HIV Individuals Research Articles

Human Immunodeficiency Virus–Related Infection in the Hand

Abstract Chronic HIV infection is increasingly common in clinical practice, and it is necessary for clinicians to have an understanding of specific infections and know how to treat them in this patient cohort. Delayed or incomplete treatment of infection in the hand may cause irreversible stiffness and loss of function. A literature review was conducted using the databases MEDLINE, Embase, EmCare, and CINAHL. Nineteen full-text articles were used to assimilate current evidence on the nature and implications of hand and upper extremity infection in HIV individuals. The HIV patients commonly require multiple surgical episodes to establish control of infection, prolonged hospital stay, and prolonged antimicrobial therapy to establish cure. Prompt referral to the hand surgery team is vital in HIV patients with hand infections to avoid long-lasting sequelae.

Relationships among Substance Use, Sociodemographics, Pre-Exposure Prophylaxis (PrEP) Awareness and Related Attitudes among Young Adult Men Who Have Sex with Men

Introduction: Men who have sex with men (MSM) account for two-thirds of new HIV diagnoses. Pre-exposure prophylaxis (PrEP), a highly efficacious HIV preventive medication, is underutilized. Identifying correlates of PrEP awareness and attitudes may help increase PrEP use. Thus, we evaluated (1) PrEP awareness; (2) differences in awareness related to substance use and sociodemographics; (3) initial PrEP information sources; and (4) possible associations between information sources and PrEP-related attitudes. Methods: Young adult (ages 18–30) HIV-negative MSM from Southern U.S. undertook a web survey including questions about substance use, sexual behaviors, perceived HIV risk, and PrEP. Participants were recruited using in-person and online approaches between January 2018–January 2020. Results: Of 506 participants, 89% were aware of PrEP. Participants with high alcohol consumption and greater perceived HIV risk had higher odds of PrEP unawareness with a trend for minority race/ethnicity. PrEP-aware participants reported high overall perceived safety, confidence in PrEP’s efficacy, and low perceived difficulties with adherence though those with higher perceived HIV risk and individuals who used tobacco had less favorable attitudes. Most participants first heard about PrEP from the internet. There were no statistically significant differences in PrEP-related attitudes across initial information sources. Discussion: Associations between substance use and racial/ethnic minority status and lack of PrEP awareness suggest priority subgroups for educational campaigns. Future campaigns may tailor outreach materials to the respective audience (e.g., Spanish materials for Hispanic people) and disseminate where individuals who use substances may be more likely to see them (e.g., liquor and convenience stores). Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2022.2040030.

Factors associated to neurocognitive impairment in older adults living with HIV

ObjectiveThe HIV infection is a chronic disease that causes neurocognitive impairment (NI) and has been related with early development of frailty. We aimed to study the main risk factors for neurocognitive disorders and frailty in HIV older adults.Materials and methodsCross-sectional study with 40 HIV individuals older than 65 years under antiretroviral therapy in Hospital del Mar (Barcelona) recruited between November 2019 and October 2020. Data has been obtained through clinical scores and a blood sample to evaluate NI and frailty and has been analyzed with non-parametric tests and a multivariate logistic regression model.ResultsAmong the 40 patients admitted for the study, 14 (35%) had positive screening for NI. We found that HIV individuals with nadir CD4+ T-cell count lower than 350 cells/mm3 had 39.7 more risk for NI (95% CI 2.49–632.10; p = 0.009). Those with a lower education level had 22.78 more risk for neurocognitive disorders (95% CI 2.13–242.71; p = 0.01) and suffering any comorbidity with a punctuation ≥ 1 in the Charlson Comorbidity index had an increased risk of 18.26 of developing NI and frailty (95% CI 1.30–256.33; p = 0.031), among them diabetes was significantly more frequent in NI.ConclusionWe observed that the main risk factors for a positive NI screening in HIV older adults were low education level, a nadir CD4+ T-cell count < 350 cells/mm3 and the presence of any comorbidity, highlighting diabetes among them.

