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The presence of HIV in sequestered reservoirs is a central impediment to a functional cure, allowing HIV to persist despite life-long antiretroviral therapy (ART), and driving a variety of comorbid conditions. Our understanding of the latent HIV reservoir in the central nervous system is incomplete, because of difficulties in accessing human central nervous system tissues. Microglia contribute to HIV reservoirs, but the molecular phenotype of HIV-infected microglia is poorly understood. We leveraged the unique "Last Gift" rapid autopsy program, in which people with HIV are closely followed until days or even hours before death. Microglial populations were heterogeneous regarding their gene expression profiles but showed similar chromatin accessibility landscapes. Despite ART, we detected occasional microglia containing cell-associated HIV RNA and HIV DNA integrated into open regions of the host's genome (∼0.005%). Microglia with detectable HIV RNA showed an inflammatory phenotype. These results demonstrate a distinct myeloid cell reservoir in the brains of people with HIV despite suppressive ART. Strategies for curing HIV and neurocognitive impairment will need to consider the myeloid compartment to be successful.

OBJECTIVES: This study aimed to develop a machine learning (ML) model to predict disengagement from HIV care, high viral load or death among people living with HIV (PLHIV) with the goal of enabling proactive support interventions in Tanzania. The algorithm addressed common challenges when applying ML to electronic medical record (EMR) data: (1) imbalanced outcome distribution; (2) heterogeneity across multisite EMR data and (3) evolving virological suppression thresholds. DESIGN: Observational study using a national EMR database. SETTING: Conducted in two regions in Tanzania, using data from the National HIV Care database. PARTICIPANTS: The study included over 6 million HIV care visit records from 295 961 PLHIV in two regions in Tanzanias National HIV Care database from January 2015 to May 2023. RESULTS: Our ML model effectively identified PLHIV at increased risk of adverse outcomes. Key predictors included past disengagement from care, antiretroviral therapy (ART) status (which tracks a patients engagement with ART across visits), age and time on ART. The downsampling approach we implemented effectively managed imbalanced data to reduce prediction bias. Site-specific algorithms performed better compared with a universal approach, highlighting the importance of tailoring ML models to local contexts. A sensitivity analysis confirmed the models robustness to changes in viral load suppression thresholds. CONCLUSIONS: ML models leveraging large-scale databases of patient data offer significant potential to identify PLHIV for interventions to enhance engagement in HIV care in resource-limited settings. Tailoring algorithms to local contexts and flexibility towards evolving clinical guidelines are essential for maximising their impact.

BACKGROUND: Although antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter Adaptive COVID-19 Treatment Trial 1, which randomized patients to remdesivir or placebo. METHODS: Longitudinal specimens collected during hospitalization from a substudy of 642 patients with COVID-19 were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed. RESULTS: Higher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95% CI, 1.40-2.71) for levels >245 pg/mL vs 1.04 (95% CI, .76-1.42) for levels

Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor. Apart from three uninfected historic controls, nine Indian rhesus macaques were infected acutely with SIVmac251 and divided into three groups (n = 3 each): an untreated control and two groups treated for 20-30 days with low- (10 mg/kg/day) or high- (30 mg/kg/day) dose BLZ945. With the high-dose BLZ945 treatment, there was a significant reduction in cells expressing CD163 and CD206 across all four brain areas examined, compared with the low-dose treatment and control groups. In 9 of 11 tested regions, tissue viral DNA (vDNA) loads were reduced by 95%-99% following at least one of the two doses, and even to undetectable levels in some instances. Decreased numbers of CD163+ and CD206+ cells correlated significantly with lower levels of vDNA in all four corresponding brain areas. In contrast, BLZ945 treatment did not significantly affect the number of microglia. Our results indicate that doses as low as 10 mg/kg/day of BLZ945 are sufficient to reduce the tissue vDNA loads in the brain with no apparent adverse effect. This study provides evidence that infected PVMs are highly sensitive to CSF1R inhibition, opening new possibilities to achieve viral clearance.

To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.

BACKGROUND: Many persons with HIV remain out of care (PWH-OOC). We evaluated InstaCare, a complex intervention integrating the brief behavioral intervention 60 minutes for Health with the rapid restart of antiretroviral therapy (rapid ART). SETTING: Prospective open-label randomized controlled trial among PWH-OOC in San Diego, USA. METHODS: PWH-OOC were randomized 1:1 to InstaCare or a time-and-attention control integrating a diet-and-nutrition behavioral intervention also with rapid ART initiation (restart ≤7 days from enrollment). All participants had access to support services (free transport, HIV peer navigation, adherence counseling, and linkage to care) and primary care services (mental health, case management, social work, medication-assisted treatment, and specialist pharmacy). The primary outcomes were viral suppression (90 days apart) by 24 weeks. Outcomes were reported on an intention-to-treat basis. RESULTS: Between November 2020 and August 2022, 52 PWH-OOC were enrolled. Baseline substance use in the preceding month (49%), unstable housing (51%), moderate/severe depression (49%), and moderate/severe anxiety (41.7%) were prevalent. Rapid ART was provided for all participants. At week 24, the proportion with HIV viral load

Researchers and clinicians often rely on molecular assays like PCR to identify and monitor viral infections, instead of the resource-prohibitive gold standard of viral culture. However, it remains unclear when (if ever) PCR measurements of viral load are reliable indicators of replicating or infectious virus. The recent popularity of PCR protocols targeting subgenomic RNA for SARS-CoV-2 has caused further confusion, as the relationships between subgenomic RNA and standard total RNA assays are incompletely characterized and opinions differ on which RNA type better predicts culture outcomes. Here, we explore these issues by comparing total RNA, subgenomic RNA, and viral culture results from 24 studies of SARS-CoV-2 in non-human primates (including 2167 samples from 174 individuals) using custom-developed Bayesian statistical models. On out-of-sample data, our best models predict subgenomic RNA positivity from total RNA data with 91% accuracy, and they predict culture positivity with 85% accuracy. Further analyses of individual time series indicate that many apparent prediction errors may arise from issues with assay sensitivity or sample processing, suggesting true accuracy may be higher than these estimates. Total RNA and subgenomic RNA showed equivalent performance as predictors of culture positivity. Multiple cofactors (including exposure conditions, host traits, and assay protocols) influence culture predictions, yielding insights into biological and methodological sources of variation in assay outcomes-and indicating that no single threshold value applies across study designs. We also show that our model can accurately predict when an individual is no longer infectious, illustrating the potential for future models trained on human data to guide clinical decisions on case isolation. Our work shows that meta-analysis of in vivo data can overcome longstanding challenges arising from limited sample sizes and can yield robust insights beyond those attainable from individual studies. Our analytical pipeline offers a framework to develop similar predictive tools in other virus-host systems, including models trained on human data, which could support laboratory analyses, medical decisions, and public health guidelines.

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA  LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p

PurposeGay, bisexual, and other cisgender men who have sex with men, and racial minority youth are at elevated risk of acquiring HIV infection. The Adolescent Trials Network 147 recruited youth with acute/recent HIV-infection for early antiretroviral treatment. The cohort make-up is described here.MethodsTreatment-naïve, recently identified HIV + youth, aged 12-24 years, from Los Angeles and New Orleans were recruited from community centers, clinics, social media, and a high-risk seronegative cohort (n = 1,727, the Adolescent Trials Network 149) using point-of-care assays. Acute HIV infection was determined by Fiebig staging. HIV RNA viral load (VL) and CD4 cell counts, along with demographic and behavioral data were assessed at enrollment.ResultsBetween July 2017 and July 2021, 103 newly diagnosed youth were enrolled, initiating antiretroviral treatment within a week. Mean age was 20.8 years (standard deviation: 2.4); 90.3% identified as cis male, 83.5% were single or in casual relationships, 71.8% were gay, bisexual, and other cisgender men who have sex with men; 60.2% were Black. One-fourth (24.3%) reported homelessness ever; 10.7% within last 4 months. At enrollment, median plasma VL was 37,313 HIV RNA copies/ml (interquartile range: 5,849-126,162) and median CD4 count 445.5 cells/mm3 (interquartile range: 357-613). 40% of youth reported acute retroviral symptoms before or at enrollment. Acutely infected, seroconverting youth had the highest VL. Sexually transmitted coinfections were present at enrollment in 56% of the cohort, with syphilis being most frequent (39%).DiscussionEarly identification and treatment of HIV can increase positive HIV outcomes. A high sexually transmitted infection burden was present in recently HIV-infected youth. Acute retroviral symptoms were not reported by most participants, demonstrating that broad universal HIV screening is needed for identification of recent infection in youth.

