Median CD4 Count Research Articles

Association between CD4 count, CD4/CD8 ratio, and fragility fractures in people living with HIV: a retrospective cohort study in China.

People living with HIV (PLHIV) often exhibit reduced CD4+ T cell counts and altered CD4/CD8 ratios, but their impact on fragility fractures remains underexplored. This study investigated the association between CD4 count, CD4/CD8 ratio, and fragility fractures in PLHIV in China. A retrospective cohort study was conducted on PLHIV treated at Beijing Ditan Hospital from January 2011 to September 2023. Data on demographics, clinical status, and bone mineral density were collected. Fragility fractures were identified through medical records. Multivariate Cox regression was used to assess the relationship between CD4 count, CD4/CD8 ratio, and fracture risk, with restricted cubic splines (RCS) applied to explore potential nonlinear associations. Subgroup analyses evaluated the consistency of these findings. The study included 1,107 participants (median age 37 years, 92.6% male). The median CD4 count was 547 cells/μL, and the median CD4/CD8 ratio was 0.7. Fragility fractures occurred in 185 participants (16.7%). Lower CD4 counts (<200 cells/μL) were associated with a higher risk of fractures (aHR = 2.78; 95% CI: 1.66-4.65; p < 0.001), as were lower CD4/CD8 ratios (<0.5) (aHR = 3.43; 95% CI: 2.16-5.44; p < 0.001). RCS indicated a curvilinear association, with increased fracture risk at CD4/CD8 ratios below 1.16. Subgroup analyses confirmed the stability of these associations. Lower CD4 counts and CD4/CD8 ratios are linked to an increased risk of fragility fractures in PLHIV, underscoring the importance of immune function in bone health.

Lipid Profile Improvement after Switching to Dolutegravir-Based Regimen in People Living with HIV: A Cohort Study

Background: Integrase inhibitor (INSTI) based antiretroviral therapy is the mainstay for people living with HIV (PLHIV). Due to its favorable efficacy and safety profile, dolutegravir (DTG) is widely used in combination with nucleoside reverse transcriptase inhibitors (NRTIs). TLD, a fixed-dose combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and DTG, is the first-line treatment for PLHIV in Thailand. However, data on metabolic complications from DTG-based regimens in the Thai population have not been thoroughly investigated. Materials and Methods: A cohort study non-randomized trial was conducted at Buddhachinaraj Hospital, Phitsanulok, Thailand. Data on demographics, baseline antiretroviral regimens, and metabolic profiles such as triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting blood sugar, and aminotransferases, were collected at baseline and six months after switching to a DTG-based regimen in virologically suppressed PLHIV between November 1, 2022 and August 31, 2023. Informed consents were obtained from all participants. Results: One hundred thirty-eight PLHIV were enrolled, with a majority being men, at 59%, and a median age of 47.5 years (IQR 36.2, 55.1). Median CD4 count was 608 cells/mm³ (IQR 452, 805) and median duration of antiretroviral treatment was 13 years (IQR 8, 18). Underlying conditions included dyslipidemia with 44.2%, hypertension for 29.7%, and type II diabetes for 14.5%. Of the participants, 107 out of 138 (77.5%) were on TDF, 3TC, or emtricitabine (FTC) combined with a non-nucleoside reverse transcriptase inhibitor (NNRTI) such as efavirenz (EFV) or rilpivirine (RPV) as their baseline regimen. After six months, significant changes were observed in median triglycerides, from 138.5 to 97.5 mg/dL (p&lt;0.001), total cholesterol from 201 to 173 mg/dL (p&lt;0.001), and LDL cholesterol from 117 to 103 mg/dL (p&lt;0.001). Median body weight increased from 63.2 to 63.35 kg (p&lt;0.001). Conclusion: DTG, a second-generation INSTI, is widely used as a key antiretroviral therapy in Thailand. While it demonstrates favorable effects on lipid profiles, body weight gain, which is a crucial factor for cardiovascular outcomes, should be monitored closely. Keywords: Integrase inhibitor; People living with HIV (PLHIV); Dolutegravir (DTG); Triglyceride; Total cholesterol; LDL-cholesterol; HDL-cholesterol; Fasting blood sugar; Aminotransferase

Survival of HIV associated diffuse large B-cell lymphoma and Burkitt lymphoma in China

