CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

during the 1st year after ART initiation. Here, we present data on the evolution of HIV persistence and immune-associated parameters in peripheral blood. Methods: DUALITY is a 48-week, single-centre, randomized, open-label clinical trial in ART-naïve people with HIV (PWH). Participants were randomized (1:1) to receive DTG+3TC (2DR group), or with DTG+FTC/TAF (3DR group). Total and intact proviral HIV-1 DNA and cell-associated RNA (ca-RNA) in CD4+ T cells were longitudinally determined by ddPCR. The inducible reservoir was measured as the frequency of HIV-infected CD4+ T cells able to produce p24 by the VIP-SPOT assay. Soluble inflammatory markers (IL-6, sCD14, TRAIL, IP10, FABP2, CRP and D-dimer) were quantified by ELISA. Activation (HLA-DR/CD38) and exhaustion markers (PD-1/TIGIT) in CD4+ and CD8+ T cells were determined by multiparametric flow cytometry. Results: Fourty-for participants were included (22 per study arm). At baseline, mean (SD) log 10 pVL and CD4+ T cell count were 4.4 (0.7) copies/mL and 493 (221) cells/mm 3 . Two participants were lost, and one withdrew informed consent before week 48. All participants completing the study (2DR n=20; 3DR n=21) had pVL <50 copies/mL at week 48, except one in the 2DR group who was resuppressed after treatment for syphilis. Changes from baseline to week 48 in all reservoir parameters were similar between 2DR and 3DR groups (Table). At week 48, levels of total and intact proviruses were similar between both groups, and correlated with pre-ART pVL (Rho 0.50, p=0.002 for intact HIV-1 DNA). Changes in soluble inflammatory biomarkers and in levels of activated/ exhausted CD4+ and CD8+ T cells were also comparable between study groups. Complementary data on anatomic distribution of antiretroviral drugs and viral expression in lymph nodes are under study. Conclusion: First-line dual ART with DTG+3TC resulted in a similar decay in parameters of HIV-1 persistence in periphery as well as in immune-associated markers compared to 3DR with DTG+FTC/TAF. Our results further support recommendation of DTG/3TC as one preferred option for first-line ART in PWH. 48-Week Outcomes After Programmatic Transition to Dolutegravir in South Africa Suzanne McCluskey 1 , Gugulethu Shazi 2 , Njabulo Dayi 2 , Ashley Stuckwisch 1 , Taing N. Aung 1 , Bethany Hedt-Gauthier 3 , Vincent Marconi 4 , Mahomed-Yunus S. Moosa 5 , Winnie Muyindike 6 , Deenan Pillay 7 , Ravindra K. Gupta 8 , Mark J. Siedner 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 Africa Health Research Institute, Durban, South Africa, 3 Harvard Medical School, Boston, MA, USA, 4 Emory University, Atlanta, GA, USA, 5 University of KwaZulu-Natal, Durban, South Africa, 6 Mbarara University of Science and Technology, Mbarara, Uganda, 7 University College London, London, United Kingdom, 8 University of Cambridge, Cambridge, United Kingdom Background: South Africa introduced tenofovir/lamivudine/dolutegravir (TLD) as the preferred first-line antiretroviral therapy (ART) regimen in 2019. Few data are available from individuals who transitioned from efavirenz (EFV)-based ART to TLD in rural public sector clinics in South Africa. Our objective was to evaluate viral suppression and regimen tolerability for individuals who were transitioned to TLD in this setting. Methods: We conducted a prospective cohort study in rural KwaZulu-Natal. We enrolled adults ages >18 years who were transitioned from EFV-based ART to TLD by the clinic. Participants were enrolled on the date of TLD transition with follow-up visits 24 and 48 weeks later. We obtained blood specimens at each visit for retrospective viral load (VL) testing. Our primary outcome was viral suppression <50 copies/mL with retention in care at 48-weeks post-TLD transition. We fitted a multivariable logistic regression model to assess predictors of the composite outcome of viral suppression with retention in care. Results: We enrolled 499 participants with a median age of 39 years (IQR 32–50 years), and 80% were female. The median duration of ART prior to TLD transition was 6 years (IQR 4-9 years). At the time of TLD transition, 93% had VL <50 copies/mL, 3% had VL between 50 and 1,000 copies/mL, and 3% had VL >1,000 copies/mL. By 48 weeks, 81% were suppressed and in care, 5% were unsuppressed and in care, 9% were lost from care, 0.5% were deceased,

