Anemia and Iron Supplementation in Relation to Viral Load and Mortality among 70,442 People Living with Human Immunodeficiency Virus in Tanzania.

BACKGROUND: Anemia may be associated with poor clinical outcomes among people living with human immunodeficiency virus (HIV) (PLHIV) despite highly active antiretroviral therapy (HAART). There are concerns that iron supplementation may be unsafe to prevent and treat anemia among PLHIV. OBJECTIVE: The objective of the study was to evaluate the associations of anemia and iron supplementation with mortality and viral load among PLHIV in Tanzania. METHODS: We analyzed data from a cohort of 70,442 nonpregnant adult PLHIV in Tanzania conducted between 2015 and 2019. Regression models evaluated the relationships between anemia severity and iron supplement use with mortality and unsuppressed HIV-1 viral load among all participants and stratified by whether participants were initiating or continuing HAART. RESULTS: Anemia was associated with an increased risk of mortality and unsuppressed viral load for participants who initiated or continued HAART. Iron supplement use was associated with reduced mortality risk but also had a greater risk of an unsuppressed viral load among participants continuing HAART. There was no association of iron supplement use with mortality, and unsuppressed viral load among PLHIV that were initiating HAART. There was a stronger negative association between iron supplement use and the risk of having an unsuppressed viral load among participants with stage III/IV disease compared with stage I/II disease. CONCLUSIONS: Anemia is associated with increased risk of mortality and unsuppressed viral load, but the benefits and safety of iron supplements appear to differ for those initiating compared with continuing ART as well as by HIV disease severity.

Alcohol Impairs Bioenergetics and Differentiation Capacity of Myoblasts from Simian Immunodeficiency Virus-Infected Female Macaques.

Alcohol misuse and HIV independently induce myopathy. We previously showed that chronic binge alcohol (CBA) administration, with or without simian immunodeficiency virus (SIV), decreases differentiation capacity of male rhesus macaque myoblasts. We hypothesized that short-term alcohol and CBA/SIV would synergistically decrease differentiation capacity and impair bioenergetic parameters in female macaque myoblasts. Myoblasts from naïve (CBA-/SIV-), vehicle [VEH]/SIV, and CBA/SIV (N = 4-6/group) groups were proliferated (3 days) and differentiated (5 days) with 0 or 50 mM ethanol (short-term). CBA/SIV decreased differentiation and increased non-mitochondrial oxygen consumption rate (OCR) versus naïve and/or VEH/SIV. Short-term alcohol decreased differentiation; increased maximal and non-mitochondrial OCR, mitochondrial reactive oxygen species (ROS) production, and aldolase activity; and decreased glycolytic measures, ATP production, mitochondrial membrane potential (ΔΨm), and pyruvate kinase activity. Mitochondrial ROS production was closely associated with mitochondrial network volume, and differentiation indices were closely associated with key bioenergetic health and function parameters. Results indicate that short-term alcohol and CBA non-synergistically decrease myoblast differentiation capacity. Short-term alcohol impaired myoblast glycolytic function, driving the bioenergetic deficit. Results suggest potentially differing mechanisms underlying decreased differentiation capacity with short-term alcohol and CBA, highlighting the need to elucidate the impact of different alcohol use patterns on myopathy.

Cannabis Use Associates With Reduced Proviral Burden and Inflammatory Cytokine in Tissues From Men With Clade C HIV-1 on Suppressive Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis's effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored. METHODS: To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1ß, IL-6, IL-10, and TGF-ß1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use. RESULTS: The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1ß and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower. CONCLUSIONS: Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.