Combination antiretroviral therapy (ART) has improved outcomes for human immunodeficiency virus (HIV) associated non-Hodgkin lymphoma. This is an analysis of 127 patients with HIV with Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL) treated at the Zhongnan Hospital of Wuhan University over a 17-year period during the ART and rituximab era. The median CD4 count for the cohorts was 0.141 × 109/L (range, 0.001-0.861 × 109/L). DA-EPOCH ± R (54%) were most commonly used in HIV-BL. CHOP± R (42%) was most commonly used to treat HIV-DLBCL. The complete response rate after first-line curative therapy was 10/28 (36%) in HIV-BL and 25/57 (44%) in HIV-DLBCL. The 2-year progression-free survival (PFS) and overall survival (OS) for the HIV-BL cohort was 50% and 41% respectively. The 2-year PFS and OS for the HIV-DLBCL cohort was 55% and 47% respectively. Current China practice favours the treatment of HIV-BL and HIV-DLBCL similarly to the HIV-negative population with the use of concurrent ART. However, due to the extremely low percentage of patients receiving ART prior to the lymphoma diagnosis, the high percentage of patients with poor performance status, and the advanced stage at diagnosis, the treatment of HIV-related lymphoma remains the major challenge in China.

Urine-Xpert Ultra for the diagnosis of tuberculosis in people living with HIV: a prospective, multicentre, diagnostic accuracy study

Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM. In this prespecified secondary analysis of the same cohort, we aimed to determine the diagnostic yield and accuracy of Urine-Xpert Ultra for tuberculosis in people with HIV, compared with an extended microbiological reference standard (eMRS) and composite reference standard (CRS) and also compared with Determine TB LAM Ag (AlereLAM, Abbott). In this prospective, multicentre, diagnostic accuracy study, we recruited consecutive inpatients and outpatients (aged ≥18 years) with HIV from 13 hospitals and clinics in seven countries (Malawi, South Africa, Tanzania, Thailand, Uganda, Viet Nam, and Zambia). Patients with no isoniazid preventive therapy in the past 6 months and fewer than three doses of tuberculosis treatment in the past 60 days were included. Reference and index testing was performed in real time. The primary outcome of this secondary analysis was the diagnostic yield and accuracy of Urine-Xpert Ultra compared with the eMRS and CRS. Diagnostic accuracy was compared with AlereLAM and diagnostic yield was compared with both AlereLAM and Sputum-Xpert Ultra. This study was registered with ClinicalTrials.gov, NCT04089423, and is complete. Between Dec 13, 2019, and Aug 5, 2021, 3528 potentially eligible individuals were screened and 1731 were enrolled, of whom 1602 (92·5%) were classifiable by the eMRS (median age 40 years [IQR 33-48], 838 [52·3%] of 1602 were female, 764 [47·7%] were male, 937 [58·5%] were outpatients, 665 [41·5%] were inpatients, median CD4 count was 374 cells per μL [IQR 138-630], and 254 [15·9%] had microbiologically confirmed tuberculosis). Against eMRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 32·7% (95% CI 27·2-38·7) and 30·7% (25·4-36·6) and specificities were 98·0% (97·1-98·6) and 90·4% (88·7-91·8), respectively. Against CRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 21·1% (95% CI 17·6-25·1), and 30·5% (26·4-34·9), and specificities were 99·1% (98·3-99·6) and 95·1% (93·5-96·3), respectively. The combination of Sputum-Xpert Ultra with AlereLAM or Urine-Xpert Ultra diagnosed 202 (77·1%) and 204 (77·9%) of 262 eMRS-positive participants, respectively, in incompletely overlapping groups; combining all three tests diagnosed 214 (81·7%) of 262 eMRS-positive participants INTERPRETATION: Urine-Xpert Ultra could offer promising clinical utility in addition to AlereLAM and Sputum-Xpert Ultra. In inpatient settings where both AlereLAM and Urine-Xpert Ultra are possible, both should be offered to support rapid diagnosis and treatment. Global Health Innovative Technology Fund, KfW Development Bank, Commonwealth of Australia represented by the Department of Foreign Affairs and Trade, and the Netherlands Enterprise Agency.

