CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Genomic DNA was available for 21 donors and 43 recipients. Recipients were older (median age=37; IQR=33-48), evenly split between male (51%) and female (49%), and were black African (91%) or mixed ethnicity (9%). Donors were significantly younger (Age=31; IQR=26-40; p=0.006), primarily male (76%), and had a significantly more diverse ethnicity (57% black African, 33% mixed ethnicity, 10% white; p=0.004). Donors had relatively low rates of APOL1 high-risk alleles with seven (33.3%) possessing 1 risk allele, and zero with two risk alleles. Conversely, KTR had significantly higher rates of high-risk alleles, with 17 with two risk alleles (39.5%), and 5 with one risk allele (11.6%). HIV associated nephropathy (HIVAN) was the original cause of native kidney failure in 15 of the 17 (88.2%) KTR with two APOL1 variants. 38 KTR had donor APOL1 typing available of whom 12 (31.6%) received kidneys from donors with one risk allele. Over five years of follow-up post transplantation, a composite outcome of graft failure, development of HIVAN, or rejection in the graft was significantly higher in KTR whose donor had one versus zero APOL1 risk alleles [9/12, (75%) versus 9/12 (35%) respectively, p=0.03; Figure 1]. This composite outcome was not associated with recipient APOL1 status [composite outcome 8/15, (53%) in those with 2 risk alleles versus 10/23, (43%) in those with 0/1 risk allele, p=0.55]. Conclusions: Dual APOL1 risk variant status is frequent in South African PLWH undergoing kidney transplantation. In addition, graft outcomes were worse in those who received kidneys from donors with HIV and one high-risk APOL1 allele.

United States. It has been recently shown these transplants are safe and effective, but a possible unique risk of HIV D+/R+ transplantation is the potential for the recipient to become HIV superinfected with the donor HIV strain. Previous studies have shown HIV-superinfection may rarely occur, but only a limited number of transplant recipients have been evaluated. Methods: In a multicenter observational HIV D+/R+ study in the US, we evaluated recipients for HIV-superinfection. Recipient peripheral blood mononuclear cells (PBMCs) were collected pre-transplant and at 13, 26, 52, 104, 156, and 208 weeks post-transplant. Recipients were eligible for this analysis if they had a pre-transplant PBMC sample and at least one follow-up sample available. Donor and recipient proviral genomic DNA was extracted from PBMCs and sequenced using a site-directed next-generation sequencing assay targeting two regions of the genome ( gp41 and pol , Illumina). If successful amplification occurred in at least one region at two time points for a recipient, the corresponding donor was then sequenced to exclude the possibility of cross-contamination. Sequences were analyzed phylogenetically to assess for donor-derived HIV-superinfection. Results: Twenty-three kidney transplant recipients were followed from June 2021–May 2024. Of these, 18 had both baseline and follow-up samples that successfully amplified in at least one region of interest. Three recipients had newly observed distinct viral populations 26 weeks post-transplant. One of the three was confirmed as a case of donor-derived superinfection, with the new viral population matching the donor’s ( Figure 1 ). The other two were classified as potential cases of donor-derived superinfection/dual infections because the donor sequence data was not available. Among these three recipients there were no clinically significant changes in viral load or CD4 count. Conclusions: Among recipients screened for HIV superinfection in this study, three cases of HIV superinfection/dual infection were identified, with one being a confirmed donor derived superinfection case. Although HIV superinfection in organ transplants is possible, the clinical ramifications appear negligible among individuals on well-maintained ART regimen.

Poster Abstracts

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Human Antibody Repertoire and Allograft Rejection Among Kidney Transplant Recipients With HIV Xianming Zhu 1 , William R. Morganlander 1 , Christine M. Durand 2 , Dorry L. Segev 3 , Andrew D. Redd 4 , Jonah Odim 4 , Diane Brown 2 , Yolanda Eby 2 , Serena M. Bagnasco 1 , Benjamin Larman 1 , Aaron A. R. Tobian 2 , for the HOPE in Action Investigators 1 The Johns Hopkins University, Baltimore, MD, USA, 2 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 3 New York University Langone Medical Center, New York, NY, USA, 4 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA Background: Kidney transplantation (KT) between donors and recipients with HIV is promising. However, allograft rejection risk among recipients with HIV (R+) is higher than recipients without HIV (R-). This study evaluated predictive antibody markers of KT allograft rejection among R+. Methods: The HOPE in Action Multicenter Kidney Trial performed KT in R+ between 2018-2021 from donors with HIV (D+) and without HIV (D-) and followed KT R+ for adverse events and survival. Targets of plasma antibody reactivity in donors and recipients were quantified using phage immunoprecipitation sequencing (PhIP-Seq). Antibody targets with 5%-95% reactivity were included: 4667 viral peptides and 130 viral species, 667 toxin peptides, and 1427 human peptides. We used continuous Viral Aggregate Reactivity score (VARscore) to integrate the intensity and breadth of response to all antibody peptides for each viral species. Fisher’s exact tests and wilcoxon rank sum tests were used to evaluate the association between pre-KT antibodylevels and rejection after KT. We used the Bonferroni method to correct multiple comparisons. Analyses were additionally stratified by sex. Results: There were 64 D+ and 82 D-, and 198 R+ (99 D+/R+ and 99 D-/R+). Most donors (69%) and R+ (82%) were male. Seven female and 31 male R+ had either antibody or cellular mediated rejection after KT. The median total hits of human peptides was higher in D+ (127 [IQR=103-144]) than D- (111 [IQR=78-130]) (p=0.006). Donor HIV status was associated with reactivity

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APOL1 Genotype and Graft Function in South African HIV+-to-HIV+ Kidney Transplant Recipients Robert Freercks 1 , Kathryn Manning 2 , Swetha Ashokkumar 3 , Miruthula T. Selvan 4 , Savania Nagiah 1 , Jurgen Heymann 5 , Jeffrey B. Kopp 5 , Elmi Muller 6 , Andrew D. Redd 3 1 Nelson Mandela University, Gqeberha, South Africa, 2 University of Cape Town, Cape Town, South Africa, 3 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 4 The Johns Hopkins University, Baltimore, MD, USA, 5 National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA, 6 Stellenbosch University, Cape Town, South Africa Background: APOL1 gene risk variants (G1: S342G and I384M; and G2: del N388 and Y389) significantly contribute to genetic risk of chronic kidney disease (CKD), particularly in people living with HIV (PLWH). Shorter renal allograft survival has been demonstrated in kidney transplant recipients (KTR) without HIV where either donor or recipient kidney genotype included a high-risk phenotype (two APOL1 risk alleles). Methods: Genomic DNA was extracted from Peripheral blood mononuclear cells (PBMC) from deceased kidney donors with HIV, as well as KTR with HIV that were transplanted as part of the seminal HIV+-to-HIV+ transplant study in Cape Town, South Africa. APOL1 genotypes were genotyped by TaqMan probe assays (ABI, Foster City, California) specific for APOL1 G1 SNPs (rs73885319 and rs60910145) and the G2 deletion (rs717185313).

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