Impact of Cannabis Use on Immune Cell Populations and the Viral Reservoir in People With HIV on Suppressive Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus (HIV) infection remains incurable due to the persistence of a viral reservoir despite antiretroviral therapy (ART). Cannabis (CB) use is prevalent amongst people with HIV (PWH), but the impact of CB on the latent HIV reservoir has not been investigated. METHODS: Peripheral blood cells from a cohort of PWH who use CB and a matched cohort of PWH who do not use CB on ART were evaluated for expression of maturation/activation markers, HIV-specific T-cell responses, and intact proviral DNA. RESULTS: CB use was associated with increased abundance of naive T cells, reduced effector T cells, and reduced expression of activation markers. CB use was also associated with reduced levels of exhausted and senescent T cells compared to nonusing controls. HIV-specific T-cell responses were unaffected by CB use. CB use was not associated with intact or total HIV DNA frequency in CD4 T cells. CONCLUSIONS: This analysis is consistent with the hypothesis that CB use reduces activation, exhaustion, and senescence in the T cells of PWH, and does not impair HIV-specific CD8 T-cell responses. Longitudinal and interventional studies with evaluation of CB exposure are needed to fully evaluate the impact of CB use on the HIV reservoir.

Saline nasal irrigation and gargling in COVID-19: a multidisciplinary review of effects on viral load, mucosal dynamics, and patient outcomes.

With unrelenting SARS-CoV-2 variants, additional COVID-19 mitigation strategies are needed. Oral and nasal saline irrigation (SI) is a traditional approach for respiratory infections/diseases. As a multidisciplinary network with expertise/experience with saline, we conducted a narrative review to examine mechanisms of action and clinical outcomes associated with nasal SI, gargling, spray, or nebulization in COVID-19. SI was found to reduce SARS-CoV-2 nasopharyngeal loads and hasten viral clearance. Other mechanisms may involve inhibition of viral replication, bioaerosol reduction, improved mucociliary clearance, modulation of ENaC, and neutrophil responses. Prophylaxis was documented adjunctive to personal protective equipment. COVID-19 patients experienced significant symptom relief, while overall data suggest lower hospitalization risk. We found no harm and hence recommend SI use, as safe, inexpensive, and easy-to-use hygiene measure, complementary to hand washing or mask-wearing. In view of mainly small studies, large well-controlled or surveillance studies can help to further validate the outcomes and to implement its use.

Preliminary Effects of an Urban Gardens and Peer Nutritional Counseling Intervention on HIV Treatment Adherence and Detectable Viral Load Among People with HIV and Food Insecurity: Evidence from a Pilot Cluster Randomized Controlled Trial in the Dominican Republic.

A pilot cluster randomized controlled trial involving two HIV clinics in the Dominican Republic assessed preliminary efficacy of an urban garden and peer nutritional counseling intervention. A total of 115 participants (52 intervention, 63 control) with moderate or severe food insecurity and sub-optimal antiretroviral therapy (ART) adherence and/or detectable viral load were assessed at baseline, 6- and 12-months. Longitudinal multivariate regression analysis controlling for socio-demographics and accounting for serial cluster correlation found that the intervention: reduced the prevalence of detectable viral load by 20 percentage points at 12 months; reduced any missed clinic appointments by 34 and 16 percentage points at 6 and 12 months; increased the probability of "perfect" ART adherence by 24 and 20 percentage points at 6 and 12 months; and decreased food insecurity at 6 and 12 months. Results are promising and warrant a larger controlled trial to establish intervention efficacy for improving HIV clinical outcomes.Trial registry Clinical Trials Identifier: NCT03568682.

RESUMEN: Un estudio piloto de un ensayo controlado aleatorio por conglomerados que involucró a dos clínicas del VIH en la República Dominicana evaluó de forma preliminar la eficacia de una intervención de huertos urbanos y consejería nutricional entre pares. Un total de 115 participantes (52 de intervención, 63 de control) con inseguridad alimentaria moderada o grave y con adherencia subóptima a la terapia antirretroviral (TARV) y/o carga viral detectable fueron evaluados al inicio del estudio, y a los 6 y 12 meses. El análisis de regresión longitudinal multivariada controlando por variables sociodemográficas y tomando en cuenta la correlación serial de clúster encontró que la intervención: redujo la prevalencia de carga viral detectable en 20 puntos porcentuales a los 12 meses; redujo las citas clínicas perdidas en 34 y 16 puntos porcentuales a los 6 y 12 meses; aumentó la probabilidad de adherencia "perfecta" al TARV en 24 y 20 puntos porcentuales a los 6 y 12 meses; y disminuyó la inseguridad alimentaria a los 6 y 12 meses. Los resultados son prometedores y justifican un ensayo controlado más grande para establecer la eficacia de la intervención en mejorar los resultados clínicos del VIH.

