CD4 Lymphocyte Count Research Articles

Generalities in canine papillomavirus: systematic review of case reports

Canine papillomavirus (CPV) is a common entity in dogs that can be transmitted by direct and indirect contact and cause lesions in various parts of the body. It is the main cause of benign tumors; however, if not detected in time, it is a risk factor for the development of squamous cell carcinoma, documented with high mortality. To clarify demographic generalities, location of lesions, and findings involved in CPV detection, a systematic review of case reports of CPV was performed. The PRISMA statement was followed. Literature was searched in PubMed, DOAJ, and CAB Abstracts from 2011 to date. The articles collected were tabulated in Excel with the variables of interest. A total of 54 articles were obtained from the search, and 11 were included in the review after the screening and selection process. The analysis of the information allowed us to identify that among the case reports there were 4 investigations with male dogs, 2 females and 5 unspecified. Age ranged from 2 to 12 years. The breed with more cases reported was the Labrador retriever and 6 reported cases with neutered patients. Regarding the location of the lesions, the most common was the oral cavity, and the main findings were the need to identify new subtypes of CPV, and the development of lesions at lower CD4 and CD8 lymphocyte counts. Further research, encouragement of veterinary medical personnel, and dissemination of CPVrelated literature are needed to make this pathology visible and initiate future public health actions.

Emergomycosis in Africa: Time to Pay Attention to This Emerging Deadly Fungal Infection.

Emergomycosis is an emerging deadly infectious disease caused primarily by a little-known airborne pathogen Emergomyces africanus, which can cause clinical management challenge especially in patients with advanced HIV disease. This minireview describes Es. africanus as the main cause of emergomycosis in Africa as well as considers contributing factors to the difficulties encountered in managing this infection. Emergomycosis is common in HIV-positive persons with low CD4 lymphocyte count and has an estimated fatality of 50%. The infection exhibits airborne transmission with pulmonary and extrapulmonary manifestations leading to skin lesions. However, the pathogenesis of Es. africanus is still poorly understood. The management of the infection is complicated due to lack of defined diagnostic and therapeutic guidelines. Limited expertise, poor research funding, and lack of awareness and national surveillance are thought to impact the recognition and prioritisation of the infection. These factors may ultimately assign emergomycosis a 'neglected infection status' even as it is suspected to be prevalent in more African countries than previously recognised. Increased awareness and integrated and targeted strategies such as mobilising manpower in clinical mycology are of paramount importance in managing emergomycosis in Africa and beyond.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with a poor prognosis for relapsed/refractory disease. The WHO classification of NK and T-cell lymphomas includes 39 entries; the 3 most common subtypes in the US are PTCL-NOS (not otherwise specified), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL). Except for brentuximab vedotin in CD30-positive disease, agents were generally approved based on overall response rates (ORR) of less than 30%. The PRIMO Trial (NCT03372057; sponsored by Secura Bio, Inc.) evaluated duvelisib (DUV), an oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ and PI3K-γ isoforms in PTCL. Anti-tumor activity of single agents may not be uniform across different PTCL subtypes. Here we present data on 3 specific subtypes of some of the patients (pts) included in the PRIMO trial (fully enrolled as of January 2022). Methods: Eligibility criteria included adults with pathologically confirmed PTCL after ≥2 cycles of at least 1 prior standard regimen. A criterion for CD4 lymphocyte count ≥50/mm3 was added for the Expansion Phase (EP). Based on dose optimization results, the EP dose was DUV 75 mg BID for 2 cycles, to maximize disease control, followed by 25 mg BID, to mitigate late toxicities, until progressive disease/unacceptable toxicity. Pneumocystis jirovecii prophylaxis was required; herpes simplex and varicella zoster virus prophylaxis were indicated as needed. The primary endpoint was ORR by IRC assessment (Lugano 2014 criteria); efficacy is or will be assessed in all pts who received ≥1 dose of DUV. Secondary objectives included additional outcome measures, safety, and pharmacokinetics. Exploratory endpoints included pharmacodynamics and biomarkers. Results: The PRIMO study included 101 pts from the EP (data cutoff October 1, 2021), with a median follow-up of 8.7 months (mo) from time of first response. In the overall PRIMO study (N = 101), pts had a median age of 67.0 (21–92) years, a median of 3 (1–9) prior lines of therapy, an ORR (by IRC) of 49%, a CR rate of 34%, and a median PFS of 3.6 mo. Pts with the 3 most common histology subtypes from the PRIMO study are included in the current analysis (n = 97); these are PTCL-NOS (n = 52), AITL (n = 30), and ALCL (n = 15). Median PFS stratified by baseline histology was 3.5 mo (PTCL-NOS), 9.1 mo (AITL), and 1.5 mo (ALCL). Table 1 shows additional outcomes by histology. Adverse events seen were consistent with those observed previously in the PRIMO trial with no additional unexpected treatment-related toxicities. Conclusions: The ORR (by IRC) of DUV was higher in pts with PTCL-NOS (48%) and AITL (67%), compared with ALCL (13%). This corresponded to a longer median PFS of 3.5 mo in PTCL-NOS and 9.1 mo in AITL compared with 1.5 mo in ALCL. Although not powered for subset analyses, this analysis suggests activity of DUV may not be uniform across different types of lymphomas. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Secura Bio, Inc. Keywords: molecular targeted therapies, ongoing trials Conflicts of interests pertinent to the abstract. N. Mehta-Shah Consultant or advisory role: AstraZeneca, Celgene/BMS, C4 Therapeutics, Celgene, Corvus, Daiichi Sankyo, Genentech/Roche, Innate Pharmaceuticals, Karyopharm, Kyowa Kirin, ONO Pharmaceuticals, Secura Bio, Verastem ​ E. D. Jacobsen Consultant or advisory role: Ascerta, Astra-Zeneca, Merck; Pharmacyclics, F. Hoffman-LaRoche, Novartis, Takeda P. L. Zinzani Consultant or advisory role: Celltrion, Gilead, Janssen-cilag, BMS, Servier, Sandoz, MSD, TG therapeutics, Takeda, Roche, Eusapharma, Kyowa Kirin, Novartis, ADC Therapeutics, Incyte, Beigene, Secura Bio​ J. Zain Consultant or advisory role: Kyowa Kirin, Mundi, Seattle Genetics​ G. Gritti Consultant or advisory role: Beigene, Clinigen, Genmab, Ideogen, Incyte, IQVIA, Italfarmaco, Kite-Gilead, Roche, Sandoz, Takeda K. Izutsu Consultant or advisory role: Celgene/BMS, MSD, AstraZeneca, AbbVie, Eisai, Incyte, Solasia, Novartis, Bayer, Pfizer, Janssen, Yakult, Kyowa Kirin, ONO Pharmaceuticals, Daiichi Sankyo, Chugai, Takeda, Beigene, Genmab, Otsuka, Loxo Oncology, FUJIFILM Toyamachemical, Symbio​ S. Waters Employment or leadership position: Secura Bio, Inc. J. E. Brammer Consultant or advisory role: BMS, Verastem Consultancy: Kymera, Seattle Genetics B. Pro Consultant or advisory role: Takeda, Seattle Genetics, Celgene, Verastem, Astex pharmaceuticals S. M. Horwitz Consultant or advisory role: ADC Therapeutics, Affimed, Celgene, Crispr Therapeutics, Daiichi Sankyo, Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Verastem/SecuraBio, Acrotech Biopharma, C4 Therapeutics, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, SecuraBio, Shoreline Biosciences, Inc., Takeda, Trillium Therapeutics, Tubulis, Cimieo Therapeutics

