Human Immunodeficiency Virus Research Articles

Structures of the Foamy virus fusion protein reveal an unexpected link with the F protein of paramyxo- and pneumoviruses.

Foamy viruses (FVs) constitute a subfamily of retroviruses. Their envelope (Env) glycoprotein drives the merger of viral and cellular membranes during entry into cells. The only available structures of retroviral Envs are those from human and simian immunodeficiency viruses from the subfamily of orthoretroviruses, which are only distantly related to the FVs. We report the cryo-electron microscopy structures of the FV Env ectodomain in the pre- and post-fusion states, which unexpectedly demonstrate structural similarity with the fusion protein (F) of paramyxo- and pneumoviruses, implying an evolutionary link between the viral fusogens. We describe the structural features that are unique to the FV Env and propose a mechanistic model for its conformational change, highlighting how the interplay of its structural elements could drive membrane fusion and viral entry. The structural knowledge on the FV Env now provides a framework for functional investigations, which can benefit the design of FV Env variants with improved features for use as gene therapy vectors.

HIV co-infection increases the risk of post-tuberculosis mortality among persons who initiated treatment for drug-resistant tuberculosis

Little is known regarding the relationship between common comorbidities in persons with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) and post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant or multi/extensively drug-resistant (RR or M/XDR) TB reported to the country of Georgia’s TB surveillance during 2009–2017. Exposures included HIV serologic status, diabetes, and HCV status. Our outcome was all-cause post-TB mortality determined by cross-validating vital status with Georgia’s death registry through November 2019. We estimated adjusted hazard rate ratios (aHR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without comorbidities using cause-specific hazard regressions. Among 1032 eligible participants, 34 (3.3%) died during treatment and 87 (8.7%) died post-TB treatment. The median time to post-TB death was 21 months (interquartile range 7–39) after TB treatment. After adjusting for confounders, the hazard rates of post-TB mortality were higher among participants with HIV co-infection (aHR = 3.74, 95%CI 1.77–7.91) compared to those without HIV co-infection. In our cohort, post-TB mortality occurred most commonly in the first 3 years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates.

Improving Predictive Efficacy for Drug Resistance in Novel HIV-1 Protease Inhibitors through Transfer Learning Mechanisms.

The human immunodeficiency virus presents a significant global health challenge due to its rapid mutation and the development of resistance mechanisms against antiretroviral drugs. Recent studies demonstrate the impressive performance of machine learning (ML) and deep learning (DL) models in predicting the drug resistance profile of specific FDA-approved inhibitors. However, generalizing ML and DL models to learn not only from isolates but also from inhibitor representations remains challenging for HIV-1 infection. We propose a novel drug-isolate-fold change (DIF) model framework that aims to predict drug resistance score directly from the protein sequence and inhibitor representation. Various ML and DL models, inhibitor representations, and protein representations were analyzed through realistic validation mechanisms. To enhance the molecular learning capacity of DIF models, we employ a transfer learning approach by pretraining a graph neural network (GNN) model for activity prediction on a data set of 4855 HIV-1 protease inhibitors (PIs). By performing various realistic validation strategies on internal and external genotype-phenotype data sets, we statistically show that the learned representations of inhibitors improve the predictive ability of DIF-based ML and DL models. We achieved an accuracy of 0.802, AUROC of 0.874, and r of 0.727 for the unseen external PIs. By comparing the DIF-based models with a null model consisting of isolate-fold change (IF) architecture, it is observed that the DIF models significantly benefit from molecular representations. Combined results from various testing strategies and statistical tests confirm the effectiveness of DIF models in testing novel PIs for drug resistance in the presence of an isolate.

Reduced mother-to-child transmission rates of HIV between 2017 and 2020 in Kenya. What changed?