Parietal intrahemispheric source connectivity of resting-state electroencephalographic alpha rhythms is abnormal in Naïve HIV patients

Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4 Hz) and alpha (8–12 Hz) rhythms in treatment-Naïve HIV (Naïve HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder.The present EEG database regarded 128 Naïve HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals.Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naïve HIV than in the control group. Furthermore, those abnormalities were greater in the Naïve HIV subgroup with executive and visuospatial deficits than the Naïve HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75–0.88) in the discrimination between the Naïve HIV individuals with executive and visuospatial deficits vs. Naïve HIV individuals with normal cognition and control individuals.In quiet wakefulness, Naïve HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal “hub” oscillating at the alpha frequency in quiet wakefulness as a brain network disorder.

Impact of human immunodeficiency virus status on laryngeal cancer survival and locoregional control.

ObjectivesTo compare long‐term outcomes of laryngeal cancer (LC) in people living with HIV (PLWH) versus uninfected individuals and determine how clinical and viral factors—such as demographics, cancer stage, HIV viral load, and CD4 nadir—contribute to these outcomes.MethodsThis was a retrospective case–control study of 749 patients seen for LC at a single tertiary care center between 2003 and 2017. Of these, 22 had HIV at the time of LC diagnosis, and they were matched in a 1:4 ratio to uninfected controls based on sex, presence of smoking history, and age at cancer diagnosis. Kaplan–Meier survival curves and Cox proportional hazards models were constructed to identify overall and disease‐free survival differences based on HIV status, as well as other clinical and viral factors.ResultsCompared to all uninfected individuals, PLWH were diagnosed with LC approximately 6 years younger (p = .013). 1‐, 2‐, and 5‐year overall survival for PLWH were 86.4% (63.4%–95.4%), 77.3% (53.7%–89.9%), and 65.8% (40.8%–82.2%), respectively following LC diagnosis, and HIV was not significantly associated with overall (HR = 3.34 [0.59–18.79]) or disease‐free survival (HR = 2.12 [0.71–6.36]). The incidence rate of locoregional recurrence among PLWH was 541 compared to 371 per 10,000 person‐years in controls, which were not significantly different (p = .420). Furthermore, among PLWH, peak viral load and CD4 nadir were not associated with overall or disease‐free survival.ConclusionWhile previous work has shown that HIV is associated with elevated risk of LC, survival did not differ significantly between PLWH and uninfected individuals in this study.Level of evidence3.

Prevalence of occult hepatitis B among HIV-positive individuals in Africa: A systematic review and meta-analysis.

The prevalence of hepatitis B virus among HIV-seropositive individuals is believed to be high, and yet the disease remains neglected in many areas of the continent. Little is known about occult hepatitis in HIV individuals. This review assessed occult hepatitis B infection and its prevalence in the different regions of the African continent. It also determines its prevalence in the HIV population which is endemic in the region. Studies were searched from the Cochrane, google scholar, PubMed/Medline, and African Journals online. Authors included cross-sectional studies, case controls, and cohorts, from 2010 to January 2021, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Participants, Interventions, Comparisons, Outcomes, and Study design frameworks to develop the search strategy. All studies had participants who were HIV-positive, covering different regions of the continent. Risk ratio was used to measure effect size, and Stata 14 software was used for analysis. Eleven studies met the eligibility criteria, with 2567 participants. Overall prevalence of occult hepatitis B was 11.2%. Regional prevalence was 26.5% for the south, 11% for the north, 9.1% for the east, and 8.5% for the western region. Approximately 10% of HIV-seropositive individuals were co-infected with occult hepatitis B virus. Regionally, the prevalence was highest in the southern region and lowest in the west. The prevalence of occult HBV infection was compared between the southern region and the other regions. It was higher in the south compared to the east (risk ratio = 0.87, 95% confidence interval (0.83–0.91)). It was also higher in the south compared to the north (risk ratio = 0.82, 95% confidence interval (0.79–0.85)), and it was also higher in the south compared to the west (risk ratio = 0.85, 95% confidence interval (0.82–0.87)). Public health measures and interventions are required to raise awareness, increase prevention, and reduce spread of the disease. More evidence-based studies need to be carried out.

HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization.

