Mean CD4 Research Articles

1262. Dolutegravir Plus 3TC In Antiretroviral Experienced Adults: Immunovirological Outcomes In a Multicenter Retrospective Cohort In Spain

Abstract Background Dolutegravir-based dual therapies for treating people living with HIV (PLHIV) are strategies strongly recommended in several practice guidelines. The safety and efficacy combination of Dolutegravir (DTG) plus 3TC as a switching strategy in virologically suppressed patients was demonstrated in the TANGO study. Wide multicenter real life data supporting this treatment is needed. The aim of the current study was to describe the efficacy in terms of immunovirological outcomes in patients treated with this antiretroviral combination. Methods From November 1st 2020 to August 1st 2021, data from 1062 PLHIV collected from 13 Spanish institutions were recorded in a multicenter, retrospective study; After discarding cases in which relevant variables were missing, finally 694 cases underwent statistical analysis. Inclusion criteria were age >18 years, and to receive treatment with DTG/3TC as a switch strategy. Immunovirological impact of this strategy ( CD4+, CD8+ and CD4+/CD8+ cell count, as well as HIV plasma viral load through weeks 24, 48 and 96 of follow up) was evaluated using multivariable mixed models where the individual was considered as a random effect. Sex and age were added as demographic covariables. Results 78% of patients were men, 16% had been previously diagnosed of AIDS. Mean age was 48 years old. Mean CD4 T cell count nadir was 300 cell/ml (160-480). We found a significant increase in CD4+ counts at 24, 48 and 96 weeks after switching drug strategy. We also detected a small increase in the CD4+/CD8+ count rate at 48 and 96 weeks. No significant change was found in CD8+ count. No differences were found on behalf of sex, between backbone drugs (73% switched from a TDF/FTC backbone and 26.9% from ABC/3TC) or amongst the different third agents used (62% switched from integrase inhibitors). We identified a strong and negative effect of having AIDS in the CD4+ count. However, this effect did not interact with the effect of switching drug strategies. CD4, CD8 and CD4/CD8 after switch at 24, 48 and 96w Log OR Conclusion PLHIV who, being virologically suppressed, switched to dual therapy based on DTG/3TC, experienced a statistically significant increase of CD4+ T cell count at weeks 24, 48 and 96, as well as an increase in CD4/CD8 T cell ratio, as well as high efficacy in terms of viral replication suppression, independently of the stage of HIV infection. Disclosures Luis Buzón-Martín, MD, ViiV, GILEAD, Jannsen, MSD: Lecture fees Carlos Dueñas Gutierrez, MD, ViIV, GILEAD, Jannsen, MSD: Lecture fees Jesús Troya, Staff, ViiV, GILEAD, Jannsen, MSD: Lecture fees.

1424. Central Nervous System Tuberculosis in a Large Healthcare System

Abstract Background Central nervous system tuberculosis (CNS-TB) accounts for 5-10% of extrapulmonary TB cases. It takes 3 clinical forms: meningitis, tuberculoma, and arachnoiditis. Modern case descriptions of the presentation of CNS-TB are rare. The goal of this study is to examine the presentation, diagnostic studies, and associated comorbidities of CNS-TB. Methods In our academic healthcare system, cases of culture confirmed CNS-TB were identified in a database maintained by the infection control group. This is a retrospective case series of the 11 adults with confirmed CNS-TB. Results 273 patients were identified with TB infection from 2008 to 2022. 104 (38%) had extra pulmonary disease. 11 (4%) had CNS infection. Patient characteristics are described in Table 1. 5 (45%) of the patients with CNS disease also had pulmonary disease. Mean age of diagnosis was 42. 5 (45%) were male and 9 (82%) were African American. 5 (45%) had HIV; mean CD4 count was 100 (8-255). Diagnostics are shown in Table 2. CSF studies revealed a mean WBC of 295/mm3 (4-808), protein of 605 mg/dL (27-4476), and Glucose of 31 (12-64) mg/dL. 4 (36%) patients presented with British Research Medical Council (BMRC) clinical stage I disease and 7 (64%) with stage II disease. 8 (73%) patients had an abnormal CT or MRI scan of the head, with representative images seen in Figure 1. 5 patients (45%) had lesions consistent with tuberculomas. 1 (9%) had arachnoiditis identified on imaging. 1 (9%) patient died. Conclusion 38% of patients diagnosed with TB at our center had extrapulmonary disease compared to 17.5% reported in the literature. The 4% rate of CNS-TB was similar to previously reported. Our series describes abnormal imaging as well as CSF studies showing leukocytosis, pleocytosis, and hypoglycorrhachia consistent with previously described findings. Though numbers were small, no significant difference was found between HIV positive and negative patients. Although mortality was rare in our series, the patient who died had advanced AIDS and multidrug resistant meningitis. Given the significant global mortality of this disease, this series highlights the need for more current studies describing the presentation and diagnostic characteristics of modern CNS-TB so clinicians can better recognize and treat the condition without delay. Disclosures All Authors: No reported disclosures.

