BACKGROUND: Inflammation has been associated with whole heart coronary artery calcification (CAC) among people with HIV (PWH) on antiretroviral therapy (ART); however, prior studies have not evaluated the distribution of...BACKGROUND: Inflammation has been associated with whole heart coronary artery calcification (CAC) among people with HIV (PWH) on antiretroviral therapy (ART); however, prior studies have not evaluated the distribution of calcium or separated mass versus volume scores, which are differentially associated with clinical events in the general population. Statins may also have a greater effect on CAC mass compared with volume. METHODS: 147 PWH were randomized 1:1 to rosuvastatin 10 mg or placebo and followed for 96 weeks. We re-analysed coronary calcium scans from 0, 48 and 96 weeks to determine mass and volume scores and measures of CAC diffusivity. Mixed effects models and generalized estimating equations were used to examine longitudinal associations of CAC with treatment and biomarkers. RESULTS: Median age at study entry was 46 years; 78% were male and 68% African American. Median CD4+ was 613 and half were on protease inhibitors. Randomization to statin therapy was not associated with a change in mass score, volume score, number of involved vessels or diffusivity index (all P>0.1). Soluble CD14 was associated with the presence of CAC (P=0.05) and borderline associated with number of involved vessels (P=0.07) across all three time points. CONCLUSIONS: In PWH on ART, moderate intensity rosuvastatin does not appear to have a significant effect on volume, mass or regional distribution of CAC over 96 weeks. We extend previous cross-sectional observations to show that soluble CD14 is associated with whole heart CAC over time and independently of age and systolic blood pressure.
Jiamsakul A, Azwa I, Zhang F
… +21 more, Yunihastuti E, Ditangco R, Kumarasamy N, Ng OT, Chan YJ, Ly PS, Choi JY, Lee MP, Pujari S, Kiertiburanakul S, Chaiwarith R, Merati TP, Sangle S, Khusuwan S, Sim BL, Avihingsanon A, Duy C, Tanuma J, Ross J, Law M, Asia-Pacific TAHODOI
BACKGROUND: The World Health Organization recommends continuation with the failing second-line regimen if third-line option is not available. We investigated treatment outcomes among people living with HIV in Asia who co...BACKGROUND: The World Health Organization recommends continuation with the failing second-line regimen if third-line option is not available. We investigated treatment outcomes among people living with HIV in Asia who continued with failing second-line regimens compared with those who had treatment modifications after failure. METHODS: Treatment modification was defined as a change of two antiretrovirals, a drug class change or treatment interruption (TI), all for >14 days. We assessed factors associated with CD4 changes and undetectable viral load (UVL <1,000 copies/ml) at 1 year after second-line failure using linear and logistic regression, respectively. Survival time was analysed using competing risk regression. RESULTS: Of the 328 patients who failed second-line ART in our cohorts, 208 (63%) had a subsequent treatment modification. Compared with those who continued the failing regimen, the average CD4 cell increase was higher in patients who had a modification without TI (difference =77.5, 95% CI 35.3, 119.7) while no difference was observed among those with TI (difference =-5.3, 95% CI -67.3, 56.8). Compared with those who continued the failing regimen, the odds of achieving UVL was lower in patients with TI (OR=0.18, 95% CI 0.06, 0.60) and similar among those who had a modification without TI (OR=1.97, 95% CI 0.95, 4.10), with proportions of UVL 60%, 22% and 75%, respectively. Survival time was not affected by treatment modifications. CONCLUSIONS: CD4 cell improvements were observed in those who had treatment modification without TI compared with those on the failing regimen. When no other options are available, maintaining the same failing ART combination provided better VL control than interrupting treatment.
This is a report of a case of severe intraocular inflammation associated with cytomegalovirus in an untreated HIV+ patient with a marked CD4 T-cell depletion. The atypical presentation shown could confuse and delay the d...This is a report of a case of severe intraocular inflammation associated with cytomegalovirus in an untreated HIV+ patient with a marked CD4 T-cell depletion. The atypical presentation shown could confuse and delay the diagnosis. Early suspicion and appropriate treatment (ganciclovir, valganciclovir, HAART) increase the likelihood of a favourable outcome.
