Low CD4 T-cell Counts Research Articles

Association among therapeutic adherence, health literacy, and engagement in care: How to increase health-conscious management of HIV disease.

In the context of People Living with HIV (PLWH), poor health literacy (HL) seems to be linked to poorer health outcomes and reduced engagement in care. Additionally, the level of HL can affect HIV knowledge and may impact adherence to antiretroviral therapy (ART). This research explored the connection between ART adherence, HL, and engagement in care in a cohort of 250 PLWH receiving ART in Italy. A questionnaire was given to PLWH at Policlinico Gemelli in Rome to assess their health literacy and adherence to therapy. The Brief Health Literacy Screening (BHLS) and the Newest Vital Sign (NVS) were used to evaluate subjective and objective HL. Adherence levels were self-reported as poor, good, or excellent, and the assessment included the Patient Health Engagement Scale (PHE-S). Notably, the majority of the sample comprised male individuals (67.9%), with 69.2% reporting a 10-years or longer duration between their HIV diagnosis and their initiation of ART. It was found that PLWH with poor adherence had low schooling, had been living with HIV for 1-5years, were HCV co-infected, had a viremia >50copies/mL, poor health status, poor engagement in care, and poor HL (p = <0.001). They exhibited lower mean scores on the subjective HL scale and lower CD4 T-cell counts and nadir CD4 T-cell counts (p < .001). Our study demonstrated a positive correlation between higher HL levels and improved disease management, treatment adherence, and overall physical and mental well-being. Enhanced HL capabilities are paramount in bolstering health management and treatment adherence.

Diagnostic Value of Metagenomic next-generation sequencing and X-pert in Bronchoalveolar lavage fluid for pneumonia in HIV-infected and HIV-uninfected patients

BackgroundThe pathogens causing unexplained pneumonia in both HIV-infected or HIV-unfected patients are likely to be complex. This retrospective study aimed to characterize the etiology of pneumonia in HIV-infected and HIV-uninfected patients using bronchoalveolar lavage fluid (BALF) analysis with metagenomic next-generation sequencing (mNGS) and X-pert MTB/RIF. MethodsBetween January 2022 and May2024, 141 HIV-infected and 104 HIV-uninfected patients admitted to Nanjing Second Hospital with pneumonia were included. BALF samples were collected and analyzed using mNGS to detect bacteria, fungi, viruses, tuberculosis (TB) and non-tuberculous mycobacteria (NTM), and X-pert for TB detection. Clinical data including CD4 T-cell counts, comorbidities, and ART status were collected and analyzed. ResultsHIV-uninfected patients were found to be older and exhibited a higher prevalence of comorbidities compared to HIV-infected patients. Despite higher median CD4 T-cell counts in HIV-uninfected individuals (412 cells/μL vs. 31 cells/μL in HIV-infected), TB detection rates using X-pert and mNGS were lower than anticipated, particularly in HIV-infected patients. Mixed-pathogen infections were significantly more prevalent in HIV-infected patients, especially those with lower CD4 T-cell counts. ART use showed variable impacts on pathogen diversity, with longer treatment durations associated with reduced infection complexity but persistent immunodeficiency in some cases.In patients with pneumonia, whether HIV-infected or HIV-uninfected, pathogens often exhibit complexity, underscoring the critical role of timely mNGS and X-pert analysis of BALF for early pathogen detection.

COVID-19 Severity in People With HIV Compared With Those Without HIV.