Immunogenicity of quadrivalent meningococcal conjugate vaccine in frequent platelet donors

AbstractFrequent plateletpheresis is associated with severe lymphopenia of uncertain clinical significance. We assessed the functional impact of frequent platelet donations and associated lymphopenia on the response to neoantigens. We conducted a prospective study of 102 platelet donors (HIV uninfected) who were naive to meningococcal vaccination recruited at Brigham and Women’s Hospital. One dose of quadrivalent meningococcal conjugate vaccine was administered. Seroresponse was defined as a fourfold increase of serum bactericidal antibody titers and seroprotection was defined as postvaccination titers of ≥1:8, for each of the 4 vaccine antigens (A, C, W, and Y). Mean age of participants was 61 years, 69% were male, and medial number of platelet donations in prior year was 14 (interquartile range, 4-20). Frequent platelet donors had a low CD4 count (14% with ≤200/μL and 34% with ≤350/μL). Seroresponse rates varied from 68% for serogroup Y to 86% for serogroup A and were higher for participants with baseline titers of <1:8. Postvaccination seroprotection rates varied from 76% for serogroup Y to 96% for serogroup A. After adjustments for age, sex, and frequent donations, lower total lymphocyte or lower CD4 counts were not associated with lower responses. These data suggest no impairment by plateletpheresis-associated lymphopenia on response to these neoantigens. This trial was registered at www.clinicaltrials.gov as #NCT04224311.

Factors associated with survival in patients with lymphoma and HIV: the largest cohort study in Brazil.