Gender-specific consequences after HCV eradication are unexplored. MicroRNAs (miRNAs) play a crucial role in the immune response against viral infections. However, few have highlighted miRNA role in sex-biased disease or therapy response. We aim to assess gender differences reflected in the miRNA expression of HIV/HCV-coinfected patients who achieve sustained virological response (SVR) with direct acting antivirals (DAAs). We conducted a prospective study of miRNA expression in PBMCs from 28 chronic HIV/HCV-coinfected patients (HIV/HCV) at baseline and after achieving SVR with DAAs. Sixteen HIV-monoinfected patients (HIV) and 36 healthy controls (HC) were used as controls. Identification of significant differentially expressed (SDE) miRNAs was performed with generalized linear model and mixed GLMs. We also explored putative dysregulated biological pathways. At baseline, the HIV/HCV patients showed differences in the miRNA profile concerning the HIV group (165 and 102 SDE miRNAs for males and females, respectively). Gender-stratified analysis of HIV/HCV group at baseline versus at SVR achievement showed higher differences in males (80 SDE miRNAs) than in females (55 SDE miRNAs). After SVR, HIV/HCV group showed similar values to HIV individuals, especially in females (1 SDE miRNA). However, ten miRNAs in males remained dysregulated, which were mainly involved in cancer, fatty acid, and inflammatory pathways. Taken together, our results show gender-biased dysregulation in the miRNA expression profile of PBMCs after HCV eradication with DAAs. These differences were normalized in females, while miRNA profile and their target-related pathways in males lack of normalization, which may be related to a high-risk of developing liver-related complications.

FEARS AND CHALLENGES IN PARENTING WITH HIV STATUS AMONG CONCORDANT COUPLES IN PAKISTAN

HIV is known as one of the most life-threatening illnesses of the contemporary era and 240,000 individuals have been estimated to live with HIV in Pakistan. The current research paper intended to find out the child-bearing and rearing concerns among HIV concordant couples. The present research has inspired a four phase model of HIV by Tasker, 1992. The researcher used a phenomenological design of qualitative research with an in-depth interview technique. We have conducted interviews with 08 HIV concordant couples by using an interview guide. Field data was analyzed through NVIVO 11 and the thematic analysis technique was used to draw the themes from field data. The four key themes of the research paper were discussed in the results and discussion section. The researchers have used only four themes mentioned as, childbearing anxieties among couples, child-rearing and family maintenance, fears for parental disclosure of HIV status to children, stigmatization &amp; discrimination in medical treatment in the health care system. Furthermore, HIV individuals need familial, social, and governmental support to fight against HIV and give HIV-free generation to Pakistan. Keywords: HIV concordant couples, childbearing, child-rearing, family maintenance, fear of disclosure, stigmatization

Bifurcation and Stabillity Analysis of HIV Transmission Model with Optimal Control

A mathematical model of HIV transmission is built and studied in this paper. The system’s equilibrium is calculated. A next-generation matrix is used to calculate the reproduction number. The novel method is used to examine the developed model’s bifurcation and equilibrium stability. The stability analysis result shows that the disease-free equilibrium is locally asymptotically stable if 0 &lt; R 0 &lt; 1 but unstable if R 0 &gt; 1 . However, the endemic equilibrium is locally and globally asymptotically stable if R 0 &gt; 1 and unstable otherwise. The sensitivity analysis shows that the most sensitive parameter that contributes to increasing of the reproduction number is the transmission rate β 2 of HIV transmission from HIV individuals to susceptible individuals and the parameter that contributes to the decreasing of the reproduction number is identified as progression rate η of HIV-infected individuals to AIDS individuals. Furthermore, it is observed that as we change η from 0.1 to 1 , the reproduction number value decreases from 1.205 to 1.189, where the constant value of β 2 = 0.1 . On the other hand, as we change the value of β 2 from 0.1 to 1 , the value of the reproduction number increases from 0.205 to 1.347, where the constant value of η = 0.1 . Further, the developed model is extended to the optimal control model of HIV/AIDS transmission, and the cost-effectiveness of the control strategy is analyzed. Pontraygin’s Maximum Principle (PMP) is applied in the construction of the Hamiltonian function. Moreover, the optimal system is solved using forward and backward Runge–Kutta fourth-order methods. The numerical simulation depicts the number of newly infected HIV individuals and the number of individuals at the AIDS stage reduced as a result of taking control measures. The cost-effectiveness study demonstrates that when combined and used, the preventative and treatment control measures are effective. MATLAB is used to run numerical simulations.

