Daclatasvir as a hepatitis C infection treatment option: an up-to-date evaluation.

INTRODUCTION: Globally, it is estimated that 290,000 patients infected with hepatitis C virus (HCV) died from hepatitis C consequences, including cirrhosis and hepatocellular carcinoma in 2019. Although daclatasvir (DCV), combined with sofosbuvir (SOF), is effective in HCV patients, the new pan-genotypic combinations are considered by many as more cost-effective and successful in eradicating HCV infection. AREAS COVERED: This review discusses the safety, efficacy, and cost-effectiveness of DCV as an HCV treatment option based on real-world studies and pharmacoeconomic evaluations. EXPERT OPINION: Real-life studies suggest that SOF/DCV has acceptable sustained virological response and can be used successfully to manage HCV. Nonetheless, the use of SOF/DCV is limited by the longer treatment duration in genotype (GT)-3 patients and the need for ribavirin (RBV) in treatment-experienced patients which increases the likelihood of adverse effects. DCV is likely to remain as a therapeutic option for the management of GT-1, GT-2, and GT-4 patients in resource limited settings, while GT-3 patients are more likely to benefit from RBV-free direct-acting antiviral combinations such as SOF/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks. The introduction of generics for these new pan-genotypic drugs would likely eliminate the need for SOF/DCV in the near future.

Serial changes in renal indices in chronic HCV patients with and without HIV co-infection receiving sofosbuvir and tenofovir-based therapies.

BACKGROUND: Sofosbuvir (SOF) is authorized for hepatitis C virus (HCV) patients. The nephrotoxicity of SOF on HCV mono-infected and HCV-human immunodeficiency virus (HIV) individuals receiving antiretroviral therapy (ART) remains controversial. METHODS: A prospective study including 159 HCV mono-infected and 124 HCV-HIV individuals (47 were ART naïve and 77 were tenofovir [TDF]-based ART) who presented with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2 at baseline and were treated with SOF-daclatasvir for 12 weeks. The eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation over the study period. RESULTS: HCV patients had a progressive decline in median levels of eGFR compared with HCV-HIV patients who were ART naïve and those receiving TDF-based ART during and after discontinuing SOF-DAC treatment (96, 109 and 114 at baseline vs 94, 117 and 108 at the end of treatment [EOT]) vs 95, 114 and 115 ml/min/1.73 m2 at 12 weeks after treatment [SVR12], respectively). Moreover, the rate of eGFR stage worsening was more pronounced in HCV mono-infected compared with HCV-HIV individuals who were ART naïve and those receiving TDF-based ART (21.4% vs 8.5% and 14.3% at EOT; 21.4% vs 2.1% and 6.5% at SVR12, respectively). Multivariable regression analysis showed that baseline variables were not independent predictors of eGFR stage worsening either at EOT or SVR12. CONCLUSIONS: Because the changes in eGFR were minimal and not of clinical significance, and TDF was not associated with an increase in renal dysfunction, SOF-based direct-acting antivirals could be safely used in HCV mono-infected and HCV-HIV individuals, even in those on TDF-based ART.

Incidence of hepatitis C virus infection among people living with HIV: An Egyptian cohort study.