To analyze the factors associated with survival in the largest cohort of individuals with HIV and lymphoma so far described in Brazil. A retrospective, observational, multicenter study involving five institutions in São Paulo, Brazil. The medical records of consecutive patients with HIV diagnosed with lymphoma between January 2000 and December 2019 were screened. Inclusion criteria consisted of age over 17 years and a biopsy-confirmed diagnosis of lymphoma. The data collected included age, sex, staging (Ann Arbor system), duration of HIV infection, CD4+ lymphocyte count, HIV viral load, lactate dehydrogenase, erythrocyte sedimentation rate and serum beta-2-microglobulin levels, treatment and outcome. Overall, 276 patients were included. Median age was 42 years. Most patients were male (74.3%) and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (28.6% and 46.4%, respectively). Most had non-Hodgkin lymphomas (89.2%, n = 246), particularly diffuse large B-cell lymphoma (40.9%) and Burkitt lymphoma (26.4%). Hodgkin lymphoma accounted for 9.4%. Advanced stages III/IV were predominant (86.8%). HIV viral load at the moment of lymphoma diagnosis was detectable in 52.9% of patients. A CD4 count of <200 cells/mm3 was recorded for 53% of the patients. Most patients (62.4%) were on combination antiretroviral therapy. The factors that significantly affected survival were: the ECOG performance status, lymphoma subtype, staging, beta-2-microglobulin level, central nervous system (CNS) infiltration, site of CNS infiltration, relapsed/refractory lymphoma and International Prognostic Index score. HIV status, CD4-lymphocyte count and relapsed/refractory disease affected survival. Rituximab did not appear to improve outcome in HIV-related lymphomas.

The restorative effect of immunoglobulin G on indicators of cellular immunity in patients with co-infection drug-resistant tuberculosis/HIV with a CD4 lymphocyte cоunt from 200 to 50 cells/μL

Objective — to study the restorative effect of immunoglobulin G (IgG) in patients on indicators of cellular immunity in patients with drug-resistant tuberculosis (DR-TB)/HIV co-infection at the level of CD4+ lymphocytes from 200 to 50 cells/μL. Materials and methods. The study involved 52 patients aged 20 to 55 years, the average age was (37.2 ± 7.8) years. All patients were HIV-positive with laboratory-confirmed DR-TB with mycobacterium resistance to first- and second-line drugs. Patients on DR-TB/HIV were divided as follows: Group 1 (cont­rol) — 26 patients with DR-TB/HIV with the CD4 lymphocyte count from 200 to 50 cells/μL, who received standard treatment with second-line antimycobacterial therapy (AMBT) and antiretroviral therapy (ARVT); Group 2 (basic) — 26 patients with DR-TB/HIV with a CD4 lymphocyte count from 200 to 50 cells/μL, who also received standard treatment of second-line AMBD and ARVT, with the addition of complex therapy with intravenous IgG. Results and discussion. In patients of Group 2, at the end of the 20th month of treatment, the normalization of T-helpers level was noted in 69.2 % of people, which reached the average values of (830.0 ± 15.2) cells/μL, with an increase to a subnormal level (408,0 ± 1.6) cells/μL in 30.8 % of patients (p &lt; 0.05). Normalization of the T-helpers indicator in Group 1 was noted on the 20th month only in 42.3 % of people, and it amounted to (670.0 ± 14.5) cells/μL (р &lt; 0.05). The relative (percentage) level of the T-helpers indicator in the 20th month reached normal values in 61.5 % (р &lt; 0.05) of patients of Group 2, among patients of Group 1 — in 34.6 % of people (р &lt; 0.05 ). The absolute number of T-suppressors at the end of the 20th month decreased to the norm in 76.9 % of patients and 46.2 % of patients in Groups 2 and 1, respectively (p &lt; 0.05). In patients of Group 2, on the 20th month of treatment, the physiological level of the T-suppressors indicator (19—35) % was reached in 65.4 % of cases (р &lt; 0.05); in Group 1, the normal level was registered in 38.5 % of patients (p &lt; 0.05). The CD4+/CD8+ Ratio was below the norm in 100 % of patients of Group 1 during 14 months inclusive, and only on the 20th month it reached the norm in 23.1 % of patients (p &lt; 0.05). Group 2 patients had normalization in 57.7 % of cases at the 20th month (р &lt; 0.05). Conclusions. The additional use of intravenous IgG in the complex treatment of patients with DR-TB/HIV contributed to a faster recovery of the cellular link of immunity, which makes it possible to prescribe antiretroviral therapy to patients with DR-TB/HIV at an earlier time, prevent the development of systemic inflammation and improve the prognosis for survival.

Health-related quality of life and associated factors among people living with HIV/AIDS in Sichuan, China: A cross-sectional study.

This study aimed to explore health-related quality of life (HRQoL) and its associated factors among people living with HIV/AIDS (PLWH) in Sichuan, China. A total of 401 PLWH were recruited from the city of Panzhihua between August 2018 and January 2019. Demographic characteristics and disease-related data were collected by self-administered questionnaires and medical system records. Health-related quality of life (HRQoL) was measured by the medical outcome study HIV health survey (MOS-HIV), which measured ten subdimensions and two summarized dimensions, the physical health summary score (PHS) and the mental health summary score (MHS). Logistic regression models were used to explore the variables independently associated with quality of life. The PHS and MHS measured by MOS-HIV were 53.66 ± 6.80 and 51.31 ± 7.66, respectively. Younger age, higher educational level, no methadone use, higher CD4 lymphocyte counts, less symptom counts and heathy BMI significantly were associated with higher HRQOL in the univariate χ2-test analysis. Education level was found to have a significant influence on patients' quality of life, both in physical health (P = 0.022) and mental health (P = 0.002) dimensions. Younger age (P = 0.032), higher CD4 lymphocyte counts (P = 0.007), less symptom counts (P < 0.001) and health BMI level (P < 0.001) were positively related to the PHS of quality of life in the multivariable logistic regression model. The HRQoL of PLWH in Sinchuan Province was relatively low. Age, educational level, methadone use, CD4 lymphocyte counts, symptom counts and BMI were positively related to quality of life. This study indicates that health caregivers should pay more attention to comorbidity issues and mental health in PLWH, especially for those with lower education levels, unhealthy body mass index, more symptomatic presentation and older age.