Change in Nutritional and Biochemical Status in People Living with HIV-1 on Antiretroviral Therapy.

Antiretroviral therapy (ART) improves the quality of life of people living with HIV-1 (PLHIV) and reduces the mortality rate, but some individuals may develop metabolic abnormalities. This study evaluated changes in the nutritional status and biochemistry of PLHIV on antiretroviral therapy in a cohort that had not previously received ART and to follow up these individuals for 24 months after starting treatment. The initial cohort consisted of 110 individuals and ended with 42 people, assessed by a physical examination. A biochemical assay was performed using the colorimetric enzyme reaction technique, the proviral load was detected by qPCR and the quantification of the CD4/CD8 T lymphocytes was conducted by flow cytometry. PLHIV had increased levels of total cholesterol, LDL, triglycerides, ALT, urea and creatinine after 24 months of ART use (p < 0.05). In the assessment of the nutritional status, PLHIV had increased measures of Triciptal Skinfold, body mass index and arm circumference after the use of ART (p < 0.05). The viral load levels decreased and the CD4 levels increased after 24 months of ART use (p < 0.05). The change in the nutritional status in PLHIV on antiretroviral therapy seems to be a slow process, occurring in the long term, therefore, there is the need for a constant evaluation of these people to identify patients who need a nutritional intervention.

Cohort profile: the South African National Health Laboratory Service (NHLS) National HIV Cohort.

PURPOSE: South Africa's National Health Laboratory Service (NHLS) National HIV Cohort was established in 2015 to facilitate monitoring, evaluation and research on South Africa's National HIV Treatment Programme. In South Africa, 84.8% of people living with HIV know their HIV status; 70.7% who know their status are on ART; and 87.4% on ART are virologically suppressed. PARTICIPANTS: The NHLS National HIV Cohort includes the laboratory data of nearly all patients receiving HIV care in the public sector since April 2004. Patients are included in the cohort if they have received a CD4 count or HIV RNA viral load (VL) test. Using an anonymised unique patient identifier that we have developed and validated to linked test results, we observe patients prospectively through their laboratory results as they receive HIV care and treatment. Patients in HIV care are seen for laboratory monitoring every 6-12 months. Data collected include age, sex, facility location and test results for CD4 counts, VLs and laboratory tests used to screen for potential treatment complications. FINDINGS TO DATE: From April 2004 to April 2018, 63 million CD4 count and VL tests were conducted at 5483 facilities. 12.6 million unique patients had at least one CD4 count or VL, indicating they had accessed HIV care, and 7.1 million patients had a VL test indicating they had started antiretroviral therapy. The creation of NHLS National HIV Cohort has enabled longitudinal research on all lab-monitored patients in South Africa's national HIV programme, including analyses of (1) patient health at presentation; (2) care outcomes such as 'CD4 recovery', 'retention in care' and 'viral resuppression'; (3) patterns of transfer and re-entry into care; (4) facility-level variation in care outcomes; and (5) impacts of policies and guideline changes. FUTURE PLANS: Continuous updating of the cohort, integration with available clinical data, and expansion to include tuberculosis and other lab-monitored comorbidities.

A randomized control trial of high-dose micronutrient-antioxidant supplementation in healthy persons with untreated HIV infection.

BACKGROUND: Although micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH). METHODS: This study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/µL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/µL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months. RESULTS: Of 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/µL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/µL and -79.763 cells/µL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/µL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed. CONCLUSIONS: In ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00798772.

Clinical profile of HIV-infected adults receiving a holistic approach of care model in Nakawa, Kampala District.