Background: Egypt used to have one of the highest hepatitis C virus (HCV) infection prevalence rates worldwide, with an estimated HCV prevalence of around 4.5% to 6.7%. Objectives: To determine the HCV infection incidence rate amid Egyptian patients living with HIV. Method: A total of 460 HIV-positive patients were recruited in a retrospective cohort study from Imbaba Fever Hospital, Cairo, between January 2016 and March 2019. The patients had a negative baseline and at least one other HCV antibody test. Hepatitis C virus antibody testing was done by antibody sandwich third-generation enzyme-linked immunosorbent assay. The hepatitis C virus infection incidence rate among HIV-infected patients was calculated using the person-time incidence rate. Results: Two hundred and eighteen patients were finally included: 146 (31.7%) patients were excluded for having a positive baseline HCV Ab result and 96 patients were excluded for not having a follow-up HCV Ab test. Eighteen patients had HCV seroconversion (8.3%), achieving an incidence rate of 4.06 cases per 100 person-years (95% confidence interval: 3.87-4.24). Injection drug use (IDU) was the commonest risk factor among seroconverters, with an HCV incidence rate of 7.08 cases per 100 person-years. Injection drug use history was reported in 83.3% of the seroconverters and in only 47.2% of non-seroconverters; P = 0.005. Conclusion: Egyptian HIV-infected patients show a high incidence rate of HCV infection especially among those who have a history of IDU. Accordingly, attention should be paid for prevention, screening and timely treatment of HCV in patients infected with HIV. What this study adds: The demonstration of a high HCV infection incidence rate among HIV-infected patients and shows the need for screening and prevention in this population.

COVID-19 vaccine acceptance and associated factors among people living with HIV in the Middle East and North Africa region.

Background: Identifying coronavirus disease 2019 (COVID-19) vaccine acceptance and associated factors among people living with HIV (PLHIV) in the Middle East and North Africa region is important to meet the need for broad-scale vaccination against COVID-19. Objectives: To investigate the COVID-19 vaccine acceptance rate and factors among PLHIV in the Middle East and North Africa region. Method: An online cross-sectional survey was conducted among PLHIV currently living in Egypt, Tunisia and Saudi Arabia between March 2021 and August 2021. Results: Of the 540 respondents, 19.3% reported already being vaccinated against COVID-19 (n = 104), 32.0% responded 'definitely yes' (n = 173), and 13.3% responded 'probably yes' (n = 72) for intention to receive a COVID-19 vaccine, with an overall COVID-19 vaccine acceptance rate of 64.6% among PLHIV in the region. The most significant predictors of COVID-19 vaccine acceptance included feeling less worried about COVID-19 transmission post-vaccination (221.0% higher odds), and believing the disease is vaccine-preventable (160.0% higher odds). Reported barriers to COVID-19 vaccine acceptance include concerns about vaccine effectiveness and belief that HIV medications protect against COVID-19 transmission, living in a rural area and reporting less-frequent engagement with HIV care. Nine out of 10 participants reported that the chances of them getting COVID-19 vaccine would increase if given adequate information and if their doctor recommended it. Conclusion: Findings of the study can help researchers, health officials, and other health system actors understand the predictors and barriers to COVID-19 vaccine acceptance reported by PLHIV. This understanding could inform the future planning of interventions tailored to PLHIV.

Safety and efficacy of ustekinumab in the treatment of Crohn Disease: a systematic review and meta-analysis

ABSTRACT Background and Aims The present systematic review and meta-analysis was designed to estimate the safety and effectiveness of ustekinumab in the treatment of Crohn disease (CD) in clinical trials and observational studies. Methods We retrieved all the related publications from the PubMed, Cochrane, EBSCO, Google Scholar and EMBASE databases using a systematic search strategy. We only included clinical trials and observational studies that were published in English. Results Only 31 studies that met the eligibility criteria out of the 733 identified studies were included. The overall clinical response rate in the cohort studies was of 0.539 (95% confidence interval [95%CI]: 0.419-0.659), and in the clinical trials it was of 0.428 (95%CI: 0.356-0.501). The pooled clinical remission rate was of 0.399 (95%CI: 0.295-0.503) in randomized control trials (RCTs,) and of 0.440 (95%CI: 0.339-0.542) in cohort studies. The rate of adverse effects was of 0.158 (95%CI: 0.109-0.207) in cohort studies and of 0.690 (95%CI: 0.633-0.748) in RCTs. Conclusion Ustekinumab is effective in the treatment of CD. However, more research is required on the safety profiles because there was considerable variation among the included studies. (AU)

HIV-related stigma and discrimination by healthcare workers in Egypt.