1252. A Real-World Observational Study on HIV-Infected Patients who Switched from Nevirapine + 2 Nucleoside Reverse Transcriptase Inhibitors to Dolutegravir/Lamivudine in British Columbia, Canada

Abstract Background Although convenient single-tablet antiretroviral regimens have been developed to treat HIV in recent years, some patients have continued to take a multi-tablet treatment, nevirapine extended-release (NVP XR) plus two nucleoside reverse transcriptase inhibitors (NRTIs) due to its excellent safety profile. This observational study examined the demographic and clinical characteristics of HIV-positive patients who switched to dolutegravir plus lamivudine (DTG/3TC) from NVP XR plus 2 NRTIs, following discontinuation of NVP XR from the Canadian market. Methods Virally suppressed (< 50 cps/mL) HIV-positive adults ≥18 years who switched from NVP XR plus 2 NRTIs to DTG/3TC between 20 August 2019 and 30 April 2020 were retrospectively identified from Electronic Medical Records housed at Spectrum Health in British Columbia, Canada. Baseline demographic and clinical characteristics were summarized using descriptive statistics at the date of first DTC/3TC prescription. Virologic control, CD4 cell count, weight-related changes and exploratory characteristics related to metabolic syndrome were summarized at baseline and at 12 ± 6-months post-switch using descriptive statistics. Reasons for treatment discontinuation were also captured. Results Sixty-nine patients were identified (mean age ± SD = 54.2 ± 8.5 years; 100% male). Mean length of use (±SD) of NVP XR was 4.6 ± 2.6 years. Sixty-three (91.3%) persisted on DTG/3TC at the 12-month timepoint post-switch with 61 (96.8%) virally suppressed < 50 cps/mL and all 63 (100%) virally suppressed < 200 cps/mL. Among persistent patients with CD4 cell counts available, mean CD4 cell count (±SD) remained stable, increasing slightly from 724.4 ± 238.4 to 740.3 ± 240.6 cells/uL. All six (8.7%) patients who discontinued DTG/3TC, discontinued due to tolerability and not effectiveness reasons. Conclusion Our findings are the first to examine real-world use of single-tablet, 2-drug DTC/3TC among patients who switched from multi-tablet, 3-drug NVP XR plus 2 NRTIs in Canada. The majority persisted on DTG/3TC and remained virally suppressed at the < 50 cps/mL level 12-months post-switch. This, coupled with excellent tolerability, demonstrates the effectiveness of DTG/3TC in maintaining viral suppression among a unique and stable group of older men. Disclosures Joss de Wet, MBChB CCFP FCFP, Gilead: Advisor/Consultant|Gilead: Board Member|Gilead: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Board Member|ViiV: Grant/Research Support Joann K. Ban, PharmD, MSc, GlaxoSmithKline Canada Inc.: Employee Gustavo Verdier, BSc, BPharm, MBA, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare ULC: Salary Juejing Ling, MSc, GSK: Employee of IQVIA , a company that receives consulting fees from GSK. Andrean Bunko, MPH, GlaxoSmithKline Inc.: GSK contracted with IQVIA for this and other projects. I am acting as an author in capacity of my employment with IQVIA. Michael McKimm, BSc, ViiV Healthcare: employee.

LB1576. High Prevalence of Oral Treponema pallidum by PCR among US Adults with Early Syphilis

Abstract Background Treponema pallidum (T. pallidum) is transmitted from person to person by direct contact with widespread dissemination early after acquisition. Current syphilis diagnostic testing is limited to darkfield microscopy from visible lesions and serologic antibody detection. T. pallidum molecular diagnostics are urgently needed. Methods As part of a multicenter US syphilis treatment trial that completed enrollment in March 2022 (NCT 3637660), we randomized 249 adults with early syphilis infection to 1 vs 3 weekly doses of benzathine penicillin G to compare treatment response at 6 months. In a small substudy (n=32) presented here, consenting participants at the University of Alabama at Birmingham (UAB) and Emory University had pre-treatment oral (buccal mucosa and posterior pharynx) and lesion swab samples collected. Following DNA extraction, T. pallidum burden in samples was quantified by targeting the tp0574 gene. Syphilis was staged by experienced providers according to physical examination and serology. Results Study participants were men (100%) and most were living with HIV (91%) with mean CD4 count 477 cells/mm3. Syphilis stage was categorized as primary in 6 (19%), secondary in 18 (56%) and early latent in 8 (25%). Oral swab qPCR positivity rates were 17% in primary disease, 44% in secondary disease, and 63% in early latent disease (see Figure). Lesion PCR positivity was similar in primary and secondary syphilis (40% and 38.5%). Mean treponemal burden was highest on oral swabs of participants with early latent syphilis (13,128,969) and lesion swabs of participants with secondary syphilis (2,033,309). Conclusion Among adult males, many living with HIV, data suggest a role for oral and lesion swabs for the molecular detection of T. pallidum. Widespread availability of PCR, the relative ease of oral specimen collection, and the opportunity to directly demonstrate T. pallidum in persons with early latent syphilis suggest the opportunity for PCR testing to enhance and refine syphilis diagnostic testing. The elevated proportion of positive oral samples and significant organism burden in secondary and early latent syphilis is consistent with potential for transmission. Disclosures All Authors: No reported disclosures.

Razão e contagem de linfócitos T CD4+ e linfócitos T CD8+ em gatos com gengivoestomatite crônica e infectados naturalmente pelo vírus da imunodeficiência felina: estudo preliminar

This study aimed to evaluate the CD4+ and CD8+ T lymphocytes counts and CD4+: CD8+ ratio in a colony of cats with chronic gingivostomatitis (CGS). We used forty domestic short-haired cats inhabiting the same colony. Ten cats with CGS were immunodeficiency virus-positive (group IV), and ten with CGS were immunodeficiency virus-negative (group III). As a control, twenty cats without CGS were used: ten cats were immunodeficiency virus-positive (group II) and ten cats were immunodeficiency virus-negative (group I). We employed flow cytometry to count CD4+ and CD8+ T lymphocytes. In cats infected with the immunodeficiency virus, the presence of CD4+ lymphocytes were lower both for animals with and without CGS. Conversely, not immunodeficiency virus-infected cats with CGS had a higher amount of CD4+ when compared to seronegative animals without CGS. The counts of CD8+ T lymphocytes showed no significant difference among cats with CGS, whether infected with immunodeficiency virus or not. The CD4+: CD8+ ratio was only different for group III, which was higher than any other group. No difference was observed for total lymphocyte number and CD8+ among groups. By contrast, mean CD4+ levels were different, with cats from groups III and IV showing higher levels than those from groups I and II. The flow cytometry could be a useful tool for the diagnosis and prognosis of cats with CGS infected by the immunodeficiency virus.