People Living with HIV (PLHIV) are often dealing with a range of issues that make life more difficult because of the limited emotional, spiritual, psychological, social, physical and clinical support which consequently lead to poor physical health and quality of life. The holistic care of individuals infected with HIV/AIDS involves promoting psychological and physiological well-being as well as fostering socio-cultural relationships and supporting the fulfillment of spiritual aspirations. We conducted a retrospective cross-sectional study among HIV-infected patients receiving a holistic approach of care model from January 2015 to December 2018 in Kampala district, Uganda. The study involved adult individuals aged 18 and above from whom demographics and other information were obtained. All eligible participants were selected using stratified random sampling from the parishes and systematic random sampling to select study participants. We investigated the clinical profile and the factors associated with viral load suppression among HIV-infected patients receiving a holistic approach of care model in Kampala District. The data was analyzed using STATA version 13. 0. Results: A total of 910 patients were enrolled. 676 (74.3%) were female; 453 (49.8%) were between 18 and 39 years. 324 (35.6%) were either overweight or obese. 769 (84.5%) had viral load beyond detectable limits, 904 (99.3%) were adhering to HIV treatment. 867(95.3%) were virally suppressed. The age group 40-59 years (Adjusted Odds Ratio (aOR) = 2.85, 95% Confidence Interval (CI):1.36-5.97, P = 0.005) and good adherence (aOR = 12.9, 95%CI:1.86-81.07, P = 0.009) were significantly associated with viral load suppression. Conclusion: The holistic care model supports patients in all facets of their lives, resulting into improved treatment outcomes. Our findings show that age and adherence are linked to viral load suppression among HIV-infected adults receiving a holistic approach of care model.

Traditional Vietnamese medicine Kovir capsule in patients with mild COVID-19: A double-blind randomized controlled trial.

Kovir capsule, a polyherbal medicine developed from Ren Shen Bai Du San formulation, has been used in various diseases including respiratory infections. A randomized, placebo-controlled, double-blind study was conducted to evaluate the safety and efficacy of Kovir capsule (TD0069) in the treatment of mild COVID-19 patients. Patients aged from 18 to 65 years who were PCR-confirmed with SARS-CoV-2 and had the mild disease were recruited and randomized to either Kovir capsule (34 patients) or placebo (32 patients) for up to 14 days or until discharge. Efficacy outcomes were time to viral clearance, daily viral load, time to symptom resolution, daily symptom score based on 16 pre-defined symptoms, and progression to severe/critical COVID-19. Safety outcomes were adverse events. Viral load decreased over time similarly in the two groups. Viral clearance time was also similar in both groups (median: 8 days). Kovir group had a more rapid decrease of symptom score and significantly lower time to symptom resolution than placebo (median: 4 vs. 7 days). Two patients in the placebo group developed severe COVID-19. No patient experienced adverse events. Kovir capsule is safe and can improve symptom resolution in mild COVID-19 patients. A large-scale trial is required to confirm these findings.

Ascorbic acid addition during dehydration improves garlic shoot tip cryopreservation but does not affect viral load.

Cryopreservation is known be an effective method for virus elimination in garlic. However, oxidative damage during the cryopreservation seriously affects the survival of garlic after cryopreservation. Ascorbic acid (AsA) can reduce oxidative damage and improve regrowth following cryopreservation, and its effect may be influenced by the step during which it is added. In this study, AsA was added at the osmoprotection (O) and dehydration (DE) steps of cryopreservation. By observing the dynamic changes in cell viability and reactive oxygen species (ROS) components with different AsA treatments, AsA has been linked to the reduced accumulation of ROS in the shoot tips. Increased gene expression levels of antioxidant enzymes also explained the ROS scavenging effect of AsA. The correlation analysis between cell viability, ROS, membrane lipid peroxidation-related indicators and antioxidant-related indicators showed that membrane lipid peroxidation caused by excess ROS was the main factor affecting cell viability. Ascorbic acid added during dehydration minimized the accumulation of ROS from dehydration to dilution and alleviated the oxidative damage during cryopreservation. Thus, the survival and regrowth of the garlic was significantly improved after cryopreservation. Dehydration was found to be the suitable step for the addition of AsA during garlic cryopreservation. We further evaluated the virus elimination effect under optimal AsA treatment. However, there was no significant difference in virus content in regenerated plants when compared with the control.

