CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: HIV-infected MSM were recruited in Atlanta, GA; Baltimore, MD; Birmingham, AL; and Boston, MA (N=155 with a viral load >1,000 c/mL; screening/enrollment 2016-2017); 85%were Black, 76% reported a prior positive HIV test, and 65% reported prior or current ART. Population sequencing and next-generation sequencing (NGS) methods were performed using samples collected at study entry. HIV drug resistance was evaluated using the Stanford v8.7 algorithm.HIV-infected MSM were recruited in Atlanta, Georgia; Baltimore, Maryland; Birmingham, Alabama; and Boston, Massachusetts (N=155; screening/enrollment 2016-2017). Population sequencing and next-generation sequencing (NGS) methods were performed using samples collected at study entry (all available samples with a viral load >1,000 copies/mL). HIV drug resistance was evaluated using the Stanford v8.7 algorithm. Results: High-level INSTI resistance was detected in 11 (8.0%) of 138 cases with integrase test results. All 11 cases had high-level resistance to elvitegravir; four also had high-level resistance to raltegravir and intermediate-level resistance to the second-generation INSTIs, bictegravir and dolutegravir. All cases with INSTI resistance also had resistance to additional drug classes (multi-class resistance); 11 had NRTI resistance, including five who also had NNRTI resistance, and one who also had PI resistance. NGS data for the integrase region was available for 114 (82.6%) of the 138 samples. NGS identified 10 additional cases with lower-level INSTI resistance (5%-45%); five of those 10 cases also had resistance to drugs in other drug classes. Potential transmitted resistance mutations were detected in three (37.5%) of eight MSM who reported no prior HIV diagnosis; two cases had INSTI resistance mutations (one had E92Q+M184V, one had T97A). Conclusion: High prevalence of INSTI resistance and intermediate-level resistance to second generation INSTIs was observed among viremic MSM recruited for the HPTN 078 study. Many of those with INSTI resistance had multi-class resistance, further limiting their ART options. Two cases of potential transmitted INSTI resistance mutations were identified. These findings highlight the need for improved HIV care in this high-risk population, and the importance of including baseline integrase resistance testing when selecting ART regimens for MSM in the US. Philip L. Tzou 1 , Diane Descamps 2 , Soo-Yon Rhee 1 , Dana Raugi 3 , Charlotte Charpentier 2 , Florence Damond 2 , Nuno Taveira 4 , Robert A. Smith 3 , Vincent Soriano 5 , Carmen De Mendoza Fernández 5 , Susan Holmes 1 , Geoffrey S. Gottlieb 3 , Robert Shafer 1 1 Stanford University, Stanford, CA, USA, 2 INSERM, Paris, France, 3 University of Washington, Seattle, WA, USA, 4 Universidade de Lisboa, Lisbon, Portugal, 5 Puerta de Hierro Research Institute and University Hospital, Madrid, Spain Background: There has been no systematic review of treatment-selected HIV-2 mutations. Methods: We reviewed published HIV-2 sequences to identify previously unreported ARV-selected HIV-2 mutations. Prevalence of each PR, RT, and IN mutation was determined by ARV status. Nonpolymorphic mutations (NPMs) were defined as occurring in <1% of ARV-naïve persons. Nonpolymorphic treatment selected mutations (NP-TSMs) were defined as NPMs significantly associated with ARV therapy (Fishers Exact Test; p<0.05 after adjusting for multiple comparisons [Holm’s test]). Established drug-resistance mutations (DRMs) were determined by literature review. Correlated NP-TSMs were defined as mutation pairs with a Spearman coefficient >=0.2 and p<0.05. Results: We analyzed PR sequences from 481 PI-naïve and 232 PI-treated persons; RT sequences from 332 NRTI-naïve and 252 NRTI-treated persons; and IN sequences from 236 INSTI-naïve and 60 INSTI-treated persons. In PR, 12 NP-TSMs occurred in >=11 persons: V33I, K45R, V47A, I50V, I54M, T56V, V62A, A73G, I82F, I84V, F85L, and L90M. Additional PR NPMs at HIV-1 DRM positions G48V, I54L, I82L, and I84L occurred in 2-3 persons. Among novel PR-TSMs, V33I correlated with V47A and I50V; K45R with I47A; T56V with I54M; and F85L with A73G. In RT, 9 NP-TSMs occurred in >=10 persons: K40R, A62V, K70R, Y115F, Q151M, M184VI, and S215Y. Additional RT NPMs at HIV-1 DRM positions M41I, D67N, N69T, K70N, I75V, and S215F occurred in 6-9 persons. The novel RT-TSM K40R correlated with S215Y. In IN, 11 NP-TSMs occurred in >=4 persons: Q91R, E92AQ, T97A, G140S, Y143G, Q148R, A153G, N155H, H156R, and R231 5-amino acid insertions. Additional IN NPMs at HIV-1 DRM positions H51Y, E92G, G118R, G140A, Y143CHR, Q148HK, and R263K occurred in 1-3 persons. Among novel IN-TSMs, A153G correlated with E92A and N155H; H156R with E92Q and T97A.