Higher levels of plasmatic saturated fatty acid were significantly associated with liver fibrosis in HIV mono-infection: A case-control study

BackgroundThe relationship between plasmatic fatty acid (FA) composition and liver fibrosis remains scarce in people living with HIV/AIDS (PLWHA). We aimed to evaluate the association of plasmatic FAs and liver fibrosis in HIV mono-infected individuals. MethodsThis case-control study included PLWHA with liver fibrosis (cases) and randomly selected subjects without fibrosis (controls) from the PROSPEC-HIV study (NCT02542020). Participants with viral hepatitis, abusive alcohol consumption and lipid supplements use were excluded. Liver fibrosis was defined using transient elastography (TE) by liver stiffness measurement (LSM) ≥ 7.1 kPa or ≥ 6.2 kPa with M or XL probe, respectively. All HIV mono-infected participants with liver fibrosis identified at the baseline PROSPEC-HIV visit were included. Controls (1:1) were randomly selected among those HIV mono-infected participants without liver fibrosis. Plasmatic FA profile, dietary lipid intake, anthropometric measures, and blood samples were assessed. Plasmatic fatty acid was analyzed using gas chromatography and intake of fats lipids were assessed by two 24-h dietary recall (24-HDR). Multivariate logistic regression models adjusted by age, sex at birth and duration of antiretroviral therapy (ART) were performed. ResultsA total of 142 participants (71 cases and 71 controls) [62 % female, median age = 46 (IQR, 37–53) years, 14.8 % with diabetes, median CD4 count = 655 cells/mm3, 96.5 % under ART] were included. Higher percentages of plasmatic palmitc acid (16:0) and saturated fatty acids (SFA) were observed in participants with liver fibrosis (cases) compared to those without (controls). Presence of higher percentage of plasmatic palmitc acid (16:0) was associated with an increased odds for liver fibrosis [adjusted OR = 1.23 (95%CI 1.04–1.46); p = 0.02] in multivariate models. ConclusionThis study showed the potential role of the plasmatic FA composition in the pathogenesis of liver fibrosis in PLWHA.

Loneliness and social isolation in people with HIV aged ≥50 years. The No One Alone (NOA)-GeSIDA study conducted by the GeSIDA 12021 study group.

There is a growing number of people with HIV who are aged 50 years or older, and the prevalence of loneliness and social isolation remains unknown. A multicentre study was conducted across 22 GeSIDA centres. A survey was carried out to assess loneliness [UCLA 3-item Loneliness Scale-3 (UCLA-3)] and social isolation [Lubben Social Network Scale-Revised (LSNS-R)], along with sociodemographic aspects, HIV-related factors, comorbidities, tobacco, alcohol and drug consumption, quality of life, anxiety and depression, and stigma. The prevalence of loneliness (UCLA-3 ≥ 6) and evident social isolation (LSNS-R ≤ 20) was calculated, and multivariable multinominal logistic regression models were used to identify associated factors. A total of 399 people with HIV were included; 77.4% were men, of average age 59.9 years (SD 6.5); 45.1% were aged ≥60 years; 86% were born in Spain; 86.7% in urban areas; 56.4% with secondary or higher education; 4.5% living alone against their wishes. A total of 66.9% were infected through sexual transmission, with a median of 22.9 years since diagnosis [interquartile range (IQR): 12.6-29.5] and a median nadir CD4 count of 245 cells/μL (IQR: 89-440). Overall, 90.7% had viral load <50 copies/mL, 93.5% had adherence >95%, and 26.3% had a prior AIDS diagnosis. In all, 29.1% and 21% reported significant symptoms of anxiety and depression, respectively, 24.3% had mobility issues, and 40.8% reported pain. Overall, 77.7% of participants reported neither loneliness nor social isolation, 10.0% loneliness only, 5.8% social isolation only and 6.5% both. Multivariable analyses identified that being aged 50-59, unemployed or retired, living alone unwillingly, single, poor quality of life, anxiety, and HIV-related stigma were associated with loneliness. Meanwhile, lower education, living alone unwillingly, and depressive symptoms were associated with social isolation. Individuals living alone unwillingly, with depressive symptoms and experiencing HIV-related stigma were at higher risk for both loneliness and social isolation. There is a relatively high prevalence of loneliness and social isolation in our population. Living alone against one's wishes, being unmarried, and experiencing mobility issues could predispose individuals to feel lonely and socially isolated. Those with anxiety and stigma are more prone to loneliness, while individuals with depression are more predisposed to social isolation. It is necessary to develop strategies for the detection and management of loneliness and social isolation in people with HIV aged >50 years.

Population-Specific Predictors of Immunologic Reconstitution Following Initiation of Combined Antiretroviral Therapy in Children: A Retrospective Observational Study from a 15-Year Cohort of HIV-Positive Children and Adolescents in Eritrea.

