Immunological Recovery Research Articles

DTG + 3TC dual therapy for the treatment Naïve patients with viral load exceeding 500,000 copies/mL: a retrospective study

BackgroundAntiretroviral therapy (ART) has transformed HIV management, with various regimens available. Dolutegravir (DTG) plus lamivudine (3TC) dual therapy is now the one of the first line regimens.MethodsA retrospective, observational study included treatment naïve people living with HIV (PLWH) with baseline HIV RNA viral load (VL) greater than 500,000 copies/mL from March 2020 to June 2022. PLWH on DTG + 3TC were included in the 2DR group, while others on INSTI-based three-drug regimens were divided in the 3DR group. Viral suppression, immunological recovery, and safety were assessed.ResultsThe study included 52 PLWH, with no significant baseline differences. Virologic suppression rates at weeks 24 and 48 were similar in both groups, even with baseline HIV RNA VL greater than 1,000,000 copies/mL. CD4 + T cell counts improved rapidly. No serious adverse effects were reported.ConclusionsDTG + 3TC dual therapy demonstrates effectiveness in treatment naïve PLWH with high baseline HIV RNA VL, suggesting its potential as a first line regimen for all treatment naïve PLWH.

HIV-Induced Thymic Insufficiency and Aging-Related Immunosenescence on Immune Reconstitution in ART-Treated Patients.

The mechanisms underlying unsatisfactory immune reconstitution in HIV-1 positive patients under ART have not been fully elucidated, even after years of investigation. Thus, this study aimed to assess the correlation between age and thymic production profile, and its influence on inadequate immunological recovery. Here, 44 ART-treated patients with undetectable plasma HIV-1 load (<40 copies/mL) were classified as 31 immunological responders (IR) and 13 immunological non-responders (INR), according to their CD4+ T-cell count after 18 months of ART. The thymic function was assessed by identifying recent thymic emigrants (RTEs) CD4+ T cells (CD4+/CD45RA+CD31+) in PBMCs using flow cytometry. Clinical data were also analyzed from medical records. The INR group showed a higher age at ART initiation (41 ± 3.0) compared to the IR (33.7 ± 2.1) group (p = 0.041). Evaluating RTE CD4+ T-cells, we observed a lower percentage in the INR group (19.5 ± 6.3) compared to the IR group (29.9 ± 11.5) (p = 0.012). There was a strong negative correlation between age at ART initiation and RTE CD4+ T-cells in INRs (r = -0.784, p = 0.004). Our study has highlighted the thymic insufficiency and aging-related immunosenescence with unsatisfactory immunological recovery during ART in HIV-1 positive patients.

Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study.

Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes. The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm3, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm3 at any time during 48-week analysis periods through week 192. Through a median of 258 weeks (range, 0.14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm3, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm3 at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm3 at any time vs those sustaining <200 cells/mm3. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm3. Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment. NCT02362503, https://clinicaltrials.gov/study/NCT02362503.

Treatment intensity affects immune reconstitution even after childhood cancer not treated with hematopoietic stem cell transplantation.

Only a few previous studies examine immune system recovery after completed cancer treatment. The aim of this study was to analyze immune reconstitution after childhood cancer therapy in a non-hematopoietic stem cell transplantation setting. We analyzed children (N = 79) who received chemotherapy with/without irradiation for cancer diagnosed between 2014 and 2019 at Turku University Hospital, Finland. We retrospectively collected data on baseline parameters and post-treatment immunological recovery, namely neutrophil and lymphocyte counts, IgG levels, CD19, CD4 and natural killer cell counts. Immunological parameters were followed until their normalization. Treatment intensity was stratified according to the Intensity of Treatment Rating Scale (ITR-3). We analyzed the effects of treatment intensity on normalization of immunological parameters across the entire treatment range. Treatment intensity had a major effect on immune system recovery after completion of treatment. Most patients had normal immunological parameters 1-4 months post-treatment both in high- and low-intensity treatment groups, but patients classified in the high-intensity group had low parameters more often than patients in the low-intensity group. Our data suggest a fast recovery of studied immunological parameters after the majority of current pediatric oncologic treatments. Treatment for high-risk acute lymphoblastic leukemia, acute myeloid leukemia, medulloblastoma, and mature B-cell lymphoma was associated with prolonged recovery times for a substantial proportion of cases. High treatment intensity was associated with prolonged immunological recovery.

