CROI 2020 Abstract eBook
510 TRANSMITTED DRUG RESISTANCE IN PEOPLE LIVING WITH DIAGNOSED HIV IN CALIFORNIA Jing Feng 1 , Deanna Sykes 1 , Philip Peters 1 , Joel O. Wertheim 2 1 California Department of Public Health, Sacremento, CA, USA, 2 University of California San Diego, San Diego, CA, USA Background: Increased antiretroviral use for treatment and prevention raises concern that rates of transmitted drug resistance may increase. We analyzed a population-based dataset of HIV-1 pol sequences to estimate the prevalence of transmitted drug resistance-associated mutations (DRAMs) in people living with HIV in California from 2008-2018 and evaluated the transmission potential of identified mutations. Methods: HIV-1 pol sequences reported to the California HIV surveillance systemwere analyzed via the SIERRA HIV Drug Resistance Database to determine resistance mutations and COMET to determine subtype. This analysis was limited to sequences that were obtained within 3 months of an HIV diagnosis with documentation of no previous exposure to antiretrovirals. DRAMs were defined based on the CDC surveillance resistance mutation list. We used HIV-TRACE to construct genetic transmission networks. Clustering was defined as two or more linked sequences with a pairwise genetic distance of ≤ 1.5%. Among ART-naïve persons, we compared the frequency of clustering of sequences with at least one DRAM compared with sequences without any DRAMs. Results: Of 17,103 sequences (93.9% subtype B) obtained within 3 months of an HIV diagnosis, antiretroviral history was available for 5,740 sequences and 3,616 sequences had documentation of no prior antiretroviral exposure. Of the 3,616 sequences from antiretroviral-naïve persons, 1,480 (40.9%) clustered with at least one other sequence in 212 dyads and 194 larger clusters ranging from 3 to 28 sequences (median=4). In most clusters (83.3%), male-to-male sexual contact was the most common reported risk behavior. The prevalence of any DRAM in a sequence from an antiretroviral-naïve person was 20.0%; NNRTI, NRTI, and PI mutations were detected in 11.7%, 7.5%, and 4.3% of sequences, respectively. The integrase region was sequenced in a subset of 473 persons and the prevalence of an integrase DRAMwas 1.5%. Compared to sequences without a mutation, a higher proportion of sequences with an NNRTI mutation clustered (rate ratio [RR] 1.20) whereas a lower proportion of NRTI mutations clustered (RR=0.70) [Table]. Conclusion: This population-based drug-resistance analysis demonstrated sustained DRAM transmission, particularly NNRTI mutations, among antiretroviral-naïve people. Although reassuring that NRTI mutations were associated with less clustering, a proxy for reduced further transmission, this finding should continue to be monitored as exposure to NRTIs increases with the expansion of pre-exposure prophylaxis.
Background: Initial regimens currently recommended by treatment guidelines include high genetic barrier antiretrovirals (ARVs), thus it may be of interest to evaluate drug resistance mutations (DRM) and, specially, clinically relevant resistance. Here, we present data on trends in DRM and clinically relevant transmitted drug resistance to ARVs recommended for first-line treatment in Spain. Methods: We analysed 6090 RT & Pro Fasta sequences from CoRIS (2007-2018). As Integrase resistance is not part of routine testing in naïve patients in Spain, we run a surveillance programme (2012-2018) and tested 1404 patients. We evaluated the prevalence of Transmitted DRM using the WHO 2009 list, and clinically relevant resistance with Stanford v8.8 Algorithm. First line regimens for each study period were those recommended by the Spanish treatment guidelines (GESIDA). Results: Our results indicated a similar trend in NNRTIs and NRTIs TDR prevalence with values ranging from 2.4-5%. In regard to INsTIs TDR, we also described similar values with no significant changes over years. However, we observed a decrease in PIs TDR from 2016 (≤1% of prevalence). Clinically Relevant resistance to recommended first line