BACKGROUND: HIV-related stigma and discrimination (SAD) have imposed serious adverse health consequences on people living with HIV (PLHIV), including limited access to medical care and delayed diagnosis, which in turn limits the prevention and control of the disease. This study was conducted to explore the stigmatizing attitudes and behaviors of healthcare workers (HCWs) towards HIV patients and PLHIV. METHODS: A cross-sectional study targeted HCWs who attended the United Conference of Hepatogastroenterology and Infectious Diseases that was held on 25-28 September 2019 in Cairo governorate. A self-administrated questionnaire was completed by 359 HCWs. RESULTS: The majority of HCWs reported some discriminatory practices when rendering care to HIV patients, with nurses showing the highest significant number of discriminatory practices. A considerable proportion of HCWs reported witnessing HIV-related SAD at their health facilities. CONCLUSIONS: HIV-related SAD was prevalent among HCWs. Hence, HIV-related training relevant to the needs of different groups of HCWs is recommended. Provision of infection control supplies to protect against occupational exposure is also needed. The setting and enforcement of anti-stigma policies and guidelines in various healthcare settings are crucial.

The evolving challenges confronting adults living with HIV in three North African countries during the COVID-19 crisis: a survey-based study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has resulted in a huge burden on healthcare systems, especially on programs for chronic illnesses such as HIV. We aimed to assess the challenges confronting adult people living with HIV (PLHIV) in three countries in North Africa during the COVID-19 crisis and their awareness of COVID-19 non-pharmaceutical preventive measures. METHODS: This online survey included PLHIV aged ≥18 y from three countries in North Africa recruited by a snowball sampling technique, who were asked to complete a modified questionnaire originally developed by the University of Antwerp in Belgium, which was then disseminated through social media tools to assess the study outcomes. RESULTS: Out of 369 respondents, 260 (70.5%) were males and 237 (64.2%) were aged 18-39 y. Adherence to COVID-19 preventive measures, wearing facemasks (308 [83.2%]), applying hand-sanitizers (299 [80.8%]) and following cough etiquette (261 [70.5%]), were predominantly reported. Only 48 (13%) were vaccinated against influenza. One hundred and forty-five participants (42%) experienced flu-like symptoms, 29 (20%) were tested for COVID-19, with only one confirmed case identified. Among 344 (93.2%) on antiretroviral therapy (73.8% efavirenz- vs 6.4% dolutegravir-based regimens), 219 (63.7%) attended their scheduled visits, 144 (41.9%) had limited access to care due to lockdown and 29 (8.4%) became less adherent to their antiretroviral therapy. Covariates associated with challenges during access to care were age ≥60 y (OR=6.5; 95% CI 1.8 to 23.2) and receiving second-line HIV treatment such as protease inhibitors (OR=2.7; 95% CI 1.3 to 5.8). CONCLUSION: The pandemic adversely affected PLHIV. New innovative strategies should be implemented to ensure the continuity of HIV services.

HCV/HIV coinfected Egyptian patients: a cross-sectional study of their main characteristics and barriers to HCV treatment initiation.

BACKGROUND: This study investigates different barriers preventing a cohort of Egyptian HIV/HCV coinfected patients from accessing HCV treatment, despite being available and free of charge, aiming to improve the long-term outcomes of coinfected patients and decreasing their liver-related morbidity and mortality. METHODS: This study included HIV patients who were referred to Kasr Alainy Viral Hepatitis Center to receive HCV treatment and who had to continue pretreatment assessment in order to receive direct acting antiviral agents free of charge. Patients who did not attend within 90 d were questioned via a telephone interview. Questions addressed sociodemographic status, HIV status and the main barriers to accessing healthcare. RESULTS: Overall, 474 HIV/HCV coinfected patients were eligible for HCV treatment and 223 (47.1%) patients did not complete work-up for HCV treatment. Fear of community stigma concerning HIV/HCV was the most important barrier to compliance with treatment (73.3%), followed by lack of a supportive work environment and employment opportunities (51.5%), whereas 39.3% stopped follow-up due to the lack of integrated services in the healthcare facility. CONCLUSIONS: Managing HCV in HCV/HIV coinfected patients still represents a major challenge, not only for healthcare providers, but also at a community level, to improve community awareness and manage the major obstacle facing those patients regarding community stigma.