BACKGROUND: Both falls and fractures are increased in older persons living with HIV (PLWH). Low serum total 25-hydroxyvitamin D (25-OHD) levels have been associated with falls, fractures and poor muscle strength. We hypo...BACKGROUND: Both falls and fractures are increased in older persons living with HIV (PLWH). Low serum total 25-hydroxyvitamin D (25-OHD) levels have been associated with falls, fractures and poor muscle strength. We hypothesized that vitamin D (VitD) supplementation would improve muscle strength in postmenopausal PLWH. METHODS: In a 12-month prospective, randomized, double-blind, study of 69 African American and Hispanic postmenopausal PLWH on antiretroviral therapy with 25-OHD ≥10 ng/ml and ≤32 ng/ml, we investigated the effects of daily low (1,000 IU; n=31) and moderate (3,000 IU; n=38) cholecalciferol doses on lean mass and strength. Change in lean body mass was assessed by dual-energy X-ray absorptiometry (DXA), and isometric and isokinetic muscle strength in the dominant lower extremity was assessed using the Biodex System 4 Pro. RESULTS: Mean age was 56 ±5 years, median CD4 T-cell count 722 cells/mm and 74% had HIV RNA≤50 copies/ml. Serum 25-OHD did not differ at baseline, but was higher in the moderate than low VitD group at 6 and 12 months. In both groups, there were significant increases in lower extremity isokinetic torque, work and power at 12 months, with no change in lean mass. CONCLUSIONS: VitD supplementation was associated with a modest increase in lower extremity strength in postmenopausal PLWH, without a concomitant increase in muscle mass. Magnitude of increase in strength were similar with 3,000 IU and 1,000 IU daily. Future larger studies will be required to determine the optimal dose of VitD to improve muscle strength and to determine whether supplementation reduces the risk of falls and fractures in PLWH.
BACKGROUND: Herpes simplex virus 1 (HSV-1) affects a large part of the adult population. Anti-HSV-1 drugs, such as acyclovir, target thymidine kinase and viral DNA polymerase. However, the emerging of resistance of HSV-1...BACKGROUND: Herpes simplex virus 1 (HSV-1) affects a large part of the adult population. Anti-HSV-1 drugs, such as acyclovir, target thymidine kinase and viral DNA polymerase. However, the emerging of resistance of HSV-1 alerts for the urgency in developing new antivirals with other therapeutic targets. Thus, this study evaluated a series of 1,4-disubstituted-1,2,3-triazole derivatives against HSV-1 acute infection and provided deeper insights into the possible mechanisms of action. METHODS: Human fibroblast cells (HFL-1) were infected with HSV-1 17syn+ and treated with the triazole compounds at 50 μM for 24 h. The 50% effective drug concentration (EC) was determined for the active compounds. Their cytotoxicity was also evaluated in HFL-1 with the 50% cytotoxic concentration (CC) determined using CellTiter-Glo solution. The most promising compounds were evaluated by virucidal activity and influence on virus egress, DNA replication and transcription, and effect on an acyclovir-resistant HSV-1 strain. RESULTS: Compounds 3 ((E)-4-methyl-N'-(2-(4-(phenoxymethyl)-1H-1,2,3-triazol1yl)benzylidene)benzenesulfonohydrazide) and 4 (2,2'-(4,4'-((1,3-phenylenebis(oxy))bis(methylene))bis(1H-1,2,3-triazole-4,1 diyl)) dibenzaldehyde) were the most promising, with an EC of 16 and 21 μM and CC of 285 and 2,593 μM, respectively. Compound 3 was able to inhibit acyclovir-resistant strain replication and to interfere with virus egress. Both compounds did not affect viral DNA replication, but inhibited significantly the expression of ICP0, ICP4 and gC. Compound 4 also affected the transcription of UL30 and ICP34.5. CONCLUSIONS: Our findings demonstrated that these compounds are promising antiviral candidates with different mechanisms of action from acyclovir and further studies are merited.