A Link Between Methylglyoxal and Heart Failure During HIV-1 Infection.

Early-onset heart failure (HF) continues to be a major cause of morbidity and mortality in people living with human immunodeficiency virus type one (HIV-1) infection (PLWH), yet the molecular causes for this remain poorly understood. Herein NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ humanized mice (Hu-mice), plasma from PLWH, and autopsied cardiac tissues from deceased HIV seropositive individuals were used to assess if there is a link between the glycolysis byproduct methylglyoxal (MG) and HF in the setting of HIV-1 infection. At five weeks post HIV infection, Hu-mice developed grade III-IV diastolic dysfunction (DD) with an associated two-fold increase in plasma MG. At sixteen-seventeen weeks post infection, cardiac ejection fraction and fractional shortening also declined by 26 and 35%, and plasma MG increased to four-fold higher than uninfected controls. Histopathological and biochemical analyses of cardiac tissues from Hu-mice 17 weeks post-infection affirmed MG increase with a concomitant decrease in expression of the MG-degrading enzyme glyoxalase-1 (Glo1). The endothelial cell marker CD31 was found to be lower, and coronary microvascular leakage and myocardial fibrosis were prominent. Increasing expression of Glo1 in Hu-mice five weeks post-infection using a single dose of an engineered AAV2/9 (1.7 × 1012 virion particles/kg), attenuated the increases in plasma and cardiac MG levels. Increasing Glo1 also blunted microvascular leakage, fibrosis, and HF seen at sixteen weeks post-infection, without changes in plasma viral loads. In plasma from virally suppressed PLWH, MG was also 3.7-fold higher. In autopsied cardiac tissues from seropositive, HIV individuals with low viral log, MG was 4.2-fold higher and Glo1 was 50% lower compared to uninfected controls. These data show for the first time a causal link between accumulation of MG and HF in the setting of HIV infection.

Current status of hepatitis C virus among people living with human immunodeficiency virus in Egypt.

Human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infection is increasing due to their similar routes of transmission. Co-infection poses a big challenge. Information on the prevalence of HCV infection in Egyptian HIV individuals is scarce. A cross-sectional study was conducted on 1004 HIV individuals who were recruited from July 2018 to March 2019. Blood samples obtained from HIV individuals were subsequently screened for HCV antibodies using the Murex anti-HCV (version 4) enzyme-linked immunosorbent assay test. HCV RNA was performed only on anti-HCV antibody-positive samples. Logistic regression was used to identify factors associated with HCV seroprevalence using SPSS (IBM, Armonk, NY, USA). Among 1004 participants, 349 exhibited a positive result for anti-HCV antibodies (34.8% [95% confidence interval 31.81 to 37.8]). The most commonly self-reported risk factor of HIV infection by the co-infected participants was intravenous drug use (IDU) (303/349 [86.8%]). In multinomial analysis, risk factors identified as statistically associated with HCV seroprevalence include IDU, history of surgical operations and dental procedures and HIV viral load (p<0.001, 0.032, <0.001 and 0.006, respectively). Under combination antiretroviral therapy (cART), the proportion of HIV mono-infected individuals with an undetectable HIV viral load was significantly higher than those with co-infection (p<0.0007). We also found that HIV-HCV co-infected participants exhibited significantly higher CD4+ cell counts than those with HIV mono-infection (p=0.04). The prevalence of HIV-HCV co-infection is higher in Egypt compared with other countries in Africa. It is essential to screen all HIV-infected patients for HCV infection for early identification, counselling and initiation of anti-HCV treatment.