BACKGROUNDIdentifying factors that predict the timing of HIV rebound after treatment interruption will be crucial for designing and evaluating interventions for HIV remission.METHODSWe performed a broad evaluation of viral and immune factors that predict viral rebound (AIDS Clinical Trials Group A5345). Participants initiated antiretroviral therapy (ART) during chronic (N = 33) or early (N = 12) HIV infection with ≥ 2 years of suppressive ART and restarted ART if they had 2 viral loads ≥ 1,000 copies/mL after treatment interruption.RESULTSCompared with chronic-treated participants, early-treated individuals had smaller and fewer transcriptionally active HIV reservoirs. A higher percentage of HIV Gag-specific CD8+ T cell cytotoxic response was associated with lower intact proviral DNA. Predictors of HIV rebound timing differed between early- versus chronic-treated participants, as the strongest reservoir predictor of time to HIV rebound was level of residual viremia in early-treated participants and intact DNA level in chronic-treated individuals. We also identified distinct sets of pre-treatment interruption viral, immune, and inflammatory markers that differentiated participants who had rapid versus slow rebound.CONCLUSIONThe results provide an in-depth overview of the complex interplay of viral, immunologic, and inflammatory predictors of viral rebound and demonstrate that the timing of ART initiation modifies the features of rapid and slow viral rebound.TRIAL REGISTRATIONClinicalTrials.gov NCT03001128FUNDINGNIH National Institute of Allergy and Infectious Diseases, Merck.

Adenosine to inosine (A-to-I) RNA editing by ADAR1 has been implicated in maintaining self-tolerance, preventing autoimmunity, and mediating antiviral immunity. Foreign viral double-stranded RNA triggers rapid interferon response and activates ADAR1 in the host immune system. Emerging data points to a role of ADAR1 A-to-I editing in the inflammatory response associated with severe COVID-19 disease. We identify A-to-I editing events within human whole transcriptome data from SARS-CoV-2 infected individuals, non-infected individuals, and individuals with other viral illnesses from nasopharyngeal swabs. High levels of RNA editing in host cells are associated with low SARS-CoV-2 viral load (p = 9.27 E-06), suggesting an inhibitory effect of ADAR1 on viral infection. Additionally, we find differentially expressed genes associated with RNA-modifications and interferon response. Single cell RNA-sequencing analysis of SARS-CoV-2 infected nasopharyngeal swabs reveals that cytotoxic CD8 T cells upregulate ADAR1 in COVID-19 positive samples (p = 0.0269). We further reveal ADAR1 expression increases with CD4 and CD8 T cell activation, and knockdown of ADAR1 leads to apoptosis and aberrant IL-2 secretion. Together, our data suggests A-to-I RNA editing is required to maintain healthy homeostasis of activated T cells to combat SARS-CoV-2 infection.

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3-4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response antiviral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection.

BACKGROUND: Smoking and alcohol use frequently co-occur and are the leading causes of preventable death in sub-Saharan Africa (SSA) and are common among people living with HIV (PLWH). While alcohol use has been shown to be associated with reduced adherence to antiretroviral treatment (ART), which may affect HIV viral suppression, the independent effect of smoking on HIV outcomes in SSA is unknown. We aimed to 1) describe the prevalence of current smoking and correlates of smoking; 2) assess the association of smoking with viral suppression, adjusting for level of alcohol use; 3) explore the relationship between smoking and CD4 cell count

Objective: This study explores the risk factors for low-level viremia (LLV) occurrence after ART and develops a risk prediction model. Method: Clinical data and laboratory indicators of people living with HIV (PLWH) at Hangzhou Xixi Hospital from 5 April 2011 to 29 December 2022 were collected. LASSO Cox regression and multivariate Cox regression analysis were performed to identify laboratory indicators and establish a nomogram for predicting LLV occurrence. The nomogram's discrimination and calibration were assessed via ROC curve and calibration plots. The concordance index (C-index) and decision curve analysis (DCA) were used to evaluate its effectiveness. Result: Predictive factors, namely, age, ART delay time, white blood cell (WBC) count, baseline CD4+ T-cell count (baseline CD4), baseline viral load (baseline VL), and total bilirubin (TBIL), were incorporated into the nomogram to develop a risk prediction model. The optimal model (which includes 6 variables) had an AUC for LLV after 1-year, 3-year, and 5-year of listing of 0.68 (95% CI, 0.61–0.69), 0.69 (95% CI, 0.65–0.70), and 0.70 (95% CI, 0.66–0.71), respectively. The calibration curve showed high consistency between predicted and actual observations. The C-index and DCA indicated superior prediction performance of the nomogram. There was a significant difference in CD4 levels between LLV and non-LLV groups during the follow-up time. The dynamic SCR, ALT, TG and BG levels and occurrence of complications differed significantly between the high- and low-risk groups. Conclusion: A simple-to-use nomogram containing 6 routinely detected variables was developed for predicting LLV occurrence in PLWH after ART. [ABSTRACT FROM AUTHOR]

Background: Aggregated samples such as oral fluids (OFs) display an animal friendly and time and cost-efficient sample type for swine Influenza A virus (swIAV) monitoring. However, further molecular and biological characterization of swIAV is of particular significance. The reportedly inferior suitability of aggregated samples for subtyping of swIAV presents a major drawback compared to nasal swabs, still considered the most appropriate sample type for this purpose (Garrido-Mantilla et al. BMC Vet Res 15(1):61, 2019). In addition, the viral load in the original sample, storage conditions and characteristics of different swIAV strains might further compromise the eligibility of aggregated samples for molecular detection and subtyping. Therefore, the present study aimed to evaluate the suitability of stabilizing media to minimize the degradation of viral RNA and thus increase the detection and subtyping rate of swIAV by RT-qPCR in spiked OFs under different conditions (virus strain, storage temperature and viral load in the original sample) over a time span of 14 days. Results: The use of stabilizing media in spiked OFs resulted in a significant higher probability to detect swIAV RNA compared to OFs without stabilizers (OR = 46.1, p < 0.001). In addition, swIAV degradation over time was significantly reduced in samples suspended with stabilizer (OR = 5.80, p < 0.001), in samples stored at 4 °C (OR = 2.53, p < 0.001) and in samples spiked with the avian derived H1N2 subtype (OR = 2.26, p < 0.01). No significant differences in swIAV RNA detection and degradation of swIAV RNA in spiked OFs over time were observed between the three different stabilizing media. Conclusion: Addition of stabilizers and storage of samples under cooled conditions significantly improved detection and subtyping of swIAV in spiked OFs. [ABSTRACT FROM AUTHOR]

Porcine dermatitis and nephropathy syndrome (PDNS) is a severe condition that affects mainly growing pigs and is considered to be caused by a type III hypersensitivity reaction. Although porcine circovirus 2 (PCV-2) is the antigen linked to this condition, porcine circovirus 3 (PCV-3) has also been proposed to be causally associated with PDNS. Moreover, the initial description of porcine circovirus 4 (PCV-4) also related this novel agent to this clinicopathological entity. Therefore, this retrospective study included a large number of PDNS cases (n = 102) fulfilling specific histologic criteria in search of known porcine circoviruses (PCV-1 to PCV-4) by conventional and/or quantitative PCR (qPCR). All the samples were subjected to PCV-2 immunohistochemistry (IHC) or conventional in situ hybridization (C-ISH), and RNAscope® (R-ISH) was used to study PCV-2 and PCV-3 localization in a subset of the samples. All PDNS cases were PCV-2 positive by qPCR, while 30 of them (29.4%) yielded PCV-3 qPCR positivity; PCV-2 viral loads were significantly greater than PCV-3 viral loads. All animals were negative for PCV-1 and PCV-4. By C-ISH/IHC, 63 cases (61.8%) were positive for PCV-2, with low to moderate amounts of antigen. R-ISH demonstrated higher sensitivity, as all studied cases were positive; however, neither PCV-2 nor PCV-3 were consistently found within characteristic PDNS lesions. These results indicate that all PDNS-affected pigs were infected with PCV-2, emphasizing the likelihood that this viral antigen is causally linked to this condition. In contrast, no evidence of the association of PCV-1, PCV-3 or PCV-4 with PDNS was found. [ABSTRACT FROM AUTHOR]

