Association of ITPA gene polymorphisms and the risk of ribavirin-induced anemia in HIV/hepatitis C virus (HCV)-coinfected patients receiving HCV combination therapy.

Polymorphisms of the ITPA gene have been associated with anemia during combination therapy in hepatitis C virus (HCV)-monoinfected patients. Our aim was to confirm this association in HIV/HCV-coinfected patients. In this prospective, observational study, 73 HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin (RBV) were enrolled. Two single nucleotide polymorphisms within or adjacent to the ITPA gene (rs1127354 and rs7270101) were genotyped. The associations between the ITPA genotype and anemia or treatment outcome were examined. Fifty-nine patients (80.8%) had CC at rs1127354, whereas 14 (19.2%) had a CA/AA ITPA genotype. Percent decreases from baseline hemoglobin level were significantly greater in patients with the CC genotype than in those with the CA/AA genotype at week 4 (P = 0.0003), week 12 (P < 0.0001), and week 36 (P = 0.0102) but not at the end of treatment. RBV dose reduction was more often needed in patients with the CC genotype than in those with the CA/AA genotype (odds ratio [OR] = 11.81; 95% confidence interval [CI] = 1.45 to 256.17; P = 0.0039), as was erythropoietin therapy (OR = 8.28; 95% CI = 1.04 to 371.12; P = 0.0057). Risk factors independently associated with percent hemoglobin nadir decrease were RBV dose reduction (OR = 11.72; 95% CI = 6.82 to 16.63; P < 0.001), baseline hemoglobin (OR = 1.69; 95% CI = 0.23 to 3.15; P = 0.024), and body mass index (OR = -0.7; 95% CI = -1.43 to 0.03; P = 0.061). ITPA polymorphism was not an independent predictor of sustained virological response. Polymorphisms at rs1127354 in the ITPA gene influence hemoglobin levels during combination HCV therapy and the need for RBV dose reduction and erythropoietin use in HIV/HCV-coinfected patients.

High coverage COVID-19 mRNA vaccination rapidly controls SARS-CoV-2 transmission in Long-Term Care Facilities.

Residents of Long-Term Care Facilities (LTCFs) represent a major share of COVID-19 deaths worldwide. Information on vaccine effectiveness in these settings is essential to improve mitigation strategies, but evidence remains limited. To evaluate the early effect of the administration of BNT162b2 mRNA vaccines in LTCFs, we monitored subsequent SARS-CoV-2 documented infections and deaths in Catalonia, a region of Spain, and compared them to counterfactual model predictions from February 6th to March 28th, 2021, the subsequent time period after which 70% of residents were fully vaccinated. We calculated the reduction in SARS-CoV-2 documented infections and deaths as well as the detected county-level transmission. We estimated that once more than 70% of the LTCFs population were fully vaccinated, 74% (58%-81%, 90% CI) of COVID-19 deaths and 75% (36%-86%) of all documented infections were prevented. Further, detectable transmission was reduced up to 90% (76-93% 90%CI). Our findings provide evidence that high-coverage vaccination is the most effective intervention to prevent SARS-CoV-2 transmission and death. Widespread vaccination could be a feasible avenue to control the COVID-19 pandemic.

High coverage COVID-19 mRNA vaccination rapidly controls SARS-CoV-2 transmission in Long-Term Care Facilities.

Residents of Long-Term Care Facilities (LTCFs) represent a major share of COVID-19 deaths worldwide. Measuring the vaccine effectiveness among the most vulnerable in these settings is essential to monitor and improve mitigation strategies. We evaluated the early effect of the administration of BNT162b2 mRNA vaccines to individuals older than 64 years residing in LTCFs in Catalonia, a region of Spain. We monitored all the SARS-CoV-2 documented infections and deaths among LTCFs residents from February 6th to March 28th, 2021, the subsequent time period after which 70% of them were fully vaccinated. We developed a modeling framework based on the relation between community and LTFCs transmission during the pre-vaccination period (July -December 2020) and compared the true observations with the counterfactual model predictions. As a measure of vaccine effectiveness, we computed the total reduction in SARS-CoV-2 documented infections and deaths among residents of LTCFs over time, as well as the reduction on the detected transmission for all the LTCFs. We estimated that once more than 70% of the LTCFs population were fully vaccinated, 74% (58%-81%, 90% CI) of COVID-19 deaths and 75% (36%-86%, 90% CI) of all expected documented infections among LTCFs residents were prevented. Further, detectable transmission among LTCFs residents was reduced up to 90% (76-93%, 90%CI) relative to that expected given transmission in the community. Our findings provide evidence that high-coverage vaccination is the most effective intervention to prevent SARS-CoV-2 transmission and death among LTCFs residents. Conditional on key factors such as vaccine roll out, escape and coverage --across age groups--, widespread vaccination could be a feasible avenue to control the COVID-19 pandemic.