Background: In 205 health facilities, mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) rates were reduced from 7.4% to 2.1% between 2017 and 2020, respectively.Aim: To determine characteristics that potentially correlate to the change in MTCT rates between two time points.Setting: Study was conducted in Kenya, semi-urban and rural areas.Methods: A retrospective, cross-sectional, exploratory analysis of programme implementation at two points in time (2017 and 2020). Between 2017 and 2020, we compared over 170 mother–infant pairs where MTCT occurred to over 6000 mother–infant pairs where MTCT did not occur through the following factors: (1) location of health facilities, (2) mother and infant characteristics, (3) access to antiretroviral therapy (ART), and (4) viral load suppression. Bivariate and multivariable logistic regression models were used to identify factors associated with MTCT.Results: Factors significantly associated with reduced MTCT rates were time points, mother’s age, infant age at first test, proportions of mothers receiving ART, and maternal viral load. When restricting the analysis to the sub-counties contributing data at both time points, the results were similar; however, counties’ location became significant in the updated model, as did the interaction term for mother and infant receipt of antiretrovirals (odds ratio [OR]: 0.228; p = 0.04).Conclusion: What changed between 2017 and 2020 is a higher proportion of pregnant women living with HIV received ART. Also, unlike in 2017, in 2020, tenofovir disoproxil fumarate was the backbone of the ART regimen for the prevention of MTCT.Contribution: The findings can potentially inform efforts on elimination of mother-to-child transmission of HIV.

Prevalence, incidence, and residual risk for human immunodeficiency virus among blood donors from 2003 to 2022 in Guangzhou, China.

China's significant population affected by HIV poses a substantial threat to blood transfusion safety. Despite advancements in blood testing techniques, a residual risk of HIV transmission persists. Accurately assessing HIV epidemic and the residual risk is vital for monitoring blood supply safety and evaluating the effectiveness of new screening tests. We conducted a retrospective analysis of HIV detection results among voluntary blood donors from 2003 to 2022. The study included data on HIV-confirmed positive donors, HIV prevalence, infection risk factors, and an incidence-window period mathematical model to estimate the residual risk of HIV. Between 2003 and 2022, HIV prevalence among blood donors in Guangzhou showed a peak-shaped trend, initially increasing before declining. The overall HIV prevalence was 18.9 infections per 100,000 donations. Male donors had a significantly higher prevalence compared with female donors. Donors aged 26-35 years had the highest prevalence. Ethnic minority donors had a higher prevalence compared with Han donors. Repeat donors had a lower prevalence compared with first-time donors. Donors from other provinces had a higher prevalence compared with local donors. During the period of 2003 to 2022, the residual risk of HIV in Guangzhou steadily decreased, reaching a notable 1 in 526,316 donations in the past two years. The HIV epidemic among blood donors in Guangzhou remains severe, but the residual risk of HIV is decreasing. Novel detection methods have proven advantageous in reducing this residual risk. Implementing additional effective measures is imperative to ensure blood safety and curb the spread of HIV.

Empirically establishing drug exposure records directly from untargeted metabolomics data.

Despite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies on exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data independent of clinical records. Our library facilitates stratification of individuals in clinical studies based on the empirically detected medications, exemplified by drug-dependent microbiota-derived N -acyl lipid changes in a human immunodeficiency virus cohort. The GNPS Drug Library holds potential for broader applications in drug discovery and precision medicine.

Interventions during Early Infection: Opening a Window for an HIV Cure?

Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure has remained elusive. Elimination of latent HIV reservoirs that persist throughout HIV infection is the most challenging barrier to an HIV cure. The progressive HIV infection is marked by the increasing size and diversity of latent HIV reservoirs until an effective immune response is mobilized, which can control but not eliminate HIV infection. The stalemate between HIV replication and the immune response is manifested by the establishment of a viral set point. ART initiation during the early stage limits HIV reservoir development, preserves immune function, improves the quality of life, and may lead to ART-free viral remission in a few people living with HIV (PLWH). However, for the overwhelming majority of PLWH, early ART initiation alone does not cure HIV, and lifelong ART is needed to sustain viral suppression. A critical area of research is focused on determining whether HIV could be functionally cured if additional treatments are provided alongside early ART. Several HIV interventions including Block and Lock, Shock and Kill, broadly neutralizing antibody (bNAb) therapy, adoptive CD8+ T cell therapy, and gene therapy have demonstrated delayed viral rebound and/or viral remission in animal models and/or some PLWH. Whether or not their application during early infection can improve the success of HIV remission is less studied. Herein, we review the current state of clinical and investigative HIV interventions and discuss their potential to improve the likelihood of post-treatment remission if initiated during early infection.

