CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

515

Host and Viral Factors Shape the Composition of the HIV-1 Viral Reservoir in the 2000HIV Cohort Mareva Delporte 1 , Kavita Mehta 1 , Maxime Verschoore 1 , Elizabeth R. Wonderlich 2 , Wilhelm A. Vos 3 , Albert L. Groenendijk 4 , Louise E. van Eekeren 5 , Marc Blaauw 5 , Evy E. Blomme 1 , Sofie Rutsaert 1 , Sarah Gerlo 1 , Wim Trypsteen 1 , Mihai Netea 5 , Andre J. van der Ven 5 , Linos Vandekerckhove 1 1 Ghent University, Ghent, Belgium, 2 ViiV Healthcare, Brentford, United Kingdom, 3 OLVG, Amsterdam, Netherlands, 4 Erasmus University Medical Center, Rotterdam, Netherlands, 5 Radboud University Medical Center, Nijmegen, Netherlands Background: The HIV-1 host interaction exhibits remarkable diversity, resulting in various clinical profiles and virological traits, including coreceptor tropism. The 2000HIV study, which is a multi-omics study including 1895 people living with HIV-1 (PLWH) (NTC03994835), reflects this notable variability by including different clinical phenotypes, such as elite controllers (EC), viremic controllers (VC), transient controllers (TC), immunological non-responders (INR), rapid progressors (RP) and normal HIV-1 progressors (NP). Methods: We quantified the total and intact HIV-1 reservoir by using the Rainbow proviral HIV-1 DNA digital PCR assay in CD4 T cells from blood in a subset of PLWH from the 2000HIV cohort (n = 863). In this study, we identified two distinct groups of PLWH, LoViReT-like and HiViReT-like, based on their total HIV-1 DNA levels (10% cut-off). Coreceptor tropism was determined by sequencing the viral env region and using the Geno2pheno algorithm (10% false positive rate). Results: Quantification by the Rainbow HIV-1 DNA assay resulted in a median of 456.1 (CI95%: 410.2-521.4) total HIV-1 DNA copies/10 6 CD4+ T cells (n = 863) and 8.7 (CI95%: 6.7-10.6) intact HIV-1 DNA copies/10 6 CD4+ T cells (n = 565). Total HIV-1 DNA levels in EC and VC were significantly lower than the NP (P <0.0001), whereas total HIV-1 DNA levels in INR were higher than NP (P = 0.0097). Intactness levels were significantly lower in the different controller groups versus NP (P <0.05) (Figure1). The selected samples for the LoViReT-like PLWH and HiViReT-like PLWH harbor total HIV-1 DNA levels of <50 copies/10 6 CD4 T cells and >2170 copies/10 6 CD4 T cells, respectively. Clinical parameters associated with infection (CD4 nadir, latest CD4 count, plasma viral load before ART and viral zenith) were significantly different between both groups (Mann Whitney U test). In addition, PLWH infected by X4-tropic viruses (n = 144) harbor significantly higher levels of total and intact HIV-1 DNA compared to PLWH infected by R5-tropic viruses (n = 561) (P = 0.003 and P = 0.04). Conclusion: Intactness levels differ significantly among controller groups and NP, highlighting the importance of intact HIV-1 DNA as a relevant virological parameter. Additionally, the study highlights the role of coreceptor tropism in influencing the reservoir size. This study marks a significant milestone in HIV research, as it represents a pioneering effort to comprehensively characterize the viral reservoir in a substantial number of PLWH.