Efficacy and safety of Mianyi granules (+mianyi+) for reversal of immune nonresponse following antiretroviral therapy of human immunodeficiency virus-1: a randomized, double-blind, multi-center, placebo-controlled trial.

OBJECTIVE: To investigate whether Mianyi granules (+mianyi+) are effective and safe in reversing immune nonresponse following antiretroviral therapy (ART) in individuals with human immunodeficiency virus (HIV) infection. METHODS: Randomized, double-blind, multi-center, placebo-controlled trial (factorial design) of daily oral Mianyi granules versus placebo for 72 weeks. A total of 361 HIV-positive individuals receiving ART at five Class III Grade I hospitals in China between September 2013 and January 2016 completed the study. The primary endpoints were frequencies of CD3+, CD4+, CD8+, and CD45RA+ cells at seven timepoints over the 72 weeks. Secondary endpoints included viral loads, clinical symptoms, and quality of life at 72 weeks. RESULTS: A total of 400 participants were enrolled in the study and randomized, of whom 361 completed the study: 189 individuals (140 men and 49 women) in the Mianyi granule group and 172 individuals (135 men and 37 women) in the placebo group. In the intent-to-treat population, CD4+ T cell counts increased from (193 ± 71) cells/mm at baseline to (288 ± 131) cells/mm post-treatment in the Mianyi granule group and from (200 ± 75) cells/mm at baseline to (264 ± 124) cells/mm post-treatment in the placebo group. Patients treated with Mianyi granule had higher increases in CD4+ T cell counts than those treated with placebo ( = 0.045). Reversal of immune nonresponse was defined as a CD4+ T cell increase of more than 100 cells/mm3. After treatment for 72 weeks, Mianyi granule was effective in reversing immune nonresponse in a higher proportion of individuals (20.2%) compared with placebo (9.7%). CD45RA+ cell counts increased from (34 ± 32) cell/mm at baseline to (51 ± 61) cells/mm post-treatment in the Mianyi granule group and from (37 ± 33) cells/mm at baseline to (48 ± 37) cells/mm post-treatment in the placebo group. Mianyi granules were more effective than placebo in increasing CD45RA+ cell counts. CONCLUSIONS: In ART-treated HIV-positive adults with immune nonresponse, treatment with Mianyi granules for 72 weeks was safe and significantly increased CD4+ and CD45RA+ cell counts, thereby promoting immune reconstitution.

Increased biomarkers of cardiovascular risk in HIV-1 viremic controllers and low persistent inflammation in elite controllers and art-suppressed individuals.

HIV controllers (HICs) are models of HIV functional cure, although some studies have shown persistent inflammation and increased rates of atherosclerosis in HICs. Since immune activation/inflammation contributes to the pathogenesis of cardiovascular diseases (CVD), we evaluated clinical data and inflammation markers in HIV-1 viremic controllers (VC), elite controllers (EC), and control groups (HIV positive individuals with virological suppression by antiretroviral therapy-cART; HIV negative individuals-HIVneg) to assess whether they presented elevated levels of inflammation markers also associated with CVD. We observed the highest frequencies of activated CD8+ T cells in VCs, while EC and cART groups presented similar but slightly altered frequencies of this marker when compared to the HIVneg group. Regarding platelet activation, both HICs groups presented higher expression of P-selectin in platelets when compared to control groups. Monocyte subset analyses revealed lower frequencies of classical monocytes and increased frequencies of non-classical and intermediate monocytes among cART individuals and in EC when compared to HIV negative individuals, but none of the differences were significant. For VC, however, significant decreases in frequencies of classical monocytes and increases in the frequency of intermediate monocytes were observed in comparison to HIV negative individuals. The frequency of monocytes expressing tissue factor was similar among the groups on all subsets. In terms of plasma markers, VC had higher levels of many inflammatory markers, while EC had higher levels of VCAM-1 and ICAM-1 compared to control groups. Our data showed that VCs display increased levels of inflammation markers that have been associated with CVD risk. Meanwhile, ECs show signals of lower but persistent inflammation, comparable to the cART group, indicating the potential benefits of alternative therapies to decrease inflammation in this group.