High coverage COVID-19 mRNA vaccination rapidly controls SARS-CoV-2 transmission in long-term care facilities.

Background: Residents of Long-Term Care Facilities (LTCFs) represent a major share of COVID-19 deaths worldwide. Measuring the vaccine effectiveness among the most vulnerable in these settings is essential to monitor and improve mitigation strategies. Methods: We evaluate the early effect of the administration of BNT162b2-mRNA vaccine to individuals older than 64 years residing in LTCFs in Catalonia, Spain. We monitor all the SARS-CoV-2 documented infections and deaths among LTCFs residents once more than 70% of them were fully vaccinated (February-March 2021). We develop a modeling framework based on the relationship between community and LTCFs transmission during the pre-vaccination period (July-December 2020). We compute the total reduction in SARS-CoV-2 documented infections and deaths among residents of LTCFs over time, as well as the reduction in the detected transmission for all the LTCFs. We compare the true observations with the counterfactual predictions. Results: We estimate that once more than 70% of the LTCFs population are fully vaccinated, 74% (58-81%, 90% CI) of COVID-19 deaths and 75% (36-86%, 90% CI) of all expected documented infections among LTCFs residents are prevented. Further, detectable transmission among LTCFs residents is reduced up to 90% (76-93%, 90% CI) relative to that expected given transmission in the community. Conclusions: Our findings provide evidence that high-coverage vaccination is the most effective intervention to prevent SARS-CoV-2 transmission and death among LTCFs residents. Widespread vaccination could be a feasible avenue to control the COVID-19 pandemic conditional on key factors such as vaccine escape, roll out and coverage.

Drug therapies for HIV-related metabolic disorders.

INTRODUCTION: Human immunodeficiency virus (HIV) has become a chronic disease often associated with dyslipidaemia and insulin resistance. Combination antiretroviral therapy (cART) may contribute to metabolic disturbances, eventually leading to increased cardiovascular disease (CVR) in this population. Escalating interventions to decrease CVR include promoting a healthy lifestyle, such as quitting smoking, diet and regular exercise. If they do not achieve the goals, a change of cART should be considered, followed by or used concomitantly with the use of chemical therapies. AREAS COVERED: The aim of this article is to review the available drug therapies for the treatment of metabolic disorders in HIV-infected patients and to examine their safety and effectiveness in this population. A review of the literature was conducted, highlighting the most relevant articles. EXPERT OPINION: Switching strategies can be useful but its expected benefit is not high. Therefore, chemical intervention is often needed. Statins have been proven to reduce CVR in the general population and in HIV-infected patients. Simvastatin is contraindicated in patients treated with boosted PI due to interactions; atorvastatin is safe at submaximal dose and needs close monitoring, while pravastatin lacks lipid-lowering potency, and rosuvastatin and pitavastatin are safe. Ezetimibe and fibrates are also safe and effective in HIV-infected patients and can be used in combination with statins. The management of glucose homeostatic disorders in HIV-infected patients follows the same guidelines as in the general population. However, there are specific considerations with respect to the interactions of particular medications with cART. When drug therapy is needed, metformin is the first-line drug. Decisions regarding second- and third-line drugs should be carefully individualized.

A 48-week study of fat molecular alterations in HIV naive patients starting tenofovir/emtricitabine with lopinavir/ritonavir or efavirenz.

BACKGROUND: Conflicting reports on the effects of efavirenz (EFV) and lopinavir/ritonavir (LPV/r) on subcutaneous adipose tissue (SAT) have been described. OBJECTIVE: The aim was to assess the 48-week molecular and clinical effects of LPV/r and EFV, combined with tenofovir/emtricitabine (TDF/FTC), on SAT of HIV-infected, antiretroviral-naive patients. METHODS: Forty-four adults were started on LPV/r or EFV combined with TDF/FTC. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by dual x-ray absorptiometry scans were obtained at study entry and week 48. Mitochondrial DNA (mtDNA) and transcripts for mtDNA-encoded proteins and genes involved in inflammation, adipocyte differentiation, and metabolism were assessed in paired SAT biopsies. RESULTS: Whole-body fat and limb fat mass increased in the LPV/r and EFV groups. MtDNA and cytochrome oxidase subunit II did not change, and cytochrome b increased significantly in EFV-treated patients. Tumor necrosis factor alpha and monocyte chemotactic protein-1 gene expression did not change in the LPV/r group, but these significantly increased in the EFV group. Interleukin 18 decreased in the LPV/r group, whereas it increased in the EFV group. CONCLUSIONS: Starting TDF/FTC plus EFV was associated with an increased expression of genes encoding for inflammatory cytokines in SAT in naive patients. Therapy with TDF/FTC plus LPV/r or EFV was associated with an increase in subcutaneous fat mass.