log c/106 cells, IQR, 2.3-3.1) (p=0.002). There was a further steady decline over the next 3 years (median=2.05 log c/106 cells, IQR, 0.5-2.7) (p<0.0001). However, total HIV DNA remained detectable in 9/12 (75%) participants after 4 years. There was no difference in proviral load at ART initiation between sexes but after 4 years the HIV reservoir size decreased significantly in males (p=0.006) but not in females. Conclusion: Decline in total HIV DNA is observed after 1 year of treatment and is still detectable after 4 years of treatment. The faster reservoir decay in males is novel, suggesting that sex differences should be considered to optimize HIV cure strategies in children. Earlier Initiation of ART Reduces Intact Proviruses but Not Residual Viremia After 48 Weeks Joshua C Cyktor 1 , Joseph Puleo 2 , Gregory M. Laird 3 , Dianna Hoeth 1 , Justin Ritz 2 , Albine Martin 3 , Gert U. van Zyl 4 , Eric Daar 5 , Trevor A. Crowell 6 , Joseph J. Eron 7 , Lu Zheng 2 , John W. Mellors 1 , for the ACTG A5354 Team 1 University of Pittsburgh, Pittsburgh, PA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 Accelevir Diagnostics, Baltimore, MD, USA, 4 Stellenbosch University, Cape Town, South Africa, 5 Harbor–UCLA Medical Center, Torrance, CA, USA, 6 Henry M Jackson Foundation, Bethesda, MD, USA, 7 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: The timing of antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) may affect the size of the latent and expressed HIV reservoir but its specific influence on intact proviral DNA (IPD) or low-level viremia has not been fully described. Methods: AIDS Clinical Trials Group study A5354 enrolled 192 adults who started ART during AEHI at 30 sites in the Americas, Africa, and Asia. Participants were retrospectively centrally categorized as Group 1 (Fiebig I-II), Group 2 (Fiebig III-IV), or Group 3 (Fiebig V) and measures of HIV persistence were evaluated on a subset of 106 US study participants or those with confirmed subtype B. The intact proviral DNA assay (IPDA®) was performed on CD4+ T cells isolated from peripheral blood at weeks 24 (not shown), 48, and 72 after ART initiation. Plasma HIV RNA was measured by automated single copy assay (SCA) at week 48. Wilcoxon rank-sum and Fisher's exact test were used for pairwise comparisons between Groups and Jonckheere-Terpstra test for trends across the 3 Groups. Results: Participants had a median (IQR) age of 29 (24, 39) years, 11 (10%) were female, 3 (3%) identified as transgender, 58 (57%) were Black, and 103 (97%) initiated a regimen of EVG/COBI/FTC/TAF. Participants in Group 1 had a nominally lower level of total proviral DNA (IPD + defective DNA) than Groups 2 and 3 at weeks 24 and 48 (p≤0.038). Participants who started ART during the earliest study groups had significantly lower IPD levels at all three timepoints (trend tests p≤0.033) but with substantial variation and overlap in IPD copies per million CD4+ T cells (Figure 1). No significant longitudinal trends were observed in the decline of IPD across Groups. Persistent plasma HIV RNA was detected by SCA in >75% of participants at week 48 with no significant differences in the proportions with detectable HIV RNA (76-85%; p≥0.41) or the levels of HIV RNA between pairwise groups (p≥0.22). IPD and plasma HIV RNA at week 48 were significantly but modestly correlated (r=0.42, p<0.001). Conclusion: Here we show that earlier ART lowers the levels of total and IPD in Groups 1 and 2 (Fiebig I-IV) compared with Group 3 (Fiebig V). Surprisingly, residual plasma HIV RNA was detected in >75% of participants at week 48 with no significant differences in proportions or levels between study Groups. These results provide new evidence that earlier ART does not affect the active HIV reservoir measured by plasma HIV RNA.

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Poster Abstracts

516

Intact HIV DNA Decay During 15 Years of Suppressive ART: Comparisons by Timing of ART Initiation Trevor A Crowell 1 , Mackensie Horn 2 , Hsing-Chuan Hsieh 2 , Xiuping Chu 2 , Catherine M. Berjohn 3 , Jason M. Blaylock 2 , Joseph M. Yabes 4 , Anuradha Ganesan 2 , Timothy H. Burgess 2 , Robert J. O'Connell 2 , Gregory M. Laird 5 , Lydie Trautmann 1 , Brian K. Agan 2 , for the Infectious Disease Clinical Research Program (IDCRP) HIV Working Group 1 US Military HIV Research Program, Silver Spring, MD, USA, 2 Uniformed Services University of the Health Sciences, Bethesda, MD, USA, 3 Naval Medical Center San Diego, San Diego, CA, USA, 4 Brooke Army Medical Center, San Antonio, TX, USA, 5 Accelevir Diagnostics, Baltimore, MD, USA Background: People who initiate antiretroviral therapy (ART) during acute HIV may be ideal candidates for curative interventions due to small reservoirs

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