People with HIV (PWH) may be at risk for more severe COVID-19 outcomes. We compared risk for severe COVID-19 in PWH with matched individuals without HIV. We identified adults in Massachusetts with a positive SARS-CoV-2 test, March 2020-July 2022, using electronic medical record data from 3 large clinical practice groups. We then used regression models to compare outcomes among PWH versus propensity score-matched people without HIV (matched 20:1) for severe COVID-19 (pneumonia or acute respiratory distress syndrome), hospitalization, and hospital length of stay. We identified 171,058 individuals with COVID-19; among them, 768 PWH were matched to 15,360 individuals without HIV. Overall, severe COVID-19 and hospitalization were similar in PWH and those without HIV (severe COVID-19: 3.8% vs 3.0%, adjusted odds ratio [OR] 1.27, 95% confidence interval [CI]: 0.86-1.87; hospitalization: 12.1% vs 11.3%, adjusted OR: 1.08, 95% CI: 0.87 to 1.35). Compared with people without HIV, PWH with low CD4 T-cell counts (<200 cells/mm 3 ) had more severe COVID-19 (adjusted OR: 3.99, 95% CI: 2.06 to 7.74) and hospitalization (adjusted OR: 2.26, 95% CI: 1.35 to 3.80), but PWH with high CD4 counts had lower odds of hospitalization (adjusted OR: 0.73, 95% CI: 0.52 to 1.03). PWH with low CD4 T-cell counts had worse COVID-19 outcomes compared with people without HIV, but outcomes for those with high CD4 counts were similar to, or better than, those without HIV. It is unclear whether these findings are generalizable to settings where PWH have less access to and engagement with health care.

Risk Factors Associated with Opportunistic Infections among People Living with HIV/AIDS and Receiving an Antiretroviral Therapy in Gabon, Central Africa.

The Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the main causes of death in sub-Saharan Africa. Antiretroviral therapies (ARTs) have significantly improved the health conditions of people living with HIV/AIDS (PLWHA). Consequently, a significant drop in morbidity and mortality, along with a reduced incidence of opportunistic infections (OIs), has been observed. However, certain atypical and biological profiles emerge in ART patients post-examination. The objective of this study was to identify the risk factors that contributed to the onset of OIs in HIV patients undergoing ART in Gabon. Epidemiological and biological data were obtained from medical records (2017 to 2019) found at the outpatient treatment centre (CTA) of Franceville in Gabon. Samples for blood count, CD4, and viral load analysis at CIRMF were collected from PLWHA suffering from other pathogen-induced conditions. A survey was carried out and data were analysed using Rstudio 4.0.2 and Excel 2007 software. Biological and socio-demographic characteristics were examined concerning OIs through both a univariate analysis via Fisher's exact tests or chi2 (χ2), and a multivariate analysis via logistic regression. Out of the 300 participants initially selected, 223 were included in the study, including 154 (69.05%) women and 69 (30.95%) men. The mean age was 40 (38.6; 41.85), with individuals ranging from 2 to 77 years old. The study cohort was classified into five age groups (2 to 12, 20 to 29, 30 to 39, 40 to 49, and 50 to 77 years old), among which the groups aged 30 to 39 and 40 to 49 emerged as the largest, comprising 68 (30.5%) and 75 (33.6%) participants, respectively. It was noted that 57.9% of PLWHA had developed OIs and three subgroups were distinguished, with parasitic, viral, and bacterial infections present in 18%, 39.7%, and 55.4% of cases, respectively. There was a correlation between being male and having a low CD4 T-cell count and the onset of OIs. The study revealed a high overall prevalence of OIs, and extending the study to other regions of Gabon would yield a better understanding of the risk factors associated with the onset of these infections.

4 Methamphetamine, cannabis, HIV, and their combined effects on neurocognition

Objective:Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.Participants and Methods:HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p&lt;.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores&gt;0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.Results:Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4&lt;200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.Conclusions:In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.

Cortical and trabecular bone deficit in middle-aged men living with HIV.