Clinical Perspective on Human Immunodeficiency Virus Care of Ukrainian War Refugees in Poland.

The Russian invasion of Ukraine forced migration for safety, protection, and assistance. Poland is the primary sheltering country for Ukrainian refugees, providing support including medical care, which resulted in the rapid ∼15% increase in the number of followed-up people with human immunodeficiency virus (HIV) (PWH) in the country. Here, we present the national experience on HIV care provided for refugees from Ukraine. Clinical, antiretroviral, immunological, and virologic data from 955 Ukrainian PWH entering care in Poland since February 2022 were analyzed. The dataset included both antiretroviral-treated (n = 851) and newly diagnosed (n = 104) patients. In 76 cases, protease/reverse transcriptase/integrase sequencing was performed to identify drug resistance and subtype. Most (70.05%) of the patients were female, with a predominance of heterosexual (70.3%) transmissions. Anti-hepatitis C antibody and hepatitis B antigen were present in 28.7% and 2.9% of the patients, respectively. A history of tuberculosis was reported in 10.1% of cases. Among previously treated patients, the viral suppression rate was 89.6%; 77.3% of newly HIV diagnosed cases were diagnosed late (with lymphocyte CD4 count <350 cells/μL or AIDS). The A6 variant was observed in 89.0% of sequences. Transmitted mutations in the reverse transcriptase were found in 15.4% treatment-naive cases. Two patients with treatment failure exhibited multiclass drug resistance. Migration from Ukraine influences the characteristics of HIV epidemics in Europe, with an increase in the proportion of women and hepatitis C coinfected patients. Antiretroviral treatment efficacy among previously treated refugees was high, with new HIV cases frequently diagnosed late. The A6 subtype was the most common variant.

Influence of HIV infection on clinical course of the new coronavirus infection (COVID-19)

BACKGROUND: Human immunodeficiency virus (HIV)-associated severe immunosuppression, high viral load, non-HIV-related comorbidities and conditions, and lack of antiretroviral therapy may exacerbate the clinical course of coronavirus disease 2019 (COVID-19).&#x0D; AIM: To assess the effect of HIV infection on the clinical course of COVID-19, disease severity, and its outcomes.&#x0D; MATERIALS AND METHODS: Medical records of 35,328 patients who had COVID-19 in 2020 were analyzed, including 46 cases of COVID-19 in individuals with HIV infection. Clinical variants and COVID-19 severity, frequency of COVID-19 detection by polymerase chain reaction, CD4 lymphocyte count, viral load in individuals with HIV infection, and mortality rates were assessed.&#x0D; RESULTS: In 76% of patients with coinfection, signs of HIV infection progression, opportunistic infections, and concomitant diseases were noted. Moreover, 52.2% of the patients analyzed were users of psychoactive substances. Among patients with HIV and COVID-19, men predominated in groups aged 30 years, whereas among the HIV-negative population, women were predominant in groups aged 18 years. The proportion of severe COVID-19 in individuals with HIV infection (47.8%) exceeds that in the group without HIV (12.3%). The mortality rate from COVID-19 in the HIV-infected group was more than seven times higher than that in the HIV-negative group (t=1.81; p=0.01).&#x0D; CONCLUSIONS: In the HIV-infected group, extremely severe COVID-19 was more common. Weakness, cough, shortness of breath, and myalgia were significantly more common in the HIV-infected group. Moreover, the HIV-infected group with an undetectable viral load and adequate CD4 lymphocyte count in the blood was exposed to the same risks of the disease and its progression as the HIV-negative group.

Intensified pulmonary tuberculosis case finding among HIV-infected new entrants of a prison in Malaysia: implications for a holistic approach to control tuberculosis in prisons

PurposeThis intensified case finding study aimed to evaluate the prevalence of tuberculosis (TB) disease among people with HIV entering the largest prison in Malaysia.Design/methodology/approachThe study was conducted in Kajang prison, starting in July 2013 in the men’s prison and June 2015 in the women’s prison. Individuals tested positive for HIV infection, during the mandatory HIV testing at the prison entry, were consecutively recruited over five months at each prison. Consented participants were interviewed using a structured questionnaire and asked to submit two sputum samples that were assessed using GeneXpert MTB/RIF (Xpert) and culture, irrespective of clinical presentation. Factors associated with active TB (defined as a positive result on either Xpert or culture) were assessed using regression analyses.FindingsOverall, 214 incarcerated people with HIV were recruited. Most were men (84.6%), Malaysians (84.1%) and people who inject drugs (67.8%). The mean age was 37.5 (SD 8.2) years, and median CD4 lymphocyte count was 376 cells/mL (IQR 232–526). Overall, 27 (12.6%) TB cases were identified, which was independently associated with scores of five or more on the World Health Organization clinical scoring system for prisons (ARR 2.90 [95% CI 1.48–5.68]).Originality/valueLimited data exists about the prevalence of TB disease at prison entry, globally and none from Malaysia. The reported high prevalence of TB disease in the study adds an important and highly needed information to design comprehensive TB control programmes in prisons.