In the landscape of HIV treatment, combined antiretroviral therapy (cART) is a cornerstone in managing viral loads and boosting CD4+ T-cell counts. Nevertheless, disparities in treatment outcomes remain persistent, and a subset of children fail to achieve adequate immunologic reconstitution (IR). This study aims to investigate the demographic and clinical factors associated with inadequate IR in HIV-infected children in Eritrea. A retrospective observational study was conducted on 822 children followed at Orotta National Pediatric Referral Hospital between 2005 and 2020. Two distinct analyses were performed, with univariate and multivariate logistic regression models employed to investigate risk factors contributing to inadequate immunologic reconstitution (IR) at the study endpoints of 6- and 12-months post-cART initiation. From the initial cohort of 822 patients [53.4% were males, cohort median age at cART initiation was 78 (IQR: 48-101) months and median absolute CD4 count 270 (151-441) cells/µL]. Two separate analyses were conducted on two cohort subsets with complete data, including 456 children at the 6-month mark and 495 children at 12 months of follow-up. Following 6 months on cART, Immunologic reconstitution was achieved in 87.8% (95% CI: 84.3-91.2) and increased to 90.4% (95% CI: 87.3-93.5) after 12 months of treatment. Independent predictors of inadequate IR after 6 months of cART were higher baseline absolute CD4 counts (aOR = 1.003, (95% CI: 1.002-1.005); p-value <0.001) and NNRTI (EFV: aOR = 3.9, (95% CI: 1.3-11.9); p-value = 0.01). Meanwhile, gender (females: aOR = 0.3, (95% CI: 0.1-0.9, p-value = 0.03) and higher baseline absolute CD4 counts (aOR = 1.003, (95% CI: 1.002-1.005); p-value < 0.001) were independent risk factors of inadequate IR after 12 months of treatment. The study underscores the interplay of baseline CD4 count, gender, and regimen choice in shaping the effectiveness of cART in children. Lower baseline absolute CD4 count was associated with IR after starting cART. Notably, children on EFV had a higher likelihood of inadequate IR after 6 months, and male children were more prone to insufficient IR at 12 months. Targeting these population-specific factors may be pivotal in advancing gender-responsive therapeutic strategies and improving health outcomes for HIV-infected children in sub-optimal clinical settings and resource-constrained environments.

Diagnoses of children living with HIV before and during the COVID-19 pandemic.

There is limited data on diagnoses during hospital stay among children living with HIV(CLHIV) in the antiretroviral and coronavirus disease 2019 (COVID-19) era. The aim of this study was to describe hospital diagnoses and clinical characteristics of CLHIV before and during the COVID-19 pandemic. A retrospective descriptive cross-sectional study was performed. Clinical and laboratory data were retrieved by reviewing folders and discharge summaries from January 2019 to December 2021. Period A (pre-COVID-19) was defined as the period from January 2019 to March 2020. Period B (During COVID-19) was defined as being from April 2020 to December 2021. Ninety-six children contributed 215 diagnoses over the study period. The five most common diagnoses were unspecified HIV disease (47/215, 21.9%), tuberculosis (TB) (42/215, 19.5%), pneumonia (13/215, 6.0%), encephalopathy (11/215, 5.1%) and malnutrition (11/215, 5.1%). Median CD4 count was 377 cells/mm (IQR 126, 726) and 8.0% of the children were virally suppressed. Ninety-five per cent of the children had WHO Stage 3 and 4 (95%) disease and 12.5% of children required ICU admission. No child was diagnosed with COVID-19 despite universal screening. Moreover, 81.7% of the children had a social worker referral documented. Advanced HIV disease (AHD) remains prevalent with TB being the most common diagnosis. There were no cases of COVID-19 recorded in CLHIV. The findings provide a description of the diagnoses of CLHIV in the South African setting prior to and during the COVID-19 pandemic. It highlights the need for more specific documentation of diagnoses to inform better prevention of AHD in children.

Epigenetic associations with kidney disease in individuals of African ancestry with APOL1 high-risk genotypes and Human Immunodeficiency Virus.

