing is recommended to guide therapy in resource-rich countries. However, drug resistance screening is expensive, is not widely available, and its impact on treatment outcomes in resource-limited countries remains unclear. Methods: We investigated TDR mutations and their clinical impact in antiretroviral-naïve patients initiating first-line ART in the VMVN study, a randomized controlled trial of routine virological monitoring versus targeted virological monitoring at Bach Mai Hospital in Vietnam between April 2011 and May 2017. TDR mutations were identified by Sanger sequencing of the partial pol gene and were defined based on the 2009 WHO surveillance drug resistance mutation list. The association of TDR and virological failure (defined as confirmed HIV RNA >200 copies/mL) or death over 36 months was investigated using Logistic regression analyses. Results: Among 650 patients enrolled in the trial, 603 patients were ART-naïve, successful sequencing was obtained for 564 patients. The median age was 33; 65%were male; the median CD4 count was 119 (IQR: 29-273) cells/mm 3 . TDR mutations were identified in 32 (5.6%) patients: 15 (46.9%) patients harbor mutations conferring resistance to NRTIs, 10 (31.3%) to NNRTIs, 11 (34.4%) to PIs, 4 (12.5%) to both NRTIs and NNRTIs. Complete outcome data were available for 500 patients. 50 (10%) patients died after a median of 4.9 (IQR: 2.2-14.8) months. In both univariable and multiple variable analyses (with routine versus targeted virological monitoring as a covariable), the risks of virological failure or death at 36 months were higher in patients who had TDR; however, the differences in risk were not statistically significant, univariable OR=1.30, 95% CI: 0.37-3.52, P=0.664 and adjusted OR=1.30, 95% CI: 0.37-3.54, P=0.641, respectively. ... Conclusion: TDR remains stable at <10% despite over 10 years of ART scale up in Vietnam and does not increase the risk of virological failure or death over 36 months of follow up. Our data do not support baseline drug resistance testing in Vietnam. 526 PREVALENCE OF HIV-1 ANTIRETROVIRAL DRUG RESISTANCE IN FLORIDA, 2015-2016 Karalee Poschman 1 , Emma C. Spencer 2 1 CDC, Atlanta, GA, USA, 2 Florida Department of Health, Tallahassee, FL, USA Background: Antiretroviral (ARV) use is pivotal in the treatment and prevention of the spread of HIV and has significantly reduced the morbidity of those living with HIV. Continued use of ARV drugs has led to resistance to certain drug classes as the HIV-1 virus mutates, reducing drug efficacy for patients to achieve viral load suppression (<200 copies/ml). Determining baseline drug resistance using nucleotide genotyping on treatment-naïve patients is recommended to ascertain appropriate therapies to use in the presence of resistance. Surveillance of HIV-1 ARV drug resistance in Florida’s population is essential for the development of local and statewide treatment and prevention programs. Methods: HIV-1 nucleotide genotype sequences and epidemiological data reported to the Florida Department of Health HIV/AIDS surveillance system were analyzed for persons whose HIV was diagnosed in Florida with a sequence obtained within three months of diagnosis in 2015 (n=2071) and 2016 (n=1952). ARV drug resistance was determined using the Stanford HIV Drug Resistance Database. Results: From sequences obtained for persons whose HIV was diagnosed in 2015 and 2016, transmitted drug resistance (TDR) to any drug class was identified in 11.9% (10.9-13.0% CL). For specific drug classes, TDR for non- nucleoside reverse transcriptase inhibitors (NNRTIs) was identified in 9.1% (8.2-10.0% CL), 1.4% (1.1-1.9% CL) for nucleoside reverse transcriptase inhibitors (NRTIs), 0.9% (0.6-1.2% CL) for protease inhibitors (PI), and 1.8% (1.4-2.3% CL) for integrase inhibitors (IN). From 2015 to 2016, resistance to NNRTIs decreased (p=0.006), and resistance to IN increased (p=0.033). Among persons whose HIV was diagnosed in 2016, resistance to multiple drug classes occurred more frequently in women (p=0.002) and persons with HIV attributable