Hepatoprotective and immune-reconstitution potentials of carrot-ginger blend among HIV-infected patients taking antiretroviral therapy in Kaduna, Nigeria

Hepatotoxicity, micronutrients insufficiency and cost of micronutrient supplements are challenges faced by HIV infected patients on antiretroviral therapy (ART). This study investigated the effect of natural plant micronutrients (vitamins A, C, and E, selenium and Zinc supplements from carrot-ginger (75:25) blend on liver enzymes: Alanine transaminase (ALT) and Aspartate transaminase (AST), CD4 + T lymphocytes and body mass index (BMI) of HIV-infected-patients taking ART. Ninety HIV-infected-patients attending Special Treatment Clinic, Kafanchan General Hospital, Kaduna State, Nigeria, were randomized into three groups of thirty patients each: Group 1 is control group and received ART alone, Group 2 is standard group and received ART with ready to use commercial micronutrient supplement (SelACER supplement) while Group 3 is supplement group and received ART + Carrot-Ginger blend for 90 days. Serum Alanine, Aspartate transaminase, CD4 + T lymphocytes and BMI were assessed using standard methods at baseline (day 0), 30 days, 60 days and 90 days. The results indicated that patients on CarrotGinger blend and SelACER micronutrients supplements show significant (p&lt;0.05) reduction in ALT and AST level. However, there was no significant (p&gt;0.05) difference in patients treated with ART alone when compared to their baseline values. The results indicated that patients on carrot-ginger blend and SelACE® supplements had significant (p&lt;0.05) increase in BMI, CD4+ T-cell counts, serum vitamins A, C, E, selenium and zinc from day zero. There was no significant (p&gt;0.05) difference in patients treated with ART alone compared to their baseline values. In addition, patients on SelACE® supplement revealed significant (p&lt;0.05) difference in their mean BMI, CD4+ T-cell counts, serum vitamins A, C, E, Selenium and Zinc compared to patients on carrot-ginger blend after 90 days. The results also indicated a strong positive association (r=0.97) between serum ALT and AST activity and between CD4+ T cell counts and body mass index (r=0.77) after 90 days. Therefore, micronutrients supplementation of HIV patients during ART treatment with Carrot-Ginger blend could also be a beneficial adjunct to ART due to its potentials to reconstitute the immune system and protect the liver in HIV individuals on ART.

Associations of alcohol use, HIV infection, and age with brain white matter microstructure.

Heavy drinking and HIV infection are independently associated with damage to the brain's white matter. The purpose of the current study was to investigate whether current alcohol consumption, HIV infection, and associated characteristics were associated with indices of white matter microstructural integrity in people living with HIV (PLWH) and seronegative individuals. PLWH and controls were categorized as non-drinkers, moderate drinkers, or heavy drinkers. White matter fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were assessed using diffusion tensor imaging (DTI). Voxelwise analyses using tract-based spatial statistics were followed by confirmatory region-of-interest (ROI) analyses. Data from 108 participants (62 PLWH, 46 controls) were suitable for analysis. Average age (± standard deviation) was 45.2 ± 11.1years, and the sample was 42% female. The majority of PLWH were on antiretroviral therapy (94%) and were virally suppressed (69%). PLWH and controls did not differ on substance use. Heavier alcohol intake was significantly associated with lower FA and higher RD in widespread areas. Heavy drinking was significantly associated with higher AD in a small region. The main effect of HIV was not significant, but a significant HIV-age interaction was observed. Follow-up ROI analyses confirmed the main effect of drinking group and HIV-age interaction. In conclusion, results are consistent with a dose-dependent association of alcohol use with lower white matter microstructural coherence. Concordance between FA and RD findings suggests dysmyelination as a mechanism. Findings underscore the need to address unhealthy alcohol use in HIV-positive and seronegative individuals, the consequences of which may be exacerbated by aging.

Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial.

We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma.

Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency

BackgroundA critical step in the HIV-1 replication cycle is the assembly of Gag proteins to form virions at the plasma membrane. Virion assembly and maturation are facilitated by the cellular polyanion inositol hexaphosphate (IP6), which is proposed to stabilize both the immature Gag lattice and the mature capsid lattice by binding to rings of primary amines at the center of Gag or capsid protein (CA) hexamers. The amino acids comprising these rings are critical for proper virion formation and their substitution results in assembly deficits or impaired infectiousness. To better understand the nature of the deficits that accompany IP6 binding deficiency, we passaged HIV-1 mutants that had substitutions in IP6 coordinating residues to select for compensatory mutations.ResultsWe found a mutation, a threonine to isoleucine substitution at position 371 (T371I) in Gag, that restored replication competence to an IP6-binding-deficient HIV-1 mutant. Notably, unlike wild-type HIV-1, the assembly and infectiousness of resulting virus was not impaired when IP6 biosynthetic enzymes were genetically ablated. Surprisingly, we also found that the maturation inhibitor Bevirimat (BVM) could restore the assembly and replication of an IP6-binding deficient mutant. Moreover, using BVM-dependent mutants we were able to image BVM-induced assembly of individual HIV-1 particles assembly in living cells.ConclusionsOverall these results suggest that IP6-Gag and Gag-Gag contacts are finely tuned to generate a Gag lattice of optimal stability, and that under certain conditions BVM can rescue IP6 deficiency. Additionally, our work identifies an inducible virion assembly system that can be utilized to visualize HIV-1 assembly events using live cell microscopy.

Metabolic phenotype of B cells from young and elderly HIV individuals

BackgroundHIV infection induces inflammaging and chronic immune activation (IA), which are negatively associated with protective humoral immunity. Similar to HIV, aging is also associated with increased inflammaging and IA. The metabolic requirements of B cell responses in HIV infected (HIV+) individuals are not known, although metabolic abnormalities have been reported in these individuals. How these metabolic abnormalities are exacerbated by aging is also not known.MethodsB cells were isolated by magnetic sorting from the blood of young and elderly HIV + individuals, as well as from the blood of age-matched healthy controls. We evaluated the composition of the B cell pool by flow cytometry, the expression of RNA for pro-inflammatory and metabolic markers by qPCR and their metabolic status using a Seahorse XFp extracellular flux analyzer.ResultsIn this study we have evaluated for the first time the metabolic phenotype of B cells from young and elderly HIV + individuals as compared to those obtained from age-matched healthy controls. Results show that the B cell pool of HIV + individuals is enriched in pro-inflammatory B cell subsets, expresses higher levels of RNA for pro-inflammatory markers and is hyper-metabolic, as compared to healthy controls, and more in elderly versus young HIV + individuals, suggesting that this higher metabolic phenotype of B cells is needed to support B cell IA. We have identified the subset of Double Negative (DN) B cells as the subset mainly responsible for this hyper-inflammatory and hyper-metabolic profile.ConclusionsOur results identify a relationship between intrinsic B cell inflammation and metabolism in HIV + individuals and suggest that metabolic pathways in B cells from HIV + individuals may be targeted to reduce inflammaging and IA and improve B cell function and antibody responses.

Antiretroviral Drug Transporters and Metabolic Enzymes in Circulating Monocytes and Monocyte-Derived Macrophages of ART-Treated People Living With HIV and HIV-Uninfected Individuals.

Membrane-associated drug transport proteins and drug metabolic enzymes could regulate intracellular antiretroviral (ARV) drug concentrations in HIV-1 target cells such as myeloid cells. We investigated the expression of these transporters and enzymes in monocyte subsets and monocyte-derived macrophages (MDMs) isolated from peripheral blood mononuclear cells (PBMCs) of HIV-uninfected individuals (HIV-negative) and people living with HIV receiving viral suppressive antiretroviral therapy (ART; HIV+ART) and examined plasma and intracellular ARV concentrations. Monocytes were isolated from PBMCs of 12 HIV-negative and 12 HIV+ART donors and differentiated into MDMs. The mRNA and protein expression of drug transporters and metabolic enzymes were analyzed by quantitative real-time polymerase chain reaction and flow cytometry, respectively. ARV drug concentrations were quantified in plasma, PBMCs, monocytes, and MDMs by LC-MS/MS. The mRNA expression of relevant ARV transporters or metabolic enzymes, ABCB1/P-gp, ABCG2/BCRP, ABCC1/MRP1, ABCC4/MRP4, SLC22A1/OCT1, SLC29A2/ENT2, CYP2B6, CYP2D6, and UGT1A1, was demonstrated in monocytes and MDMs of 2 to 4 HIV-negative donors. P-gp, BCRP, and MRP1 proteins were differentially expressed in classical, intermediate, and nonclassical monocytes and MDMs of both HIV+ART and HIV-negative donors. Intracellular concentrations of ARVs known to be substrates of these transporters and metabolic enzymes were detected in monocytes of HIV+ART donors but were undetectable in MDMs. In this study, we demonstrated the expression of drug transporters and metabolic enzymes in monocytes and MDMs of HIV-negative and HIV+ART individuals, which could potentially limit intracellular concentrations of ARVs and contribute to residual HIV replication. Further work is needed to assess the role of these transporters in the penetration of ARVs in tissue macrophages.