findings strengthen switching to DTG+3TC as an effective strategy for maintaining virologic suppression in clinical practice. Impact of Switch to 3TC/DTG on the HIV-1 Transcriptional Reservoir in a Randomized Controlled Trial Evy E Blomme 1 , Evelien De Smet 1 , Mareva Delporte 1 , Wim Trypsteen 1 , Sophie Degroote 2 , Sophie Vanherrewege 2 , Els Caluwe 2 , Marie-Angélique De Scheerder 2 , Linos Vandekerckhove 1 1 Ghent University, Ghent, Belgium, 2 Ghent University Hospital, Ghent, Belgium Background: The Rumba study is the first randomized clinical trial evaluating the impact on the viral reservoir of switch from a 2nd generation integrase inhibitor (INI)-based triple ART regimen towards 3TC/DTG vs. B/F/TAF. We observed no differences in the dynamics of the total and intact HIV-1 DNA reservoir after 48 weeks. Here, we quantified the mean change from baseline at 48 weeks of different HIV-1 RNA transcripts as a secondary objective, to ensure switching to 3TC/DTG does not increase transcriptional activity. Methods: In this prospective controlled switch trial, participants with HIV-1 RNA<50 copies/ml plasma at least 3 months on any stable 2nd generation INI-based triple ART were randomized to switch to 3TC/DTG (N=89) or to switch or stay on B/F/TAF (N=45). HIV-1 transcripts that define distinct blocks to transcription were analyzed on CD4 T cell cDNA of subtype B participants in duplicate. An in-house 4-plex Rainbow transcriptional RNA dPCR assay for long LTR, pol, polyA and tat-rev was run on the QIAcuity system. RNA concentrations were used to normalize HIV-1 RNA transcripts. Statistical analysis was performed with an ordinary linear regression model on log-transformed data, adjusted for baseline response value, CD4 nadir and time on ART. Data analysis was performed with an in-house R script, a modified version of ddpcrquant to accommodate QIAcuity data analysis. Results: Baseline characteristics are reported in Table 1. In this complete case analysis (3TC/DTG n=52; vs. B/F/TAF n=23), the mean baseline copy number per µg RNA was 207.7 for long LTR (elongated transcripts), 24.5 for pol (unspliced transcripts) and 77.9 for polyA (completed transcripts), suggesting a block to completion of transcription. Tat-rev (multiple-spliced transcripts, surrogate for productive infection) was undetectable in the majority of the samples at both timepoints. After 48 weeks, the relative change from baseline of elongated, unspliced and completed HIV-1 RNA transcript copies was not significantly different between 3TC/DTG and B/F/TAF, (1.11 [0.78-1.56], 0.83 [0.55-1.25] and 1.17 [0.85-1.61] respectively, point estimates and 95% CI). Also, within the treatment arms, no evidence of a significant mean difference over time was observed. Conclusion: There is no evidence that simplification of a triple ART INI-based regimen to 3TC/DTG impacts the overall size of the reservoir, neither the fraction of intact virus nor the transcriptional activity.

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Poster Abstracts

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Impact of DTG+3TC as First-Line ART on HIV-1 Reservoir and Inflammatory Markers in Peripheral Blood Jose Molto 1 , Maria C. Garcia-Guerrero 2 , Lucía Bailón 1 , Igor Moraes-Cardoso 2 , Ester Aparicio 2 , Pep Coll 2 , Angel Rivero 1 , Elias P. Rosen 3 , Jacob D. Estes 4 , Julià Blanco 2 , Alex Olvera 2 , Maria C. Puertas 2 , Beatriz Mothe 2 , Javier Martinez-Picado 2 , for the DUALITY Study Group 1 Hospital Germans Trias i Pujol, Barcelona, Spain, 2 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 3 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 4 Oregon Health and Sciences University, Portland, OR, USA Background: Data on the effect of dual therapy with DTG/3TC as first-line ART on the evolution of the HIV-1 reservoir and inflammatory biomarkers are lacking. Our objective was to compare the effect of first-line ART with DTG+3TC versus one standard 3-drug regimen (3DR) on the dynamics of viral persistence in lymph nodes and peripheral blood and on immune activation biomarkers

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