Capillaroscopy, microangiopathy, and HIV. Descriptive study of capillaroscopy findings in HIV positive patients

In this study, we aim to evaluate microangiopathy in HIV positive patients by using capillaroscopy. To date, few studies have been published on the topic. Capillaroscopy may be a tool for early diagnosis of cardiovascular involvement in this patient population. Cross-sectional study with HIV positive patients >18 years. The enrolment period was set from January to June 2018. The following data were collected: demographic (sex, age), laboratory tests (duration of infection, CD4 cell count, CD4:CD8 ratio, coinfection with other viruses), antiretroviral treatment, dyslipidemia, and comorbidities (active smoking, alcoholism, high blood pressure, dyslipidaemia, diabetes, cardiopathy). The capillaroscopy and blood tests were performed simultaneously. The following alterations were evaluated in the capillaroscopy: congestion, tortuosity, haemorrhage, dilations, capillary loss, and presence of megacapillaries. One hundred and two patients were included; 73.5% were male, mean age was 40 years (SD: 10), and mean duration of infection 4.5 years (SD: 3.1). At diagnosis, mean CD4 cell count was 408/mm3 and CD4/CD8 ratio 0.4. A number of patients (14.7%) were coinfected with the hepatitis B virus; 31.3% were active smokers and 13.7% alcoholics. Capillaroscopy alterations were found in most study patients (93.1%): congestion (78.5%), tortuosity (77.5%), haemorrhage (13.8%), dilations (11.8%), capillary loss (5%), and megacapillaries (1%). Capillary tortuosity was associated with age and smoking; and haemorrhage with age, CD4, antiretroviral treatment, and hypertension. Prevalence of capillaroscopy alterations is high in HIV positive patients, particularly tortuosity and congestion. To the best of our knowledge, the later alteration has not been previously reported in this group of patients.

The influence of low-level viremia on CD4+ cell count in human immunodeficiency virus–infected patients

Following initiation of combined antiretroviral therapy, the majority of human immunodeficiency virus-infected patients experience immune reconstitution indicated by virologic suppression and an increase in peripheral CD4+ T-cell counts. Some patients may suffer from low-level viremia, which was reported to be significantly associated with acquired immunodeficiency syndrome cases, virologic failure, and death. We aimed to further investigate the influence of low-level viremia on CD4+ T-cell count. In our study, we included human immunodeficiency virus-seropositive patients on combined antiretroviral therapy, for at least 6 months, who received at least one assessment of human immunodeficiency virus plasma viral load and CD4+ cell count every 6 months, from January 2009 to January 2019. The copy-year viremia was determined by calculating the area under the curve of the plasma human immunodeficiency virus viral load. When comparing patients with a mean CD4+ cell count <200 cells/μL, there was no significant difference between patients with a mean viral load <1000 copies/mL and patients with a mean viral load ≥1000 copies/mL (p = 0.219). Among those with a mean viral load <1000 copies/mL, a higher proportion of patients had a mean CD4+ cell count ≥500 cells/µL (p < 0.001). The mean CD4+ cell count of patients with copy-years viremia (log10) <4 (577.7, interquartile range 429.2-736.7) was significantly higher than that of patients with copy-years viremia (log10) ≥4 (443.3, interquartile range 319.0-558.4) (p < 0.001). In multivariate logistic regression analysis, we observed that malignancy without history, lower copy-years viremia, and high nadir CD4+ cell count were independent predictors of mean CD4+ cell count ≥500 cells/µL. Human immunodeficiency virus-infected patients with a history of malignancy, high copy-year viremia, and lower nadir CD4+ cell counts should be monitored carefully in clinical settings.

Pregnancy in Women With HIV in a Tuberculosis Preventive Therapy Trial.

Tuberculosis preventive therapy (TPT) is recommended for people with HIV infection, including during pregnancy. The effect of TPT exposure at conception and during pregnancy is poorly documented. We report pregnancy outcomes among South African women with HIV enrolled in a randomized trial of 4 TPT regimens (two 3-month regimens, rifapentine/isoniazid [3HP] or rifampin/isoniazid [3HR], isoniazid for 6 months, or isoniazid continuously). Descriptive statistics and risk ratios were assessed to examine relationships between study regimens and outcomes. 216/896 women (24%) conceived during the study. Women who conceived were younger (27.9 vs 31.3 years) and had higher mean CD4 counts (589.1 vs 536.7). The odds of pregnancy were higher in women in the rifamycin-isoniazid arms than those in the isoniazid arms (3HP: relative risk [RR] 1.73, P = 0.001; 3HR:RR 1.55, P = 0.017) despite increased contraceptive use compared with the standard 6H therapy. Thirty-four women became pregnant while taking preventive treatment (8 rifamycin and 26 isoniazid monotherapy). Pregnancy outcomes in these women were as follows: 17 (50%) mother/baby healthy, 3 (9%) spontaneous abortions, 6 (18%) elective abortions, 1 (3%) premature delivery, 2 (6%) neonatal deaths [1 rifamycin-isoniazid and 1 isoniazid], and 5 (15%) unknown. Pregnancy was common in women who had received TPT and more frequent in women who had received rifamycin-isoniazid-based regimens.

Stimulation of the Vascular Endothelium and Angiogenesis by Blood-Flow-Restricted Exercise

Blood-flow-restricted exercise (BFRE) has been gaining constantly increasing interest in rehabilitation, but its influence on endothelial functions has not been well studied yet. Our aim is to examine the influence of low-resistance BFRE on endothelial functions and angiogenesis. This prospective cross-over study involved 35 young healthy adults. They conducted a 21-min low-resistant exercise with blood flow restricted by pressure cuffs placed on arms and tights. They also did the same training but without blood flow restriction. Endothelial parameters and angiogenesis biomarkers were evaluated before and up to 20 min after exercise. Both types of exercise increased Flow-Mediated Dilatation (FMD) but elevation after BFRE was more significant compared to the controls. The stiffness index decreased only after BFRE, while the reflection index decreased significantly after both types of exercise but was higher after BFRE. Platelet endothelial cell adhesion molecule (PECAM-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) concentrations were increased by both exercise types but elevations were higher after BFRE compared to the controls. Only BFRE elevated the mean serum CD34 protein concentration. Based on these results, we can assume that low-resistance BFR exercise stimulates angiogenesis and improves endothelial functions more significantly compared to the same training performed without blood flow restriction.