Altered Surrogate Markers of Inflammation in Perinatal HIV-Exposed Children with Caries.

Dental caries is associated with immunologic response, yet its association with hematologic parameters and inflammatory markers is unclear. This study aimed to examine the relationship between some surrogate markers of inflammation and dental caries in the context of perinatal exposure to human immunodeficiency virus (HIV). This cross-sectional study involved 2 groups of children aged 4 to 11 y who were (1) HIV exposed but uninfected (HEU) and (2) HIV unexposed/uninfected (HUU) and recruited from HIV pediatric and child outpatient clinics, respectively, at a tertiary health facility in Nigeria. Medical records were reviewed, and trained dentists conducted oral and dental examinations. Five milliliters of EDTA blood was obtained and used for CD4 and CD8 and complete blood analysis, from which other inflammatory markers such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic inflammatory index (SII), CD4/CD8 ratio were calculated using referenced formulas. In total, 245 (125 HEU and 120 HUU) children with a mean (standard deviation) age of 7 (2) y were included in this study. No differences in caries experience were observed in both groups of children (38 children [16%] were caries affected; 19 [16%] and 19 [15%] from the HEU and HUU groups, respectively). Examining the relationship between studied inflammatory markers and caries showed that leucocyte counts were slightly lower in caries-affected children compared with their caries-free counterparts (P = 0.05). Lower levels of neutrophils (P = 0.04) and higher levels of lymphocytes (P = 0.02) were associated with caries prevalence. Although not significant, NLR, PLR, and SII were lower in caries-affected children. Caries is associated with leucocytes and some of its subsets in both groups of children and independent of perinatal HIV exposure, highlighting the potential of evaluating inflammatory markers in caries prevention, treatment, and research. This study provides evidence that a relationship exists between dental caries, HIV exposure, and inflammation using affordable methods and advocates the inclusion of these markers in caries care in resource-limited settings.

Occurrence and seroprevalence of infectious viral, bacterial, and protozoal diseases among patients attending the Ore General Hospital in southwestern Nigeria

Infectious diseases caused by viruses, bacteria, protozoans, and fungi continue to pose significant challenges globally, with transmission routes including person-to-person contact, animal vectors, and environmental exposure. Despite global efforts to control these diseases, limited studies and resource constraints in Ore, Nigeria, have led to increasing prevalence, highlighting the need for targeted public health interventions. This study aimed to determine the distribution of infectious diseases among patients attending General Hospital Ore, Odigbo, Nigeria. Serum samples from consenting patients were assayed for the presence of malaria parasites, human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), Salmonella infection, Helicobacter pylori infection, high vaginal swab (HVS) results, and urinary tract infections (UTIs). The subjects included 1900 males (38.8%) and 3000 females (61.2%). The overall prevalence rates were as follows: HIV (40%), malaria (35%), typhoid (37.5%), HBsAg (20%), H. pylori (6.3%), HVS (45%), and UTIs (10%). The high rates of infectious diseases observed in this study, compared to rates reported elsewhere, suggest the need to strengthen public health measures and infection prevention strategies in the area. In addition, routine screening for these diseases and early passive or active immunization for vaccine-preventable diseases are essential to further reduce the burden of these infections.

Discovery of new acetamide derivatives of 5-indole-1,3,4-oxadiazol-2-thiol as inhibitors of HIV-1 Tat-mediated viral transcription.