Anatomic Distribution of Intravenously Injected IgG Takes Approximately 1 Week to Achieve Stratum Corneum Saturation in Vaginal Tissues.

i.v. injected Abs have demonstrated protection against simian HIV infection in rhesus macaques, paving the way for the Antibody Mediated Prevention trial in which at-risk individuals for HIV received an i.v. infusion of the HIV broadly neutralizing Ab VRC01. However, the time needed for these Abs to fully distribute and elicit protection at mucosal sites is still unknown. In this study, we interrogate how long it takes for Abs to achieve peak anatomical levels at the vaginal surface following i.v. injection. Fluorescently labeled VRC01 and/or Gamunex-C were i.v. injected into 24 female rhesus macaques (Macaca mulatta) with vaginal tissues and plasma acquired up to 2 wk postinjection. We found that Ab delivery to the vaginal mucosa occurs in two phases. The first phase involves delivery to the submucosa, occurring within 24 h and persisting beyond 1 wk. The second phase is the delivery through the stratified squamous epithelium, needing ∼1 wk to saturate the stratum corneum. This study has important implications for the efficacy of immunoprophylaxis targeting pathogens at the mucosa.

Epigenetic Mechanisms of HIV-1 Persistence.

Eradicating HIV-1 in infected individuals will not be possible without addressing the persistence of the virus in its multiple reservoirs. In this context, the molecular characterization of HIV-1 persistence is key for the development of rationalized therapeutic interventions. HIV-1 gene expression relies on the redundant and cooperative recruitment of cellular epigenetic machineries to cis-regulatory proviral regions. Furthermore, the complex repertoire of HIV-1 repression mechanisms varies depending on the nature of the viral reservoir, although, so far, few studies have addressed the specific regulatory mechanisms of HIV-1 persistence in other reservoirs than the well-studied latently infected CD4+ T cells. Here, we present an exhaustive and updated picture of the heterochromatinization of the HIV-1 promoter in its different reservoirs. We highlight the complexity, heterogeneity and dynamics of the epigenetic mechanisms of HIV-1 persistence, while discussing the importance of further understanding HIV-1 gene regulation for the rational design of novel HIV-1 cure strategies.

Diverse Mucosal-Associated Invariant TCR Usage in HIV Infection.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that specifically target bacterial metabolites but are also identified as innate-like sensors of viral infection. Individuals with chronic HIV-1 infection have lower numbers of circulating MAIT cells compared with healthy individuals, yet the features of the MAIT TCR repertoire are not well known. We isolated and stimulated human PBMCs from healthy non-HIV-infected donors (HD), HIV-infected progressors on antiretroviral therapy, and HIV-infected elite controllers (EC). We sorted MAIT cells using flow cytometry and used a high-throughput sequencing method with bar coding to link the expression of TCRα, TCRβ, and functional genes of interest at the single-cell level. We show differential patterns of MAIT TCR usage among the groups. We observed expansions of certain dominant MAIT clones in HIV-infected individuals upon Escherichia coli stimulation, which was not observed in clones of HD. We also found different patterns of CDR3 amino acid distributions among the three groups. Furthermore, we found blunted expression of phenotypic genes in HIV individuals; most notably, HD mounted a robust IFNG response to stimulation, whereas both HIV-infected progressors and EC did not. In conclusion, our study describes the diverse MAIT TCR repertoire of persons with chronic HIV-1 infection and suggest that MAIT clones of HIV-infected persons may be primed for expansion more than that of noninfected persons. Further studies are needed to examine the functional significance of unique MAIT cell TCR usage in EC.