Apolipoprotein L1 (APOL1) high-risk variants are major determinants of chronic kidney disease (CKD) in people of African ancestry. Previous studies have identified epigenetic changes in relation to kidney function and CKD, but not in individuals with APOL1 high-risk genotypes. We conducted an epigenome-wide analysis of CKD and estimated glomerular filtration rate (eGFR) in in people of African ancestry and APOL1 high-risk genotypes with HIV. DNA methylation profiles from peripheral blood mononuclear cells of 119 individuals with APOL1 high-risk genotypes (mean age 48 years, 49% female, median CD4 count 515 cells/mm3, 90% HIV-1 RNA <200 copies/mL, 23% with CKD) were obtained by Illumina MethylationEPIC BeadChip. Differential methylation analysis of CKD considered technical and biological covariates. We also assessed associations with eGFR. Replication was pursued in three independent multi-ancestry cohorts with and without HIV. DNA methylation levels at 14 regions were associated with CKD. The strongest signals were located in SCARB1, DNAJC5B and C4orf50. Seven of the 14 signals also associated with eGFR, and most showed evidence for a genetic basis. Four signals (in SCARB1, FRMD4A, CSRNP1 and RAB38) replicated in other cohorts, and 11 previously reported epigenetic signals for kidney function or CKD replicated in our cohort. We found no significant DNA methylation signals in, or near, the APOL1 promoter region. We report several novel as well as previously reported epigenetic associations with CKD and eGFR in individuals with HIV having APOL1 high-risk genotypes. Further investigation of pathways linking DNA methylation to APOL1 nephropathies is warranted.

Implementation of Antigen-Based Diagnostic Assays for Detection of Histoplasmosis and Cryptococcosis among Patients with Advanced HIV in Trinidad and Tobago: A Cross-Sectional Study.

The Caribbean continues to have high HIV prevalence globally with concurrently high mortality rates due to opportunistic Infections. This study addresses the prevalence of histoplasmosis and cryptococcosis among patients living with advanced HIV disease (AHD) in Trinidad and Tobago, focusing on the implementation of antigen-based diagnostic assays. Conducted as a cross-sectional survey across five HIV treatment sites, 199 participants with advanced HIV disease were enrolled between July 2022 and September 2023. Diagnostic testing was performed using the Clarus Histoplasma Galactomannan Enzyme Immunoassay (EIA), and the Immy CrAg® LFA Cryptococcal Antigen Lateral Flow Assay on urine and blood samples, respectively. Results revealed that 14.6% of participants were found to be co-infected with either histoplasmosis or cryptococcosis, with histoplasmosis being more prevalent (10.5%) than cryptococcosis (4.0%). The study found no significant demographic differences between newly diagnosed and previously diagnosed participants. However, a lower median CD4 count was associated with a higher risk of fungal opportunistic infections. The findings underscore the critical role of systematic use of fungal antigen-based diagnostic assays among patients with AHD to improve the timely diagnosis and treatment of fungal infections among people living with HIV in resource-limited settings and to improve patient outcomes and survival.

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.

Immuno-virological and Clinical Follow-up of Persons Living With HIV-2 (PWHIV-2) Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate (BIC/FTC/TAF): A Retrospective Study.

This retrospective study evaluated Bictegravir/FTC/TAF in 24 PWHIV, 5 naive and 19 pretreated. After a median follow-up of 37.5 months, all PWHIV-2 had a plasma viral load < 40 copies/mL. Median CD4 count increased significantly from 580 to 625 cells/mm3, suggesting the effectiveness of Bictegravir/FTC/TAF to treat HIV-2 infection.

Infective endocarditis in HIV-infected patients. Analysis of a national cohort

Background There is limited recent evidence about infective endocarditis (IE) in HIV-infected patients. Our aim was to compare IE according to HIV infection presence. Methods Consecutive inclusion of IE patients at 46 Spanish hospitals between 2008 and 2021. Results From 5667 patients, 99 were HIV-infected (1·7%; 50 intravenous drugs users). Compared to patients without HIV, HIV-infected patients were more frequently male (84% vs. 67%), had younger median age (46 vs. 69 years), and less comorbidities, except liver disease (52% vs. 9%) and intravenous drug use (51% vs. 1%). They had more common tricuspid location (36% vs. 5%) and community-acquired IE (82% vs. 63%), vascular (29% vs. 17%) and cutaneous (22% vs. 7%) foci of infection, and Staphylococcus aureus aetiology (46% vs. 22%). Vegetations (84% vs. 72%), vascular phenomena (17% vs. 9%), splenomegaly (30% vs. 11%), and embolisation (41% vs 21%) were also more common. Surgical indication and surgery were less frequent in HIV-infected patients (54% vs 67%, 28% vs 47%, respectively). Median CD4 count in HIV-infected patients was 318 cells/mm3. In-hospital mortality (23% vs. 26%) and one-year mortality (25% vs. 32%) were similar in both groups. HIV infection was not independently associated with in-hospital (odds ratio 1·1, 95% CI 0·6–1·9) nor one-year mortality (hazard ratio 0·8, 95% CI 0·4–1·3). Conclusions In the combined antiretroviral therapy era, less than 2% of IE patients have HIV infection. HIV-infected patients have a different clinical profile than those without HIV, but the presence of HIV does not seem to impact on IE prognosis.