Efficacy of combined Sofosbuvir and Daclatasvir in the treatment of COVID-19 patients with pneumonia: a multicenter Egyptian study.

BACKGROUND: Limited experimental and clinical evidence suggests a potential role for sofosbuvir/daclatasvir in treating COVID19. We aim to evaluate the efficacy of generic sofosbuvir/daclatasvir in treating COVID-19 patients with pneumonia. RESEARCH DESIGN AND METHODS: This multicenter prospective study involved 174 patients with COVID-19. Patients were randomized into two groups. Group A (96 patients) received sofosbuvir (400 mg)/daclatasvir (60 mg) for 14 days in combination with conventional therapy. Group B (78 patients) received conventional therapy alone. Clinical, laboratory, and radiological data were collected at baseline, after 7, 14, and 28 days of therapy. Primary endpoint was rate of clinical/virological cure. RESULTS: A lower mortality rate was observed in group (A) (14% vs 21%, P = 0.07). After 1 month of therapy, no differences were found in rates of ICU admission, oxygen therapy, or ventilation. Additionally, a statistically significant shorter duration of hospital stay (9% vs 12%, P < 0.01) and a faster achievement of PCR negativity at day 14 (84% versus 47%, P < 0.01) were noticed in group (A). CONCLUSION: Adding sofosbuvir/daclatasvir to conventional therapy of COVID-19 is promising. Their use is associated with shorter hospital stay, faster PCR negativity and may be reduced mortality.

Real-life experience of treating HCV co-infection among HIV-infected population in Egypt: single-center experience.

BACKGROUND: Liver disease has emerged as a leading cause of death among PLHIV coinfected with HCV. METHODS: A retrospective study involving all HCV viremic patients coinfected with HIV who presented to HCV/HIV multidisciplinary clinics located at Embaba fever hospital. Patients were assigned to receive DAAs according to the national treatment guidelines. The primary endpoint was SVR12. RESULTS: Of the 519 patients enrolled, 38.73% LTFU; either not initiated (n = 170) or did not complete the treatment (n = 31). The main identified reasons behind LTFU were schedule conflict (19%) or hospitalization (13%). Among 318 patients who completed their DAAs course, nine patients had a relapse after the end of treatment and 97% had attained SVR12. There were significant differences among different virological response groups in baseline factors including smoking (p = 0.005), history of dental procedure (p = 0.007), CD4 count (p = 0.007), and HIV viral load (p = <0.001). Among responders (n = 309), there was a significant reduction of baseline hemoglobin and significant improvement of baseline platelets (p = 0.005) at on-treatment week 8. Baseline necro-inflammatory markers showed significant improvement across follow-up time points (p < 0.001). CONCLUSIONS: DAAs are an effective and safe choice to treat HCV in PLHIV. Social stigma could be a major cause for lacking adherence to follow-up visits.Abbreviations: ALT: Alanine Aminotransferase; ARV: Antiretroviral treatment; AST: Aspartate Aminotransferase; DAAs: Direct acting antivirals; ARVs: antiretroviral therapy; EMR: Eastern Mediterranean region; HCV: Hepatitis C virus; kPa: Kilopascal; LTFU: Patient lost to follow up; NCCVH: The National Committee for Control of Viral Hepatitis; PWID: People who inject drugs; SVR: Sustained virological response;UNAIDS: The Joint United Nations Programme on HIV/AIDS.

Current status of hepatitis C virus among people living with human immunodeficiency virus in Egypt.