Dynamics of Matricellular Protein Levels in Blood Predict Recovery in Patients with Human Immunodeficiency Virus-Tuberculosis Coinfection.

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6-18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection.

Evaluation of the effects of Artemisia Annua L. and Moringa Oleifera Lam. on CD4 count and viral load among PLWH on ART at Mbarara Regional Referral Hospital: a double-blind randomized controlled clinical trial

BackgroundInitiation of ART among people living with HIV (PLWH) having a CD4 count ≤ 350cells/µl, produces poor immunological recovery, putting them at a high risk of opportunistic infections. To mitigate this, PLWH on ART in Uganda frequently use herbal remedies like Artemisia annua and Moringa oleifera, but their clinical benefits and potential antiretroviral (ARV) interactions remain unknown. This study examined the impact of A. annua and M. oleifera on CD4 count, viral load, and potential ARV interactions among PLWH on ART at an HIV clinic in Uganda.Methods282 HIV-positive participants on antiretroviral therapy (ART) with a CD4 count ≤ 350cells/µl were randomized in a double-blind clinical trial to receive daily, in addition to their routine standard of care either; 1) A. annua leaf powder, 2) A. annua plus M. oleifera, and 3) routine standard of care only. Change in the CD4 count at 12 months was our primary outcome. Secondary outcomes included changes in viral load, complete blood count, and ARV plasma levels. Participants were followed up for a year and outcomes were measured at baseline, 6 and 12 months.ResultsAt 12 months of patient follow-up, in addition to standard of care, administration of A. annua + M. oleifera resulted in an absolute mean CD4 increment of 105.06 cells/µl, (p < 0.001), while administration of A. annua plus routine standard of care registered an absolute mean CD4 increment of 60.84 cells/µl, (p = 0.001) compared to the control group. The A. annua plus M. oleifera treatment significantly reduced viral load (p = 0.022) and increased platelet count (p = 0.025) and white blood cell counts (p = 0.003) compared to standard care alone, with no significant difference in ARV plasma levels across the groups.ConclusionA combination of A. annua and M. oleifera leaf powders taken once a day together with the routine standard of care produced a significant increase in CD4 count, WBCs, platelets, and viral load suppression among individuals on ART. A. annua and M. oleifera have potential to offer an affordable alternative remedy for managing HIV infection, particularly in low-resource communities lacking ART access.Trial registrationClinicalTrials.gov NCT03366922.

Abstract 5557: Stem-like T cells maintain latent anticancer activity and underly therapy resistance

Abstract Pre-cancerous cells are normally recognized and eliminated by immune cells. Cancer progresses only when this immunosurveillance system fails. Although immunotherapy has driven the most significant and exciting advances in cancer treatment in modern times, current approaches are running into barriers. An emerging area of interest includes evidence for rare but highly potent stem cell-like T cells. Stem-like T cells combine long-term persistence and high potency with immunological memory. Our recent findings reveal insights into the nature and regulation of stem-like T cells and their potential anticancer activity. Minimal residual disease (MRD) underlies therapeutic resistance, dictates treatment escalation, and predicts patient outcomes. We have shown that the Wnt and PI3K pathways promote the transformation of hematopoietic stem cells (HSCs) into chemoresistant leukemia stem cells (LSCs), which form the root of leukemia initiation and post-treatment recurrence. High-throughput screening revealed that LSCs could be targeted by low dose anthracycline treatment. Mechanistically, low dose, but not high dose anthracyclines indirectly target LSCs by inhibiting their unique properties of immune escape, allowing for their elimination by CD8+ T cells. We employed single-cell genomic and proteomic analysis to investigate immunological changes during development of HSCs, LSCs, and their progeny in response to low dose anthracycline treatment. While leukemia progression results in exhaustion of differentiated CD8+ T cells, stem-like T cells accumulate. However, low dose anthracycline treatment reverses this imbalance. Comparing MRD+ and MRD- patient samples, we found that differential proportions of stem-like T cells persist in the bone marrow of leukemia patients. While T cells of MRD- patients recover following chemotherapy induction, T cell recovery is severely attenuated in MRD+ patients. Furthermore, failure of immunological recovery is driven at least partially by a lack of stem-like T cells in MRD+ leukemia patients. Overall, our studies have revealed that low dose anthracyclines, in contrast to high dose, induce opposing, dichotomous effects on LSCs vs. HSCs and stem-like vs. differentiated T cells. Citation Format: Fang Tao, Sara McElroy, Jacqelyn Nemechek, Irina Pushel, John Szarejko, Santosh Khanal, Todd Bradley, Doug Myers, John M. Perry. Stem-like T cells maintain latent anticancer activity and underly therapy resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5557.