Introduction: Viral suppression is a critical component for preventing mother-to-child transmission of HIV(MTCT). Mothers' perceptions of viral load suppression is crucial in the attainment of successful outcomes in preventing mother to child transmission of HIV. We therefore aimed to explore the experiences and perceptions of women on viral suppression. Methods: This was a qualitative sub-study embedded in a cluster-randomized trial (NCT04122144) designed to improve viral load outcomes among pregnant and breastfeeding mothers living with HIV in four level III/IV health facilities in South-western Uganda. Thirty-two in-depth interviews were conducted with pregnant and breastfeeding women with HIV from 1st March 2020 to 30th September 2020 to explore their understanding and interpretation of viral suppression. Interviews were audio-recorded, transcribed, and coded in Dedoose software for analysis. Results: A total of 32 Women living with HIV were enrolled in this qualitative study. WLHIV explained viral suppression in the context of attaining good health and having HIV-free babies. Adherence to ART was presented as a key avenue to viral suppression. The level of engagement with providers was presented as a key attribute of attaining viral suppression. The participants narrated their experiences with viral load testing within the routine services. However, they revealed experiencing some proximate barriers to suppression including anticipated stigma, challenges with non-disclosure of HIV status, pregnancy distress, and distance to the health facility. Conclusion: The understanding and interpretation of viral suppression among pregnant and breastfeeding mothers living with HIV provides a basis for adopting behaviors leading to prevention of vertical transmission of HIV. Health care workers can support women by providing clear and culturally appropriate education about viral suppression, adherence strategies and creating a supportive and non-judgmental environment. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients. Methods: Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-SNEG, IP-SPOSVLNEG and IP-SPOSVLPOS groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator®) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency. Results: Polyfunctional CD8+ T cells indicated previous EBV contact (IP-SNEG 0.00% vs IP-SPOS 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-SNEG 0.01% vs IP-SPOS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-SPOSVLPOS 0.43% vs IP-SPOSVLNEG 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-SNEG 0.00% vs IP-SPOS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-SNEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-SPOSVLPOS patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81). Conclusion: Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults. [ABSTRACT FROM AUTHOR]

Background: Menstrual irregularities significantly distress women living with HIV (WLHIV), impacting their reproductive health and quality of life. Although the underlying mechanism remains inconclusive, studies have outlined possible contributory factors. This narrative review explores the burden of menstrual irregularities and associated hormonal dysregulation among women living with HIV in Nigeria. It synthesises data from studies to present an overview of the prevalence, patterns, potential etiology, and impacts of menstrual irregularities among WLHIV. Main body: A literature search across electronic databases such as PubMed, Google Scholar, and Web of Science was conducted, and information was extracted and synthesized to delineate the burden of menstrual irregularities in WLHIV. Eligibility criteria included original studies assessing the prevalence, aetiology, and impact of menstrual abnormalities among WLHIV in Nigeria. A narrative data synthesis approach utilized common themes and key concept extraction, including identifying patterns in the literature to present specific trends such as prevalence, patterns, etiology, and determinants. Menstrual irregularities were found to be prevalent among Nigerian WLHIV, varying from 29 to 76% across different regions, exceeding reports of similar studies in developed nations. Similarly, menstrual disorders including amenorrhea, oligomenorrhea, and polymenorrhea, were attributed to factors like HIV acquisition, antiretroviral therapy, low body mass index, and hormonal imbalances. Low CD4 count and high viral load with associated complications have been identified as major contributing factors. Distortion of the hypogonadal-pituitary-ovarian axis by viral-induced pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) may disrupt the hormonal balance necessary for regular menstrual cycles. Fluctuating levels of follicle-stimulating hormone (FSH), luteinising hormone (LH), estradiol, and prolactin have been reported among WLHIV. Although adherence to antiretroviral therapy has offered immense relief, its direct therapeutic effects on menstrual irregularities are inconclusive.. Conclusions: This study highlights the burden of menstrual disorders among WLHIV. It underscores the interplay between clinical, therapeutic, and client-associated factors as determinants of these abnormalities. Exploring associated complications like secondary infertility, reduced bone mineral density, and resultant osteoporosis, mirrors the significant impact of menstrual and hormonal irregularities on the reproductive health and quality of life of WLHIV. [ABSTRACT FROM AUTHOR]

Introduction: The mechanisms of the SARS-CoV-2-triggered complex alterations in immune cell activation and production of cytokines in lung tissue remain poorly understood, in part because of the limited use of adequate tissue models that simulate the structure and cell composition of the lung in vivo. We developed a novel ex vivo model of SARS-CoV-2 infection of lung explants, that maintains the intact tissue composition and the viral load for up to 7-10 days. Using this model, we studied cytokine production during SARS-CoV-2 infection. Materials and methods: Lung tissue was monitored for viability and cell composition using flow cytometry and histological analysis. SARS-CoV-2 infection was verified immunohistochemically, viral loads in tissue and culture medium were monitored by qPCR. A panel of 41 cytokines was measured in culture medium using xMAP technology. Results: The explant lung tissue was viable and maintained viral infection that influenced the cytokine production. Elevated concentrations of G-CSF, GM-CSF, GRO-a, IFN-g, IL-6, IL-8, IP-10, MCP-3, MIP-1a, PDGF-AA, and VEGF, and decreased IL-1RA concentration were observed in infected tissue compared to non-infected tissue. Discussion: Our results generally reflect the data obtained in COVID-19 patients. GRO-a, IFN-g, IL-6, IL-8, MCP-1, MCP-3, and RANTES correlated with the viral load, forming a distinct pro-inflammatory cluster. Thus, our lung ex vivo model faithfully reproduces some aspects of cytokine alterations in COVID-19 patients at an early disease stage, making the investigation of SARS-CoV-2 infection mechanisms more accessible and providing a potential platform for antiviral drug testing. [ABSTRACT FROM AUTHOR]

Background: CMV reactivation represents a frequent complication after HSCT. The aim of this study was to describe the incidence of CMV reactivation in a pediatric HSCT cohort and analyze the potential impact of recipient/donor-related or transplant-related factors on this complication. Furthermore, we analyzed the management of CMV reactivation in order to purpose criteria for pre-emptive therapy. Methods: Allogeneic HSCTs, performed at IRCCS Istituto Gaslini between 2012 and 2022, were included in this analysis. CMV–DNAemia was regularly monitored. Risk stratification was based on donor/recipient serological status and additional potential risk factors were considered: haploidentical transplant; any HSCT subsequent to the first; acute and chronic GvHD; steroids; and other immunosuppressive therapies. We described also the approach for pre-emptive therapy during the period 2012–2019. Results: A total of 214 allogeneic HSCTs were performed in 189 patients. In total, 100 (46.7%) HSCTs were complicated by at least one reactivation. CMV reactivation was significantly associated with high serological risk and steroid treatment. Pre-emptive therapy was administered in 59/69 (85.5%) HSCTs during 2012–2019. In the presence of predefined risk conditions, therapy was started at a median viremia of 2050 copies/mL. No difference was observed in OS between patients with CMV reactivation versus patients who did not present this complication. Conclusions: These results suggest the potential effectiveness of the approach used in providing pre-emptive therapy based on viral load monitoring and individualized risk factors. [ABSTRACT FROM AUTHOR]

Over the last four years, each successive wave of the COVID-19 pandemic has been caused by variants with mutations that improve the transmissibility of the virus. Despite this, we still lack tools for predicting clinically important features of the virus. In this study, we show that it is possible to predict the PCR cycle threshold (Ct) values from clinical detection assays using sequence data. Ct values often correspond with patient viral load and the epidemiological trajectory of the pandemic. Using a collection of 36,335 high quality genomes, we built models from SARS-CoV-2 intrahost single nucleotide variant (iSNV) data, computing XGBoost models from the frequencies of A, T, G, C, insertions, and deletions at each position relative to the Wuhan-Hu-1 reference genome. Our best model had an R2 of 0.604 [0.593–0.616, 95% confidence interval] and a Root Mean Square Error (RMSE) of 5.247 [5.156–5.337], demonstrating modest predictive power. Overall, we show that the results are stable relative to an external holdout set of genomes selected from SRA and are robust to patient status and the detection instruments that were used. This study highlights the importance of developing modeling strategies that can be applied to publicly available genome sequence data for use in disease prevention and control. [ABSTRACT FROM AUTHOR]

Background: Malaria and HIV/AIDS are the two most common infections responsible for morbidity and mortality in sub‐Saharan Africa. The studies were carried out worldwide. However, no study has targeted HIV‐positive patients at the Bafoussam Regional Hospital (West Cameroon), one approved treatment center, where patients are adhering well to their HIV treatment. The objective of this study was to identify the Plasmodium species and to determine the prevalence of the malaria parasite in relationship with associated factors in HIV+ patients followed at the Bafoussam Regional Hospital. Methods: A prospective study included 585 patients who responded to the questionnaires from May to December 2021. Parents or legal guardians of children under 15 responded on their behalf on knowledge, attitudes, and practices towards malaria. Venous blood samples collected in EDTA tubes were subjected to malaria diagnosis by rapid tests (Standard Diagnostics Boline), and the results were confirmed by microscopy. The blood count was undertaken on hematology analyzer (Mindray Company, Shenzhen, China). Results:Plasmodium vivax (4.3%) and mostly Plasmodium falciparum (95.7%) were identified. In this study population, 46 (7.9%) of the patients carried one or the other Plasmodium species, and 532 (90.9%) had undetectable HIV viral loads. The prevalence of malaria was significantly higher among those using traditional pharmacopoeia (9 (16.7%)) compared to patients taking generic treatments (37 (7.0%)) (p < 0.01; OR: 2.69). Factors associated with malaria prevalence, such as sociodemographic characteristics, viral load, type of protocol, duration of antiretroviral treatment, monthly income, subdivision, and knowledge attitudes and practices towards malaria, showed no significant differences (p > 0.05). Conclusion: This study showed that HIV+ patients were carriers of Plasmodium falciparum and Plasmodium vivax with an appreciable overall prevalence. The only factor influencing the prevalence of malaria was using traditional medicine. [ABSTRACT FROM AUTHOR]