BACKGROUND: Human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infection is increasing due to their similar routes of transmission. Co-infection poses a big challenge. Information on the prevalence of HCV infection in Egyptian HIV individuals is scarce. METHODS: A cross-sectional study was conducted on 1004 HIV individuals who were recruited from July 2018 to March 2019. Blood samples obtained from HIV individuals were subsequently screened for HCV antibodies using the Murex anti-HCV (version 4) enzyme-linked immunosorbent assay test. HCV RNA was performed only on anti-HCV antibody-positive samples. Logistic regression was used to identify factors associated with HCV seroprevalence using SPSS (IBM, Armonk, NY, USA). RESULTS: Among 1004 participants, 349 exhibited a positive result for anti-HCV antibodies (34.8% [95% confidence interval 31.81 to 37.8]). The most commonly self-reported risk factor of HIV infection by the co-infected participants was intravenous drug use (IDU) (303/349 [86.8%]). In multinomial analysis, risk factors identified as statistically associated with HCV seroprevalence include IDU, history of surgical operations and dental procedures and HIV viral load (p<0.001, 0.032, <0.001 and 0.006, respectively). Under combination antiretroviral therapy (cART), the proportion of HIV mono-infected individuals with an undetectable HIV viral load was significantly higher than those with co-infection (p<0.0007). We also found that HIV-HCV co-infected participants exhibited significantly higher CD4+ cell counts than those with HIV mono-infection (p=0.04). CONCLUSIONS: The prevalence of HIV-HCV co-infection is higher in Egypt compared with other countries in Africa. It is essential to screen all HIV-infected patients for HCV infection for early identification, counselling and initiation of anti-HCV treatment.

Gastrointestinal manifestations of human immunodeficiency virus and coronavirus disease 2019: Understanding the intersecting regions between the two epidemics.

In March 2020, the World Health Organization declared coronavirus disease (COVID-19) a pandemic. As of February 2021, there were 107 million COVID-19 cases worldwide. As a comparison, there are approximately 38 million people living with human immunodeficiency virus (PLHIV) worldwide. The coexistence of both epidemics, and the syndemic effect of both viruses could lead to a delirious impact both at individual and community levels. Many intersecting points were found between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, and HIV; among which, gastrointestinal (GI) manifestations are the most notable. GI manifestations represent a common clinical presentation in both HIV and SARS-CoV-2. The emergence of GI symptoms as a result of SARS-CoV-2 infection provides a new dynamic to COVID-19 diagnosis, management, and infection control measures, and adds an additional diagnostic challenge in case of coinfection with HIV. The presence of GI manifestations in PLHIV during the COVID-19 pandemic could be referred to HIV enteropathy, presence of opportunistic infection, adverse effect of antiretrovirals, or coinfection with COVID-19. Thus, it is important to exclude SARS-CoV-2 in patients who present with new-onset GI manifestations, especially in PLHIV, to avoid the risk of disease transmission during endoscopic interventions. Structural similarities between both viruses adds a valuable intersecting point, which has mutual benefits in the management of both viruses. These similarities led to the hypothesis that antiretrovirals such as lopinavir/Rironavir have a role in the management of COVID-19, which was the target of our search strategy using the available evidence. These similarities may also facilitate the development of an efficient HIV vaccine in the future using the advances in COVID-19 vaccine development.

Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study.

Researchers around the world are working at record speed to find the best ways to treat and prevent coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID-19 infected patients. This was a randomized open-label controlled study that included 164 patients with COVID-19. Patients were randomized into two groups where Group 1 (Ivermectin group) included patients who received ivermectin 12 mg once daily for 3 days with standard care and Group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay, and the need for mechanical ventilation. All patients were followed up for 1 month. Overall, 82 individuals were randomized to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had a shorter length of hospital stay (8.82 ± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant (p = 0.085). Three patients (3.7%) in each group required mechanical ventilation (p = 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups (p = 1.00). Although there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin-treated group.