Plasma metabolomic profile is near-normal in people with HIV on long-term suppressive antiretroviral therapy.

Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender. We carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4+ ≥500 cells/mm3, and CD4+/CD8+ ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value). PCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls. PWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.

Linking Immunological Parameters and Recovery of Patient’s Motor and Cognitive Functions In The Acute Period of Ischemic Stroke

Objective. To evaluate the relationship between immunological parameters and functional outcome in patients with varying severity of ischemic stroke based on statistical methodology.Materials and methods. The prospective study included 78 patients diagnosed with ischemic stroke, who were distributed into two groups: group 1 — 38 mild stroke patients, NIHSS score &lt; 5, group 2 — 40 moderate stroke patients, NIHSS score 5–15. Signs of stroke severity, degree of disability, cognitive decline, and activities of daily living were chosen as criteria to estimate the functional outcome by calculating the difference between the NIHSS, mRS, MoCA, and BI scales at the time of admission and on Day 12 of hospital stay. Lab tests included assessment of plasma concentrations of CXC and CC subfamilies of cytokines, interleukins and TNF-a on Day 2 of hospital stay. Machine learning algorithms, the Python programming language, the Pandas and SciPy libraries, and discriminant analysis were used for statistical processing.Results. The following parameters were found as significant: concentrations of IL-1b and MPIF-1/CCL23 for — for group 1, and concentrations of IL-16, MPIF-1/CCL23, Eotaxin-2/CCL24, Gro-a/CXCL1 and IL-8/CXCL8 for group 2 patients. Positive correlation was established between NIHSS dynamics and concentrations of TNF-a (R=0.227, P=0.001), MPIF-1/CCL23 (R=0.380, P=0.00061) and Gro-a/CXCL1 (R=0.211, P=0.00001), and between changes in mRS and concentrations of MPIF-1/CCL23 (R=0.277, P=0.00006), Gro-a/CXCL1 (R=0.211, P=0.0075) and IL-16 (R=0, 211, P=0.00001). There was a significant negative correlation between cognitive dysfunction and concentrations of Eotaxin-2/CCL24 (R=–0.378, P=0.00075), Gro-a/CXCL1 (R=–0.313, P=0.0035), and IP-10/CXCL1 (R=–0.214, P=0.00023), and between limited activities of daily living (IB) and concentrations of MPIF-1/CCL23 (R=–0.345, P=0.0024) and Gro-a/CXCL1 (R=–0.210, P=0.00001).Conclusion. Chemokines form the CC family — MPIF-1/CCL23 and Eotaxin-2/CCL24, and the CXC-Gro-a/CXCL1 and IL-16 clusters are the principal cytokines associated with the dynamics of patient’s motor and cognitive functions recovery in the acute period of ischemic stroke. Although obtained results demonstrate negative effect of increased MPIF-1/CCL23, Gro-a/CXCL1, IL-16 and Eotaxin-2/CCL24 concentrations on the improvement of motor and cognitive impairments, further studies are needed to verify the CXC and CC subfamilies chemokines as prognostic markers of patient’s functional outcome in the acute period of ischemic stroke.

Effects of Prolonged Administration of Tenofovir Disoproxil Fumarate-Containing Antiviral Regimen on Renal Function in Low-Risk of Kidney Injury HIV Patients.