Background: Protease inhibitor (PI)-based Antiretroviral Therapy (ART) regimens are key drugs in HIV management, especially when used as second line drugs. However, some PI-based ART have high adherence demands or tolerable adverse effects which may affect adherence and subsequently viral suppression. We assessed the extent of viral suppression, its determinants, and the experiences of clients on PI-based ART undergoing intensive adherence counselling (IAC) in a public HIV clinic. Methods: Mixed methods sequential explanatory study involving a quantitative retrospective chart review for clients on PI-based ART who had received IAC from Dec 2016 to May 2023 and qualitative interviews for clients on PI-based ART who had received IAC in the past six months at an urban public HIV clinic in Uganda. Results: In this study, a total of 189 client charts were included. The median number of IAC sessions received was three (interquartile range, IQR, of 3 to 4) with median time of receiving IAC of three (IQR, of 2 to 4). One half (51%, 95/186) of the clients had achieved viral suppression and the odds of suppression increased by 30% for every additional month on IAC. Respondents perceived the effectiveness of PI-based ART and IAC in achieving and supporting viral suppression, respectively. Conclusion: Despite the perceived effectiveness of PI-based ART and IAC, suboptimal levels of viral suppression were observed among clients on PI-based ART who had received IAC. Therefore, it is important to provide IAC for optimal duration as it increases the chances of viral suppression. Further investigation of the barriers of viral suppression for clients on PI-based ART undergoing IAC is needed. [ABSTRACT FROM AUTHOR]

Background: HIV treatment programs in Africa have implemented centralized testing for routine viral load monitoring (VLM), which may result in specimen processing delays inhibiting timely return of viral load results. Decentralized, point-of-care (PoC) VLM is a promising tool for expediting HIV clinical decision-making but remains unavailable in most African settings. We qualitatively explored the perceived feasibility and appropriateness of PoC VLM to address gaps along the viral load monitoring continuum in rural Uganda. Methods: Between May and September 2022, we conducted 15 in-depth interviews with HIV clinicians (facility in-charges, clinical officers, nurses, counselors) and six focus group discussions with 47 peer health workers from three south-central Ugandan districts. Topics explored centralized VLM implementation and opportunities/challenges to optimizing routine VLM implementation with PoC testing platforms. We explored perspectives on PoC VLM suitability and feasibility using iterative thematic analysis. Applying the Framework Method, we then mapped salient constraints and enablers of PoC VLM to constructs from the Consolidated Framework for Implementation Research. Results: Clinicians and peers alike emphasized centralized viral load monitoring's resource-intensiveness and susceptibility to procedural/infrastructural bottlenecks (e.g., supply stockouts, testing backlogs, community tracing of clients with delayed VLM results), inhibiting timely clinical decision-making. Participants reacted enthusiastically to the prospect of PoC VLM, anticipating accelerated turnarounds in specimen processing, shorter and/or fewer client encounters with treatment services, and streamlined efficiencies in HIV care provision (including expedited VLM-driven clinical decision-making). Anticipated constraints to PoC VLM implementation included human resource requirements for processing large quantities of specimens (especially when machinery require repair), procurement and maintenance costs, training needs in the existing health workforce for operating point-of-care technology, and insufficient space in lower-tier health facilities to accommodate installation of new laboratory equipment. Conclusions: Anticipated implementation challenges, primarily clustering around resource requirements, did not diminish enthusiasm for PoC VLM monitoring among rural Ugandan clinicians and peer health workers, who perceived PoC platforms as potential solutions to existing inefficiencies within the centralized VLM ecosystem. Prioritizing PoC VLM rollout in facilities with available resources for optimal implementation (e.g., adequate physical and fiscal infrastructure, capacity to manage high specimen volumes) could help overcome anticipated barriers to decentralizing viral load monitoring. [ABSTRACT FROM AUTHOR]

Yellow mosaic disease (YMD) is a major constraint for the low productivity of mungbean, mainly in South Asia. Addressing this issue requires a comprehensive approach, integrating field and challenge inoculation evaluations to identify effective solutions. In this study, an infectious clone of Begomovirus vignaradiataindiaense (MYMIV) was developed to obtain a pure culture of the virus and to confirm resistance in mungbean plants exhibiting resistance under natural field conditions. The infectivity and efficiency of three Agrobacterium tumefaciens strains (EHA105, LBA4404, and GV3101) were evaluated using the susceptible mungbean genotype PS16. Additionally, a recombinant inbred line (RIL) population comprising 175 lines derived from Pusa Baisakhi (MYMIV susceptible) and PMR-1 (MYMIV resistant) cross was developed and assessed for YMD response. Among the tested Agrobacterium tumefaciens strains, EHA105 exhibited the highest infectivity (84.7%), followed by LBA4404 (54.7%) and GV3101 (9.80%). Field resistance was evaluated using the coefficient of infection (CI) and area under disease progress curve (AUDPC), identifying seven RILs with consistent resistant reactions (CI≤9) and low AUDPC (≤190). Upon challenge inoculation, six RILs exhibited resistance, while RIL92 displayed a resistance response, with infection occurring in less than 10% of plants after 24 to 29 days post inoculation (dpi). Despite some plants remaining asymptomatic, MYMIV presence was confirmed through specific PCR amplification of the MYMIV coat protein (AV1) gene. Quantitative PCR revealed a very low relative viral load (0.1–5.1% relative fold change) in asymptomatic RILs and the MYMIV resistant parent (PMR1) compared to the susceptible parent (Pusa Baisakhi). These findings highlight the potential utility of the developed infectious clone and the identified MYMIV-resistant RILs in future mungbean breeding programs aimed at cultivating MYMIV-resistant varieties. [ABSTRACT FROM AUTHOR]

Peptide-based inhibitors represent a promising approach for the treatment of HIV-1, offering a range of potential advantages, including specificity, low toxicity, and the ability to target various stages of the viral lifecycle. This review outlines the current state of research on peptide-based anti-HIV therapies, highlighting key advancements and identifying future research directions. Over the past few years, there has been significant progress in developing synthetic peptide-based drugs that target various stages of the viral life cycle, including entry and replication. These approaches aim to create effective anti-HIV therapies. Additionally, peptides have proven valuable in the development of anti-HIV vaccines. In the quest for effective HIV vaccines, discovering potent antigens and designing suitable vaccine strategies are crucial for overcoming challenges such as low immunogenicity, safety concerns, and increased viral load. Innovative strategies for vaccine development through peptide research are, therefore, a key focus area for achieving effective HIV prevention. This review aims to explore the strategies for designing peptides with anti-HIV activity and to highlight their role in advancing both therapeutic and preventive measures against HIV. [ABSTRACT FROM AUTHOR]

Background: The Joint United Nations Programme on Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) (UNAIDS) aims to eradicate AIDS by 2030 through 95:95:95 targets: identifying 95% of persons living with HIV (PLHIV), initiating 95% of those identified on antiretroviral therapy (ART), and ensuring that 95% of those initiated on ART are virally suppressed. Virally suppressed patients pose minimal risk of HIV transmission. ART aims to suppress the HIV-viral load (VL) and increase immunity, reducing morbidity and mortality. This study aimed to determine the trends in VL suppression among HIV patients on ART from 2019 to 2023 at Asante Mampong Municipal Hospital. Methods: This study adopted a retrospective Hospital-based design in which secondary data from 842 patients on ART from 2019 to 2023 were used. The study design specifically involved conducting serial cross-sectional studies to measure the prevalence of VL suppression each year from 2019 to 2023. This approach allowed the researchers to analyse the annual prevalence of VL suppression among study participants without following individual participants longitudinally throughout the entire period. The data were analysed via STATA version 17.0. Chi-square and logistic regressions were used to determine the associations between VL suppression and the independent variables at p < 0.05 and 95% confidence intervals (CIs). Results: In 2019, VL suppression was 79.6%, decreasing to 40.0% in 2020 and then rising to 82.7% in 2021, dropping to 67.8% in 2022 and 66.7% in the first quarter of 2023. Clients aged 40–49, 50–59, and 60–69 years were more likely to have VL suppression [aOR = 4.4 (1.36–14.25), p = 0.013], [aOR = 5.5 (1.65–18.39), p = 0.006] and [aOR = 5.0 (1.42–17.46), p = 0.012], respectively. Clients who were consistently on the same type of ART for more than a year were more likely to have VL suppression [aOR = 10.6 (4.18–26.76), p < 0.001]. Conclusion: VL suppression was low among patients. Advanced age and being on the same ART for more than 12 months were significantly associated with VL suppression. Health promotion activities are needed for people who have been suppressed to maintain and achieve a lifetime undetectable VL, targeting the younger age group. [ABSTRACT FROM AUTHOR]

