A comparison of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for the treatment of hepatitis C infection among people who inject drugs
To eliminate hepatitis C (HCV) infection as a public health concern by 2030, there is a need to develop comprehensive programs among key populations such as people who use drugs (PWUD). Two highly effective regimens are available for initial therapy: glecaprevir/pibrentasvir (G/P) given as 3 tablets/day for 8 weeks and sofosbuvir/velpatasvir (S/V) given as 1 tablet/day for 12 weeks. Data evaluating the safety and efficacy comparing one regimen over another in a population of PWUD is limited.
Vaccines coverage and associated factors among children aged 12-23 months in the Pawie district, Ethiopia: A cross-sectional study
Although access to vaccines for children is increasing at healthcare facilities, outbreaks of vaccine preventable diseases and deaths have been reported in different areas of the Benishangul Gumuz region, in Ethiopia. Various interventions have been designed to provide vaccines for each child at an appropriate age. Still there is limited information on full vaccination coverage and associated factors among children aged 12-23 months in the Benishangul-Gumuz region, particularly in the Pawie district.
Knowledge and attitude among Bangladeshi healthcare workers regarding the management and infection prevention and control of Nipah virus
The Nipah virus (NiV) is a zoonotic pathogen that belongs to the Paramyxoviridae family. It can cause severe respiratory and neurological diseases in humans, with varying clinical symptoms. Recognized as a critical public health concern by the World Health Organization, it requires concerted efforts in research and development to prevent outbreaks.
Partner protections in HIV cure-related trials involving analytical treatment interruption: Updated toolkit to mitigate HIV transmission risk
Analytical treatment interruptions (ATIs) are widely used to evaluate HIV cure-related research interventions. However, sex partners of cure-related trial participants might be at risk of acquiring HIV during ATIs. Addressing this risk is key to ensuring the continued success of trials involving ATIs and offer greater acceptability across multiple trials sites. In 2022, the Advancing Clinical Therapeutics Globally (ACTG) Network convened a Partner Protections Working Group (PPWG) to update the 2020 HIV transmission risk toolkit developed by Peluso and colleagues. In our review of the original toolkit, we identified new challenges and needs at the participant, partner and study levels, as well as new evidence on measures to address these needs and more advanced ethical thinking on partner protections in HIV cure-related trials with ATIs. Based on these findings, we developed an updated toolkit that will provide trial participants and their partners with better support to address new and unfamiliar situations and protect partners from undue harm. We present this toolkit, make it available as a resource for cure-related trials with ATIs and discuss possible future directions.
Indomethacin inhibits human seasonal coronaviruses at late stages of viral replication in lung cells: Impact on virus-induced COX-2 expression
Coronaviruses (CoV), zoonotic viruses periodically emerging worldwide, represent a constant potential threat to humans. To date, seven human coronaviruses (HCoV) have been identified: HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, globally circulating in the human population (seasonal coronaviruses, sHCoV), and three highly-pathogenic coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2. Although sHCoV generally cause only mild respiratory diseases, severe complications may occur in specific populations, highlighting the need for broad-spectrum anti-coronavirus drugs. Herein we show that indomethacin (INDO), a non-steroidal anti-inflammatory drug widely used in the clinic for its potent anti-inflammatory and analgesic properties, effectively inhibits the replication of coronavirus HCoV-229E and coronavirus HCoV-OC43 in human lung-derived cells. Indomethacin does not interfere with HCoV binding or entry into target cells, but acts at late stages of the virus life cycle, inhibiting viral RNA synthesis and infectious viral particles production. Although INDO anti-inflammatory action is mediated by blocking cyclooxygenase-1 and -2 (COX-1/2) enzymatic activity, the antiviral effect appears to be cyclooxygenase-independent and is not mimicked by the potent COX-1/2 inhibitor aspirin. Interestingly we found that both seasonal HCoVs markedly (>100 fold) induce the expression of the pro-inflammatory mediator COX-2 in lung cells; notably, INDO-treatment was found to effectively inhibit virus-induced COX-2 expression at the transcriptional level, revealing an additional mechanism to prevent COX-2-mediated inflammatory reactions in HCoV-infected lung cells, besides COX activity inhibition. Altogether the results indicate that indomethacin, possessing both potent anti-inflammatory properties and a direct antiviral activity against HCoV, could be effective in the treatment of and coronavirus infections.
Staging of immuno-virological dynamics during acute HIV infection in a Belgian prospective cohort study
The events during acute HIV infection (AHI) set the stage for the subsequent course of the disease. Early initiation of antiretroviral therapy (ART) has been associated with favorable immunovirological outcomes, yet the precise impact of ART timing during AHI remains unclear, particularly on lymphoid tissues.