This study intended to investigate the impact of long-termtenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)-infected patients with low-risk of kidney injury. The observational study involving 100 HIV-infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine β2 microglobulin, and other parameters, was assessed every 3 months over a period of 2.5 years. The eGFR showed a slight increasement from 116.0 at month 0 to 119.7 at month 30. Blood β2 microglobulin increased from 2.02 mg/L at month 0 to 2.77 mg/L at month 30. Compared to month 0, the difference in blood β2 microglobulin was statistically significant at month 6 and months 12-30 (P<.05). The incidence of proximal renal tubular dysfunction fluctuated from 2% at month 0 to 2.5% at month 30. The urine β2 microglobulin fluctuated from 0.5 (0.3-1.1) to 0.8 (0.5-1.35) mg/L at months 18-30, which was higher than 0.41 (0.18-1.1) mg/L at month 0 (P<.05). The abnormal concentration proportion of urine β2 microglobulin fluctuated from 72.7% to 81.3% at months 18-30, which was higher than the proportion of 57.0% at month 0. The abnormal proportion of blood β2 microglobulin, urine β2 microglobulin, and proximal renal tubular dysfunction were not correlated with eGFR (r1 = 0.119, r2 = -0.008, r3 = -0.165, P>.05). Long-term TDF antiviral regimen in low-risk of kidney injury HIV-infected patients may lead to damage in the proximal renal tubules and glomeruli. Blood and urine β2 microglobulin levels may be helpful in screening for renal dysfunction.

Loneliness, immunological recovery patterns, and health-related quality of life (HRQOL) outcomes in patients receiving hematopoietic stem cell transplantation.

Loneliness may compromise health-related quality of life (HRQOL) outcomes and the immunological impacts of loneliness via neuroendocrinological mechanisms likely have consequences for patients who have undergone a hematopoietic stem cell transplantation (HSCT). Loneliness (pre-transplant), immunological recovery (Day 30, Day 100, 1-year post-transplant), and HRQOL (Day 100, 1 year) were measured in a sample of 205 patients completing a HSCT (127 autologous, 78 allogenic). Greater levels of pre-transplant loneliness predicted poorer HRQOL at Day 100 and 1-year follow-up. Loneliness also was associated with higher absolute neutrophil to absolute lymphocyte (ANC/ALC) ratios in the entire sample at Day 30, which in turn was associated with Day 100 HRQOL. Findings demonstrate that pretransplant loneliness predicts HRQOL outcomes and associates with inflammatory immunological recovery patterns in HSCT patients. The balance of innate neutrophils to adaptive lymphocytes at Day 30 present a distinct profile in lonely individuals, with this immunity recovery profile predicting reduced HRQOL 100 days after the transplant. Addressing perceptions of loneliness before HSCT may be an important factor in improving immunological recovery and HRQOL outcomes.

Plasma concentrations of IL-6, MIP-1β, IP-10, and PTX-3 as predictors of the immunological response to antiretroviral treatment in people with HIV.

Despite effective antiretroviral therapy (ART), 15-30% of people with HIV experience poor CD4+ T-cell recovery, termed immunologic non-responders (INR). This study aims to evaluate whether pre-ART plasma levels of interleukin-6 (IL-6), interferon gamma-induced protein-10 (IP-10), macrophage inflammatory protein-1-β (MIP-1β), and/or pentraxin-3 (PTX-3) could predict subsequent immunologic recovery. Seventy-four participants were enrolled and classified as INR and immunologic responders (IR) based on CD4+/CD8+ ratio increase over 24 months after starting ART. The results showed no significant differences in cytokine levels between INR and IR. Therefore, IL-6, IP-10, MIP-1β, and PTX-3 were unsuitable as predictive markers of poor immune recovery.

Thirteen-year viral suppression and immunologic recovery of LPV/r-based regimens in pediatric HIV treatment: a multicenter cohort study in resource-constrained settings of China.