Targeting ectromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia.

Viral causes of pneumonia pose constant threats to global public health, but there are no specific treatments currently available for the condition. Antivirals are ineffective when administered late after the onset of symptoms. Pneumonia is caused by an exaggerated inflammatory cytokine response to infection, but tissue necrosis and damage caused by virus also contribute to lung pathology. We hypothesized that viral pneumonia can be treated effectively if both virus and inflammation are simultaneously targeted. Combined treatment with the antiviral drug cidofovir and etanercept, which targets tumor necrosis factor (TNF), down-regulated nuclear factor kappa B-signaling and effectively reduced morbidity and mortality during respiratory ectromelia virus (ECTV) infection in mice even when treatment was initiated after onset of clinical signs. Treatment with cidofovir alone reduced viral load, but animals died from severe lung pathology. Treatment with etanercept had no effect on viral load but diminished levels of inflammatory cytokines and chemokines including TNF, IL-6, IL-1ß, IL-12p40, TGF-ß, and CCL5 and dampened activation of the STAT3 cytokine-signaling pathway, which transduces signals from multiple cytokines implicated in lung pathology. Consequently, combined treatment with a STAT3 inhibitor and cidofovir was effective in improving clinical disease and lung pathology in ECTV-infected mice. Thus, the simultaneous targeting of virus and a specific inflammatory cytokine or cytokine-signaling pathway is effective in the treatment of pneumonia. This approach might be applicable to pneumonia caused by emerging and re-emerging viruses, like seasonal and pandemic influenza A virus strains and severe acute respiratory syndrome coronavirus 2.

Effect of Silymarin as an Adjunct Therapy in Combination with Sofosbuvir and Ribavirin in Hepatitis C Patients: A Miniature Clinical Trial.

Silymarin is proclaimed to be a blend of flavonolignans or phytochemicals. An era of new generation of direct-acting antivirals (DAAs) has commenced to have facet effect in swaying of the hepatitis C virus (HCV). Nonetheless, this therapy has serious side effects that jeopardize its efficacy. This study is aimed at probing the effects of ribavirin (RBV) and sofosbuvir (SOF) along with silymarin as an adjunct therapy on hematological parameters and markers of obscured oxidative stress. The effect of DAAs along with silymarin was also examined on variable sex hormone level and liver function markers such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin. The study was followed to determine viral load and viral genotypes. A total of 30 patients were randomly divided into two equal groups comprising the control group (n = 15) and treatment group (n = 15). The control group was solely administered with DAAs (SOF and RBV; 400 mg/800 mg each/day). Conversely, the treatment group was dispensed with DAAs, but with adjunct therapy of silymarin (400 mg/day) along with DAAs (400/800 mg/day) over period of 8 weeks. Sampling of blood was performed at pre- and posttreatment levels for the evaluation of different propound parameters. Our data showed that silymarin adjunct therapy enhances the efficiency of DAAs. A decrease in menace level of liver markers such as ALT, ALP, AST, and bilirubin was observed (p > 0.05). The adjunct therapy concurrently also demonstrated an ameliorative effect on hematological indices and oxidative markers, for instance, SOD, TAS, GSH, GSSG, and MDA (p < 0.05), diminishing latent viral load. The silymarin administration was also found to revamp the fluster level of sex hormones. Our outcomes provide evidence that systematic administration of silymarin effectively remits deviant levels of hematological, serological, hormonal, and antioxidant markers. This demonstrates a possibly unique role of silymarin in mitigating hepatitis C.