Nail Disorders in Patients Living with HIV Coinfected with Monkeypox: A Clinical Study in 69 Mexican Cases

Introduction: Several infectious diseases can present nail manifestations, which may be useful for diagnosis and prognosis, and only a few reports have been made regarding monkeypox (mpox). The objective of this study was to describe the clinical characteristics of nail alterations in patients living with HIV coinfected with mpox. Methods: A prospective, cross-sectional study included patients living with HIV/AIDS, coinfected with mpox. We examined all 20 nails in search of nail plate alterations. Patients were divided into two groups, with and without nail disease, and the CD4 count was noted according to the Centers for Disease Control and Prevention (CDC) classification. A χ2 or Fisher’s exact test for qualitative variables and Mann-Whitney U and Kruskal-Wallis tests with post hoc Bonferroni test for quantitative variables were used to compare them. Data were analyzed with the SPSS Statistics 25 software. Results: Sixty-nine patients were included. The frequency of nail involvement was 58%. Papulonodular lesions were the most frequent type identified, with 21 cases (30.4%). A significant difference was observed between patients with nail disease versus median CD4 count (160 vs. 700/mm3; p = 0.002) and median HIV viral load (45,000 vs. 900/mL; p = 0.009). When comparing the characteristics of the nail lesions with the CDC Classification System for HIV infection by the CD4 count, a significant difference was observed in foot involvement, splinter hemorrhages, papulo-nodular lesions, anonychia, onychomadesis, acute paronychia, and nail bed ulcer-atrophy (p < 0.05). Conclusions: The frequency of nail lesions is high in patients living with HIV coinfected with mpox. In addition, they tend to be more destructive in patients with lower CD4 counts and higher viral loads.

Prevalence of Hepatitis D in People Living with HIV: A National Cross-Sectional Pilot Study.

This study assesses the prevalence of hepatitis D virus (HDV) in people living with HIV (PLWHIV) in Greece. Given the compounding effects of HDV and hepatitis B (HBV) on liver disease progression, as well as the emergence of new therapeutic options such as bulevirtide, understanding regional disparities and the epidemiological impact of such co-infections is vital. A cross-sectional analysis was conducted utilizing 696 serum samples from PLWHIV attending five major university hospitals. The methodology included HDV antibody detection by ELISA and HDV RNA confirmation. Of the 30 HBsAg-positive samples analyzed, the study population was primarily male (93%), with a median age of 54 years. Participants had been on antiretroviral therapy for a median of 10 years, and the median CD4 count was 738 (539-1006) copies/mL. Additional serological findings revealed a 7% prevalence of hepatitis C virus (HCV) IgG antibodies and a 55% prevalence of hepatitis A virus (HAV) IgG antibodies. Seroreactivity for syphilis (RPR/VDRL/TPHA positive) was identified in 33% of the participants. The results indicated a low HDV prevalence, with only one individual (3%) testing positive for anti-HDV IgG antibodies and none for HDV RNA. This indicates a lower prevalence of HDV among PLWHIV with chronic HBV in Greece compared to global data.

Comparison of clinical outcomes of pulmonary nocardiosis between AIDS and non-AIDS patients

BackgroundNocardia species can affect both immunocompetent and immunocompromised people.MethodThis retrospective study, from 2009 to 2022, aims to compare the survival analyses of pulmonary nocardiosis in AIDS and non-AIDS patients in northeastern Thailand.ResultsA total of 215 culture-confirmed cases of pulmonary nocardiosis: 97 with AIDS and 118 without AIDS. The median CD4 count of AIDS patients was 11 cells/µL (range: 1–198), and 33% had concurrent opportunistic infections. 63.6% of 118 non-AIDS patients received immunosuppressive medications, 28.8% had comorbidities, and 7.6% had no coexisting conditions. Disseminated nocardiosis and pleural effusion were more prevalent among AIDS patients, whereas non-AIDS patients revealed more shock and respiratory failure. One hundred-fifty patients underwent brain imaging; 15 (10%) had brain abscesses. Patients with pulmonary nocardiosis have overall 30-day and 1-year mortality rates of 38.5% (95% CI: 32.3%, 45.4%) and 52.1% (95% CI: 45.6%, 58.9%), respectively. The Cox survival analysis showed that AIDS patients with disseminated nocardiosis had a 7.93-fold (95% CI: 2.61–24.02, p < 0.001) increased risk of death within 30 days compared to non-AIDS patients when considering variables such as age, Charlson comorbidity index, concurrent opportunistic infections, duration of illness, shock, respiratory failure, multi-lobar pneumonia, lung abscesses, and combination antibiotic therapy. While AIDS and pulmonary nocardiosis had a tendency to die within 30 days (2.09 (95% CI, 0.74–5.87, p = 0.162)).ConclusionAIDS with pulmonary nocardiosis, particularly disseminated disease, is a serious opportunistic infection. Early diagnosis and empiric treatment with a multidrug regimen may be the most appropriate approach in a resource-limited setting.