A significant increase in risk of hip fracture was observed in middle-aged men living with human immunodeficiency virus (MLWH), almost a decade earlier than those without infection. Data regarding cortical and trabecular bone deficit of hip, an important determinant of bone strength, in MLWH are limited. Quantitative computed tomography was performed in consecutive MLWH aged ≥30 years between November 2017 and October 2018 at Severance Hospital, Seoul, Korea. Volumetric bone mineral density (vBMD) and cortical bone mapping parameters of hip (cortical thickness, CTh; cortical bone vBMD, CBMD; cortical mass surface density, CMSD; endocortical trabecular density, ECTD) were compared to age- and body mass index (BMI)-matched controls (1:2), using a community-based healthy adults' cohort. Among 83 MLWH and 166 controls (mean age: 47.2 years; BMI: 23.6 kg/m2 ), MLWH had lower total hip vBMD (280 ± 41 vs. 296 ± 41 mg/cm3 ), CMSD (155 vs. 160 mg/cm2 ), and ECTD (158 vs. 175 mg/cm3 ) than controls that remained robust after adjustment for covariates (adjusted β: total hip vBMD, -18.8; CMSD, -7.3; ECTD, -18.0; p < 0.05 for all). Cortical bone mapping revealed localized deficit of CTh, CBMD, and CMSD in anterolateral trochanteric region and femoral neck in MLWH compared to controls, with more extensive ECTD deficit. In MLWH, lower CD4 T cell count (/100 cells/mm3 decrement) and protease inhibitor (PI)-based regimen (versus non-PI regimen) at the time of antiretroviral treatment initiation were associated with lower total hip vBMD (adjusted β -7.5 for lower CD4 count; -28.3 for PI-based regimen) and CMSD (adjusted β -2.6 for lower CD4 count; -12.7 for PI-based regimen; p < 0.05 for all) after adjustment for covariates including age, BMI, smoking, alcohol use, HCV co-infection, tenofovir exposure, and CT scanners types. MLWH had lower hip bone density with cortical and trabecular bone deficit compared to community-dwelling controls. This article is protected by copyright. All rights reserved.

CRYPTOCOCCAL INFECTION IN PLHIV : SERIES OF 12 CASES AT THE LABORATORY OF MOHAMMED VI UNIVERSITY HOSPITAL OF MARRAKECH

Background: Cryptococcal infection is opportunistic and causes high morbidity and mortality among severely immunocompromised patients, specially those living with HIV/AIDS (PLHIV). Cryptococcus neoformans is the most frequently identified species, incriminated in 90% of cryptococcal meningitis (CM). Methods: This is a descriptive retrospective study over a 2-years period (2021 - 2022) involving 12 PLHIV in whom we have isolated Cryptococcus neoformans from cerebrospinal fluid (CSF), blood culture, respiratory or skin specimen. All patients received antifungal therapy, associated to therapeutic lumbar punctures for those who presented with increased intracranial pressure. The clinical examination findings, laboratory data and evolution under treatment of these patients were reviewed. Results: The twelve patients were all HIV-infected adults, with median age of 41.25 ± 12.22 years and male predominance with a sex ratio of 1:2. All patients had low CD4 T-cell counts at diagnosis (&lt;100 cells/µl). Neurological involvement existed in all patients of this cohort : Isolated CM was diagnosed in three cases (25%). Nine patients (75%) had disseminated cryptococcosis: Central nervous system (CNS) with positive hemoculture in six cases, CNS and pulmonary involvement with positive hemoculture in two cases, CNS and cutaneous involvement with positive hemoculture in one case. Cryptococcus neoformans was identified in all cases. Of the twelve patients, seven (58%) survived with good response to the treatment. Lethality rate was 42%. Conclusion: This study demonstrates cryptococcal disease is a high mortality infection in PLHIV.Priority should be given to access to rapid diagnostic CrAgtests to accessibility to liposomal amphotericin B. This could improve the clinical outcome of the patients in our moroccan context.

Correlation between CD4 T-Cell Counts and Seroconversion among COVID-19 Vaccinated Patients with HIV: A Meta-Analysis.