Human immunodeficiency virus-1 (HIV-1) encodes a transcriptional factor called Tat, which is critical for viral transcription. Tat-mediated transcription is highly ordered apart from the cellular manner; therefore, it is considered a target for developing anti-HIV-1 drugs. However, drugs targeting Tat-mediated viral transcription are not yet available. Our high-throughput screen of a compound library employing a dual-reporter assay identified a 1,3,4-oxadiazole scaffold against Tat and HIV-1 infection. Furthermore, a serial structure-activity relation (SAR) study performed with biological assays found 1,3,4-oxadiazole derivatives (9 and 13) containing indole and acetamide that exhibited potent inhibitory effects on HIV-1 infectivity, with half-maximal effective concentrations (EC50) of 0.17 (9) and 0.24 µM (13), respectively. The prominent derivatives specifically interfered with the viral transcriptional step without targeting other infection step(s) and efficiently inhibited the HIV-1 replication cycle in the T cell lines and peripheral blood mononuclear cells infected with HIV-1. Additionally, compared to the wild type, the compounds exhibited similar potency against anti-retroviral drug-resistant HIV-1 strains. In a series of mode-of-action studies, the compounds inhibited the ejection of histone H3 for facilitating viral transcription on the long-terminal repeat (LTR) promoter. Furthermore, SAHA (a histone deacetylase inhibitor) treatment abolished the compound potency, revealing that the compounds can possibly target Tat-regulated epigenetic modulation of LTR to inhibit viral transcription. Overall, our screening identified novel 1,3,4-oxadiazole compounds that inhibited HIV-1 Tat, and subsequent SAR-based optimization led to the derivatives 9 and 13 development that could be a promising scaffold for developing a new class of therapeutic agents for HIV-1 infection.

Barriers and facilitators to primary care for people living with HIV and diabetes in Harare

Background: People living with human immunodeficiency virus (HIV) and comorbid diabetes mellitus (DM) face significant challenges owing to the complex interplay between these chronic conditions and the need for comprehensive and integrated care. Service availability and readiness for primary care are essential for the health of individuals and populations.Aim: This study aimed to explore barriers and facilitators to the provision of care to the patients with HIV and T2DM comorbidity.Setting: The study was conducted at Primary health centres in Harare, Zimbabwe.Methods: A mixed-methods design was applied.Results: An audit of primary care facilities identified that there was adequate infrastructure and equipment for HIV and T2DM diagnosis and treatment. However, there are gaps in the availability of essential medicines and supplies, such as test strips for blood glucose monitoring. The assessment also showed that the centres had a chronic shortage of healthcare providers, including doctors, nurses and counsellors, and there was a need for additional training and support for healthcare providers in the management of HIV and T2DM.Conclusion: The study concludes that the delivery of health services to patients with HIV and T2DM at primary care centres in Harare, Zimbabwe, faces significant challenges. Suggestions included improved resource allocation and multisectoral collaboration to improve the delivery of healthcare services.Contribution: The research contributes insight into disparities between urban and rural primary care facilities in providing services, emphasizing the need for targeted interventions to bridge gaps and enhance care quality.

Childhood trauma, substance use and depressive symptoms in people with HIV during COVID-19

Background: Adverse childhood experiences (ACEs), substance use, depressive symptoms, and HIV outcomes in people living with HIV (PLWHIV) have not been comprehensively investigated within a single study.Aim: The aim of this study was to investigate the prevalence and association of ACEs, substance use, depressive symptoms and human immunodeficiency virus (HIV) outcomes in PLWHIV accessing HIV care during the coronavirus disease 2019 (COVID-19) pandemic.Setting: District hospital HIV clinic in South Africa.Methods: A total of 196 PLWHIV completed a socio-demographic and clinical questionnaire; an adapted World Health Organization (WHO) Alcohol, Smoking and Substance Involvement Screening Test; WHO ACEs International Questionnaire, and Patient Health Questionnaire.Results: The most common ACEs were having one or no parent, parental separation or divorce (n = 131, 66.8%), exposure to collective (n = 57, 29.1%) and community violence (n = 55, 28.1%), with 40.3% (n = 79) experiencing ≥ 3 ACEs. The most commonly used substances were alcohol (n = 34, 17.3%), tobacco (n = 33, 16.8%), and cannabis (n =13, 6.6%). The prevalence of depressive symptoms was 19.4% (n = 38). Linear regression analyses indicated greater alcohol (adj β = 2.84, p 0.01), tobacco (adj β = 3.64, p 0.01) and cannabis use risk scores (adj β = 2.39, p 0.01) were associated with ≥ 3 ACEs. Logistic regression indicated depressive risk (adjusted odds ratio [OR] = 9.39, 95% confidence interval [CI] 4.78–23.51) was associated with ≥ 3 ACEs.Conclusion: A high prevalence of ACEs, substance use and depressive symptoms exists among PLWHIV, along with an association between cumulative ACEs and both substance use and depressive symptoms.Contribution: Enhanced screening and management services are recommended to address this triple burden in PLWHIV.