Exploring T cell subsets as predictors of response to BCMA targeting bispecific antibody therapy in multiple myeloma.

7567 Background: BCMA targeting bispecific Antibody (bsAb) therapy has shown unprecedented response and survival rates in patients with relapsed/refractory multiple myeloma (MM). The clinical activity of bsAb therapy has been shown to depend on T-cell function, yet clinical parameters, such as absolute lymphocyte count (ALC) have not been found to be associated with response to bsAbs. The aim of the present study was to elucidate whether distinct T cell subsets, such as CD4 and CD8 counts as well as their proportion within the ALC are associated with outcome of BCMA targeting bsAb therapy. Methods: We retrospectively collected data on 79 patients who had been treated with at least one full dose of a BCMA targeting bsAb. T cell subsets, including ALC, total CD3, CD4 and CD8, were measured from peripheral blood within 7 days prior to bsAb therapy initiation. Statistical analysis was performed with SAS version 9.4 using univariate and multivariate logistic regression models. Results: Median age of the patient cohort was 72 (31-84) years with 40/79 (51%) being male and 15/79 (19%) being African American. Median lines of therapy was 5 (2-12) with 78/79 (99%) patients being triple class refractory and 50/79 (63%) being penta-drug refractory. 59/79 (75%) of patients had at least one prior stem cell transplant (SCT) with 35/79 (44%) having had at least two SCTs. 26/79 (33%) patients had prior exposure to BCMA targeting therapy, with 18/79 (23%) and 8/79 (10%) previously having received belantamab mafodotin or BCMA targeting Car-T cell therapy respectively. Cytokine release syndrome (CRS) occurred in 38/79 (48%) of patients with the majority (92%) being grade 1 with the remainder being grade 2. Median ALC was 1.02 (0.25-5) x103/mL, median CD4 count was 0.27 (0.04-1.13) x103/mL while median CD8 count was 0.5 (0.07-2.97) x103/mL. Overall response (OR) rate of the whole cohort was 82% (69/79) with best responders (³very good partial response) comprising 51% (40/79). While total ALC, CD4 and CD8 counts did not appear to impact response to BCMA targeting bsAb therapy, the ratio of CD4 to ALC proved to be significantly associated with OR (univariate p=0.04) and best response (univariate p= 0.004, multivariate p=0.01) . The CD8 to ALC ratio had no significant impact in this patient population. The only other factor to show a significant association with response was the number of prior lines of therapy with higher numbers being associated with worse response (p=0.046). Conclusions: Our study suggests that an increased proportion of CD4 cells within the ALC is significantly associated with better response to BCMA targeting bsAb. While future studies are needed to elaborate on CD4 function in bsAB therapy, our findings imply that therapeutic strategies to increase the CD4 proportion could lead to improved bsAb therapy effectiveness.

Humoral response after mRNA COVID-19 primary vaccination and single booster dose in people living with HIV compared to controls: A French nationwide multicenter cohort study—ANRS0001s COV-POPART

BackgroundThis study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals. MethodsWe included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (<200/mm3 and ≥200/mm3 CD4 cell counts) at 1, 6, and 12 months after primary vaccination. ResultsA total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm3) and 1092 controls. At 1 month, after adjustment on age, sex, and BMI, PWH had lower seroneutralization titers than controls, and PWH with <200 CD4 cell/mm3 had lower anti-Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months postprimary vaccination, we did not observe differences between PWH and controls at 12 months. ConclusionPWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after 6 months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline.

Recently acquired HCV infection in men who have sex with men in Germany in the direct-acting antivirals era and during the COVID-19 pandemic.

