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Antivir Ther 2021 Apr 26. Epub 2021 Apr 26.

School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

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 vs. volume scores, which are differentially associated with clinical events in the general population. Statins may also have a greater effect on CAC mass compared to volume. Read More

Antivir Ther 2021 Apr 12. Epub 2021 Apr 12.

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

Background: The World Health Organisation 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 to 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. Read More

Antivir Ther 2020 ;25(6):341-344

Servicio de Reumatología, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.

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. Read More

Antivir Ther 2020 ;25(8):411-418

Columbia University Irving Medical Center, New York, NY, USA.

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. Read More

Antivir Ther 2020 ;25(8):399-410

LAMCIFAR, Laboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas, Universidade Federal do Rio de Janeiro, Macaé, Rio de Janeiro, Brazil.

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. Read More

Antivir Ther 2020 ;25(7):365-376

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

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. Read More

Antivir Ther 2020 ;25(7):353-363

Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey.

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. Read More

Antivir Ther 2020 ;25(7):419-424

School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

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. Read More

Antivir Ther 2020 ;25(8):389-397

Liver Unit, Vall d'Hebron University Hospital, Barcelona, Spain.

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. Read More

Antivir Ther 2020 ;25(6):327-333

Department of Medical Sciences, University of Turin at the Unit of Infectious Diseases, "Amedeo di Savoia" Hospital, Turin, Italy.

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). Read More

Antivir Ther 2020 ;25(6):335-340

HIV Surveillance Unit, Centro Nacional de Epidemiologia, Institute of Health Carlos III, Madrid, Spain.

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. Read More

Antivir Ther 2020 ;25(5):275-285

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

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. Read More

Antivir Ther 2020 ;25(6):315-325

Department of Obstetrics and Gynaecology, DMSD San Paolo Hospital Medical School, University of Milan, Milan, Italy.

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). Read More

Antivir Ther 2020 ;25(5):241-243

Department of Infectious Diseases, St George's University Hospitals NHS Foundation Trust, London, UK.

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. Read More

Antivir Ther 2020 ;25(5):267-273

Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

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. Read More

Antivir Ther 2020 ;25(5):287-292

Epividian, Durham, NC, USA.

Background: Researchers must often rely on creatinine measurements to assess kidney function because direct glomerular filtration rates (GFR) and cystatin-c are rarely measured in routine clinical settings. However, HIV treatments often include dolutegravir, raltegravir, rilpivirine or cobicistat, which inhibit the proximal tubular secretion of creatinine without impairing kidney function, thus leading to measurement bias when using creatinine-based estimated GFR (eGFR). We developed eGFR correction factors to account for this potential bias. Read More

Antivir Ther 2020 ;25(6):293-304

Bristol-Myers Squibb, Shanghai, China.

Background: In China, the optimal management of individuals living with chronic HBV infection (CHB) remains an unmet need. The EVOLVE Study was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naive CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies.

Methods: Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or hepatitis B e antigen (HBeAg) status were enrolled from tier 2 city hospitals (between 2012-2014). Read More

Antivir Ther 2020 ;25(5):257-266

Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.

Background: Viral suppression in patients on antiretroviral treatment (ART) is critical to reducing HIV transmission and HIV-related mortality. Although many studies have evaluated factors associated with viral suppression, few have assessed the extent to which missing viral load data may bias results.

Methods: We included data on all patients starting ART from 2005 to 2019 in eight South African cohorts participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration. Read More

Antivir Ther 2020 ;25(5):245-255

Beijing Youan Hospital, Capital Medical University, Beijing, China.

Background: To evaluate the impact of baseline resistance-associated substitutions (RASs) on direct-acting antiviral (DAA) treatment response among pegylated interferon in combination with ribavirin (PR) failing patients in a real-life setting.

Methods: Blood samples and clinical data from 171 patients who failed PR treatment were collected. All of them received rescue DAA regimens. Read More

Antivir Ther 2020 ;25(6):305-314

Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Background: The combination of elbasvir and grazoprevir (EBR/GZR) has been approved for treating HCV infection. This study aimed to evaluate the efficacy of EBR/GZR in terms of sustained virological response (SVR) and improvement of liver fibrosis in Thai patients with HCV genotype-1 (GT1). The utility of serum HCV core antigen (HCVcAg) as an alternative to HCV RNA in assessing SVR was also investigated. Read More

Antivir Ther 2020 ;25(4):217-222

Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Background: Serum hepatitis B core-related antigen (HBcrAg) levels reflect intrahepatic HBV replication activity. We aimed to study whether HBcrAg levels predict response to pegylated interferon (PEG-IFN) treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.