Malaria an opportunistic infection in HIV/AIDS patients? - A Nigerian experience.

HIV and malaria interact at the level of the host's susceptibility to infection, but little is known about the effect of HIV on malaria infection in Nigeria. This study estimated the prevalence of malaria parasitaemia and its relationship with HIV immunodeficiency. This cross-sectional study was conducted in two hospitals in Abuja, Nigeria between October 2012 and March 2013 among 600 respondents, comprising 200 HIV-negative controls, 200 HIV-positive patients on antiretroviral therapy (ART), and 200 HIV-positive patients not on ART. Malaria parasites, malaria density and absolute CD4 counts were carried out on all three groups. Participants with CD4 counts below 350 cells/mm3 were considered immunocompromised and likely to develop opportunistic infections. Most study participants were aged 21-40 years (65.2%). The mean CD4 counts of HIV-positive patients not on ART (300 ± 211 cells/mm3) and those on ART (354 cells/mm3) were significantly lower than among controls (834 cells/mm3) (p < 0.001). Malaria prevalence was not statistically different between the controls (44.5%), patients on ART (40.5%), and those not on ART (39.5%) (p = 0.562). Compared to 7% immunodeficiency among controls, 56% of patients on ART and 65.5% of those not on ART had a CD4 count < 350 cells/mm3 (p < 0.001). The prevalence of malaria parasitaemia among immunodeficient individuals (42.4%) was similar to prevalence among those with CD4 counts > 350 cells/mm3 (40.8%; p = 0.695). These findings suggest that malaria parasitaemia is not an opportunistic infection among HIV-positive individuals in Nigeria.

Seroprevalence and effect of HBV and HCV co-infections on the immuno-virologic responses of adult HIV-infected persons on anti-retroviral therapy.

Chronic hepatitis negatively affects persons living with HIV. While varying in their transmission efficiency, HIV, HBV, and HCV have shared routes of transmission. Available data suggest widely variable rates of HBV and HCV infections in HIV-infected populations across sub-Saharan Africa. With prolonged survival rates due to increased accessibility to antiretroviral drugs, HBV and HCV have the potential to complicate the prognosis of HIV co-infected patients by contributing significantly to continued morbidity and mortality. The study sought to determine the seroprevalence of HIV/HBV and HIV/HCV co-infections among HIV patients on antiretroviral therapy and to evaluate the effect of HIV/HBV and HIV/HCV co-infections on the immunologic and virologic responses of patients. A cross-sectional study in which samples were taken from 500 people living with HIV and attending ART clinic at the Fevers unit of the Korle Bu Teaching Hospital and tested for Hepatitis B Surface Antigen (HBsAg) and Hepatitis C virus antibody (HCV). CD4 cell counts and HIV-1 RNA levels were estimated as well. Data generated were analysed using IBM SPSS version 22. The seroprevalence of HIV/HBV and HIV/HCV co-infections among people living with HIV was 8.4% and 0.2% respectively. HIV/HBV coinfection included 15/42 (35.7%) males and 27/42 (64.3%) females out of which the majority (97.6%) were in the 21-60 years old bracket. HIV/HBV and HIV/HCV co-infections have varied effects on the immunological and virological response of HIV patients on ART. The mean CD cell count was 361.0 ± 284.0 in HIV/HBV co-infected patients and 473.8 ± 326.7 in HIV mono-infected patients. The mean HIV-1 RNA level was not significantly different (X2 [df] = .057 [1]; P = .811) among HIV/HBV co-infected patients (Log102.9±2.0 copies/mL), compared to that of HIV mono-infected patients (Log102.8±2.1 copies/mL) although HIV mono-infected patients had lower viral load levels. One-third (14/42) of HIV/HBV co-infected patients had virologic failure and the only HIV/HCV co-infected patient showed viral suppression. 336/500 (67.2%) patients had HIV-1 viral suppression (females [66.1%]; males [33.9%]) while 164/500 (32.8%) had virologic failure (females [67.7%]; males [32.3%]). The mean CD4 count of patients with viral suppression and patients with virologic failure was 541.2 cells/μL (95% CI 508.5-573.8) and 309.9 cell/μL (95% CI 261.9-357.9) respectively.The study concludes that, HIV/HBV and HIV/HCV coinfections do not significantly affect the immunologic and virologic responses of patients who have initiated highly active antiretroviral therapy, and treatment outcomes were better in females than in males. There was no HBV/HCV co-infection among patients.

Risk factors associated with pulmonary arterial hypertension among HIV-infected adults: A meta-analysis and systematic review.

Pulmonary arterial hypertension (PAH) occurs more frequently in patients with HIV infection than in general population. The predictive value of HIV-related factors and traditional cardiovascular factors with PAH is inconsistent across studies. The objective is to determine the roles of HIV-related risk factors and traditional cardiovascular risk factors in the development of PAH in adults with HIV. We searched Pubmed/Medline, Embase, Web of Science, and Google Scholar to identify studies published between January 1, 2000 and February 23, 2021 on risk factors associated with PAH among people living with HIV (PLWH). Ten studies were included for final analysis. PLWH with PAH had higher mean age (weighted mean difference [WMD] = 2.27, 95% confidence interval [CI] 0.31 ~ 4.24), and lower mean CD4 cell count (WMD = -95.8, 95% CI -153.41 ~ -38.2). Meanwhile, they were more likely to have detectable viral load (odds ratio [OR] = 1.36, 95% CI 1.16 ~ 1.60), to accompany arterial hypertension (OR = 2.02, 95% CI 1.51 ~ 2.71) and less likely to receive antiretroviral therapy (ART) (OR = 0.84, 95% CI 0.72 ~ 0.99). Besides, more intravenous drug users were observed in HIV-infected adults with PAH (OR = 2.25, 95% CI 1.51 ~ 3.33). HIV infection itself and ART impact PAH in two opposite ways. Traditional cardiovascular factors such as arterial hypertension, and older age are also important to the development of PAH. Screening HIV-related factors and traditional cardiovascular factors may help to target and manage patients at risk.