To evaluate the potential factors for predicting seroconversion due to the coronavirus disease 2019 (COVID-19) vaccine in people living with HIV (PLWH). We searched the PubMed, Embase and Cochrane databases for eligible studies published from inception to 13th September 2022 on the predictors of serologic response to the COVID-19 vaccine among PLWH. This meta-analysis was registered with PROSPERO (CRD42022359603). A total of 23 studies comprising 4428 PLWH were included in the meta-analysis. Pooled data demonstrated that seroconversion was about 4.6 times in patients with high CD4 T-cell counts (odds ratio (OR) = 4.64, 95% CI 2.63 to 8.19) compared with those with low CD4 T-cell counts. Seroconversion was about 17.5 times in patients receiving mRNA COVID-19 vaccines (OR = 17.48, 95% CI 6.16 to 49.55) compared with those receiving other types of COVID-19 vaccines. There were no differences in seroconversion among patients with different ages, gender, HIV viral load, comorbidities, days after complete vaccination, and mRNA type. Subgroup analyses further validated our findings about the predictive value of CD4 T-cell counts for seroconversion due to COVID-19 vaccines in PLWH (OR range, 2.30 to 9.59). The CD4 T-cell counts were associated with seroconversion in COVID-19 vaccinated PLWH. Precautions should be emphasized in these patients with low CD4 T-cell counts, even after a complete course of vaccination.

Immunogenicity of COVID-19 Vaccination in People Living with HIV: Progress and Challenges

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in numerous confirmed cases and deaths worldwide. Recent studies have shown that people living with HIV (PLWH) are prone to develop severe illness and poor outcomes if they experience coronavirus disease 2019 (COVID-19), especially those with uncontrolled viremia and low CD4 T-cell count. Therefore, many countries prioritized PLWH for COVID-19 vaccination. However, lower magnitude or faster waning humoral immune responses elicited by other vaccines have been documented in PLWH, raising concerns regarding the efficacy of the COVID-19 vaccine in these specific populations. Here, we summarize the current progress in the immunogenicity and efficacy of different types of SARS-CoV-2 vaccinations in PLWH and highlight several challenges faced by PLWH in the current COVID-19 pandemics.

Diagnostic Value of Metagenomic Next-Generation Sequencing for Multi-Pathogenic Pneumonia in HIV-Infected Patients.

To evaluate the value and challenges of real-world clinical application of metagenomic next-generation sequencing (mNGS) for bronchoalveolar lavage fluid (BALF) in HIV-infected patients with suspected multi-pathogenic pneumonia. Fifty-seven HIV-infected patients with suspected mixed pneumonia who were agreed to undergo the bronchoscopy were recruited and retrospectively reviewed the results of mNGS and conventional microbiological tests (CMTs) of BALF from July 2020 to June 2022. 54 patients were diagnosed with pneumonia including 49 patients with definite pathogens and five patients with probable pathogens. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs in HIV-infected patients with suspected pulmonary infection. The sensitivity of mNGS in diagnosis of pneumonia in HIV-infected patients was much higher than that of CMTs (79.6% vs 61.1%; P < 0.05). Patients with mixed infection had lower CD4 T-cell count and higher symptom duration before admitting to the hospital than those with single infection. The detection rate of mNGS for mixed infection was significantly higher than that of CMTs and more co-pathogens could be identified by mNGS. The most common pattern of mixed infection observed was fungi-virus (11/29, 37.9%), followed by fungi-virus-bacteria (6/29, 20.7%) coinfection in HIV-infected patients with multi-pathogenic pneumonia. mNGS improved the pathogens detection rate and exhibited advantages in identifying multi-pathogenic pneumonia in HIV-infected patients. Early performance of bronchoscopy and mNGS are recommended in HIV-infected patients with low CD4 T cell counts and long duration of symptoms. The most common pattern of mixed infection observed was fungi-virus, followed by fungi-virus-bacteria coinfection in HIV infected patients with multi-pathogenic pneumonia.

Changing roles of CD3 + CD8 low T cells in combating HIV-1 infection.

Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low ) or high levels (CD8 high ) on HIV-1 replication inhibition after HIV-1 invasion into individual. Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 + CD8 low T cells and their counterpart CD3 + CD8 high T cells at different stages of HIV-1 infection. Compared with healthy donors, CD3 + CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 + CD8 low T cells gradually decreased. Simultaneously, CD3 + CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 + CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 - HLA-DR + CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 + CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 + CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 + CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3 + CD8 low T cells, but comparable amounts of CD3 + CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 + CD8 low T cells than CD3 + CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Our findings suggest that CD3 + CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 + CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 + CD8 high T cells.

Mean Coronary Cross-Sectional Area as a Measure of Arterial Remodeling Using Noncontrast CT Imaging in Persons With HIV.