Т-клеточный иммунный ответ на SARS-CoV-2 у больных ВИЧ-инфекцией

Objective. To assess the T-cell immune status against SARS-CoV-2 in HIV patients with or without antiretroviral therapy. Patients and methods. The study included 21 HIV patients who had laboratory-confirmed COVID-19 between September and December 2021 without previous immunization against SARS-CoV-2. The characteristics of HIV infection (CD4-lymphocytes count, HIV viral load in blood plasma, the presence of antiretroviral therapy) and COVID-19 (the severity degree and duration of the disease) were analyzed, the T-cell immune response to SARS-CoV-2 was assessed using the ELISPOT method 1 month after COVID-19. Statistical analysis was carried out by non-parametric methods (Mann–Whitney U test, Spearman's rank correlation coefficient) using the IBM SPSS Statistics 22 software package. Results. The study showed a more favorable course of COVID-19 in HIV-infected persons who achieved HIV suppression in the blood: a mild form of the disease was significantly more common, and the virus was eliminated faster. T-cell immune response to SARS-CoV-2 was recorded more frequently in these patients. Significant correlation of T-cell immune status with the CD4-lymphocytes count and HIV suppression in the blood was revealed. Conclusion. Thus, T-cell immune response to SARS-CoV-2 as assessed using the ELISPOT method was registered significantly more frequently in patients with HIV infection controlled by effective antiretroviral therapy. Key words: COVID-19, antiretroviral therapy, HIV infection, T-cell immune response

Avaliação de tuberculose latente em adolescentes e adultos jovens vivendo com o vírus da imunodeficiência humana em um serviço de referência no Brasil

To avoid the occurrence of tuberculosis reactivation in people living with HIV (PLHIV) who have latent tuberculosis infection (LTBI), the therapeutical indications to this population were expanded in Brazil in 2018, with the recommendation of treatment for those with CD4 T lymphocyte count less than or equal to 350 cells/mm3, regardless of the result of the tuberculin test (TT). To evaluate the practical application of this recommendation, we decided to determine the prevalence of LTBI in PLHIV followed in our outpatient clinic. Ninety-nine adolescents and young adults living with HIV accompanied in a Reference Service were evaluated for the occurrence of LTBI with TT and TCD4 cell count application. The prevalence of LTBI was estimated at 7.1% considering the result of TT, and 18% when considering patients with CD4 lymphocyte count less than or equal to 350 cells/mm3. This difference reinforces the idea that the detection of patients with TCD4 lymphocytes less than or equal to 350 cells/mm3 effectively expands the indication for treatment of LTBI. However, only 4 (22.2%) of 18 patients with TCD4 less than or equal to 350 cells/mm3 adhered to the therapeutic proposal. The rebellious aspect inherent to this population, the failure to attend consultations and the refusal to use another drug were some of the reasons for the low adherence to treatment.

Peripheral blood lymphocyte subset count in COVID-19 patients

Abstract Background: (COVID-19) pathophysiology and the predictive factors are not fully understood, but lymphocyte dysregulation appears to play a role. Aim and Objectives: To explore the clinical value of lymphocyte subset changes in COVID-19 patients’ peripheral blood, which may illustrate the pathogenesis of COVID-19. Methods: This is prospective cohort study of 73 hospitalized patients with confirmed COVID-19 who were classified into two groups: non-severe and severe. Lymphocyte subsets (CD3, CD4, CD8, CD19, and CD56) were assessed using flow cytometry. Results Lymphocyte gate, CD3, CD4, CD8, and CD56 counts were significantly reduced in severe cases compared with nonsevere cases (P0.001, 0.006, 0.016, 0.011, and 0.008 respectively). Patients were divided into two groups according to cut off age (&lt;50 and ≥ 50years) and (NLR) (NLR &lt;4.14 and NLR ≥ 4.14). There was a significant difference in severe illness probability in two groups P0.001 and 0.001 respectively). Then, patients were divided into four groups by both NLR cutoff and age, There also significant difference in severe illness probability between four groups (P&lt;0.001). Conclusion Based on our data, management of patients with COVID-19 pneumonia can be improved based on NLR and age model. We suggest that patients with NLR ≥ 4.14 should be admitted to isolation ward with close follow-up and actively transfer to intensive care unit.