Antiretroviral Therapy (ART) in children remains challenging due to resource-constrained settings. We conducted a 13-year, prospective, multicenter cohort study on the effectiveness and safety of LPV/r-based regimens in ART-naive and ART-experienced children. From January 2008 to May 2021, children living with HIV-1 were recruited with LPV/r-based regimens from 8 clinical research sites in 6 provinces in China. Effectiveness outcomes were virologic failure (defined as at least two consecutive measurements of VL > 200 copies/mL after 6 months of ART) and immune response (defined as CD4% recovered to more than 25% after 12 months of treatment). The safety outcomes were treatment-related grade 2-4 adverse events and abnormal laboratory test results. A total of 345 ART-naïve children and 113 ART-experienced children were included in this cohort study. The median follow-up time was 7.3 (IQR 5.5-10.5) years. The incidence density of virologic failure was 4.1 (95% CI 3.3-4.9) per 100 person-years in ART-naïve children and 5.0 (95% CI 3.5-6.5) per 100 person-years in ART-experienced children. Kaplan Meyer (KM) curve analysis showed children with ART experience were at a higher risk of virologic failure (p < 0.05). The risk factors of virologic failure in ART-naïve children were clinic setting in rural hospitals (aHR = 2.251, 1.108-4.575), annual missed dose times >5 days of LPV intake (aHR = 1.889, 1.004-3.554); The risk factor of virologic failure in ART-experienced children was missed dose times >5 days (aHR = 2.689, 1.299-5.604) and mother as caregivers for ART administration (aHR = 0.475, 0.238-0.948). However, during long-term treatment, viral suppression rates between ART-naïve and ART-experienced children remained similar. No significant differences were observed in the immune response, treatment-related grade 2-4 events, and abnormal laboratory test results between ART-naïve children and ART-experienced children. Our research underscores that with consistent, long-term treatment of LPV/r-based regimens, ART-experienced children can achieve therapeutic outcomes comparable to ART-naïve children. It provides crucial insights on LPV/r-based regimens in pediatric HIV treatment, especially in resource-limited settings where high-cost Integrase Strand Transfer Inhibitors (INSTs) are inaccessible. This evidence-based understanding provides an essential addition to the global therapeutic strategies for pediatric HIV treatment.

Bictegravir/Tenofovir Alafenamide/Emtricitabine: A Real-Life Experience in People Living with HIV (PLWH).

Bictegravir (BIC), a recently introduced integrase inhibitor, is available in a single tablet regimen with tenofovir alafenamide (TAF) and emtricitabine (FTC) (BIC-STR). This study aimed to describe a real-life experience with BIC-STR. We retrospectively analyzed the data of people living with HIV (PLWH) on antiretroviral therapy (ART) with BIC-STR followed by the Clinic of Infectious Diseases of Perugia (Perugia, Italy) from September 2019 to February 2023. 270 PLWH were enrolled with a median follow-up time on BIC-STR of 2.2 years (IQR 1.2-2.7). In the overall population, in treatment-experienced (N = 242), in treatment-naïve (N = 28), and in population with age > 60 years old (N = 86), we observed that CD4 cell count improved in absolute number, percentage and CD4/CD8 ratio, under BIC-STR. Patients with viremia < 50 cp/mL increased in all groups. In the overall population, previous ART with TAF and nadir CD4 cell count favored immunological recovery. In the ART-experienced group, time in therapy with BIC-STR was associated with HIV-RNA undetectability. In the older group, previous opportunistic infection and advanced age were associated with lower CD4 count. BIC-STR was demonstrated, in real-life, to be a valid option for a switch, such as initial ART.

Casting Hope, Defying Odds: Unveiling the Impact of Haplo-Identical Stem Cell Transplant in Myeloid Malignancies - a Tertiary Cancer Care Center Experience