Despite Use of Upfront Plerixafor and G-CSF, Daratumumab Exposure Reduces Stem Cell Mobilization in Patients with Multiple Myeloma

Introduction Daratumumab is an anti-CD38 IgG1k monoclonal antibody with direct tumor killing and immunomodulatory mechanisms of action which was shown to have clinical benefits when added to the standard-of-care induction regimen in transplant eligible multiple myeloma (MM) patients. However, prior studies have indicated a potential reduction in stem cell yield in patients exposed to daratumumab prior to stem cell mobilization. Additionally, prior studies have not utilized combination mobilization regimens with G-CSF and the CXCR4 antagonist plerixafor as standard-of-care, which may overcome the deleterious effect of daratumumab. In this study, we investigated the stem cell yield of plerixafor-treated patients with daratumumab exposure compared to those without. Methods We conducted a retrospective study of patients with MM at our institution who underwent autologous stem cell mobilization and collection during first-line treatment over a 15-month period from 2021-2022. Following induction, patients underwent mobilization with a regimen of G-CSF for 5 days with plerixafor on the 4th day. Circulating CD34+ stem cells were enumerated on the 5th day, after which patients underwent approximately 20L apheresis with a collection goal of 5x106 CD34+ cells/kg of body weight. The primary endpoint of this study was the comparison of circulating CD34+ cells between patients who received daratumumab during induction and those who did not. Secondary endpoints included collection CD34+ yield and proportion who met the collection goal. Results 123 patients were included in the analysis. The median age was 65 (range: 34-77), 54% were male, and 84% were White. Twenty-two percent were stage I, 58% stage II, and 19% stage III by the Revised International Staging System. Forty-seven percent received daratumumab during induction. Of those, the median number of cycles administered was 4 (range: 1-5). Ninety percent received daratumumab in combination with bortezomib, lenalidomide and dexamethasone. The two cohorts were balanced in terms of age, gender, race, and exposure to lenalidomide, alkylators and radiation during induction. Patients with daratumumab exposure had a mean mobilization of 57.5 CD34+ cells/mcl compared to 96.4 for those without (p < 0.001). The mean CD34+ cell collection yield in 1 apheresis procedure was 6.0 x 106 cells/kg compared to 10.6 x 106 cells/kg (p < 0.001). Fifty-three percent of patients with daratumumab exposure met the collection goal compared to 80% of patients without (p < 0.001). Of the patients who did not meet the goal in one apheresis procedure, the majority were able to meet the goal with 1-3 additional days of apheresis (Figure 1). However, only 86% of patients with daratumumab exposure met the collection goal compared to 97% of those without (p < 0.001). Ten patients failed to collect 2.0 x 106 cells/kg, the institutional minimum for transplantation, 9 of which received daratumumab during induction. Eight were able to collect the minimum with an additional 1-3 days of apheresis; 2 patients required an additional mobilization procedure and collection but were able to proceed to transplantation. After adjusting for covariates including age, gender, race, weight, and exposure to lenalidomide, alkylators, and radiation, daratumumab exposure was associated with a 37.9 cells/mcl decrease in mean mobilization of CD34+ and 4.2 x 106 cells/kg decrease in CD34+ cell collection (both p < 0.001). Alkylator exposure was associated with a 43.3 cells/mcl decrease in mean mobilization of CD34+ (p = 0.040) and 4.1 x 106 cells/kg decrease in CD34+ cell collection (p = 0.057). Lenalidomide exposure was associated with a 103.4 cells/mcl decrease in mean mobilization of CD34+ (p <0.001) and 8.7 x 106 cells/kg decrease in CD34+ cell collection (p <0.001). Conclusion Inclusion of daratumumab in the induction regimen for transplant-eligible patients with MM resulted in a significant reduction in stem cell mobilization and stem cell yield, even with the use of plerixafor-containing mobilization regimens. This reduction was similar to alkylator exposure but less than lenalidomide exposure. With the increasing use of quadruplet induction regimens, the frequency of mobilization failure is likely to increase in the future and new mobilization regimens and approaches are needed to guarantee adequate cell yields without the need for additional days of apheresis and/or mobilizations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of HIV Infection on Clinical Characteristics and Treatment Outcomes in African-American Patients with Multiple Myeloma: - a Retrospective Case-Control Study