High baseline body mass index predicts recovery of CD4+ T lymphocytes for HIV/AIDS patients receiving long-term antiviral therapy.

The relationship between baseline BMI and CD4+ T cells during follow-up in HIV patients in China requires further evaluation. We conducted a retrospective cohort study based on adult AIDS patients who underwent or received antiretroviral therapy from 2003 to 2019 in Guangxi, China. BMI was divided into categories and compared, and after adjusting for BMI being related to the change in CD4 lymphocyte count, with normal weight as the reference group, the BMI before treatment was positively correlated with the changes in CD4+ T cells at different time periods. Among them, obese patients had significant CD4+ cell gain. In patients with pretreatment CD4+ T lymphocyte counts <200 cells/μL, a higher BMI was associated with an increased likelihood of achieving immunologic reconstitution [≥350 cells/μL: AHR: 1.02(1.01, 1.04), P = 0.004; ≥500 cells/μL: AHR: 1.03 (1.01, 1.05), P = 0.004]. Underweight in HIV patients was a risk factor for poor viral suppression [AHR: 1.24 (1.04, 1.48), P = 0.016]. Our study demonstrated that HIV/AIDS patients receiving ART with higher baseline BMI had better immune reconstitution and that baseline BMI could be an important predictor of immune reconstitution in patients receiving ART. Baseline BMI was not associated with virological failure, but a lower baseline BMI indicated poor viral suppression during follow-up.

Once Monthly Elotuzumab and Lenalidomide Plus Dexamethasone for Multiple Myeloma: A Multicenter Observation Study

Introduction: Elotuzumab and lenalidomide plus dexamethasone (ERd) is a standard salvage chemotherapy for multiple myeloma, and elotuzumab is commonly administered every 2 weeks after cycle 3 (conventional ERd). Alternatively, elotuzumab may often be used every 4 weeks (monthly ERd) in real-world practice. The purpose of this multicenter observational study was to investigate the efficacy and tolerability of monthly ERd. Methods: We investigated the efficacy and tolerability between conventional and monthly ERd regimens for the myeloma patients in six institutes retrospectively. Results: Seventy-five patients were included in this study. The median patient age was 68 years. The median number of prior chemotherapies was two (1–5). The number of patients with prior lenalidomide exposure was 57 (76.0%). The numbers of progressive disease (PD) and non-PD before ERd were 23 (30.7%) and 52 (69.3%), respectively. The frequency of PD before ERd was significantly lower in the monthly ERd group than in the conventional ERd group. In 26.9 months of median follow-up period, the 2-year progression-free survival (PFS) rate in the monthly ERd group was significantly longer than that in the conventional ERd group (95.0% and 62.0%, hazard ratio 0.082, p = 0.002). However, no significant difference in PFS between these two ERd groups was found using multivariate analysis. The complete response rates were similar between the monthly and conventional ERd groups (55.0% and 32.7%, p = 0.109). There was no significant difference in the incidence of adverse events between the monthly and conventional ERd groups (35.0% and 54.5%, p = 0.192). There was no significant difference in the kinetics of the mean absolute lymphocyte count, CD4, CD8, CD16, CD56, and CD57 positive lymphocyte counts, and CD4 to CD8 ratio between the monthly and conventional ERd groups. Discussion: The efficacy and tolerability of monthly ERd were similar to those of conventional ERd. Thus, monthly ERd might be a reasonable option, considering the quality of life of patients and convenience.

Decrease in CD4 T-Cell Count and Risk of Severe Morbid Conditions in People With Human Immunodeficiency Virus Infection With Controlled Viral Load After Initiating Combination Antiretroviral Therapy Between 2006 and 2018.

A previous study showed an association between CD4 T-cell count decline in people with human immunodeficiency virus infection (PWH) with viral suppression and an increased risk of severe morbid conditions. We aimed to assess the risk of CD4 T-cell count decline (hereafter, CD4 decline), determine associated factors, and evaluate the association of this decline with the risk of severe morbid conditions (cardiovascular disease and cancer) or death. From the Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS) CO4 French Hospital Database on HIV cohort, we selected PWH >18 years old who had been followed up for ≥2 years after viral suppression following the initiation of combination antiretroviral therapy (cART) between 2006 and 2018. CD4 decline was defined as 2 consecutive relative differences ≥15%. Among participants with such decline, we modeled CD4, CD8, and total lymphocyte counts before and after CD4 decline, using spline regression. The remaining objectives were assessed using Poisson regression, with the association between CD4 decline and the risk of severe morbid conditions or death evaluated during or after 6 months of decline. Among 15 714 participants (75 417 person-years), 181 presented with CD4 decline (incidence rate, 2.4/1000 person-years (95% confidence interval, 2.1-2.8). CD8 and total lymphocyte counts also showed a similar decline. Older current age and lower viral load at treatment initiation were associated with the risk of CD4 decline. The risk of severe morbid conditions or death was 11-fold higher during the first 6 months for participants who presented with CD4 decline versus those who did not (incidence rate ratio, 10.8 [95% confidence interval, 5.1-22.8]), with no significant difference after 6 months. In PWH with viral suppression, CD4 decline was rare and related to global lymphopenia. It was associated with a higher risk of severe morbid conditions or death during the first 6 months.