Mpox in People With Human Immunodeficiency Virus: Predictors of Diagnosis, Outcomes, and Vaccine Effectiveness in a Multisite Cohort.

Since its global reemergence in 2022, monkeypox (mpox) has demonstrated increased incidence and severity among people with human immunodeficiency virus (HIV [PWH]). Predictors of mpox diagnosis, vaccination, and outcomes among PWH are limited. We included PWH with primary care visits after 1 January 2022 at 9 US sites participating in the Centers for AIDS Research Network of Integrated Clinic Systems Network. We identified mpox diagnosed between 1 June 2022 and 31 May 2023, through a combination of polymerase chain reaction result, diagnosis code, and/or tecovirimat receipt. We examined validated clinical diagnoses, laboratory results, vaccine data, and patient reported outcomes. We evaluated relative risks (RR) of mpox diagnosis, hospitalization, tecovirimat treatment, and vaccine receipt. Among 19 777 PWH in care, 413 mpox cases (all male sex at birth) occurred (2.2 cases/100 person-years). Age <40 years, geographic region, Hispanic/Latine ethnicity, lack of antiretroviral therapy, detectable HIV viral load, and recent bacterial sexually transmitted infection predicted mpox diagnosis. PWH with CD4 200-349 cells/mm3 were most likely to be hospitalized (adjusted RR, 3.20; 95% confidence interval: 1.44-7.09) compared to CD4 ≥500, but half as likely as those with CD4 <200 to receive tecovirimat. Overall, smallpox/mpox vaccine effectiveness of ≥1 vaccine was 71% (adjusted RR, 0.29; 95% confidence interval: .14-.47) at preventing mpox, and 86% or better with CD4 ≥350 or HIV viral suppression. Non-Hispanic Black PWH were less likely to be vaccinated than other racial/ethnic identities. PWH not on antiretroviral therapy or with unsuppressed HIV were more likely to be diagnosed with, and hospitalized for, mpox. Mpox/smallpox vaccine effectiveness was high, inclusive of those with low CD4 count and HIV viremia.

Adherence to antiretroviral therapy among HIV patients at a hospital in Tacna, Peru

ObjectiveThis study aims to provide an overview of antiretroviral therapy adherence and its related factors within a hospital in southern Peru. Materials and methodsWe conducted an analytical cross-sectional study spanning from April to October 2022. This study involved a review of medical records and the administration of a survey to individuals living with Human Immunodeficiency Virus. Adherence to antiretroviral treatment was assessed using the CEAT-HIV (Questionnaire for the Evaluation of Antiretroviral Treatment Adherence), and was categorized as high, adequate, insufficient, or low. The statistical analysis included the calculation of crude and adjusted prevalence ratios (PRs). ResultsOur study comprised 300 participants, with a median age of 30 years, predominantly male (78.3 %). Among these individuals, 83 % exhibited low or insufficient adherence to antiretroviral treatment according to the CEAT-VIH scale. Notably, patients with a viral load >50,000 copies/ml scored higher on the CEAT-VIH scale than those with a viral load <400 (adjusted PR: 2.78, 95 % CI: 1.21 to 6.40). Furthermore, a higher level of education and a viral load below 400 copies/ml were associated to higher scores in the treatment compliance dimension of the CEAT-VIH scale. ConclusionEight out of ten evaluated patients exhibited low or insufficient adherence. While lower adherence was correlated with lower education, the connection between viral load and adherence remains inconclusive.