Introduction: Although multiple myeloma (MM) is not considered an AIDS-defining malignancy such as certain types of non-Hodgkin lymphoma and Kaposi sarcoma, HIV infection can increase the risk of developing MM at a younger age. However, no robust data demonstrates that HIV infection could affect MM outcomes. Case reports or case series suggest that HIV positive MM has more aggressive biological features, clinical course, and shorter overall survival (Faure I et al, AIDS, 1999; Patra SK et al, J Clin Diagn Res, 2015). Other observational studies also reveal that HIV positive MM involves a younger population and has more extramedullary disease however survival data is yet to be explored (De Groot JJB et al, S Afr Med J, 2017; Giri S et al, Blood, 2018). NYC has only 3% of the US population but has reported nearly 16% of all AIDS cases and the Bronx carries the highest HIV infection rate among all the boroughs (NYC Department of Health and Mental Hygiene, 2021). Based on that, we initiated a retrospective study in a tertiary medical facility in the Bronx to investigate the relationship between HIV infection status and the outcome of MM. Methods: Using the electronic medical record data extraction software, we identified patients older than 18 diagnosed with HIV and MM between April 2009 and April 2022. HIV negative MM patients matched for age and ethnicity were included as control group. We conducted a retrospective chart review collecting demographic, laboratory and clinical characteristics and compared them between HIV positive and negative groups. Outcome data included response to initial therapy, presence of extramedullary disease, need for hospitalization during therapy, infectious complications, progression-free survival (PFS) and overall survival (OS). Statistical analysis was performed using chi-square testing for categorical variables and Mann-Whitney for continuous variables given the size of our sample. Results: A total of 14 patients were identified as HIV positive MM. 12 patients were on antiretroviral therapy, 2 patients were considered "long term non-progressor" who did not require treatment. In HIV positive group, mean CD4 count was 554 (71)cells/µl and mean viral load was 2477 (1634)copies/ml. The mean age on diagnosis was 61.5 years old (range 56-72), 57.1% patients were male (8/14), 100% of patients were African American. 9 had IgG subtype, 2 had IgA subtype, 2 had light chain subtype. International Staging System (ISS) stage 1, 2 and 3 were seen in 14.3% (2/14), 35.7% (5/14), 42.9% (6/14) patients, respectively. In one patient stage was unknown. Adverse risk cytogenetics were seen in 2 out of 13 patients at diagnosis (both were gain 1q). Cytogenetic information was not available in one patient. Mean number of lines of therapy was 2.1 and 8 out of 14 underwent autologous stem cell transplantation. Subsequently, 14 HIV positive patients were compared with 14 age/ethnicity-matched HIV negative patients with multiple myeloma. Median duration of follow up was 24 months (range 3-156) in HIV positive patients and 35 months (range 2-168) in HIV negative patients. No statistically significant differences were seen between the two groups in hemoglobin level, creatinine, calcium, lines of therapy, bone marrow plasma cell percentage, presence of bone lesions, number of lines of therapy, number of patients receiving autologous transplant, infectious complications, and OS (Table 1). HIV positive patients had significantly more extramedullary disease (71.4% vs. 21.7%, p=0.008), were hospitalized more often (78.6% vs 28.6%, p=0.008), had inferior response to induction therapy (21.4% vs 100%, p=0.001) (Table 1) and a shorter PFS (median 62.0 (95% CI, 22.8 to 101.9) months vs median 20.0 (95% CI, 0.0 to 42.3) months, p=0.038) (Figure 1). Conclusion: Our study is the first single-center retrospective study evaluating the outcomes and prognosis of MM in minority patients with HIV infection. Despite well-controlled HIV infection with preserved CD4 counts, suppressed viral load and low risk disease in most HIV positive patients, they had more aggressive clinical course with more extramedullary disease, higher hospitalization rate, inadequate response to induction therapy and a shorter PFS compared with age and ethnicity matched HIV negative controls with multiple myeloma. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence and Cardiovascular Risk Factors Associated with Obesity/ Overweight in Adult Patients Living with HIV/AIDS: Case of the Makokou Outpatient Treatment Center, Ogooué-Ivindo, North-Eastern Gabon

Background: Designed to fight HIV/AIDS, antiretroviral drugs (ARVs) may be responsible for certain cardiometabolic abnormalities in people living with HIV (PLWHIV). To this end, the present study evaluates the prevalence and impact of obesity/overweight on the development of cardiovascular risk factors in patients at the outpatient treatment center (CTA) of Makokou, in the Ogooué-Ivindo region, North-eastern Gabon.&#x0D; Materials and Methods: This is a cross-sectional and descriptive study, based on a retrospective analysis of the records of patients followed at the HIV/AIDS outpatient treatment center of Makokou from December 2015 to December 2020. A structured questionnaire was used to collect data such as age, gender, socio-economic level, daily habits such as alcohol consumption, tobacco consumption, and physical exercise. Other epidemiological parameters such as body mass index (BMI), and CD4 count were measured.&#x0D; Results: A total of 165 people living with HIV (PLHIV), the majority of whom were between 41 and 60 years of age (60.60%). treated with antiretrovirals from December 2016 to December 2021 were collected for this study. With a sex ratio (F/M) of 3.58, women (78.2%) were in the majority compared to men. The mean age was 51 ± 13 years. While 95.8% of the patients were from the different departments of the province of Ogooué-Ivindo, the remaining patients (4.8%) were from other provinces such as Estuaire, Haut-Ogooué or Ogooué-Lolo. Civil servants represented 21%. The self-employed represented 29%, and the unemployed represented 50%. Only 34% of the participants in the study, the majority of whom were women, engaged in regular physical activity. 5.4% of the patients, mostly men, were active smokers. 34%, especially women, consumed alcohol. 20% of the PLWHIV had a medical history of type 2 diabetes mellitus or hypertension (HTA), and the majority were female. 5.4% of the declared hypertensives were on treatment. 7.8% of the hypertensive patients were discovered in consultation. The remainder were normotensive (86.8%). A significant difference in hypertension was observed in patients aged between 41 and 60 years ( p= 0.0029*). The data revealed a positive correlation index (r=0.19) between BMI and hypertension. All the therapeutic combinations with which the patients were treated contained NRTIs, of which the most used were tenofovir disoproxil (TDF) 66.67% and lamivudine (3TC) 33.33% and finally the most used NRTI was Efavirenz (EFV) 76.36%. After 5 years of treatment, 89 PLWHIV ( 53.93%), had CD4 count ≥ 500 cells/mm3. 53 PLWHIV (32%) had CD4 count ranging from 200 - 499 mm3 and thus moderate immune deficiency and with CD4 count &lt; 200 cell /mm3, 23 PLWHIV (14%) had severe immune deficiency. HIV-infected patients under 40 years of age had a mean CD4 count of 412 cell/mm3, which was lower than that of patients 40 years of age and older, which was 556 cell/mm3. It was noted that after 5 years, treatment with ARVs was significantly associated with an increase in BMI among PLHIV, (P=0.0210). It was indicated that the increase or decrease of CD4 count in PLWHIV, depended on BMI, after 5 years of ARV treatment.&#x0D; Conclusion: This study confirms the existence of an increase in overweight and obesity in people living with HIV/AIDS under antiretroviral treatment. It also shows that obesity had an impact on the development of certain cardiovascular risk factors in these people, which require careful vigilance of the health personnel on their weight gain, due to lipidic parameters such as cholesterol, HDL, Triglycerides.