BACKGROUND: The HIV protease inhibitor lopinavir, boosted with ritonavir, has been used off-label to treat COVID-19. We aimed to synthesize the clinical evidence for lopinavir/ritonavir as a treatment for COVID-19. METHO...BACKGROUND: The HIV protease inhibitor lopinavir, boosted with ritonavir, has been used off-label to treat COVID-19. We aimed to synthesize the clinical evidence for lopinavir/ritonavir as a treatment for COVID-19. METHODS: We performed a rapid review by searching databases including PubMed, GoogleScholar, medRxiv, ClinicalTrials.gov and the Cochrane COVID-19 Study Register, for COVID-19 studies comparing outcomes between patients who did and did not receive lopinavir/ritonavir. The quality of evidence was assessed using the GRADE criteria. RESULTS: We identified five completed randomized controlled trials (RCTs) and 14 retrospective cohort studies. Two large RCTs of 5,040 and 2,771 hospitalized adults with COVID-19 found no evidence that lopinavir/ritonavir influenced the primary outcome of mortality, or secondary outcomes including progression to mechanical ventilation or time to discharge. Results remained similar in all sub-group analyses including by age, gender, baseline ventilation and time since symptom onset. The three smaller RCTs (n=86-199) also found no evidence of a benefit in the primary outcomes of time to clinical improvement or time to viral clearance. The 14 observational studies included between 50 and 415 participants, and were limited by a lack of adjustment for potential confounding variables. The majority of these studies found no evidence that lopinavir/ritonavir was associated with improved mortality or other clinical outcomes, although results regarding viral clearance were mixed. CONCLUSIONS: Good evidence from large clinical trials does not support using lopinavir/ritonavir to treat COVID-19 amongst hospitalized patients.
BACKGROUND: Viral infections are among the most common problems in health-care practice. Natural products offer great promise as potentially effective antiviral drugs. Propolis is a honeybee product with biological prope...BACKGROUND: Viral infections are among the most common problems in health-care practice. Natural products offer great promise as potentially effective antiviral drugs. Propolis is a honeybee product with biological properties and therapeutic applications. We aimed to investigate the antiviral activity of different extracts of Standardized Propolis Preparations (M.E.D.®) with glycol, ethanol, glycerol and soya oil, against herpes simplex type-1 (HSV-1) and type 2 (HSV-2) viruses. METHODS: Chemical composition and antiviral activity of each extract were determined. The selective index (SI=CC/EC) was determined as a parameter to indicate the in vitro antiviral activity of the extracts compared with acyclovir as the control. RESULTS: SI values of glycol, ethanol, glycerol, soya oil extracts and acyclovir were determined as 6.8, 4.1, 2.2, 3.3 and 6.3 against HSV-1, and as 6.4, 7.7, 1.9, 4.2 and 2.9 against HSV-2, respectively. Glycolic propolis extract was found to possess a greater antiviral activity than acyclovir for both HSV-1 and 2, while glycolic, ethanolic and soya oil preparations were found to have more significant activity than acyclovir for HSV-2. CONCLUSIONS: It was determined that standardized propolis preparations have antiviral bioactivity against HSV.
Many studies showed the existence of a positive association between cytomegalovirus (CMV) seropositivity and all-cause mortality. In this paper, we use the microcompetition model to explain how the latent CMV sequesters...Many studies showed the existence of a positive association between cytomegalovirus (CMV) seropositivity and all-cause mortality. In this paper, we use the microcompetition model to explain how the latent CMV sequesters the limiting GABP∙p300/CBP transcription complex, which causes abnormal cellular gene expression, a chronic disease and mortality. Since most people harbour the latent CMV, we urge further research on this topic.