to heterosexual contact (p=0.034). Furthermore, a baseline genotype was indicative of being retained in care (two HIV-related labs or medical visits at least three months apart) (p<0.001) and virally suppressed (p=0.004). Resistance to any drug class was associated with a decreased likelihood of viral suppression (p=0.048). Conclusion: HIV-1 ARV drug resistance within a population is dynamic in nature and should be monitored closely to inform treatment and prevention programs, especially as new drug regimens are brought to market. A baseline genotype should be conducted as an initial point of care service to validate future treatment and care plans and reduce the transmission of HIV. 527 PRETREATMENT HIV DRUG RESISTANCE IN THE START STUDY USING NEXT GENERATION SEQUENCING John D. Baxter 1 , David Dunn 2 , Rasmus L. Marvig 3 , Marc Bennedbaek 4 , Alessandro Cozzi-Lepri 2 , Shweta Sharma 5 , Anna Tostevin 2 , Michael Kozal 6 , Mark Gompels 7 , Angie N. Pinto 8 , Jens D. Lundgren 4 1 Cooper University Hospital, Camden, NJ, USA, 2 University College London, London, UK, 3 Rigshospitalet, Copenhagen, Denmark, 4 Copenhagen HIV Program, Copenhagen, Denmark, 5 University of Minnesota, Minneapolis, MN, USA, 6 Yale University, New Haven, CT, USA, 7 North Bristol NHS Trust, Bristol, UK, 8 University of New South Wales, Sydney, NSW, Australia Background: In START, an international trial of immediate verses deferred ART initiation among ART-naïve HIV-infected persons with CD4 counts >500 cells/ µL, study entry HIV-1 was characterized by next generation sequencing (NGS); a sensitive assay capable of detecting low-frequency variants associated with pre-treatment HIV-1 drug resistance (PDR). Methods: Stored plasma specimens from participants with study entry HIV RNA >1,000 copies/ml were analyzed by NGS (Ilumina MiSeq). PDR was based on the WHO 2009 surveillance definition with the addition of reverse transcriptase (RT) mutations T215N and E138K, and integrase inhibitor (INI) mutations (Stanford HIVdb). Drug resistance mutations (DRMs) detected at two thresholds are reported, ≥2% verses >20% of the viral population (the latter comparable to the detection threshold for Sanger sequencing). Results: Between 2009-2013, the START trial enrolled 4,684 ART-naïve individuals in 35 countries. Baseline NGS data at study entry was available for 3,365 participants; median CD4 count 642 cells/µL, median HIV RNA 19,800 copies/mL, and median time since diagnosis was 0.9 years. The overall prevalence of PDR in START using a detection threshold of ≥2%/>20%was 19.7/8.3% for RT-protease (PR) DRMs (6.1/2.7% for NRTIs, 7.0/4.3% NNRTIs, 9.0/2.1% PIs) and 0.9/<0.1% for INI DRMs. The prevalence of RT-PR PDR was highest in Australia and the USA, while lowest in Africa (figure). Prevalence of NNRTI PDR using the ≥2%/>20% thresholds by region was: USA 11.7/9.4%, Latin America 7.7/5.8%, Europe 6.8/3.3%, Asia 5.7/2.2%, Australia 5.5/2.7%, and Africa 4.1/2.2%. Using the ≥2% detection threshold, the six individual DRMs with the highest prevalence were: RT K103N 2.9/2.7%, M41L 1.6/1.2%, G190E 1.3/0.1%, PR M46I 3.1/0.4%, M46L 1.3/0.5%, and D30N 1.3/0.2% at the ≥2%/>20% thresholds. RT M184I 0.4/0%, D67G 0.1/0%, L74V 0.1/0%, and Y188C 0.1/0%were only detected as minor variants. The most frequently detected INI DRMs were Y143H 0.2/0%, T66I 0.1/<0.1%, and Y143C 0.1/0%. Conclusion: The START trial represents one of the largest global cohorts with NGS characterization of PDR. Overall prevalence of PDR using the ≥2% detection threshold was 19.7% for RT-PR DRMs, while only 8.3% using the 20% threshold and varied by region. INI DRMs were detected in 0.9% of the study cohort primarily as minor variants. NGS would be expected to detect a substantially higher prevalence of PDR than traditional Sanger sequencing, particularly for DRMs occurring predominately as minor variants.

Poster Abstracts

CROI 2018 192