Background: High-risk genotypes of Human Papillomavirus are responsible for 90% of cases of cervical cancer worldwide. Inflammation of squamous cells is mainly linked to HPV. In Gabon, HPV is endemic and circulates among the female population. The study aimed to determine the prevalence of HR-HPV genotypes and to investigate the correlation between squamous cell inflammation and HPV viral load in infected women in Gabon. Methods: The cross-sectional study was conducted at Libreville University Hospital Center (UHC) and National Public Health Laboratory from March to May 2024 among 399 women. Two cervical smears were taken. Genotype detection was carried out by multiplex fluorescence real-time PCR in the NPHL virology unit. Cytology was carried out in UHC's anatomic-pathology laboratory. Data were analyzed by SPSS software. Graphs were plotted using Microsoft Excel 2016. Results: The prevalence of Human Papillomavirus was 26.1% (95% CI: 22-30.6). The prevalence of HR-HPV genotypes was 24.8%. The most common HR-HPV genotypes were HPV-16/52/18/35/56/58/53/68. The rate of multiple HPV infections was 29.8% and 95.2% for the HR-HPV infection rate. Viral load was significantly correlated with squamous cell inflammation (r = 0.977 and P = 0.001). Conclusion: HR-HPV infection remains a concern in women, however early screening is necessary for optimal monitoring and management. HR-HPV viral load is a predictive marker of squamous cell inflammation. [ABSTRACT FROM AUTHOR]

Background: Human Immunodeficiency Virus (HIV) and malaria are two major diseases in sub-Saharan Africa. Co-infection can significantly impact the clinical outcomes of both conditions. We assessed the proportion of HIV-infected children at Korle Bu Teaching Hospital (KBTH) and Princess Marie Louise Hospital (PML) with malaria parasites. The association between asymptomatic malaria parasitaemia and virological non-suppression was also determined in these children. Methods: This cross-sectional study of 277 asymptomatic malaria in children receiving care at paediatric HIV clinics at KBTH and PML was conducted from September to November 2022. Patients who had been on antiretroviral therapy (ART) for at least six months were eligible to participate. Structured questionnaires were used to collect socio-demographic information, malaria prevention behaviors, and ART-related data using in-person interviews. Microscopy and PCR were used to screen for malaria, and GeneXpert was used to determine viral load. To examine the determinants of malaria PCR positivity and virological non-suppression, chi-square tests and logistic regression were performed. Results: The median age of the participants was 9 years (range: 6–12 years). Males comprised 158 (57%) of the study population. We detected 10 (3.6%) and 21 (7.6%) malaria cases by microscopy and PCR, respectively. Virological non-suppression (VL > 1000 copies/ml) was observed in 82 (29.6%) of the 277 participants. Among the suppressed individuals, 62 (22.4%) exhibited low-level viraemia (VL level 40-1000 copies/ml) and 133 (48%) had undetectable viral load levels. No factors were associated with the presence of malaria PCR positivity carriage. Poor adherence to ART was associated with a five-fold increase in the risk of viral load non-suppression (AOR = 4.89 [CI = 2.00-11.98], p = 0.001). Conclusion: The proportion of children living with HIV with asymptomatic malaria parasitaemia was low. Approximately one-third of the study population had virological non-suppression. The interaction between malaria parasitemia and viral replication may not be the main cause for virological non-suppression in this low transmission area. [ABSTRACT FROM AUTHOR]

Background: Malawi has one of the highest incidence and mortality rates of cervical cancer in the world. Despite a national strategic plan and the roll-out of VIA and screen-and-treat services, cervical cancer screening coverage in Malawi remains far below the national target.Using a nationally representative sample of women enumerated in the Malawi Population-based Impact Assessment (MPHIA) survey we estimated the prevalence and spatial distribution of self-reported cervical cancer screening as a proxy for uptake in Malawi. Methods: MPHIA was a nationally representative household survey in Malawi, targeting adults aged 15 and above, that employed a cross-sectional, two-stage, cluster design. The primary aim of MPHIA was to assess the regional prevalence of viral load suppression and the progress towards achieving the UNAIDS 95-95-95 goals among adults aged 15 and above. The survey was carried out between January 2020 and April 2021. Prevalence of self-reported cervical cancer screening by different characteristics was estimated accounting for the survey design using the Taylor series approach. We used univariable and multivariable logistic regression approaches to examine associations between the prevalence of cervical cancer screening and demographic characteristics. Findings: A total of 13,067 adult (15 years and older) female individuals were surveyed during the MPHIA 2020 to 2021 survey, corresponding to a weighted total of 5,604,578. The prevalence of self-reported cervical cancer screening was 16.5% (95% CI 15.5–18.0%), with women living with HIV having a higher prevalence of 37.8% (95% CI 34.8–40.9) compared to 14.0% (95% CI 13.0–15.0) in HIV negative women. The highest prevalence of screening was reported in the Southwest zone (SWZ) (24.1%, 95% CI 21.3–26.9) and in major cities of Blantyre (25.9%, 95% CI 22.9–29.0), and Lilongwe (19.6%, 95% CI 18.0–21.3). Higher self-reported screening was observed in women who resided in urban regions ((22.7%; 95% CI 21.4–24.0) versus women who resided in rural areas (15.2%; 95% CI 14.0–16.8). Cervical cancer screening was strongly associated with being HIV positive (aOR 2.83; 95% CI 2.29–3.50), ever having been pregnant (aOR 1.93; 95% CI 1.19–3.14), attaining higher education level than secondary education (aOR 2.74; 95% CI 1.67–4.52) and being in the highest wealth quintile (aOR 2.86; 95% CI 2.01–4.08). Interpretation: The coverage of cervical cancer screening in Malawi remains low and unequal by region and wealth/education class. Current screening efforts are largely being focussed on women accessing HIV services. There is need for deliberate interventions to upscale cervical cancer screening in both HIV negative women and women living with HIV. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B virus (HBV) infection is still a major public health problem. In response to the World Health Organization (WHO), Tanzania implemented immunization and treatment to achieve the eradication of HBV infection by 2030. To achieve this goal, frequent updates of demographic data, antiviral therapy eligibility, and uptake are essential. We therefore evaluated demographic data, antiviral therapy eligibility, and uptake among chronically HBV-infected patients attending at Bugando Medical Centre (BMC), Tanzania. Methods: A cross-sectional study enrolled 196 chronic HBV patients from April 23, 2023, to October 10, 2023, at BMC, where 100 and 96 patients were retrospectively and prospectively enrolled, respectively. Study's ethical clearance and permission were observed by the Catholic University of Health and Allied Sciences/Bugando Medical Centre research ethics and review committee and the Bugando Medical Centre management respectively. For all patients, socio-demographic data and whole blood samples were obtained. Full blood picture, alanine and aspartate amino transferases, and HBV viral load parameters were determined. Aspartate-Platelet Ratio Index (APRI) and Fibrosis Four (FIB-4) scores were calculated according to their respective formulas. Therapy eligibility and uptake were evaluated according to the 2015 WHO HBV prevention, treatment, and care guidelines. The data were summarized and analysed using STATA version 15. Results: The median age for all patients was 39 [IQR: 32–47.5] years. Nearly all study patients, 99% (194/196), were older than 20 years old, with significant male dominance (73.5% [144/196] versus 26.5% [52/196]; p<0.0001). Anti-HBV antiviral therapy eligibility was 22.4%, while uptake was 6.8% (3/4), which was significantly lower than the WHO expectation of 80% (p <0.0001). Conclusion: Almost all chronically HBV-infected patients attending at BMC were older than 20 years old and were significantly dominated by males. Antiviral therapy uptake was remarkably lower than expected by the WHO towards combating HBV infection by 2030. [ABSTRACT FROM AUTHOR]