The 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major burden worldwide, resulting in serious public health challenges. HBV infection is anot...The 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major burden worldwide, resulting in serious public health challenges. HBV infection is another widely spread virus that chronically affects about 257 million people. The management of patients with HBV infection has gained attention in the context of the COVID-19 pandemic. Patients with COVID-19 have varying levels of liver involvements, resulting from direct viral effects on the liver as well as hepatotoxic drugs. This was demonstrated by elevated levels of liver enzymes, particularly evident in those patients with severe SARS-CoV-2 infection. However, scarce information is available on the management of COVID-19 patients having an underlying chronic liver disease, including HBV infection. Studies have shown reactivation of HBV infection following treatment with tocilizumab and corticosteroids, emphasizing the need for caution when using these agents to treat COVID-19 patients with HBV infection. HBV screening and prophylaxis should be considered in patients with elevated transaminase levels and also in high prevalence populations. In patients with advanced liver disease, attention must be given to minimize the risk of liver decompensation. Nevertheless, further investigation is needed to enable an evidence-based approach for the care of these patients.
Trunfio M, Salvador E, Gaviraghi A
… +10 more, Audagnotto S, Marinaro L, Motta I, Casciaro R, Ghisetti V, Fava C, Bonora S, Di Perri G, Calcagno A, e-COVID Study Group
BACKGROUND: Antiviral and immune-modulating properties of low-molecular-weight heparin (LMWH) against Coronaviridae have been reported by in vitro studies, but no in vivo evidence is yet available. We sought to know whet...BACKGROUND: Antiviral and immune-modulating properties of low-molecular-weight heparin (LMWH) against Coronaviridae have been reported by in vitro studies, but no in vivo evidence is yet available. We sought to know whether the timing of prophylactic doses of LMWH during the course of COVID-19 may affect the time to SARS-CoV-2 nasal-oropharyngeal swab negativization. METHODS: Retrospective monocentric cross-sectional study on patients requiring sub-intensive ward admission due to first SARS-CoV-2 infection and undergoing early (EH; within 7 days from COVID-19 signs and symptoms onset) versus delayed prophylactic LMWH (DH; after 7 days). SARS-CoV-2 RNA was measured by reverse transcription real-time PCR according to scheduled time points: first swab after 2 weeks from COVID-19 onset, then at 1-week intervals until negativity. RESULTS: Time to SARS-CoV-2 swab negativity was shorter in EH (38 patients) compared with DH (55 patients): 22 versus 37 days (P=0.004). The number of confirmative negative swabs in EH was significantly higher compared with DH at week 2 (21.1% versus 3.6%; P=0.017) and 4 (60.0% versus 19.6%; P<0.001). At univariate, EH differed from DH for several disease severity and clinical management parameters. Nevertheless, after accounting for the differences, Cox regression showed early LMWH administration (hazard ratio [HR] 2.91 [1.51, 5.63]; P=0.002) and higher lymphocytes nadir (HR 1.04 [1.01, 1.08]; P=0.020) as predictors of shorter time to swab negativity. CONCLUSIONS: This potential antiviral and/or immune-modulating activity of LMWH needs further in vivo confirmations by randomized controlled trials.
BACKGROUND: To compare effectiveness and safety of initial antiretroviral therapy (ART) among premenopausal and postmenopausal women living with HIV aged 45-60 years from the cohort of the Spanish HIV/AIDS Research Netwo...BACKGROUND: To compare effectiveness and safety of initial antiretroviral therapy (ART) among premenopausal and postmenopausal women living with HIV aged 45-60 years from the cohort of the Spanish HIV/AIDS Research Network (CoRIS) who initiated ART between 2004 and 2015. METHODS: Multivariable regression models were used to compare post- versus premenopausal women regarding viral suppression (≤50 copies/ml), change in CD4 T-cell count and time to treatment change (TC) at 48 and 96 weeks after ART initiation. RESULTS: Among 230 women, 154 (67%) were premenopausal at ART initiation. The most frequent initial regimen was tenofovir disoproxil fumarate/emtricitabine/efavirenz prescribed in 49 (32%) premenopausal and 22 (29%) postmenopausal women. The proportion of TC was 35.7% and 30.3% at 48 weeks and 51.3% and 47.4% at 96 weeks, for pre- and postmenopausal women, respectively. There were no significant differences in CD4 T-cell count changes from ART initiation, viral load suppression, time to TC or reason for TC between both groups. The main reason for TC was occurrence of an adverse event, followed by simplification, in both groups. CONCLUSIONS: ART effectiveness and safety did not differ significantly between pre- and postmenopausal women.