Vaccination against COVID-19 among healthcare workers as a cocoon strategy for people living with HIV
Healthcare professionals working in infectious disease units are often engaged in the care of patients with HIV infection. A cocoon vaccination strategy may protect those who are immunocompromised from a severe course of COVID-19.
Existing knowledge, myths, and perceptions about hepatitis B and liver cancer within highly impacted immigrant communities
Immigrant groups from Southeast Asia, the Pacific Islands, sub-Saharan Africa, and the Caribbean bear the heaviest burden of chronic hepatitis B and primary liver cancer in the United States. Educational campaigns to increase knowledge about these diseases and their connection are necessary to promote protective health behaviors within these communities, to ultimately reduce the burden of disease, lessen stigma, and eliminate health disparities.
Identifying patterns of sexual behaviors and PrEP uptake characteristics among MSM who were eligible for PrEP: A national cross-section study
Men who have sex with men (MSM) are at a high risk of HIV infection and should be offered effective preventive measures, such as pre-exposure prophylaxis (PrEP). However, PrEP uptake among eligible MSM was not as high as desired. Diverse research findings on how risky sexual behaviors affect PrEP uptake highlight the necessity for a comprehensive investigation. Understanding the interconnectedness of different sexual behaviors is crucial for evaluating their impact on PrEP uptake among eligible MSM. Using a proportional sampling method, we recruited 5877 MSM aged 16 years and above in mainland China according to PrEP eligibility criteria. Through latent class analysis (LCA), three distinct sexual behavior patterns were identified among eligible MSM. Demographic variances and PrEP uptake among the three distinct sexual behavior patterns were examined using chi-squared tests and multinomial logistic regression. LCA revealed three patterns: low-risk (4,815 MSM), medium-risk (516 MSM), and high-risk (546 MSM). MSM aged 25 years or older with a monthly income of ≥¥8,000 were more likely to be in the medium-risk group. Those from areas with high HIV prevalence and engaging as "top" in anal sex were more likely to be in the medium- and high-risk groups. The medium- and high-risk groups had a higher willingness, uptake, and adherence rates for PrEP than the low-risk group. LCA is effective in identifying diverse sexual behavior patterns among MSM, aiding targeted interventions to enhance PrEP uptake. Addressing demographic variations and tailoring interventions for specific risk groups are crucial for promoting PrEP dissemination and reducing HIV infection risk in eligible MSM.
From awareness to action: Unveiling knowledge, attitudes and testing strategies to enhance human papillomavirus vaccination uptake in Jordan
Vaccination against HPV plays a crucial role in preventing cervical cancer and related health issues. This study aimed to (1) assess knowledge, awareness, intentions, and attitudes regarding HPV and vaccination among Jordanian parents, and (2) evaluate the efficacy of two intervention strategies in promoting knowledge, awareness, and attitudes towards HPV vaccinations.
Community dialogue to enhance understanding of beliefs, behaviours and barriers to care for people living with liver disease and HBV infection in KwaZulu Natal, South Africa
The World Health Organisation (WHO) has set targets for the elimination of Hepatitis B virus (HBV), which include preventing new infections and reducing deaths. We explored beliefs, behaviours and barriers to diagnosis, prevention and treatment for people living with HBV infection (PLWHB) and those with liver disease in a rural South African population in KwaZulu-Natal, to gather information to inform research and support the development of improved clinical and public health services.
Impact of interrupting antiretroviral therapy started during primary HIV-1 infection on plasma neurofilament light chain protein, a marker of neuronal injury: The SPARTAC trial
Antiretroviral therapy (ART)-conferred suppression of HIV replication limits neuronal injury and inflammation. ART interruption tests efficacy in HIV cure trials and viral rebound after ART interruption may induce neuronal injury. We investigated the impact of protocol-defined ART interruption, commenced during primary HIV-1 infection (PHI) on a biomarker of neuro-axonal injury (neurofilament light protein (NfL)), and its associations with inflammation (D-dimer and interleukin-6 (IL-6)) and HIV-1 reservoir size (total HIV-1 DNA).