Trends in Use of Combination Antiretroviral Therapy and Treatment Response from 2000 to 2016 in the Canadian Observational Cohort (CANOC): A Longitudinal Cohort Study.

Advances in treatment have turned HIV from a terminal illness to a more manageable condition. Over the past 20 years, there have been considerable changes to HIV treatment guidelines, including changes in preferred antiretrovirals and timing of initiation of combination antiretroviral therapy (cART). To examine real-world trends in cART utilization, viral control, and immune reconstitution among people living with HIV in Canada. Data were obtained from the Canadian Observational Cohort (CANOC). CANOC participants were eligible if they were antiretroviral therapy-naive at entry and initiated 3 or more antiretrovirals on or after January 1, 2000; if they were at least 18 years of age at treatment initiation; if they were residing in Canada; and if they had at least 1 viral load determination and CD4 count within 1 year of CANOC entry. Baseline and annual mean CD4 counts were categorized as less than 200, 200-350, 351-500, and more than 500 cells/mm3. Annual mean viral loads were reported as suppressed (< 50 copies/mL), low (50-199 copies/mL), or high detectable (≥ 200 copies/mL). The cART regimens were reported yearly. All CANOC participants were included (n = 13 040). Over the study period, the proportion of individuals with an annual mean CD4 count above 500 cells/mm3 increased from 16.3% to 65.8%, while the proportion of individuals with an undetectable mean viral load increased from 10.6% to 83.2%. As of 2007, the most commonly prescribed 2-agent nucleoside reverse transcriptase inhibitor backbone was tenofovir disoproxil fumarate and emtricitabine. In terms of third agents, non-nucleoside reverse transcriptase inhibitors were the most common class in the periods 2000-2003 and 2014-2015, protease inhibitors were most common in the period 2004-2013, and integrase inhibitors were most common in 2016. Concordance with treatment guidelines was demonstrated over time with respect to cART prescribing and immunologic and virologic response.

Intradermal Hepatitis B Vaccination in Non-responder People Living with Human Immunodeficiency Virus in Japan.

We performed a pilot study to assess the immunogenicity and safety of intradermal hepatitis B (HB) virus vaccines in people living with HIV (PLWH). This single-center prospective study was conducted in Yokohama, Japan. Adult PLWH with serum antibodies against HB surface antigen (anti-HBs) <10 mIU/mL at all time points after standard HB vaccination were included. We administered HB surface antigen (total dose of 10 μg) at 5 separate sites intradermally at baseline, one month, and 6-9 months and measured anti-HBs 1-3 months after administration. Eleven PLWH were included in this study. The mean age was 36 years, and all patients were men. At baseline, all patients were on antiretroviral therapy, and the mean CD4+ lymphocyte count was 588 /μL and plasma HIV-RNA was <20 copies/mL, except for one patient. Anti-HB levels were elevated to >10 mIU/mL in one patient after one dose, 6 patients after 2 doses, and 4 patients after 3 doses of the intradermal vaccines. Eight patients experienced grade 1 local adverse events. Additional vaccination via the intradermal route induced an anti-HBs level >10 mIU/mL in all patients, without serious adverse events.

BLOOD AND CEREBROSPINAL FLUID HIV LOAD INPATIENTS WITH HIV-ASSOCIATED NEUROLOGICAL DISORDERS

Relevance. The issues of replication and concentration of the human immunodeficiency virus (HIV) in various tissues and body fluids remain insufficiently studied. Solving this problem is hindered by the lack of simple, cheap and accessible methods for quantitative determination of HIV in various tissue samples.&#x0D; Objective is to establish a relationship between the presence of HIV-associated damage of the central nervous system (CNS), the number of CD4+ lymphocytes in the blood, and the level of HIV load in blood plasma and cerebrospinal fluid. The difference between the level of HIV viral load in different tissues and biological fluids may reflect the formation of several independent reservoirs of HIV replication in the human body.&#x0D; Materials and methods. 87 patients with HIV infection with clinical signs of central nervous system damage who had no experience of taking antiretroviral drugs (ARVP) were examined. Paired samples of blood and cerebrospinal fluid were analyzed to determine the level of viral load in both biological fluids, as well as the number of CD4+ lymphocytes in the blood.&#x0D; Results. It was established that the patient's presence of clinical signs of CNS damage was reliably correlated with the level of HIV load in the cerebrospinal fluid (logistic regression, P&lt;0.001) and was not associated with the content of CD4+ lymphocytes or the level of HIV load in the blood (logistic regression, P &gt;0.05).&#x0D; The level of HIV load in the cerebrospinal fluid (CSF) was on average 1.5 lg RNA copies/ml higher (P&lt;0.001) in patients with neurological disorders despite the fact that the mean CD4+-lymphocyte count and HIV load in blood in both groups of patients did not differ. The difference between the HIV load in blood and cerebrospinal fluid of patients with neurological disorders was only 0.8 lg RNA copies/ml.&#x0D; Despite the similar indicators of the content of CD4+ lymphocytes and the amount of HIV in the blood, in HIV-infected patients with clinical signs of CNS damage, the level of HIV load in CSF is 1.5 lg RNA copies/ml higher, compared with patients without symptoms of CNS dysfunction (P &lt;0.001). The difference between HIV load in blood and cerebrospinal fluid in the presence of neurocognitive disorders was reduced to 0.7 lg RNA copies/ml compared to 1.8 lg RNA copies/ml in the group of individuals without signs of CNS damage. The presence of HIV-associated damage to the central nervous system is not statistically related to the content of CD4+ lymphocytes or the level of HIV load in the blood.&#x0D; Statistical analysis showed that a CSF HIV load equal to or greater than 4.00 lg RNA copies/mL (10,000 RNA copies/mL) indicated a significant likelihood of HIV-associated CNS involvement in patients (P&lt;0.001) .&#x0D; Conclusion. The method of determining the level of HIV load in cerebrospinal fluid samples can be used to optimize the diagnostic algorithm of HIV-associated lesions of the central nervous system, differential diagnosis with neurocognitive disorders of non-infectious etiology. The threshold for making a clinical decision is the level of HIV load in the CSF sample, which is equal to or exceeds 4.00 lg RNA copies/ml, which indicates a significant probability of the presence of an HIV-associated lesion of the CNS in the patient.