Bijker R, Kumarasamy N, Kiertiburanakul S
… +12 more, Pujari S, Ng OT, Sun LP, Merati TP, Van Nguyen K, Lee MP, Cuong DD, Chan YJ, Choi JY, Ross J, Law M, IeDEA Asia-Pacific
BACKGROUND: Comprehensive treatment and clinical management are central to improving outcomes for people living with HIV (PLHIV). We explored trends in HIV clinical care, treatment outcomes, and chronic kidney disease (C...BACKGROUND: Comprehensive treatment and clinical management are central to improving outcomes for people living with HIV (PLHIV). We explored trends in HIV clinical care, treatment outcomes, and chronic kidney disease (CKD) and diabetes monitoring. METHODS: We included patients ≥18 years in care at ten clinical sites in eight Asian countries. Proportions of patients on antiretroviral therapy (ART), with annual viral load, and with viral load suppression (VLS; <1,000 copies/ml) were estimated by year for 2011-2016, stratified by country income level (lower-middle income [LMIC] and high-income countries [HIC]). Among those on ART in 2016 we evaluated factors associated with annual CKD and diabetes monitoring. RESULTS: Among 31,346 patients (67% male), the proportions of patients on ART (median ART initiation year 2011, IQR 2007-2013), with annual viral load and VLS had substantially increased by 2016 (to 94%, 42% and 92%, respectively, in LMIC and 95%, 97% and 93%, respectively, in HIC) with the larger increases over time seen in LMIC. Among those on ART in 2016, monitoring proportions in LMIC were 53% for CKD and 26% for diabetes compared with 83% and 59%, respectively, in HIC. Overall, a decreased odds of monitoring was observed for male gender, heterosexual HIV exposure, no viral load and LMIC. Diabetes monitoring was also decreased in those with viral failure. CONCLUSIONS: Our findings highlight suboptimal monitoring of viral load, CKD and diabetes in PLHIV in Asia. There is a need for affordable and scalable monitoring options to improve the joint care for HIV and non-communicable diseases.
Floridia M, Masuelli G, Tassis B
… +13 more, Franceschetti L, Savasi VM, Spinillo A, Tamburrini E, Guaraldi G, Dalzero S, Sansone M, Chiodo A, Antoni AMD, Pinnetti C, Liuzzi G, Ravizza M, Italian Group on Surveillance of Antiretroviral Treatment in Pregnancy
BACKGROUND: No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. METHODS: Data from a national cohort study were used. We compared absolute weight gain an...BACKGROUND: No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. METHODS: Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. RESULTS: Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4 T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). CONCLUSIONS: No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.
Several antiretrovirals including dolutegravir, rilpivirine and cobicistat inhibit tubular creatinine secretion, leading to benign increases in serum creatinine and reductions in estimated glomerular filtration rate (eGF...Several antiretrovirals including dolutegravir, rilpivirine and cobicistat inhibit tubular creatinine secretion, leading to benign increases in serum creatinine and reductions in estimated glomerular filtration rate (eGFR). This commentary discusses the magnitude and pattern of eGFR decline, whether this can be overcome by applying a standardized correction factor (as reported by Brunet et al. in Antiviral Therapy), the value of serial eGFR measures to detect rapid eGFR decline and the potential utility of cystatin C as an alternative biomarker of kidney function.