Opportunistic screening using point-of-care testing leads to successful linkage to care of HBV-infected migrant populations in a low endemic country
In low endemic countries, screening for hepatitis B surface antigen (HBsAg) in migrants is cost-effective in reducing the disease burden of hepatitis B virus (HBV) infections, but linkage to care (LTC) remains a challenge. This study aims to guide future screening initiatives, with 3 objectives: 1. to compare LTC between different ethnic groups screened for HBsAg with point-of-care testing (POCT) in an outreach setting; 2. to estimate the proportion of HBsAg seropositivity for ethnic minorities; and 3. to investigate the association between seropositivity and HBV risk factors.
Study on immune persistence of the CTN-1V strain rabies vaccine in humans
This study is a single-arm, single-center phase IV clinical trial on a rabies vaccine that has been marketed in China. The Vero cells and CTN-1V strain are used in the rabies vaccine product. The purpose of this study was to investigate the safety, immunogenicity and immune persistence of this product. One hundred and forty-nine participants were enrolled to the study, all of whom were included in the safety analysis set (SS), among which 116 participants were included in the protocol analysis set (PPS), One hundred and fifteen participants were included in the 6-month immune persistence analysis set (IPS6) and 111 in the 12-month immune persistence analysis set IPS12. Results showed that: 1) In the SS analysis set, adverse reactions were mainly pyrexia and pain at the vaccination site, the severity of which were mostly grade 1, and concentrated in 0-3 days after vaccination. No grade 3 or above adverse events and serious adverse events (SAE) related to the experimental vaccine were observed. 2) In the PPS analysis set, the antibody positive conversion rate reached 100% at 14 days after full immunization of the pre-immunized negative population; The antibody geometric mean titer (GMT) (95% CI) was 14.82 (13.00, 16.90). 3) The positive rate of serum neutralizing antibody was 93.91 % and the GMT at 1.58 IU/ml at 6 months after full immunization. The positive rate of neutralizing antibody was 85.59 % and GMT at 1.30 IU/ml at 12 months after immunization. Our results show that the human rabies vaccine with the CTN-1V strain and Vero cells as matrix had good safety, immunogenicity and immune persistence in our study.
Factors associated with unquantifiable total HIV-1 DNA in peripheral blood in persons living with HIV: An observational study
The human immunodeficiency virus type 1 (HIV-1) cannot be eradicated even with suppressive antiretroviral therapy because its retrotranscribed genome integrates into the DNA of host cells, creating a long-term reservoir. Quantification of total HIV-1 DNA in peripheral blood is a biomarker of this reservoir that can predict progression of the infection, treatment response, and HIV-1-related complications. A deeper understanding of the reservoir may help develop a cures.
Evaluation of HIV-1 DNA levels among adolescents living with perinatally acquired HIV-1 in Yaounde, Cameroon: A contribution to paediatric HIV cure research in Sub-Saharan Africa
With the advent of antiretroviral therapy (ART), most children living with HIV in sub-Saharan Africa (SSA) are growing toward adolescence, with scarcity of evidence on the size of viral reservoirs to enhance paediatric cure research strategies. This study aims to compare HIV-1 proviral DNA levels according to virological response among adolescents living with perinatally acquired HIV-1 (ALPHIV) and identify associated-factors in the Cameroonian context.
Engagement of AKT and ERK signaling pathways facilitates infection of human neuronal cells with West Nile virus
West Nile virus (WNV) is an important neurotropic virus that accounts for the emergence of human arboviral encephalitis and meningitis. The interaction of WNV with signaling pathways plays a key role in controlling WNV infection. We have investigated the roles of the AKT and ERK pathways in supporting WNV propagation and modulating the inflammatory response following WNV infection. WNV established a productive infection in neuronal cell lines originated from human and mouse. Expression of IL-11 and TNF-α was markedly up-regulated in the infected human neuronal cells, indicating elicitation of inflammation response upon WNV infection. WNV incubation rapidly activated signaling cascades of AKT (AKT-S6-4E-BP1) and ERK (MEK-ERK-p90RSK) pathways. Treatment with AKT inhibitor MK-2206 or MEK inhibitor U0126 abrogated WNV-induced AKT or ERK activation. Strong activation of AKT and ERK signaling pathways could be detectable at 24 h after WNV infection, while such activation was abolished at 48 h post infection. U0126 treatment or knockdown of ERK expression significantly increased WNV RNA levels and viral titers and efficiently decreased IL-11 production induced by WNV, suggesting the involvement of ERK pathway in WNV propagation and IL-11 induction. MK-2206 treatment enhanced WNV RNA replication accompanied with a moderate decrease in IL-11 production. These results demonstrate that engagement of AKT and ERK signaling pathways facilitates viral infection and may be implicated in WNV pathogenesis.
Polio eradication in Pakistan: Hope against hope or are we near eradication?