Comparison of At-Home Versus In-Clinic Receipt of Long-Acting Injectable Cabotegravir/Rilpivirine.

The need for frequent travel to a clinic could impair access to injectable antiretroviral therapy for persons living with human immunodeficiency virus type 1 (HIV-1) infection. We hypothesized that allowing persons receiving treatment with long-acting injectable cabotegravir plus rilpivirine (LA CAB/RPV) to receive and store the medication in their own refrigerator prior to in-home administration by a healthcare provider would be as safe and effective as receiving treatment in a clinic. Persons prescribed LA CAB/RPV in the Infectious Diseases clinic at the Medical University of South Carolina were offered enrollment in this non-randomized, observational study between August 2021 and December 2022. After in-clinic receipt of the initial LA CAB/RPV injection, participants chose to receive each subsequent injection over the following 12-months either in clinic or at home. The 33 enrolled participants were primarily Black (64%), male (73%), and had a median age of 46. Three participants stopped LA CAB/RPV and transitioned to oral antiretroviral therapy due to allergy (n = 1), loss of virologic suppression (n = 1), and visit adherence (n = 1) concerns. A comparable number of participants received treatment primarily in clinic (n = 18) relative to at home (n = 15). Injection site pain/soreness was common (52% of injections) but did not differ between groups. There were no differences in safety or efficacy between groups and both groups reported high treatment satisfaction. All participants were virologically suppressed and retained in care at the end of the study. At-home administration of LA CAB/RPV by a healthcare provider was comparably safe, effective, and associated with high participant satisfaction relative to in-clinic administration.

Clinicopathological study of 24 cases of monkeypox virus infection-related rashes

Objective: To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests. Methods: Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope® hybridization and electron microscopy. Results: All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri's bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope® hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions: The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

Examining the relationships between pain symptoms and psychosocial functioning among women living with and at risk for human immunodeficiency virus using a cross-sectional psychological network analysis.

Pain is prevalent among women living with HIV (WLWH); however, research on pain experience among WLWH in the United States is limited. This study used a network analysis to simultaneously examine the relationships between pain experience and psychosocial functioning among WLWH and human immunodeficiency virus (HIV)-negative women. A secondary analysis of public data from the Women's Interagency HIV Study, a U.S. longitudinal cohort study of the experiences of WLWH and women at increased risk for HIV (HIV negative), was completed. Data were from Visit 42 in 2015 and included 451 WLWH and 194 HIV-negative women who endorsed experiencing pain in the week prior to the interview. Similar to the sociodemographic characteristics of WLWH in the United States, the majority of women in the sample were racially and/or ethnically minoritized and of low socioeconomic position. Networks were modeled using measures of pain intensity, pain interference, depression symptoms, anxiety/worry symptoms, meaning in life, and emotional support. Network models for WLWH and HIV-negative women were comparable (ps > .05). Depression symptoms were a central construct (strength = 1.82 and 1.77, respectively) within the networks, and pain interference was associated with psychosocial constructs (ps < .05), while pain intensity was not (ps > .05). Meaning in life and emotional support were not directly associated with pain (ps > .05). Network findings suggest that reducing depression symptoms may result in improved pain experience and broader positive impact for WLWH and for women at increased risk of HIV. This finding is consistent with research with other pain-focused populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Compensatory reactions of B cells in response to chronic HIV-1 Tat exposure.