Background &amp; Significance: Only 30% to 40% of patients in need of a curative stem cell transplant (SCT) could find a suitable matched sibling donor. For Indian patients, the likelihood of locating a 10/10 HLA identical unrelated donor within limited donor registries is approximately 14%. However, this probability has the potential to rise to 60% if registries with over 1,000,000 registered donors are available. 1,2 Consequently, there is an increasing inclination in India to perform haploidentical transplantations utilizing the post-transplantation cyclophosphamide (PTCY) platform developed by the Johns Hopkins group. 3 The outcomes of haploidentical stem cell transplantation (haplo-SCT) for the treatment of AML were enhanced in the 1990s with the introduction of a T-cell depletion (TCD) strategy followed by a myeloablative conditioning regimen. 4,5 In the last two decades, significant progress in haplo-SCT for hematological malignancies, especially AML, includes donor selection algorithms, improved grafts, GVHD prophylaxis, and enhanced immunologic recovery, benefiting patients. 6 Here, we present our experience of haplo-identical stem cell transplants in myeloid malignancies at our centre. Study design &amp; Methods: We conducted a retrospective study at our site. Patients with myeloid malignancy who underwent haplo-identical stem cell transplant between Jan 2018 - Jan 2023 were included in the study and the follow-up was done till July 2023. Haplo-identical transplants done for diagnosis other than myeloid malignancy were excluded. The objectives of the study were to assess the non-relapse mortality [NRM] rate at day +100, relapse rate, graft-versus-host disease - free relapse-free survival [GRFS] and overall survival [OS] of the study cohort. GRFS was defined as a combined outcome including mortality from any cause, recurrence of malignancy, acute GVHD of grade 3 to 4, or chronic GVHD necessitating systemic immune suppression therapy. 7 Descriptive statistics (including median, mean, and range) were used to describe the central tendency and dispersion of variables. The probability of overall survival [OS] and graft versus host disease relapse free survival [GRFS] was estimated by the method of Kaplan and Meier. Probabilities of relapse or progression of malignancy, RRM, and day-100 NRM were summarized using cumulative incidence estimates All statistical analysis were done using statistical package for social science software (SPSS 21, IBM SPSS Statistics). Results: We have analysed 29 patients with various myeloid malignancies who have underwent haploidentical SCT from Jan 2018 to Jan 2023. There were 28 AML and 1 MDS patients. The median age was 35 (range, 16 - 59) and there were 22 males and 7 females. Conditioning intensity was myeloablative in 19 (65.5%), reduced intensity conditioning (RIC) in 8 (27.6%) and NMA in 2 (6.9%) patients. There were 10 (34.5%) patients in complete remission 1(CR1) and 19 (65.5%) in CR2. Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI] score was as low 11 (37.9%), intermediate 8 (27.6%) and high 10 (34.5%) patients respectively. Median time to neutrophil engraftment was 16 days (range, 12 - 25) and platelet engraftment was 17 days (range, 11 - 32). Median CD34 stem cell dose was 6.25 x 10*6/kg (range, 3.1 - 8.09) x 10*6/kg. Grade II-IV acute GVHD over first +100 days post SCT was observed in 6 (20.7) patients, and grade III-IV acute GVHD and chronic GVHD at follow up of one year was 3 (10.3) respectively. CMV reactivation by +100days was seen in 18 (62.06%) patients. Relapse was seen in 10 (34.5%) patients, out of which 2 patients are alive and 8 expired due to progressive disease. At median follow up of 13 months, OS is 60.3% (CI: 39.7% - 75.9%) and GRFS is at a median follow-up of 6 month was 51.2% (CI: 35.6% - 71%). Fig:1 NRM was 10.3% and 17.24% at +100 days and at last follow-up respectively. Fig:2 Conclusion: In conclusion, our study demonstrates favorable outcomes in terms of NRM (non-relapse mortality) with a low rate of 10.3% at 100 days after haploidentical SCT. The results also show promising overall survival (OS) and GVHD-free, relapse-free survival (GRFS) rates, supporting the potential of haploidentical transplants as an effective treatment option for myeloid malignancies. Further long-term follow-up and research are needed to validate and optimize these findings.