Direct-acting antivirals (DAAs) are key to eliminating hepatitis C virus (HCV). In men who have sex with men (MSM) with HIV co-infection, recently acquired HCV infection is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates. The cohort included MSM with recently acquired HCV infection from 2014 to 2021. The patients' demographic, clinical, behavioural, and laboratory data and treatment and reinfection outcomes were documented. A total of 237 men with recently acquired HCV infection were included: 216 (91%) had HIV. The median age was 46 years (interquartile range [IQR] 39-52), and the median CD4 count was 660/mm3 (IQR 527-835). The annual incidence of recently acquired HCV remained between 0.28% and 0.43% but dropped to 0.02% in 2021 during the COVID pandemic, almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95% confidence interval 12.6-18.8), and reinfection was associated with the use of crystal methamphetamine (p = 0.032) and ketamine (p = 0.042). In total, 31.3% had multiple reinfections, and four reinfections occurred in users of pre-exposure prophylaxis. High treatment and cure rates did not lead to HCV elimination. A change in sexual behaviour, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As recently acquired HCV is prevalent in MSM with and without HIV, surveillance is necessary to consolidate elimination goals.

Dolutegravir plus boosted darunavir versus recommended standard-of-care antiretroviral regimens in people with HIV-1 for whom recommended first-line non-nucleoside reverse transcriptase inhibitor therapy has failed (D2EFT): an open-label, randomised, phase 3b/4 trial

Randomised comparative data on efficacy and safety of second-line antiretroviral therapy (ART) after failure of non-nucleoside reverse transcriptase inhibitors (NNRTIs) across diverse geographical settings are scarce. The aim of this study was to evaluate optimal second-line ART for people with HIV. D2EFT is a completed international, randomised, open-label, phase 3b/4 trial evaluating three second-line ART strategies in adults (aged ≥18 years) with HIV-1 for whom first-line NNRTI therapy has failed. The study was done at 28 sites across 14 countries in Asia, Africa, and Latin America. It was originally designed to compare recommended standard of care (ritonavir-boosted darunavir [800 mg darunavir plus 100 mg ritonavir once daily] plus two nucleoside reverse transcriptase inhibitors [NRTIs; dosed once or twice daily]) with a novel nucleoside sparing regimen of dolutegravir (50 mg once daily) with ritonavir-boosted darunavir. The study was adapted during the first year to add a third arm of dolutegravir (50 mg once daily) with fixed tenofovir disoproxil fumarate (300 mg once daily) plus either lamivudine (300 mg once daily) or emtricitabine (200 mg once daily). Participants were randomly assigned with a computer-generated, blocked randomisation scheme (block size of two) stratified by site, previous tenofovir disoproxil fumarate use, and HIV viral load. The trial was designed to evaluate non-inferiority of either interventional arm against standard of care for the primary outcome of virological suppression, as determined by HIV RNA load of less than 50 copies per mL at 48 weeks. The prespecified non-inferiority margin was 12%. Comparisons were made with a modified intention-to-treat population, including all participants randomly assigned but excluding administrative withdrawals. This study is registered with ClinicalTrials.gov, NCT03017872. 1190 individuals were screened; 828 participants were enrolled between Nov 1, 2017, and Dec 31, 2021. Two participants were unable to receive their assigned regimen for administrative reasons; and 826 participants were included in analyses. Median age was 39 years (IQR 33-46), and 450 (54%) participants were female. Baseline median CD4 count was 206 cells per μL (23-354) and median HIV RNA was 15 400 copies per mL (3600-65 986). The proportion of participants with HIV RNA of less than 50 copies per mL at 48 weeks was 194 (75%) of 257 in the ritonavir-boosted darunavir plus two NRTIs group, 222 (84%) of 264 in the ritonavir-boosted darunavir plus dolutegravir group, and 227 (78%) of 291 in the dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine group. Compared with ritonavir-boosted darunavir plus two NRTIs, the difference in virological suppression was 8·6% (95% CI 1·7 to 15·5; p=0·016) for dolutegravir plus ritonavir-boosted darunavir and 6·7% (-1·2 to 14·4; p=0·093) for dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine. Six deaths occurred, none of which were related to treatment. 19 pregnancies (11 livebirths) occurred with no congenital defects. In individuals experiencing failure of an NNRTI-based first-line ART, a switch to either dolutegravir plus ritonavir-boosted darunavir or dolutegravir with tenofovir disoproxil fumarate plus either lamivudine or emtricitabine, without universal access to genotyping, was non-inferior in achieving viral suppression compared with ritonavir-boosted darunavir plus two NRTIs. These global data support the most recent WHO treatment guidelines. UNITAID; National Institute of Allergy and Infectious Diseases, USA; National Health and Medical Research Council, Australia; ViiV Healthcare; and Janssen.