BACKGROUND: For patients with HBV infection who have decompensated cirrhosis (DC), a higher dose (1.0 mg/day) of entecavir is recommended than that used for those with compensated disease (0.5 mg/day), though with very l...BACKGROUND: For patients with HBV infection who have decompensated cirrhosis (DC), a higher dose (1.0 mg/day) of entecavir is recommended than that used for those with compensated disease (0.5 mg/day), though with very little supporting data. We therefore compared the viral suppression achieved with 0.5 mg/day and 1.0 mg/day of entecavir in patients with HBV-related DC (NCT03345498). METHODS: Treatment-naive patients with HBV-related DC and serum HBV DNA titre exceeding 100,000 IU/ml received either dose of entecavir for 24 weeks. HBV DNA concentration was measured in blood specimens collected at baseline and after 2, 4, 8, 12 and 24 weeks of entecavir treatment. RESULTS: Participants in the 0.5 mg/day (n=13) and 1.0 mg/day (n=16) groups had similar baseline hepatitis B e antigen (HBeAg) positivity rates (12/13 and 12/16; P=0.34) and median (range) log serum HBV DNA levels (6.81 [5.01-8.12] and 7.45 [5.24-8.65]; P=0.17). The two doses led to similar reductions in serum HBV DNA levels after 2, 4, 8, 12 and 24 weeks of entecavir administration. At 24 weeks, 3 of the 13 patients receiving 0.5 mg/day and 1 of the 16 patients receiving 1.0 mg/day of entecavir had undetectable serum HBV DNA. Serum albumin level showed significant and similar improvement at the end of 24 weeks in the two groups. CONCLUSIONS: Treatment-naive patients with HBV-related DC can be treated with entecavir in a 0.5 mg/day dose instead of the higher 1.0 mg/day dose, without compromising the degree of virological suppression. ClincialTrials.gov number NCT03345498.
Nucleos(t)ide analogues (NAs) are a mainstay of therapy for chronic hepatitis B (CHB) infections and have a profound effect on hepatitis B virus (HBV) suppression. We report a rare case of HBV reactivation in a CHB patie...Nucleos(t)ide analogues (NAs) are a mainstay of therapy for chronic hepatitis B (CHB) infections and have a profound effect on hepatitis B virus (HBV) suppression. We report a rare case of HBV reactivation in a CHB patient without cirrhosis following cessation of NA therapy that resulted in acute liver failure requiring liver transplantation. Investigation of the viral genetics and host immune responses suggest that viral mutations known to promote virus replication are associated with reactivation, whereas adaptive immunity to HBV remained defective in this patient. Viral sequencing may be useful for identifying mutations that are unfavorable for therapy withdrawal.
BACKGROUND: Pharmacokinetics and safety of JNJ-64530440, a hepatitis B virus capsid assembly modulator producing normal empty capsids (CAM-N), in healthy volunteers were evaluated. METHODS: This Phase I study (NCT0343948...BACKGROUND: Pharmacokinetics and safety of JNJ-64530440, a hepatitis B virus capsid assembly modulator producing normal empty capsids (CAM-N), in healthy volunteers were evaluated. METHODS: This Phase I study (NCT03439488) was a double-blind, randomised, placebo-controlled study. Adults ( = 10/cohort, five Asian/five non-Asian), randomised 4:1, received single-ascending doses of oral JNJ-64530440 (first- and second-generation formulations) or placebo under fasted (50, 150, 300 and 900 mg) or fed (300, 750, 1,000, 2000 and 4000 mg) conditions. Multiple-ascending doses of 750 or 2000 mg once daily and 750 mg twice daily JNJ-64530440 (second-generation formulation) for 7 days were evaluated. Pharmacokinetic parameters were estimated from plasma concentrations. Safety was assessed throughout. RESULTS: Less than dose-proportional increases in maximum plasma concentrations (C) and area under the plasma concentration-time curves (AUCs) were observed across the doses. Mean plasma half-lives ranged from 9.3 to 14.5 h. C and AUC were ∼two fold higher under fed versus fasting conditions and slightly higher in Asians versus Caucasians. JNJ-64530440 doses ≥750 mg achieved plasma levels higher than protein-binding adjusted concentrations demonstrating antiviral activity. No serious adverse events (AEs), treatment discontinuations or dose-limiting toxicities were seen. AE frequency/severity did not increase with dose. CONCLUSIONS: Single (up to 4000 mg) and multiple doses (up to 2000 mg for 7 days) of JNJ-64530440 were well tolerated in healthy volunteers. Multiple doses ≥750 mg/day achieved plasma concentrations expected to have antiviral activity that may lower hepatitis B surface antigen. No clinically relevant differences in tolerability or pharmacokinetic parameters were seen between Asians versus Caucasians.