Background Persons with HIV have a higher prevalence of coronary artery disease compared with their HIV-negative counterparts. Earlier identification of subclinical atherosclerosis may provide a greater opportunity for cardiovascular disease risk reduction. We investigated coronary cross-sectional area (CorCSA) by noncontrasted computed tomography imaging as a noninvasive measure of arterial remodeling among virally suppressed persons with HIV. Methods and Results We assessed 105 persons with HIV with a spectrum of cardiometabolic health. All participants underwent computed tomography imaging to assess the mean corCSA of the proximal left anterior descending artery and 28 participants underwent additional coronary computed tomography angiography. Partial Spearman rank correlations adjusted for cardiovascular disease risk factors were used to assess relationships of corCSA with anthropometric measurements, HIV-related factors, and plasma cytokines. Mean corCSA measured by noncontrast computed tomography and coronary computed tomography angiography were strongly correlated (ρ=0.91, P<0.0001). Higher mean corCSA was present in those with coronary artery calcium (P=0.005) and it correlated with participants' atherosclerotic cardiovascular disease risk score (ρ=0.35, P=0.01). After adjusting for established cardiovascular disease risk factors, we observed an inverse relationship between corCSA and CD4+ T-cell count (ρ=-0.2, P=0.047). Removal of age from the model strengthened the relationships between corCSA and antiretroviral therapy duration (from ρ=0.19, P=0.08 to ρ=0.3, P=0.01). CorCSA was also inversely correlated with plasma IL-10 (ρ=-0.25, P=0.03) but had no relationship with IL-6 (ρ=0.11, P=0.4) or IL-1β (ρ=0.08, P=0.5). Conclusions Positive coronary arterial remodeling, an imaging marker of subclinical atherosclerosis, is associated with a lower CD4 T-cell count, lower circulating IL-10, and possibly a longer antiretroviral therapy duration in persons with HIV. Registration Clinicaltrials.gov; Unique identifier: NCT04451980.

Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma

AbstractCAR T-cell therapy has revolutionized the treatment of hematologic malignancies, although its use may be complicated by toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Invasive fungal disease (IFD) has been reported after CAR T-cell therapy, but the incidence in the absence of antifungal prophylaxis is unknown. Optimal prophylaxis strategies are widely debated. We performed a single-center retrospective study of 280 adults receiving CD19 CAR T-cell therapy for non-Hodgkin lymphoma (NHL) from December 2017 through September 2021. Patients did not receive routine antiyeast or antimold prophylaxis. IFD was identified between day of cell infusion and last follow-up. Cumulative incidence functions were calculated at 100 days and 18 months based on time to IFD, using dates of IFD-free death, initiation of salvage treatment, and hematopoietic cell transplantation as competing risks. Eight patients (2.9%) developed IFD, including 3 Pneumocystis jirovecii pneumonia, 3 invasive mold infections (IMIs), and 2 invasive yeast infections (IYIs). The 100-day cumulative incidence of IFD accounting for competing risks was 1.8% (95% confidence interval [CI], 0.8% to 4.4%). Among the 280 patients, early toxicities including CRS (85%) and ICANS (55%) and late toxicities after day 30 including grades 3 and 4 neutropenia (41%) and low CD4 T-cell count (20%) were common. IFD was rare among patients who received CD19 CAR T-cell therapy for NHL in the absence of routine antifungal prophylaxis, despite frequent toxicities. These results suggest that, in settings with low institutional rates of IFD, routine antifungal prophylaxis may not be indicated.

Altered white matter microstructure and neurocognitive function of HIV-infected patients with low nadir CD4.