Potential immune modulatory effect of vitamin D in HIV infection: A review.

Vitamin D is a fat soluble hormone that is majorly involved in the classical function of calcium and phosphorus hemostasis and bone mineralization as well non classical functions of immune modulation in various viral and autoimmune diseases. Both innate and adaptive immunity is aided by vitamin D. Deficiency of vitamin D is not only linked with bone and muscle disorders but it has a critical role in many infectious and noninfectious diseases. A growing body of literature suggests vitamin D deficiency in human immunodeficiency virus (HIV) infected patients. HIV affects 36.7 million people worldwide. Currently a valuation of 0.13 million people are infected with acquired immunodeficiency syndrome (AIDS) in Pakistan. Various studies showed that hypovitaminosis D may aggravate the disease severity in HIV patients by compromising the immune system. Calcidiol supplementation is credibly a promising adjuvant of combination anti-retroviral therapy (cART) for the treatment of HIV by increasing CD4 T-cells and lowering the viral load. This review accentuates vitamin D's functions as an immune modulator in HIV, the effect of hypovitaminosis D in diseases severity, and its supplementation impact on the treatment of HIV infected patients.

Ephedrae Herba and Cinnamomi Cortex interactions with G glycoprotein inhibit respiratory syncytial virus infectivity.

Although respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in children, no effective therapies are available. Recently, RSV G, the attachment glycoprotein, has become a major focus in the development of therapeutic strategies against RSV infection. Treatment of RSV-infected cultured cells with maoto, a traditional herbal medicine for acute febrile diseases, significantly reduced the viral RNA and titers. RSV attachment to the cell surface was inhibited both in the presence of maoto and when RSV particles were pre-treated with maoto. We demonstrated that maoto components, Ephedrae Herba (EH) and Cinnamomi Cortex (CC), specifically interacted with the central conserved domain (CCD) of G protein, and also found that this interaction blocked viral attachment to the cellular receptor CX3CR1. Genetic mutation of CX3C motif on the CCD, the epitope for CX3CR1, decreased the binding capacity to EH and CC, suggesting that CX3C motif was the target for EH and CC. Finally, oral administration of maoto for five days to RSV-infected mice significantly reduced the lung viral titers. These experiments clearly showed the anti-RSV activity of EH and CC mixed in maoto. Taken together, this study provides insights for the rational design of therapies against RSV infection.

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

Effect of a ward-based outreach team and adherence game on retention and viral load suppression

Background: Only 66% of South African people living with HIV (PLWH) are virologically suppressed. Therefore, it is important to develop strategies to improve outcomes.Objectives: Assess the effect of interventions on 12-month retention in care and virological suppression in participants newly initiated on antiretroviral therapy.Method: Fifty-seven clinics were randomised into four arms: Ward-based primary health care outreach teams (WBPHCOTs); Game; WBPHCOT­Game in combination; and Control (standard of care). Sixteen clinics were excluded and four re-allocated because lay counsellors and operational team leaders failed to attend the required training. Seventeen clinics were excluded due to non-enrolment. Results: A total of 558 participants from Tshwane district were enrolled. After excluding ineligible participants, 467 participants were included in the analysis: WBPHCOTs (n = 72); Games (n = 126); WBPHCOT­Games (n = 85); and Control (n = 184). Retention in care at 12 months was evaluable in 340 participants (86.2%) were retained in care and 13.8% were lost to follow-up. The intervention groups had higher retention in care than the Control group, but this only reached statistical significance in the Games group (96.8% vs 77.8%; relative risk [RR] 1.25; 95% confidence interval [CI]: 1.13­1.38; P = 0.01). The 12 month virologic suppression rate was 75.3% and was similar across the four arms.Conclusion: This study demonstrated that an adherence game intervention could help keep PLWH in care.What this study adds: Evidence that interventions, especially Games, could improve retention in care