Adherence to antiretroviral therapy (ART) is essential for the effective management of HIV, which includes keeping the HIV viral load undetectable. This study aimed to determine whether certain ART medications are more "forgiving" of poor adherence in achieving viral suppression. We identified subgroups of ART medication usage and determined the extent to which ART adherence is associated with viral suppression across those subgroups. Data came from claims and clinical records (2017–2019) of 3,552 HIV-positive adult members of a Medicaid managed care plan. Pharmacy fill data were examined to characterize ART medications using latent class analysis (LCA), which captures the complexity of real-world ART usage (i.e., multiple medications, ART switching). LCA yielded five ART medication patterns over three years, mostly characterized by recent medications and formulations of ART, though they varied in number of tablets and in medication class. Mixed effects logistic regression models were estimated to determine whether odds of viral suppression differed by ART adherence level. After adjusting for covariates, those with at least 90% adherence (i.e., 90 to < 95%) did not significantly differ from those with 95% adherence or greater in terms of viral suppression, which corroborates existing clinical recommendations. These findings can inform provider-patient communication for people with HIV, especially those who have difficulty maintaining adherence. This includes those experiencing unstable housing, mental health conditions, or substance use. [ABSTRACT FROM AUTHOR]

Introduction: Disengagement from HIV care during the perinatal period remains a challenge. Improving engagement in HIV care requires monitoring engagement across multiple indicators, including retention in HIV care, visit adherence, clinic transfers, and viral suppression to support improved clinical and programmatic outcomes. Methods: We enrolled a prospective cohort of pregnant WHIV across a network of five urban clinics in Lilongwe, Malawi from February 2020-February 2021. WHIV were followed from their first antenatal care visit through 9 months postpartum across all study sites using biometric fingerprint scanning. Study visits occurred at enrollment into antenatal care, 6 weeks', 6 months, and 9 months postpartum. In addition, all usual care HIV visits were captured via medical records. Participants who missed a study visit or usual care visit were traced. We evaluated determinants of multiple indicators of engagement in care, including retention in HIV care (attending a scheduled visit or self-reported recent visit when traced), HIV visit adherence (missed scheduled HIV visits and HIV visit coverage), clinic transfers, and viral load suppression (< 1000 copies/mL) using modified Poisson regression and sub-distributional hazard ratios to account for competing events of death and loss-to-follow-up. Associations between clinic transfer and subsequent indicators of engagement in HIV care were evaluated using generalized estimating equations. Results: Among 399 participants, 81% were on ART at baseline. Retention in HIV care was 87% at 6 weeks postpartum, 77% at 6 months postpartum and 89% at 9 months postpartum. At 9 months postpartum, 91% of participants were virally suppressed, 81% had missed a scheduled HIV visit, and 19% had transferred clinics. WHIV who transferred clinics were most likely to miss their subsequent scheduled HIV visit by ≥ 30 days. Transferring clinics was not associated with unsuppressed viral load or non-retention at 9 months postpartum. Conclusions: In a cohort of WHIV, retention and viral load suppression were high in the perinatal period, but missed HIV visits and clinic transfers were common. Transferring clinics was associated with an increased likelihood of missing a subsequent HIV visit. Clinic transfers may be important indicators of disruptions in clinical care for WHIV in the perinatal period. [ABSTRACT FROM AUTHOR]

Background The standard of care for Lassa fever is the use of ribavirin with supportive therapy. There is little information on the course of viremia and its relationship with clinical outcomes in patients treated with ribavirin. Methods We conducted a retrospective analysis of virologic and clinical parameters of 152 reverse transcription polymerase chain reaction–confirmed Lassa fever cases admitted and treated with ribavirin therapy. We describe the Lassa virus RNA kinetics in blood in relation to the clinical course of the patients. Results The overall mortality was 9%. The median duration (interquartile range [IQR]) of illness before admission was 8 (5–12) days. Median (IQR) Ct values on admission (t0) were lower among patients who died (21 [20–27]) than in those who survived (34 [30–37]; P <.01). The receiver operating characteristics curve of the association between outcome and Ct value at t0 had a high classification performance, with an AUC of 0.92 (95% CI, 0.86–0.98). The median time to viral clearance (IQR) was 10 (5–15) days. The viral load decreased steadily with the duration of treatment, and all survivors achieved viral clearance within 25 days of hospitalization. Conclusions Our study demonstrates that the Ct value on admission has prognostic value and Lassa fever patients treated with ribavirin typically clear the virus within 3–4 weeks of hospitalization. This kinetics has implications for the design of clinical case management and future clinical trial protocols. [ABSTRACT FROM AUTHOR]

Human bocavirus (HBoV) has emerged as a significant pathogen primarily associated with respiratory infections in children. This study aimed to evaluate the clinical relevance of HBoV infection by quantifying viral loads in nasopharyngeal swabs from hospitalized children with acute respiratory infections (ARIs) and investigating correlations with clinical outcomes. A total of 957 children were tested, with HBoV detected in 73 cases (7.6%), either as a sole infection or co-infection with other respiratory viruses. Quantitative polymerase chain reaction (qPCR) was employed to measure viral load, and a threshold of 104 copies/mL was used to differentiate high and low viral concentrations. Results have shown that children with lower respiratory tract infections (LRTIs) had significantly higher viral loads, most notably in cases where HBoV was the sole pathogen. Additionally, children with pre-existing health conditions were more likely to have elevated HBoV concentrations compared to those who were previously healthy. Children with higher viral loads were more likely to require oxygen supplementation and receive empirical antibiotic therapy, indicating a more severe clinical course. This study underscores the importance of considering HBoV viral load in clinical diagnostics, as higher concentrations were associated with more severe presentations, including the need for oxygen support. Future research should focus on refining diagnostic thresholds and exploring HBoV's role in co-infections to enhance patient care strategies. [ABSTRACT FROM AUTHOR]

Nonhuman primate (NHP) studies that utilize simian immunodeficiency virus (SIV) to model human immunodeficiency virus (HIV-1) infection have proven to be powerful, highly informative research tools. However, there are substantial differences between SIV and HIV-1. Accordingly, there are numerous research questions for which SIV-based models are not well suited, including studies of certain aspects of basic HIV-1 biology, and pre-clinical evaluations of many proposed HIV-1 treatment, prevention, and vaccination strategies. To overcome these limitations of NHP models of HIV-1 infection, several groups have pursued the derivation of a minimally modified HIV-1 (mmHIV-1) capable of establishing pathogenic infection in macaques that authentically recapitulates key features of HIV-1 in humans. These efforts have focused on three complementary objectives: (1) engineering HIV-1 to circumvent species-specific cellular restriction factors that otherwise potently inhibit HIV-1 in macaques, (2) introduction of a C chemokine receptor type 5 (CCR5)-tropic envelope, ideally that can efficiently engage macaque CD4, and (3) correction of gene expression defects inadvertently introduced during viral genome manipulations. While some progress has been made toward development of mmHIV-1 variants for use in each of the three macaque species (pigtail, cynomolgus, and rhesus), model development progress has been most promising in pigtail macaques (PTMs), which do not express an HIV-1-restricting tripartite motif-containing protein 5 α (TRIM5α). In our work, we have derived a CCR5-tropic mmHIV-1 clone designated stHIV-A19 that comprises 94% HIV-1 genome sequence and replicates to high acute-phase titers in PTMs. In animals treated with a cell-depleting CD8α antibody at the time of infection, stHIV-A19 maintains chronically elevated plasma viral loads with progressive CD4+ T-cell loss and the development of acquired immune-deficiency syndrome (AIDS)-defining clinical endpoints. However, in the absence of CD8α+ cell depletion, no mmHIV-1 model has yet displayed high levels of chronic viremia or AIDS-like pathogenesis. Here, we review mmHIV-1 development approaches, the phenotypes, features, limitations, and potential utility of currently available mmHIV-1s, and propose future directions to further advance these models. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) co-infections more often result in severe hepatitis compared to hepatitis B virus (HBV) infections alone. Despite a high HDV prevalence (7.1%), information regarding circulating HDV clades is very limited in Botswana. We extracted total nucleic acid from confirmed HDV-positive samples and quantified their viral load. We then sequenced the large hepatitis delta antigen (L-HDAg) using Oxford Nanopore Technology (ONT). Genotyping was performed using the HDV Database, and HDV mutation profiling was performed on AliView. All participants with HBV genotypic information belonged to sub-genotype A1, and 80% (4/5) of them had a higher HDV viral load and a lower HBV viral load. We sequenced 75% (9/12) of the HDV-positive samples, which belonged to HDV clade 8. A total of 54 mutations were discovered, with the most prevalent being Q148R (16%), D149P (16%) and G151D (16%). Known mutations such as S117A, K131R, R139K and G151D were detected, while the other mutations were novel. Our results reveal that HDV clade 8 is the predominant clade in Botswana. The significance of all mutations remains unclear. Future studies with a larger sample size to detect other HDV clades that might be circulating in Botswana and functionally characterize the detected mutations are warranted. [ABSTRACT FROM AUTHOR]