Altered white matter microstructure has been reported repeatedly using diffusion tensor imaging (DTI) in HIV-associated neurocognitive disorders. However, the associations between neurocognitive deficits and impaired white matter remains obscure due to frequent physical and psychiatric comorbidities in the patients. Severe immune suppression, reflected by low nadir CD4 T-cell counts, is reported to be associated with the neurocognitive deficits in the patients. In the present study, we examined white matter integrity using DTI and tract-based spatial statistics (TBSS), and neurocognitive functions using a battery of tests, in 15 HIV-infected patients with low nadir CD4, 16 HIV-infected patients with high nadir CD4, and 33 age- and sex-matched healthy controls. As DTI measures, we analyzed fractional anisotropy (FA) and mean diffusivity (MD). In addition, we investigated the correlation between white matter impairments and neurocognitive deficits. Among the three participant groups, the patients with low nadir CD4 showed significantly lower performance in processing speed and motor skills, and had significantly increased MD in widespread regions of white matter in both hemispheres. In the patients with low nadir CD4, there was a significant negative correlation between motor skills and MD in the right motor tracts, as well as in the corpus callosum. In summary, this study may provide white matter correlates of neurocognitive deficits in HIV-infected patients with past severe immune suppression as legacy effects.

Analyses of Kaposi Sarcoma trends among adults establishing initial outpatient HIV care in Nigeria: 2006\u20132017

BackgroundThe incidence of Human Immunodeficiency Virus (HIV)-associated Kaposi Sarcoma (KS) in the pre-antiretroviral therapy (ART) population remains high in several countries in sub-Saharan Africa. We examined trends of KS prevalence in adults, establishing initial outpatient HIV care from 2006 to 2017 in Nigeria.MethodsWe analyzed data of 16,431 adults (age ≥ 18 years) enrolled for HIV care from January 1, 2006, to December 31, 2017, in a large clinic in Jos, Nigeria. KS at enrollment was defined as KS recorded in the electronic health record within 30 days of clinic enrollment. Time trends were compared among four periods: 2006–2008, 2009–2011, 2012–2014, and 2015–2017 using logistic regression models. Annual trends were analyzed using join point regression and restricted splines.ResultsThe study population had a mean age 35.1 (standard deviation, SD 9.5) years, and were 65.7% female (n = 10,788). The mean CD4 cell count was 220 (95% CI 117–223). The overall KS prevalence at entry was 0.59% (95% CI 0.48–0.72). Compared to 2006–2008, KS prevalence was significantly higher in 2009–2011 (adjusted odds ratio 5.07 (95% CI 3.12–8.24), p < 0.001), but remained unchanged in subsequent periods. Male sex and low CD4 T-cell count independently increased odds for KS.ConclusionsDespite ART expansion, KS at enrollment showed no significant decline. The low CD4 cell count, across all periods, indicates delay in enrollment for HIV care, which increases KS risk. Interventions aimed at early HIV diagnosis and linkage to ART is critical to KS risk reduction in this population.

Retrospective study of psoriasis in people living with HIV: Thailand's experience.

Psoriasis in people living with HIV (PLHIV) has been reported as having particular clinical characteristics. However, most of the source data was derived from descriptive studies in Europe and the USA. This study was conducted to compare the characteristics of psoriasis in PLHIV to general psoriasis patients. We retrospectively reviewed the records of 73 cases of psoriasis in PLHIV and of 232 general psoriasis patients who visited a psoriasis clinic in Bangkok, Thailand. Psoriasis in PLHIV predominated in males (78.1%), with an older age of onset, significantly lower rates of nail involvement and psoriatic arthritis, but higher rates of co-infectious diseases than for general psoriasis patients. A low nadir CD4 T-cell count (<100cells/μl) and CD4 T-cell count at psoriasis diagnosis were associated with a high body surface area (BSA) involvement. The mean BSA involvement in PLHIV was 24. Although 64.4% (47/73) of the PLHIV had moderate-to-high psoriasis severity, 29.8% of those (14/47) only received topical treatment. Acitretin was the most common drug used. Other therapies were rarely used, and no biologics were administered. In conclusion, psoriasis in PLHIV has several clinical features that differ from general psoriasis. PLHIV tend to receive substandard care for psoriasis, even in upper-middle-income countries.

Interplay between Selenium, Selenoproteins and HIV-1 Replication in Human CD4 T-Lymphocytes.