CLINICAL MANIFESTATIONS AND CD4 COUNT CHARACTERISTICS OF PATIENTS WITH CYTOMEGALOVIRUS (CMV) RETINITIS

Introduction: To describe the clinical manifestations and CD4 count characteristics of patients with cytomegalovirus (CMV) retinitis.&#x0D; Methods: This is a retrospective study of patients diagnosed with CMV retinitis at the Ophthalmology Outpatient Clinic at Dr. Saiful Anwar General Hospital, Malang, between January 2016 to December 2019. The patients’ characteristics and clinical data including gender, age, visual acuity, slit lamp biomicroscopy, indirect ophthalmoscope, and laboratory findings were collected from medical records.&#x0D; Result: Twenty-one eyes from thirteen patients with CMV retinitis were enrolled. The mean age was 30.9 ± 7.12 years, with 54% of them male. Bilateral lesions were observed in 62% of the patients, and the mean visual acuity during the initial visit was 1.50 ±1.07 log MAR. All patients presented with the classic form of CMV retinitis. Mean CD4 count when commencing treatment was 62.23 ±11.82 cells/µL with 77% below 50 cells/µL. Patients with CD4 count &lt; 50 cells/µL mostly presented with posterior uveitis, bilateral lesion, and visual acuity ≤1.00 logMAR. Ten patients were given oral valganciclovir and antiretroviral therapy. Retinal detachment condition was noted at seven eyes. Candidiasis was the most presenting opportunistic infection.&#x0D; Conclusion: Cytomegalovirus retinitis was found in patients infected with AIDS with low CD4 counts. In this study, patients with CD4 counts of below 50 cells/µL tend to have more severe clinical presentations.

P461 Cryptococcosis screening and isolates characterization in asymptomatic people living with HIV in Kinshasa, DRC

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectivesCryptococcal meningitis (CM) is a life-threatening invasive mycosis affecting people living with HIV (PLHIV) and has a high prevalence and case fatality rate in sub-Saharan Africa. While most PLHIV presenting CM are symptomatic, the asymptomatic ones are diagnosed following routine screening tests indicated for all advanced PLHIV (CD4 <200/μl). We, therefore, hypothesized that asymptomatic CM patients would be infected with different Cryptococcus spp. strains than those in symptomatic CM patients (referring to the parallel study conducted in the same clinics). This study describes the prevalence of serum and meningeal cryptococcosis in asymptomatic PLHIV presenting a CD4 count of <200 cells/μl in the screening context. We then characterized and determined the antifungal susceptibility of Cryptococcus spp. strains isolated from these patients.MethodsWe performed cross-sectional screening for serum cryptococcal antigen (CrAg) in ambulant PLHIV with <200 CD4/μL in three clinics in Kinshasa (DRC). Lumbar puncture was indicated in positive patients to exclude a meningeal location for therapeutic purposes. The resulting cerebrospinal fluid (CSF) was then analyzed for CrAg and Cryptococcus spp. was isolated and characterized by MALDI TOF MS, serotyping PCR, ITS sequencing, and multilocus sequence typing (MLST). In addition, the EUCAST E.Def.7.3.2 microdilution procedure was followed to determine the susceptibility of strains to antifungal agents.ResultsA total of 47 PLHIV out of 262 included were tested positive for serum CrAg (19%, 95% CI: 14.2–24.3) from which 46.8% (22/47) had a high antigenic titer (≥1/160). The prevalence of asymptomatic CM was then estimated at 50% in CrAg serum-positive patients who consented to lumbar puncture (19/38). Although the female proportion included in the study was higher than that of men, serum CrAg was more positive in men (21.4%, 18/84 men included) than in women (18.0%, 29/161 women included). While the mean CD4 count of CrAg serum-positive patients were significantly lower than that of negative patients (P <.05), the median viral load between the two patient groups was approximately similar (P >.05). Only four CSF samples were positive in culture for Cryptococcus spp. and were all characterized as Cryptococcus neoformans/serotype A.At this stage, two isolates have been analyzed using the ISHAM MLST scheme and two different sequence type (ST) profiles were identified, namely: ST93 and ST63. While ST93 is the main Cryptococcus neoformans profile described in Congolese (DRC) PLHIV with CM, ST63 has not yet been identified in the DRC before. Of note, epidemiological and clinical specificities of ST63 have so far been poorly characterized in the literature. Susceptibility testing against the major antifungals and the MLST typing of the two remaining strains are still ongoing.Conclusions: The prevalence of cryptococcosis should not be neglected among asymptomatic PLHIV in the DRC, to meaning that screening and preventive treatment measures should be integrated into the national policy for HIV management and related diseases. For the rest of the analyses still in progress, conclusions can only be drawn once they have been fully finalized.