2661. Characterization of Mpox in Southeast Michigan

Abstract Background More than 30,000 cases of mpox have been identified in the United States. Data suggest that about 40% of affected persons are co-infected with HIV. Although most cases are self-limiting, patients with low CD4 counts are at increased risk of developing severe clinical manifestations and dying. Methods Retrospective case-control study comparing mpox cases among people with HIV (PWH) and HIV-uninfected persons from July to Dec 2022, at Henry Ford Health in Southeast Michigan. Demographic data, clinical characteristics, treatment, and outcomes were evaluated. Results 54 patients were diagnosed with mpox. Overall, 42 (78%) were MSM or bisexual men, 36 (67%) Black, and 34 (63%) PWH; median age was 34.5 years (Table 1). The majority (63%) had prior sexually transmitted infections (STIs), which were more common in PWH (82% vs 30%, p&amp;lt; 0.001). About one-third had multiple sexual partners; more than half engaged in insertive or receptive anal intercourse. 32 (94%) of PWH were on ART, 26 (76%) had CD4 counts &amp;gt;200 and 19 (60%) had undetectable viral load; mean CD4 count was 602 and viral load 7942. Of the HIV-uninfected persons, 5 (25%) were on PrEP. Receipt of mpox vaccine was uncommon in either group. All patients presented with rash that was disseminated in 35%. Fever/chills, lymphadenopathy, headache, proctitis and pharyngitis were the most common manifestations and did not differ among the two groups. Concomitant STIs were present in 22 (48%) of 46 persons tested; syphilis co-infection was more prevalent among PWH (35% vs 25%, p&amp;lt; 0.006). Hospitalization and receipt of tecovirimat were similar between the two groups; no patients died. Demographics, Risk Factors, Clinical Manifestations and Outcomes of Mpox Patients Conclusion Overall, there were no significant differences in clinical manifestations or outcomes between PWH and HIV-uninfected persons with mpox except for syphilis co-infection. Most of our PWH cohort was on ART and virally suppressed with high CD4 count. Hence, efforts should focus on rapid treatment of PWH with effective ART to achieve virological suppression and immunological recovery to minimize clinical complications and severe outcomes associated with opportunistic pathogens. Vaccinating all high-risk individuals, early mpox recognition and testing, and screening for additional STIs should be prioritized. Disclosures Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria

Comparing the efficacy and safety of a first-line regimen with emtricitabine/tenofovir alafenamide fumarate plus either bictegravir or dolutegravir: Results from clinical practice

First-line integrase strand transfer inhibitor-based regimens have become commonly used in clinical practice over the last decade. This study aimed to analyse and compare the efficacy and safety of bictegravir (BIC) and dolutegravir (DTG) when prescribed in association with emtricitabine/tenofovir alafenamide (FTC/TAF) as part of a first-line regimen for the treatment of human immunodeficiency-1 (HIV-1) infection. Treatment-naïve people living with HIV (PLWHIV) starting a first-line regimen with either BIC/FTC/TAF (BIC group) or FTC/TAF+DTG (DTG group) were analysed. Snapshot analyses were performed after 24 and 48 weeks to evaluate virological efficacy. In addition, differences in the rate of treatment discontinuation (TD) between the two groups were evaluated using the Kaplan-Meier method and the log rank test. Data from 327 PLWHIV were analysed: 140 in the DTG group and 187 in the BIC group. At 48 weeks, 90.0% of individuals in the DTG group and 86.7% of those in the BIC group achieved HIV-RNA <50 copies/mL. In total, 88 and 38 cases of TD were observed in the DTG group and BIC group, respectively. The estimated probability of maintaining the study regimen at week 48 was 59.5% in the DTG group and 84.2% in the BIC group. Analysing changes in immunological parameters after 48 weeks, median improvements of +169 cell/mm3 (P<0.001) and +233 cell/mm3 (P<0.001) were observed in the DTG group and the BIC group, respectively. Both BIC and DTG, in combination with FTC/TAF, show promising efficacy and safety as first-line strategies in clinical practice, with favourable immunological recovery even in the short term.

Effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in HIV late presenters

The efficacy of BIC/FTC/TAF in HIV late presenters initiating antiretroviral therapy (ART) has not been sufficiently evaluated. The aim of this study was to assess the effectiveness and tolerability of BIC/FTC/TAF compared to other first-line antiretroviral regimens in treatment-naïve adult individuals from the CoRIS Cohort starting ART with CD4 counts <200 cells/mm3 and/or AIDS-defining conditions between January 1st 2019 and November 30th 2020. Logistic regression models were used to estimate odds ratios (ORs) of association between initial regimen and achievement of viral suppression (VS) (primary objective), defined as HIV RNA <50 cop/mL, and immunological recovery (IR) (secondary objective), defined as CD4 count >200 cells/mm3, at weeks 24 and 48 after initiation of ART. We evaluated 314 individuals (84.7% men, median age 40 years). Of them, 158 initiated with BIC/FTC/TAF. At inclusion, 117 had an AIDS-defining condition. In multivariable analyses, individuals with AIDS-defining conditions initiating ART with BIC/FTC/TAF achieved higher rates of VS at 24 weeks than other regimens (aOR: 0.2; 95% CI: 0.06-0.64) and, at 48 weeks, than DTG/ABC/3TC (aOR: 0.06; 95% CI: 0.01-0.76) and DTG+TDF/3TC (aOR: 0.2; 95% CI: 0.47-0.9). No other differences in VS or IR were observed. At 24 and 48 weeks after ART initiation, treatment discontinuations were lower with BIC/FTC/TAF than with other regimens (3.2% and 7.6% vs. 24.4% and 37.8%, respectively; P < 0.005). Our results suggest that BIC/FTC/TAF could be a preferred regimen as initial therapy in HIV late presenters because of its high effectiveness and good tolerability.

Prevalence of and prognosis for poor immunological recovery by virally suppressed and aged HIV-infected patients.

Antiretroviral therapy (ART) prolongs lifespan and decreases mortality of HIV infected patients. However, many patients do not achieve optimal immune reconstitution. The influence of non-optimal immune recovery on non-AIDS related diseases is not well defined in aged HIV-infected patients receiving ART. A retrospective study was conducted at Tianjin Second People's Hospital, China to evaluate the association of an inadequate immunological response and non-AIDS diseases in HIV infected patients ≥60 years of age and virally suppressed for at least 2 years by ART. The study included patients (n = 666) who initiated ART between August 2009 and December 2020. The prevalence of patients with an inadequate immunological response was 29.6%. The percentage of non-AIDS diseases such as hypertension, cardiovascular disease (CVD), diabetes, tumor, and chronic kidney disease (CKD) was 32.9, 9.9, 31, 4.1, and 13%, respectively. In addition to baseline CD4+ T cell counts, CVD and tumor were associated with poor immune reconstitution in aged Chinese HIV-1 infected patients. The adjusted odds ratios (95% confidence interval) were AOR 2.45 (95% CI: 1.22-4.93) and 3.06 (95% CI: 1.09-8.56, p = 0.03). Inadequate immunological response was associated with greater mortality (AOR: 2.83, 95% CI: 1.42-5.67, p = 0.003) in this cohort. These results tend to demonstrate appropriate drug selection at ART initiation and prevention of non-AIDS complications during ART decreased mortality of and an inadequate immunological response in aged HIV infected patients.

Real-Life Experience With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Turkey.

Single-tablet regimens (STRs) can increase treatment success and even improve the quality of life of human immunodeficiency virus (HIV) patients. In this study, we aim to analyze the real-life efficacy and tolerability data of people living with HIV (PLWH) initiated on or switched to bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF)as first-line treatment. This retrospective analysis was performed in HIV-1-positive patients who were initiated BIC/FTC/TAF in the HIV clinic between June 2020 and June 2022. Patients who received BIC/FTC/TAF for at least 12 months were included in this study. Virological suppression, laboratory parameters, side effects, and immunological response were analyzed at one, three, six, nine, and 12 months. A total of 116 patients, 66 (56.9%) treatment-experienced and 50 (43.1%) naive, were evaluated within the scope of the study. In the naive patient group, baseline HIV-RNA, CD4+ and CD8+ T cell counts, CD4/CD8 ratio, and estimated glomerular filtration rate (eGFR) values weresignificantly different in different follow-up months. The number of patients with HIV-1 RNA levels below 50 copies/mL was 55.9% in the first month, 73.7% in the third month, 90.2% in the sixth month, and 100% in the ninth and 12th months. In our real-life observational study, BIC/FTC/TAF treatment achieved rapid viral suppression, maintained viral suppression in virally suppressed patients, and was effective for immunological recovery in both treatment-experienced and naive HIV patients. No serious side effects were observed. Our study has proved the potential of BIC/FTC/TAF as an important option in the treatment of HIV patients.