Patients infected with human immunodeficiency virus-1 (HIV-1) have an increased incidence of B-cell lymphoma, even though HIV-1 does not infect B cells. The development of B-cell lymphomas appears to be related to the action of the HIV-1 transactivator protein (Tat), which is released from HIV-infected cells and penetrates uninfected B cells, affecting host cell gene expression. Upon chronic HIV-1 infection, Tat acts on the cells for a long time, probably allowing the cells to adapt to the presence of the viral protein. The aim of this work was to identify and study the mechanism of adaptation of cells to prolonged (chronic) exposure to HIV-1 Tat. We performed a comparative analysis of cells expressing Tat under the action of either an inducible promoter or a constitutive promoter, allowing us to model acute and chronic Tat effects, respectively. We found that the acute action of Tat leads to the suppression of cell proliferation, probably due to the downregulation of genes associated with replication and protein synthesis. In the case of chronic action of Tat, cell proliferation was restored and the expression of genes associated with the implementation of protective (antiviral) functions of the cell was increased. Analysis using proteasome inhibitors showed that in the case of chronic action, intense Tat proteolysis occurred, which could be the main mechanism of B-cell adaptation. Thus, B cells have a powerful mechanism to adapt to the entry of HIV-1 Tat, the efficiency of which may determine the frequency of lymphomagenesis in HIV-1-infected patients.

Localized Pneumocystis jirovecii pneumonia in a malnourished, non-HIV-infected man in the absence of any established or diagnosed immunosuppressive condition: a case report

BackgroundPneumocystis jirovecii infection is an opportunistic infection that mostly affects patients with immunosuppressive conditions like human immunodeficiency virus (HIV) infection or medications, like corticosteroids. This study reports a rare case of Pneumocystis Jiroveci infection in a relatively immunocompetent patient which presented with uncommon radiological findings.Case presentationA 46-year-old man with a malnourished appearance and a history of opium dependence presented with dry cough, dyspnea, and weight loss to the hospital. There was no evidence of an immunocompromised condition or use of any immunosuppressive medication in the history of the patient. A lung high-resolution computed tomography (HRCT) scan revealed a crazy-paving appearance and localized infiltration. Methenamine silver staining and the histopathological findings in the transbronchial lung biopsy confirmed the diagnosis of PJP. Antibiotics and bronchodilators were administrated and the patient was discharged after 6 days of hospitalization. HIV testing and immunoglobulin levels were normal in the hospital course as well as his follow-up visits. After a 2-month follow-up, the patient was in good condition despite of mild remaining infiltration in his lung.ConclusionsPJP typically affects HIV-infected patients, but due to excessive use of immunosuppressive medications, its prevalence is increasing in non-HIV-infected patients. Malnutrition may predispose the patients to PJP, even in the absence of immunosuppressive conditions.

Maternal infection with SARS-CoV-2 during early pregnancy induces hypoxia at the maternal-fetal interface.

The coronavirus disease 2019 (COVID-19) pandemic increases the risk of adverse fetal outcomes during pregnancy. Maternal infection during pregnancy, particularly with cytomegalovirus (CMV), hepatitis B and C virus, and human immunodeficiency virus can have detrimental effects on both mother and fetus, potentially leading to adverse outcomes such as spontaneous abortion or neonatal infection. However, the impact of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection on the maternal-fetal interface remains poorly understood. In this study, we initially utilised immunofluorescence and immunohistochemical to investigate placental samples from pregnant women who were infected with SARS-CoV-2 during the first trimester. Our data indicate that infection in the first trimester induces an upregulation of hypoxia inducible factor (HIF) levels at the maternal-fetal interface. Subsequently, single-cell RNA sequencing and metabolomics sequencing analyses reveal alterations in maternal-fetal interface. Remarkably, immune cells exhibited low expression levels of HIF possibly associated with immune activation. Furthermore, our findings demonstrate a gradual reduction in transcriptome and metabolic changes as gestation progressed beyond 12-16 weeks compared to samples obtained at 6-8 weeks gestation. Overall, our study suggests that early-stage SARS-CoV-2 infection during the first trimester leads to severe hypoxia and aberrant cell metabolism at the maternal-fetal interface which gradually resolves as pregnancy progresses. Nevertheless, these abnormal changes may have long-term implications for maternal-fetal interface development.