Methods: We studied HBcrAg levels in 222 HBeAg-positive patients treated with PEG-IFN with or without lamivudine for 52 weeks in a global randomized trial and compared kinetics across treatment arms and types of response. Read More

Antivir Ther 2020 ;25(4):223-231

Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

Background: As the coronavirus disease 2019 (COVID-19) pandemic grows daily, we remain with no prophylactic and only minimal therapeutic interventions to prevent or ameliorate severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Prior to SARS-CoV-2 emergence, high throughput screens utilizing clinically developed drugs identified compounds with in vitro inhibitory effect on human coronaviruses that may have potential for repurposing as treatment options for COVID-19. However, caution should be applied to repurposing of these drugs when they are taken out of context of human pharmacokinetic parameters associated with normal therapeutic use. Read More

Antivir Ther 2020 ;25(3):171-180

Clinical Pharmacology, Gilead Sciences, Foster City, CA, USA.

Background: Selgantolimod is a novel oral, selective Toll-like receptor 8 (TLR8) agonist in development for the treatment of chronic hepatitis B (CHB). TLR8 is an endosomal innate immune receptor and a target for treatment of viral infections. This first-in-human study investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of selgantolimod in healthy volunteers. Read More

Antivir Ther 2020 ;25(4):203-215

Clinical Pharmacology and Pharmacometrics, Janssen China R&D, Beijing, China.

Background: In chronic hepatitis B (CHB) treatment, hepatitis B surface antigen (HBsAg) is regarded as a promising clinical end point associated with long-term clinical outcomes. We performed a meta-analysis to characterize the dynamics and influencing factors of HBsAg.

Methods: Literature search was conducted through PubMed from January 1995 to May 2015 for papers reporting HBsAg in patients receiving various antiviral treatments. Read More

Antivir Ther 2020 ;25(4):181-191

Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands.

HBV is a non-cytopathic virus and the progression of liver fibrosis is attributed to the host immune response. Complete suppression of viral replication using nucleotide or nucleoside analogues (NUCs) can prevent most complications related to chronic HBV infection. Unfortunately, antiviral treatment has to be administered lifelong to the majority of patients as HBV persists in the hepatocytes. Read More

Antivir Ther 2020 ;25(7):345-347

Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

Since the beginning of the outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV) 2, lopinavir/ritonavir was selected for treatment. The recent publication of Cao et al. in the New England Journal of Medicine showed that lopinavir/ritonavir treatment did not accelerate clinical improvement compared with standard of care. Read More

Antivir Ther 2020 ;25(3):151-162

Cancer Research Center of Lyon (CRCL), INSERM U1052, Lyon, France.

Background: A link between HBV and PLK1 was clearly evidenced in HBV-driven carcinogenesis, and we have also recently shown that PLK1 is a proviral factor in the early phases of HBV infection. Moreover, we have shown that BI-2536, a small molecule PLK1 inhibitor, was very efficient at inhibiting HBV DNA neosynthesis, notably by affecting nucleocapsid assembly as a result of the modulation of HBc phosphorylation. Yet, as small molecule kinase inhibitors often feature poor selectivity, a more specific and safer strategy to target PLK1 would be needed for a potential development against chronic HBV infections. Read More

Antivir Ther 2020 ;25(4):233-239

Department of Pharmacy, General Hospital of Central Theater of the PLA, Wuhan, China.

Since the outbreak of coronavirus disease (COVID-19) that was discovered in 2019 in Wuhan, China, no standard therapy guideline has been set despite the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its high infectivity. The globally pandemic outbreak suggests that COVID-19 is highly infectious and difficult to control. A dual-combination of ribavirin and interferon-α has been the widely used regimen for the treatment of this disease in China. Read More

Antivir Ther 2020 ;25(3):143-149

Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning, China.

Background: Hair antiretroviral concentration has served as an innovative and objective measure of antiretroviral adherence. However, some factors (for example, pharmacokinetics and hair characteristics) may contribute to the variability of hair antiretroviral concentration that may threaten the validity and reliability of the hair measure as a biomarker of adherence. This study aimed to examine the potential factors that may influence the measure of hair antiretroviral concentration. Read More

Antivir Ther 2020 ;25(3):163-169

Department of Clinical Virology, Gilead Sciences, Inc., Foster City, CA, USA.

Background: Vesatolimod (VES; GS-9620) is a Toll-like receptor 7 (TLR7) agonist that directly activates human plasmacytoid dendritic cells (pDCs) and B lymphocytes resulting in direct and indirect production of cytokines and immune activation. VES is being evaluated in HIV-1-infected people as part of an HIV remission strategy. Here we investigated the potential of VES to trigger indirect activation of HIV-specific CD8 T-cells using immune cell cultures derived from HIV+ donors. Read More