Conclusion: This systematic review of HIV-2 PR, RT, and IN sequences confirmed an ARV association of established HIV-2 DRMs and identified novel NP-TSMs. 32 NP-TSMs were significantly selected by ARVs in PR, RT, and IN. 20 additional NPMs at HIV-1 DRM positions were not statistically significant after multiple comparison adjustment. Most of the 9 novel NP-TSMs co-occurred with an established HIV-2 DRM. These results will improve approaches to predicting HIV-2 ARV susceptibility. Further clinical and phenotypic studies of HIV-2 drug resistance will be helpful in delineating it’s nuances and unique features. 540 HIV VIRAL BLIPS IN ADULTS TREATED WITH InSTI-BASED REGIMENS THROUGH 144 WEEKS Rima K. Acosta 1 , Kristen Andreatta 1 , Michelle L. D'Antoni 1 , Sean E. Collins 1 , Hal Martin 1 , Kirsten L. White 1 1 Gilead Sciences, Inc, Foster City, CA, USA Background: The clinical impact of viral blips on virologic failure and resistance development depends on the resistance barrier and forgiveness of the regimen. Here, we investigated the blip frequency and virologic outcomes of those experiencing blips among treatment-naïve people with HIV (PWH) initiating therapy on bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF), dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC), or DTG + F/TAF through 144 weeks of treatment in Studies 1489 and 1490. Methods: PWH with at least one on-treatment post-baseline HIV RNA value were included in this analysis. HIV RNA and last observation carried forward (LOCF) outcome data through week 144 were used. A blip was an HIV RNA value ≥50 c/mL preceded and followed by HIV RNA <50 c/mL, after achieving confirmed suppression (two consecutive HIV RNA values <50 c/mL). Results: Of the 1240 participants with confirmed suppression, 143 (11.5%) had ≥1 blip through week 144 with similar blip frequencies between treatment arms (Table 1). An average of 1.3% of participants experienced blips per study visit, which was similar between treatment arms (Table 1). A total of 186 blip events occurred in the 143 individuals; 110 experienced a single blip and 33 experienced multiple blips. Of the 186 blips, 87 (46.8%) were low-level (50-199 c/mL) and 99 (53.2%) were ≥200 c/mL. The proportions of participants with blips <200 c/mL or ≥200 c/mL were similar between treatment arms (Table 1). Most with blips ≥200 c/mL had adherence ≤95% by pill count (69.2%), while those with blips <200 c/mL mostly had adherence >95% (63.1%) (Table 1). Of participants without blips, 98.7% (1083/1097) had HIV RNA <50 c/mL at week 144 or last visit vs. 91.0% (71/78) with blips ≥200 c/mL (p<0.01), or vs. 96.9% (63/65) with blips <200 c/mL (p=0.2). The 7 with blips ≥200 c/mL and HIV RNA ≥50 c/mL at week 144 were all on DTG-based regimens, and 6/7 had evidence of continued low adherence. Of the 21 individuals included in the overall resistance analysis population, 5 experienced blips and none had emergent resistance to study drugs (Table 1). Conclusion: Viral blips were infrequent and similar among PWH treated with B/F/TAF, DTG/ABC/3TC, or DTG + F/TAF. Blips ≥200 c/mL but not <200 c/mL were associated with adherence ≤95%. High level blips of ≥200 c/mL were associated with lower suppression at week 144 due to poor adherence; however, none developed resistance on these 3-drug regimens with high barriers to resistance.

Poster Abstracts

539 EXPANDED SPECTRUM OF ANTIRETROVIRAL-SELECTED HIV-2 MUTATIONS

541 INVESTIGATION OF CLASSIC AND HIV-RELATED FACTORS FOR HEPATIC STEATOSIS AMONG PWID Eve-Marie A. Benson 1 , Shruti H. Mehta 1 , Jacquie Astemborski 1 , David L. Thomas 1 , Gregory D. Kirk 1 1 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

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