446. Hyperlactatemia and Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI): Still present even with modern antiretroviral therapy (ART)

Abstract Background Hyperlactatemia and lactic acidosis represent a rare but dangerous manifestation of mitochondrial toxicity associated with NRTIs. Although mitochondrial toxicity has been linked to the NRTI class, it is more prevalent with older agents such as zidovudine (AZT), didanosine (ddI) and stavudine (d4t). Methods Prompted by the diagnosis of symptomatic hyperlactatemia in 4 people with HIV on newer NRTIs between September 2019 and December 2021, we present a single-center case series to illustrate its subtle presentation and management. Hyperlactatemia was defined as a serum lactate of 1.6-4 mmol/L and lactic acidosis was defined as a serum lactate of &amp;gt; 4mmol/L. Results 75% of the patients were male, the mean age was 57.8 years, and 100% were Caucasian. 75% (3/4) were either overweight or obese (body mass index &amp;gt; 25 kg/m2). 75% had a CD4 lymphocyte count &amp;lt; 200 cells/mm3 at the time of human immunodeficiency virus (HIV) diagnosis and 50% had the diagnosis for &amp;gt;10 years. The most common symptom reported was non-specific fatigue (100%), followed by widespread myalgias (75%). 1 patient reported severe peripheral neuropathy affecting activities of daily living and 1 patient reported palpitations and night sweats. The mean duration of symptoms prior to reporting was 27.5 months. At the time of diagnosis of symptomatic hyperlactatemia, 75% had a CD4 lymphocyte count &amp;gt; 200 cells/mm3, the mean serum lactate was 2.7 mmol/L (1.9 mmol/L - 3.9 mmol/L), 50% were on abacavir (ABC) and lamivudine (3TC), and 50% were on tenofovir alafenamide (TAF) and emtricitabine (FTC). After stopping ART for 2 weeks, mean serum lactate decreased to 0.6 mmol/L (0.4 mmol/L – 1.1 mmol/L). 100% reported an improvement in quality of life after NRTI cessation and were managed with an NRTI-sparing regimen. Clinical characteristics are noted in Table 1. Conclusion This case series highlights the insidious nature of symptoms related to NRTI-associated mitochondrial toxicity including hyperlactatemia. Management strategies are not well defined for hyperlactatemia; however, NRTI-sparing regimens may offer improvement in quality of life. Despite improved tolerability of modern ART, clinicians should be aware of and monitor for symptoms of this potentially life-threatening side effect. Disclosures Carlos Malvestutto, MD MPH, Gilead Sciences: Advisor/Consultant|Viiv Healthcare: Advisor/Consultant.

1276. Noninvasive Assessment of Change in Hepatic Fibrosis Following Initiation of Integrase Inhibitors in Women Living with HIV