Background: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood. Methods: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled and completed up to three visits, in which they provided specimens from four respiratory compartments. Near full-length genome SARS-CoV-2 sequences were obtained from viral RNA, standard lineage and variant assignments were performed, and viral mutations in the RNA-dependent RNA polymerase (RdRp) region—the RDV target gene—were detected and compared between participants with and without RDV, across the four compartments, within participants across visits, and versus a larger sequence dataset. The statistical analysis used a generalized linear mixed-effects model. Results: A total of 139 sequences were obtained from 37 out of the 44 (84%) enrolled participants. The genotyping success varied across respiratory compartments, which ranged from 42% with oropharyngeal specimens to 67% with nasopharyngeal specimens and showed improvement with higher viral loads. No RdRp mutations known to be associated with RDV resistance were identified, and for 34 detected mutations at 32 amino acid positions that are not known as RDV-associated, there was no evidence of any associations with the RDV exposure, respiratory compartment, or time. At least 1 of these 34 mutations were detected in all participants, and some differed from the larger sequence dataset. Conclusions: This study highlighted the SARS-CoV-2 short-term genomic stability within hosts and across upper respiratory compartments, which suggests a lack of evolution of RDV resistance over time. This contributes to our understanding of SARS-CoV-2 genomic dynamics. [ABSTRACT FROM AUTHOR]

Direct‐acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha‐fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well‐tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Polyomavirus-associated nephropathy (BKPyVAN) is a common complication in kidney transplant recipients. The histological changes in the context of BKPyVAN and their association with the viral load and outcomes are still being investigated. Methods: This retrospective study involved 100 adult patients transplanted between 2000 and 2021, with available archived biopsy slides, aiming to analyze associations between viral load clearance in the blood (reduction in BKPyVAN-DNAemia below detection level) and histological features in biopsy-proven BKPyVAN. A kidney pathologist blinded to the clinical data reassessed the BANFF 2019 lesion scores in the BKPyVAN index biopsy. The primary endpoint was viral clearance three months after the diagnosis. Results: The presence of tubulointerstitial inflammation, peritubular capillaritis, and higher PVN Class at the diagnosis was linked to a reduced likelihood of viral clearance three months later (interstitial inflammation OR = 0.2, 95% CI [0.07–0.55], tubulitis OR = 0.39, 95% CI [0.21–0.73], peritubular capillaritis OR = 0.25, 95% CI [0.08–0.82], PVN Score OR = 0.1, 95% CI [0.03–0.4]), independently of other covariates. Combining the four lesions using the ROC analysis enhanced their capability to predict persistent BK viremia after 3 months with an AUC of 0.94. Conclusions: The presence of interstitial inflammation, tubulitis, and peritubular capillaritis, as well as the higher PVN Score, was associated with an up to 90% lower likelihood of viral load clearance three months post-diagnosis. These findings underscore the importance of histological evaluation as a surrogate of subsequent viral clearance and offer valuable insights for the management of BKPyVAN. [ABSTRACT FROM AUTHOR]

Background: We report the impact of HIV infection within a household on oral Kaposi's sarcoma-associated herpesvirus (KSHV) shedding. Methods: We enrolled 469 individuals from 90 households. Mouthwash rinse samples collected at three monthly visits were analyzed for KSHV DNA using quantitative polymerase chain reaction (qPCR). Generalized linear mixed effects logistic models were applied to analyze factors associated with KSHV ever shedding, and among shedders, always versus intermittent shedding. Linear mixed effects models were applied to models of KSHV viral loads. Intraclass correlation coefficients (ICCs) were calculated to assess the contribution of household-level factors to variations in shedding probabilities. Hotspot analyses of geospatial feature clusters were calculated using Getis-Ord Gi* statistic and visualized using inverse distance weighted interpolation. Results: Analyses included 340 KSHV seropositive individuals, aged 3 + years, with qPCR results from 89 households. Forty households had 1 + persons living with HIV (PLWH), while 49 had none. Among participants, 149(44%) were KSHV ever shedders. Of 140 who shed KSHV at two or more visits, 34(24%) were always shedders. Increasing number of KSHV seropositive household members was significantly associated with ever shedding [Odds ratio(OR) (95% Confidence Interval(95%CI)):1.14(1.03,1.26);p = 0.013]. Among KSHV shedders, a statistically significant age-related trend was identified with 10–19 years being more likely to be always shedders (type III test p = 0.039) and to have higher viral loads (type III test p = 0.027). In addition, higher viral loads were significantly associated with increasing number of household members [coefficient(95%CI):0.06(0.01,0.12);p = 0.042], increasing number of KSHV seropositive members [coefficient(95%CI):0.08(0.01,0.15);p = 0.021], and living in households with 1 + PLWH [coefficient(95%CI):0.51(0.04,0.98);p = 0.033]. Always shedders exhibited higher viral loads than intermittent shedders [coefficient(95%CI):1.62(1.19,2.05);p < 0.001], and viral loads increased with the number of visits where KSHV DNA was detected in saliva (type III test p < 0.001). Household-level factors attributed for 19% of the variability in KSHV shedding (ICC:0.191;p = 0.010). Geospatial analysis indicated overlapping hotspots of households with more KSHV seropositive individuals and KSHV shedders, distinct from areas where PLWH were clustered. Discussion: KSHV oral shedding is influenced by multiple factors at the individual, household, and regional levels. To mitigate ongoing KSHV transmission a comprehensive understanding of factors contributing to oral KSHV reactivation and transmission within households is needed. [ABSTRACT FROM AUTHOR]

Background and objective: The DNA load of EBV may play a part in CLL pathogenesis and prognosis. The objective of this cross-sectional study was to examine the prognostic value of EBV viral load in CLL patients in comparison with other common laboratory prognostic factors. Materials and methods: Whole blood and sera from forty untreated CLL patients were collected. Next, DNA was extracted from total white blood cells (WBC), and TaqMan real-time PCR was performed to determine the EBV-DNA load by amplifying a specific fragment in the BNRF1 gene. In addition, parameters such as complete blood counts (CBC) and lactate dehydrogenase (LDH) were determined using an automated clinical laboratory analyzer. Results: Twenty-one patients (52.5%) were positive for EBV by real-time PCR analysis (ranged 20 to 30000 copies/µL). The difference in LDH mean levels between EBV positive and negative patients was marginally significant (P = 0.05). Furthermore, platelet (PLT) count (P = 0.03) and CD5+/CD19+ count (P = 0.04), between EBV positive and negative subgroups, were substantially different. In addition, individuals with a severe form of illness, as defined by an increase in LDH, a decrease in PLT, and an 11q deletion, had considerably higher EBV-DNA copy numbers (the ranges of viral loads were 9966.66 ± 20033 in the severe form vs. 137.13 ± 245.41 in the mild form). Conclusion: The EBV-DNA load could be used as a prognostic factor in the initial examination of CLL patients to better characterize the disease outcome and prognosis. [ABSTRACT FROM AUTHOR]

Background: Infection of mice with mouse-adapted strains of influenza virus has been widely used to establish mouse pneumonia models. Intranasal inoculation is the traditional route for constructing an influenza virus-induced pneumonia mouse model, while intratracheal inoculation has been gradually applied in recent years. In this article, the pathogenicity of influenza virus-induced pneumonia mouse models following intranasal and aerosolized intratracheal inoculation were compared. Methods: By comparing the two ways of influenza inoculation, intranasal and intratracheal, a variety of indices such as survival rate, body weight change, viral titer and load, pathological change, lung wet/dry ratio, and inflammatory factors were investigated. Meanwhile, the transcriptome was applied for the initial exploration of the mechanism underlying the variations in the results between the two inoculation methods. Results: The findings suggest that aerosolized intratracheal infection leads to more severe lung injury and higher viral loads in the lungs compared to intranasal infection, which may be influenced by the initial site of infection, sialic acid receptor distribution, and host innate immunity. Conclusion: Intratracheal inoculation is a better method for modelling severe pneumonia in mice than intranasal infection. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the fourth most common cancer in women worldwide, and women with human immunodeficiency virus (HIV) are particularly at risk of developing it. Regular screening effectively prevents morbidity and mortality. This mixed-methods study quantitatively assessed cervical cancer screening uptake and qualitatively explored the process of undergoing cervical cancer screening to understand possible reasons for delayed screening among women with HIV in Lesotho. Methods: Between October 2020 and March 2022, the Viral load Triggered ART care in Lesotho (VITAL) trial enrolled women aged 18 years and older with HIV who were taking antiretroviral therapy (ART). Cervical cancer screening delay was defined as reporting a screening that occurred more than two years ago or never having been screened. Cervical cancer screening uptake and the association between screening delay and sociodemographic variables were assessed using a multivariable mixed-effects logistic regression model accounting for clustering at clinic level. In-depth interviews were conducted with 16 women to obtain information on awareness, perceptions, and barriers to cervical cancer screening and were analyzed using thematic analysis. Results: Quantitative data were available for 3790 women. Among them, cervical cancer screening was delayed in 1814 (47.9%), including 1533 (40.5%) who were never screened. Compared to women aged 25 to 39 years, women aged 18 to 24 years (adjusted odds ratio (aOR) 2.8; 95% confidence interval (CI) 2.1–3.7), women aged 40 to 59 years (aOR 1.3; CI 1.1–1.6), and women older than 60 years (aOR 3.9; CI 3.0-5.1) were at higher risk of screening delay. Furthermore, time on ART below 6 months (aOR 1.6; CI 1.1–2.3) compared to above 6 months was associated with screening delay. Qualitative data identified limited awareness of cervical cancer risks and screening guidelines, misconceptions and fears created by the influence of other women's narratives, and low internal motivation as the main barriers to screening uptake. Conclusions: Cervical cancer screening delay was common. Limited personal awareness and motivation as well as the negative influence of other women were the primary internal barriers to cervical cancer screening. Awareness and screening campaigns in Lesotho should consider these factors. Trial registration: clinicaltrials.gov, NCT04527874, August 27, 2020. [ABSTRACT FROM AUTHOR]