The infection of CD4 T-lymphocytes with human immunodeficiency virus (HIV), the etiological agent of acquired immunodeficiency syndrome (AIDS), disrupts cellular homeostasis, increases oxidative stress and interferes with micronutrient metabolism. Viral replication simultaneously increases the demand for micronutrients and causes their loss, as for selenium (Se). In HIV-infected patients, selenium deficiency was associated with a lower CD4 T-cell count and a shorter life expectancy. Selenium has an important role in antioxidant defense, redox signaling and redox homeostasis, and most of these biological activities are mediated by its incorporation in an essential family of redox enzymes, namely the selenoproteins. Here, we have investigated how selenium and selenoproteins interplay with HIV infection in different cellular models of human CD4 T lymphocytes derived from established cell lines (Jurkat and SupT1) and isolated primary CD4 T cells. First, we characterized the expression of the selenoproteome in various human T-cell models and found it tightly regulated by the selenium level of the culture media, which was in agreement with reports from non-immune cells. Then, we showed that selenium had no significant effect on HIV-1 protein production nor on infectivity, but slightly reduced the percentage of infected cells in a Jurkat cell line and isolated primary CD4 T cells. Finally, in response to HIV-1 infection, the selenoproteome was slightly altered.

Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease.

Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+ patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count < 100/µL) HIV+ patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+ patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral load decreased. Strikingly in LN, ART led to a rapid decrease in interferon signaling pathways and an increase in Tfh, germinal center and IgD-CD27- B cells, consistent with histological findings of post-ART follicular hyperplasia. However, there was evidence of cTfh cells with decreased helper capacity and of limited B-cell receptor diversification post-ART. In conclusion, we found early signs of immune reconstitution, evidenced by a surge in LN germinal center cells, albeit limited in functionality, in HIV+ patients who initiate ART late in disease.

Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV.

BackgroundCervical cancer - caused by persistent High Risk Human Papilloma Virus (HR HPV) infections - is the second most common cancer affecting women globally. HIV infection increases the risk for HPV persistence, associated disease progression and malignant cell transformation. We therefore hypothesized that this risk increase is directly linked to HIV infection associated dysfunction or depletion of HPV-oncoprotein-specific T-cell responses.MethodsThe 2H study specifically included HIV+ and HIV- women with and without cervical lesions and cancer to analyze HPV oncogene-specific T cell responses in relation to HPV infection, cervical lesion status and HIV status. Oncoprotein E6 and E7 specific T-cell responses were quantified for the most relevant types HPV16, 18 and 45 and control antigens (CMV-pp65) and M.tb-PPD in 373 women, using fresh peripheral blood mononuclear cells in an IFN-γ release ELISpot assay.ResultsOverall, systemic E6- and E7-oncoprotein-specific T-cell responses were infrequent and of low magnitude, when compared to CMV-pp65 and M.tb-PPD (p < 0.001 for all HR HPV types). Within HIV negative women infected with either HPV16, 18 or 45, HPV16 infected women had lowest frequency of autologous-type-E6/E7-specific T-cell responses (33%, 16/49), as compared to HPV18 (46% (6/13), p = 0.516) and HPV45 (69% (9/13), p = 0.026) infected women. Prevalent HPV18 and 45, but not HPV16 infections were linked to detectable oncoprotein-specific T-cell responses, and for these infections, HIV infection significantly diminished T-cell responses targeting the autologous infecting genotype. Within women living with HIV, low CD4 T-cell counts, detectable HIV viremia as well as cancerous and precancerous lesions were significantly associated with depletion of HPV oncoprotein-specific T-cell responses.DiscussionDepletion of HPV-oncoprotein-specific T-cell responses likely contributes to the increased risk for HR HPV persistence and associated cancerogenesis in women living with HIV. The low inherent immunogenicity of HPV16 oncoproteins may contribute to the exceptional potential for cancerogenesis associated with HPV16 infections.

Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40–50 years] and the median CD4 T-cell count was 183 cells/μl (IQR = 96–289 cells/μl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%–10%) and severity rate (up to 20%–40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/μl) and AIDS (median CD4 = 97 cells/μl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.