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in persons with HIV and can lead to hepatic fibrosis. Integrase strand-transfer inhibitors (INSTIs), first-line agents in antiretroviral therapy (ART), are associated with increased body mass index (BMI), particularly in women living with HIV (WLWH). We evaluated change in hepatic fibrosis risk following INSTI initiation in WLWH. Table 1.Change over time in hepatic fibrosis scores among group switching to INSTI-regimens versus group staying on non-INSTI regimens INSTI=integrase strand-transfer inhibitor; SD=standard deviation; FIB-4=Fibrosis-4 Score (calculated by Age*AST/[platelet count*ALT1/2]; APRI=AST to Platelet Ratio Index (calculated by [AST/AST upper limit of normal]/platelet count); NFS = Non Alcoholic Fatty Liver Disease Fibrosis Score (calculated by -1.675+(0.037*age) + (0.094*body mass index)+(1.13*hyperglycemia or diabetes [yes=1, no=0])+ (0.99*AST/ALT)-(0.013*platelet count)-(0.66*albumin)); CI=Confidence Interval. Linear regression model with unstructured covariance matrix for repeated observations with a person. Adjusted models for all outcomes included the following covariates: age, race/ethnicity, education, baseline CD4 lymphocyte count, baseline antiretroviral anchor drug, and abacavir, tenofovir disoproxil fumarate, and tenofovir alafenamide use. Body mass index was included in models for FIB-4 and APRI only. Age was included for APRI only. Methods Data from 2007-2020 were analyzed from virologically-suppressed WLWH enrolled in the Women’s Interagency HIV Study (WIHS). We excluded WLWH with untreated viral hepatitis, heavy alcohol use and autoimmune or metabolic chronic liver disease. WLWH who switched to or added an INSTI to ART were compared to women who remained on non-INSTI ART. Outcomes included change in noninvasive markers of hepatic fibrosis: Fibrosis-4 (FIB4), AST to Platelet Ratio Index (APRI), and NAFLD fibrosis score (NFS), measured 4-12 months before and 4-19 months post INSTI switch/add. Longitudinal linear regression models compared change over time in each outcome by group, adjusted for covariates. Results 872 WIHS participants (323 INSTI, 549 non-INSTI) were followed for a median 3.0 years (Q1 2.0, Q3 4.5). Mean age was 47.2 years (SD 9.0), 61% were Non-Hispanic Black, and mean BMI was 31.4 (8.8) kg/m2. Absolute mean changes in FIB4, APRI, and NFS scores were +0.021, -0.005, +0.194, respectively, in the INSTI group compared to +0.003, -0.011, +0.016, respectively, in the non-INSTI group (Table 1). No significant differences in mean AST and ALT change between the INSTI and non-INSTI groups were noted. There was a significant increase in NFS score in the INSTI group (p&amp;lt; 0.0001) and this difference remained in adjusted models (p=0.0135). Compared to the non-INSTI group, a larger proportion of participants in the INSTI group changed to a higher NFS risk category: 15.7% vs 9.0%, p=0.014. Conclusion Starting INSTIs was associated with minimal change in FIB4 and APRI scores but increased NFS score in WLWH. The increase in NFS score likely reflects BMI gain with INSTI use, as BMI is not factored into FIB4 or APRI calculators and AST and ALT did not change significantly. Nonetheless, patients starting INSTIs need close monitoring of metabolic changes and low thresholds for additional noninvasive liver fibrosis testing. Disclosures Michael A. Yu, MD, Ligera: Advisor/Consultant Maria L L. Alcaide, MD, Gilead: Advisor/Consultant Adaora A. Adimora, MD, MPH, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support Jennifer C. Price, MD, PhD, Abbvie: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support Phyllis C. Tien, MD, MSc, Gilead: Grant/Research Support|Merck: Grant/Research Support Cecile D. Lahiri, MD, MS, Theratechnologies: Advisor/Consultant.

The pattern and magnitude of T cell subsets reconstitution during ten years of ART with viral suppression in HIV-infected patients

The extent of immune reconstitution in human immunodeficiency virus (HIV) infected persons receiving long-term antiretroviral therapy (ART) with controlled viral load has been controversial. We studied the extent and speed of T cell subsets retrieval after long-term antiretroviral treatment. 662 HIV-infected patients followed at least 2 years whose plasma HIV-1 RNA load <50 copies/mL were evaluated for longitudinal and functional phenotypic indices of immune restoration. Determinants of change in magnitude and importance of recovery have been evaluated using mixed linear regression models. Almost all robust immune restorations achieved occurred after 2-3 years of ART. The median CD4 lymphocyte count increased 449 cells/μl (IQR 303-604) from 226 cells/μl (IQR 83-336) at baseline during the third year (P < 0.001); CD4+T lymphocyte rises during the sixth and tenth years were not significant. Naive and memory CD4+T cells'reconstitution occurred in the sixth and eighth years of ART but no significant change thereafter. The change of CD45RA+Naïve and CD45RA-memory CD4+T cell reconstitution is different in baseline CD4+T cell counts <100 cells/μl group and in baseline CD4+T cell counts >100 cells/μl group. Activation antigen expression (CD38 or HLA-DR) on CD8 lymphocytes declined mostly during the first till second year, and after 4 years, activation antigen expression on patient lymphocytes showed no significant change. The proportion of CD4 cells expressing CD28 climbed during the first years and reached normal levels in the second year. Immune restoration was dependent on the capacity of immune system during the first 2-3 year of ART. But the significant change of CD4 and compartments of CD4+T cells could persist until 6-8 years. The pattern of CD38+CD8+, HLA-DR+CD8+, CD28+CD4+ T cells could quickly return to normal level and no significant change after sufficient time of ART. In general, the immune response compared to the baseline status may be the overall effect from the age and time of antiretroviral treatment.

Is the definition of late diagnosis correct?

The study analysed 1711 patients of the Hospital for Infectious Diseases in Warsaw diagnosed with HIV infection in 2008-2010 and 2016-2018. Research was conducted examining the changes in CD4 cell counts before starting antiretroviral (ARV) treatment in order to find people who were misclassified as late-diagnosed. Patients with late diagnosis were distinguished on the basis of the consensus definition. The Mann-Whitney U-test was used to analyse the change in CD4 cell counts before starting ARV treatment. In the years 2008-2010, the CD4 count was remeasured before starting ARV treatment in 90 late-diagnosed patients. The median change in the CD4 count was 22 cells/μL. In 49 of these, the number of CD4 cells spontaneously increased before the start of treatment. We can suspect that these patients were misclassified as late-diagnosed. The consensus definition of late diagnosis often leads to overestimation of the number of late-diagnosed patients. The crucial problem is a transient decline in the CD4 lymphocyte count in the acute phase of HIV infection. A potential solution is to introduce serum HIV viral load measurement into the definition.