BACKGROUND: Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) are both being used to treat coronavirus disease 2019 (COVID-19), but their relative effectiveness is unknown. The purpose of this study was to compare...BACKGROUND: Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) are both being used to treat coronavirus disease 2019 (COVID-19), but their relative effectiveness is unknown. The purpose of this study was to compare the clinical outcomes of patients treated for COVID-19 with LPV/r or HCQ. METHODS: A retrospective observational study was conducted at 2 hospitals in Busan, South Korea, where approximately 90% of COVID-19 patients were hospitalised during February/March 2020. All patients aged ≥15 years that were hospitalised with mild or moderately severe COVID-19 received LPV/r or HCQ as their initial treatment and were included in the analysis. RESULTS: Among the 72 patients with mild-to-moderate disease severity on admission, 45 received LPV/r and 27 received HCQ as their initial therapy. A higher proportion of the LPV/r group had pneumonia on admission (LPV/r, 49% vs HCQ, 15%), but there were no other significant differences in the demographic or clinical characteristics between groups. Switching therapy due to clinical failure was significantly more common in the HCQ group than in the LPV/r group (41% [11/27] and 2% [1/45], respectively, .001). Disease progression was also significantly more common in the HCQ group than in the LPV/r group (44% [12/27] and 18% [8/45], respectively, = .030). CONCLUSION: Based on our study results, HCQ shows no apparent advantage compared to LPV/r for preventing progression to severe disease in patients with COVID-19.
BACKGROUND: Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4 cell counts in...BACKGROUND: Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4 cell counts in this association is poorly defined. We aimed to determine whether HIV-HBV co-infection influences changes in CD4 cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4. METHODS: 2052 HIV-positive participants from Côte d'Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4 cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4 counts ≤350, 351-500, >500/mm and were compared between HBV-status groups as incidence rate ratios (IRR). RESULTS: At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA <2000 IU/mL, 55 (29%) ≥2000 IU/mL]. Follow-up was a median 58 months (IQR = 40-69). Between co-infection groups, there were no differences in CD4 decline before ART initiation and no differences in CD4 increase after ART initiation. After adjusting for sex, age, baseline HIV RNA level, and early/deferred ART arm, mortality rates were not significantly different between HBsAg-positive versus HBsAg-negative participants across strata of CD4 levels. However, HBsAg-positive individuals with HBV-DNA ≥2000 IU/mL versus HBsAg-negative individuals had increased mortality rates at ≤350/mm (adjusted-IRR = 3.82, 95% CI = 1.11-9.70) and 351-500/mm (adjusted-IRR = 4.37, 95% CI = 0.98-13.02), but not >500/mm (adjusted-IRR = 1.07, 95% CI = 0.01-4.91). CONCLUSION: Despite no effect of HBV-infection on CD4 levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4 is <500/mm.
HSV-1 is associated with oral lesions. Recently, anti-herpetic activity of different plant species has been investigated. In this study, the effects of Artemisia aucheri aqueous extract on the HSV-1 virus-infected Vero c...HSV-1 is associated with oral lesions. Recently, anti-herpetic activity of different plant species has been investigated. In this study, the effects of Artemisia aucheri aqueous extract on the HSV-1 virus-infected Vero cells were assessed. The highest cell viability occurred in plant aqueous extracts was with a concentration of 75 μg/mL, 1-2 h before viral infection. The IC50 of the aqueous extract of 24.7 μg/ml was calculated. Most percentage of infected cell inhibition (89.6%) was with the chloroform fraction in concentration of 75 μg/ml, and the least percentage of infected cell inhibition (21.7%) was in concentration of 12.5 μg/ml with the ethyl acetate fraction in comparison with untreated control. Moreover, Q-PCR results revealed that the expression of genes UL46 and US6 were significantly reduced in the presence of different treatments utilized in the experiment. In conclusion, the present study proposes that aqueous extracts of medicinal plant have anti-viral property and may be considered as a remedy for HSV-1 treatment.