regimens showed a slow decline from 2007-2012, and peaked in 2013-2014 due to the inclusion of Rilpivirine for 1st line in the Spanish recommendations. Detailed results for 2007-2018 are shown in the enclosed table. Conclusion: While NNRTIs and NRTIs DRM prevalence remained stable in Spain through 2007-2018, we observed a slightly decrease in PIs and INsTIs DRM prevalence. Clinically relevant TDR to approved first line regimens showed a slow decline from 2007 to 2018. Resistance to INsTIs remains at very low levels. These findings, together with the very low prevalence of resistance to recommended first line NRTIs in 2015-2018 reinforce GESIDA recommendations on baseline resistance testing and test and treat strategies when starting PIs or INsTIs based regimens. 512 US HIV DRUG RESISTANCE: IMPLICATIONS FOR CURRENT AND FUTURE PrEP REGIMENS Robert P. McClung 1 , Cheryl B. Ocfemia 1 , Neeraja Saduvala 1 , Alexandra M. Oster 1 , Dawn K. Smith 1 , Walid Heneine 1 , Jeffrey A. Johnson 1 , Angela L. Hernandez 1 1 CDC, Atlanta, GA, USA Background: HIV pre-exposure prophylaxis (PrEP) is a critical HIV prevention tool and a key component of plans to end the HIV epidemic, but its effectiveness might be diminished by drug resistant virus; M184V and K65R mutations have both been associated with PrEP failure. The U.S. National HIV Surveillance System (NHSS) collects HIV sequence data from clinical drug resistance testing. We used NHSS data to describe the prevalence of drug resistance mutations (DRMs) to approved (TDF/FTC) and investigational (cabotegravir, CAB) PrEP drugs among people with diagnosed HIV infection without evidence of recent viral suppression. Methods: We analyzed all reverse transcriptase (RT) and integrase (IN) sequences in NHSS for people with HIV infection (PWH) diagnosed through December 2018 without evidence of viral suppression in 2018. DRMs were detected via the SIERRA web service and defined by the CDC HIV-1 surveillance mutation list. We reported DRM prevalence for nucleoside reverse transcriptase inhibitors (nRTIs), including TDF and FTC, and for integrase strand transfer inhibitors (INSTIs), including CAB. For people with >1 sequence, we reported combined DRMs from all sequences. Results: In all, 268,065 people had ≥1 sequence and no evidence of viral suppression in 2018. Of the 232,429 people with ≥1 RT sequence, TDF/FTC DRMs were identified for 40,809 (17.6%) people (Table), including M184V (16.0%) and K65R (2.1%). Of the 80,669 people with ≥1 IN sequence, DRMs reported to affect CAB were identified for 3,308 (4.1%) people, including N155H (1.8%) and R263K (0.3%). Mutations affecting TDF/FTC and CAB were more common among females, blacks/African Americans, and for people with a transmission risk factor of injection drug use (IDU) or men who have sex with men who also reported IDU.
511 TRENDS IN TRANSMITTED DRUG RESISTANCE IN SPAIN THROUGH THE PERIOD 2007-2018 Carlos Guerrero Beltrán 1 , Marta Alvarez 1 , Antonio Aguilera 2 , María Carmen Vidal Ampurdanes 3 , Marina Martínez 4 , Arkaitz Imaz 5 , Asunción Iborra 6 , Juan L. Gomez-Sirvent 7 , Joaquim Peraire 8 , Joaquin Portilla 9 , Estrella Caballero 10 , Mónica García-Álvarez 11 , José A. Iribarren1 2 , Mar Masiá 13 , Federico García 1 1 Hospital Universitario San Cecilio, Granada, Spain, 2 Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain, 3 Hospital Universitario de Son Espases, Palma de Mallorca, Spain, 4 Hospital Universitari Mútua de Terrassa, Terrassa, Spain, 5 Hospital Universitario de Bellvitge, Barcelona, Spain, 6 Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain, 7 Hospital Universitario de Canarias, San Cristóbal de La Laguna, Spain, 8 Hospital Universitario de Tarragona Joan XXIII, Tarragona, Spain, 9 Hospital General Universitario de Alicante, Alicante, Spain, 10 Hospital Universitario de la Vall d’Hebron, Barcelona, Spain, 11 Hospital Universitario 12 de Octubre, Madrid, Spain, 12 Hospital Donostia, San Sebastián, Spain, 13 Hospital General Universitario de Elche, Elche, Spain
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