Background: Long term respiratory complications of Corona Virus Disease-2019 (COVID-19) are of great concern. Many studies have reported altered respiratory patterns in COVID-19 recovered individuals and most of them were from severe to critically ill patients. The association of viral load at the time of infection with symptoms of long COVID-19 specifically on pulmonary functions after months of recovery is still not known. This study was aimed to assess the impact of SARS-CoV-2 viral load during mild-moderate COVID-19 disease on pulmonary functions in middle-aged population after 6–8 months of acute infection. Methods: This study included 300 (102 healthy controls and 198 COVID-19 recovered) individuals between age 30–60 of either gender. Mild-moderate COVID-19 recovered individuals were recruited between a period of 6–8 months post-acute infection. Spirometry was performed with MIR-Spirolab-III. The association of spirometry pattern was compared with SARS-CoV-2 viral loads during acute infection. Results: We observed up to 70% of the participants presented with either shortness of breath (11.5%), body aches (23.5%), recurrent cough (4.4%), recurrent respiratory infections (9.5%) and/or fatigue (33.3%) at follow up. In our study, 35.5% of COVID-19 recovered individuals had abnormal respiratory patterns (33.5% had restrictive and 2% had obstructive patterns). Viral load ≤ 20 CT value was associated with restrictive respiratory patterns (p = 0.004). No association was found between viral load and disease severity (p = 0.23). Conclusion: In this study, we found one third of mild-moderate COVID-19 recovered individuals have restrictive respiratory patterns after 6–8 months of recovery. These findings had a strong association with SARS-CoV-2 viral loads during acute infection which has been reported for the first time in our study. Studying the relationship between viral load and pulmonary functions can contribute to identifying potential risk factors for long COVID and developing preventive measures to mitigate the long-term impact on lung health. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) has been proven to be highly effective in reducing the impact of human immunodeficiency virus (HIV) infection. However, as more people receive initial ART treatment, the risk of developing resistance and eventual treatment failure increases, leading to the need for second-line treatment regimens. Understanding the factors that contribute to virologic failure to second-line ART is crucial in preventing switching to the more expensive and toxic third-line regimens. This study provides information on the prevalence, rate, and predictors of virologic failure (VF) among clients on second-line ART in Tanzania. Results: We followed 4718 clients for 15100 person-years (PY) of observations. Of them, 1402 (29.72%) experienced virologic failure at a rate of 92.85 per 1000 PY of observations (95% CI 88.11, 97.84). Factors that were associated with VF included: having a viral load count of ≥ 1000 copies/mL during first-line ART, with a hazard ratio (HR) 4.65 (95% CI 3.57, 6.07), using lopinavir (LPV/r) as a protease inhibitor during second-line ART (HR 4.20 (95% CI 3.12, 7.10), having a CD4 count < 200 cells/mm3 during second-line ART (HR 1.89 (95% CI 1.46, 2.44), and being on ART for 13–35 months (HR 8.22 (95% CI 2.21, 30.61). Paradoxically, having a CD4 count < 200 cells/mm3 during first-line ART treatment was associated with a reduced risk of virologic failure (HR 0.77 (95% CI 0.60, 0.99). Conclusions: In Tanzania, approximately 30% of adult clients on second-line ART experience VF at a rate of 92.71 per 1000 person-years. This high virologic failure rate underscores the urgent need for targeted interventions, such as enhancing adherence support, optimizing drug regimens, and regular viral load monitoring. These interventions will reduce the need for switching to the more costly and toxic third-line ART therapy and are also crucial for achieving the UNAIDS goal of 95% viral suppression among treated individuals by 2030. [ABSTRACT FROM AUTHOR]

Introduction: To analyze the effect of pharmaceutical intervention on therapeutic adherence, viral load (VL), and CD4 T lymphocyte count in human immunodeficiency virus (HIV) for strengthening the role of the pharmacist in an infectious diseases service. Methods: Retrospective observational study. Data were collected through interviews using the “Assessment of Predictive Factors of Therapeutic Adherence” questionnaire. VL and CD4 parameters were collected f were collected from the patients’ medical records at the hospital. Results: 103 patients were included, 92 % men, mean age 32.30± 10.90 years for the group of patients. After pharmaceutical intervention through strategies to promote adherence: 100 % of patients increased their knowledge of their disease, 62 % increased their knowledge of antiretroviral therapy (ART), 90 % showed tolerance to ART, and 4 % experienced adverse reactions. This was reflected in an increase in the median CD4 T lymphocyte count and a decrease in viral load (undetectable in 72 % of patients), statistically and clinically significant results (p< 0.01). Conclusions: The findings suggest that pharmaceutical intervention in therapeutic adherence to ART has beneficial effects (CD4 and VL) in the analyzed patient group. Further studies are necessary. [ABSTRACT FROM AUTHOR]

Introduction: The monoclonal antibody therapies bamlanivimab (BAM) + etesevimab (ETE) received emergency use authorization (EUA) from the US Food and Drug Administration (February 9, 2021) for treatment of mild-to-moderate COVID-19. The EUA of BAM + ETE was revoked (December 14, 2023) due to the high prevalence of BAM + ETE-resistant variants of SARS-CoV-2. Efficacy and safety of 700/1400 mg and 2800/2800 mg BAM + ETE are well established and published; however, efficacy and safety of 350/700 mg BAM + ETE have not been disclosed to date. Methods: This portion of phase 3, BLAZE-1 trial (J2X-MC-PYAB) enrolled patients (between June 17, 2020 and April 9, 2021) with mild-to-moderate COVID-19 within 3 days of laboratory diagnosis of SARS-CoV-2 infection. In total, 354 patients with at least one risk factor for severe COVID-19 were enrolled, randomized (2:3), and infused with placebo (N = 141) or 350/700 mg BAM + ETE (N = 213), over ~ 8 min. Primary endpoint was to assess proportion of patients with persistently high SARS-CoV-2 viral load (PHVL) (log viral load > 5.27) 7 days after infusion. Results: Patients were aged (mean) 53 years, 49.7% female, and 82.7% White. Seven days after drug infusion, 10.8% (95% confidence interval: 6.6, 15.0; p < 0.001) of BAM + ETE-treated patients and 34.8% (26.9, 42.6) of placebo-treated patients had PHVL, and the viral load change from baseline (least square mean [standard error]) was − 3.50 (0.15; p < 0.001) in BAM + ETE-treated patients versus − 2.51 (0.19) in placebo-treated patients. The majority of treatment-emergent adverse events were considered mild or moderate in severity (BAM + ETE: 6.6%; placebo: 14.2%). No deaths were reported. Conclusions: Consistent with previous studies, patients treated with BAM + ETE (350/700 mg) had a significantly lower proportion of PHVL and greater reduction in viral load compared with placebo. The overall safety profile is consistent with higher doses of BAM + ETE. Infusions of over ~ 8 min did not result in meaningful increase in incidence of TEAEs compared to higher doses of BAM + ETE administered over 30–60 min. Trial Registration: Clinical trial.gov identifier, NCT04427501. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus that causes the severe fever thrombocytopenia syndrome, which manifests as fever and haemorrhage, accompanied by severe neurological complications. To date, no specific antiviral drugs have been approved for this indication. Herein, we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo. An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication, plaque formation, and protein expression in a dosedependent manner. Subsequently, in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood. Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection. However, cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5, and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice. Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects. To expand the application of vitamin D derivatives, in vitro and in vivo drug combination assays were performed, which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV. The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice. This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection. [ABSTRACT FROM AUTHOR]