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Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, MHRA, with a regimen of two standard doses given with an interval of between 4 and 12 weeks. The planned rollout in the UK will involve vaccinating people in high risk categories with their first dose immediately, and delivering the second dose 12 weeks later.Here we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods: We present data from phase III efficacy trials of ChAdOx1 nCoV-19 in the United Kingdom and Brazil, and phase I/II clinical trials in the UK and South Africa, against symptomatic disease caused by SARS-CoV-2. The data cut-off date for these analyses was 7th December 2020. The accumulated cases of COVID-19 disease at this cut-off date exceeds the number required for a pre-specified final analysis, which is also presented. As previously described, individuals over 18 years of age were randomised 1:1 to receive two standard doses (SD) of ChAdOx1 nCoV-19 (5x1010 viral particles) or a control vaccine/saline placebo. In the UK trial efficacy cohort a subset of participants received a lower dose (LD, 2.2x1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. All cases with a nucleic acid amplification test (NAAT) were adjudicated for inclusion in the analysis, by a blinded independent endpoint review committee. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov; NCT04324606, NCT04400838, and NCT04444674. Findings: 17,177 baseline seronegative trial participants were eligible for inclusion in the efficacy analysis, 8948 in the UK, 6753 in Brazil and 1476 in South Africa, with 619 documented NAAT +ve infections of which 332 met the primary endpoint of symptomatic infection >14 days post dose 2.The primary analysis of overall vaccine efficacy >14 days after the second dose including LD/SD and SD/SD groups, based on the prespecified criteria was 66.7% (57.4%, 74.0%). There were no hospitalisations in the ChAdOx1 nCoV-19 group after the initial 21 day exclusion period, and 15 in the control group.Vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 post vaccination was 76% (59%, 86%), and modelled analysis indicated that protection did not wane during this initial 3 month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 day (GMR 0.66, 95% CI 0.59, 0.74).In the SD/SD group, after the second dose, efficacy was higher with a longer prime-boost interval: VE 82.4% 95%CI 62.7%, 91.7% at 12+ weeks, compared with VE 54.9%, 95%CI 32.7%, 69.7% at

Although a potential involvement of the CCR5Δ32 variant has already been suggested in relation to susceptibility to hepatitis C virus (HCV) infection, data from the literature is still quite controversial. Thus, our study evaluated the influence of the CCR5Δ32 allele variant in HCV infection, HCV/HIV co-infection, and HCV-related diseases in individuals from southern Brazil. A total of 1352 individuals were included in this study, divided into the following groups: Control (n = 274); HCV+ (n = 674); HIV+ (n = 300); HCV+/HIV+ (n = 104). Individuals from the HCV+ group were further stratified according to clinical/histological criteria, as HCV+/control (n = 124); HCV+/fibrosis (n = 268); HCV+/cirrhosis (n = 190); HCV+/hepatocarcinoma (n = 92). Considering all individuals included in this study, the following genotype frequencies were observed: wild-type homozygous (wt/wt), 88.76%; heterozygous (wt/Δ32), 10.72%; variant homozygous (Δ32/Δ32), 0.52%. Genotypic frequencies were very similar between the groups. Of note, the frequency of the Δ32 homozygous was quite similar comparing control uninfected against the HCV+ individuals (p > 0.999). The overall Δ32 allele frequency was estimated at 5.88%. Considering the number of Δ32 allele carriers and non-carriers, no statistically significant differences (p > 0.05) between the groups were observed, suggesting that the CCR5Δ32 variant does not influence the susceptibility to HCV infection, HCV/HIV co-infection, or HCV-related diseases in individuals from southern Brazil.

Introduction Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) and is frequently related to non-alcoholic fatty liver disease (NAFLD). Objective The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fibrosis. Methods HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20 g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Significant fibrosis (≥F2) was estimated if at least one of the following were present: APRI > 1.0, FIB4 > 3 and/or liver stiffness ≥7.1kPa. Subjects with TE ≥ 7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS) ≥ 3 was considered as diagnosis of NASH. Results A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%). Conclusion Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for significant liver fibrosis. Nevertheless, TE ≥ 7.1kPa was able to accurately select a subgroup of patients at risk for NASH.

The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV−), taking into account their ethnic background. Amongst the 357 HIV+ individuals with available data concerning HCV infection, 98 were positive. In European descendants, the TLR9 rs5743836 C carriers displayed a higher susceptibility to HIV infection [dominant, Odds Ratio (OR) = 1.53; 95% CI: 1.05–2.23; P = 0.027]. In African descendants, TLR9 rs5743836 CT genotype was associated with protection to HIV infection (codominant, OR = 0.51; 95% CI: 0.30–0.87; P = 0.013). Also, the TLR9 rs352140 AA variant genotype was associated with susceptibility to HIV+/HCV+ co-infection in African descendants (recessive, OR = 2.92; 95% CI: 1.22–6.98, P = 0.016). These results are discussed in the context of the different ethnic background of the studied individuals highlighting the influence of this genetic/ethnic background on the susceptibility to HIV infection and HIV/HCV co-infection in Brazilian individuals.

Objectives The purpose of this study was to evaluate the efficacy of dietary intervention on blood lipids of human immunodeficiency virus (HIV)-1–infected patients who are started on highly active antiretroviral therapy (HAART). Background Current guidelines recommend diet as first-step intervention for HIV-1–infected individuals with HAART-related dyslipidemia, but there is no evidence from randomized trials to support this recommendation. Methods Eighty-three HIV-1–infected patients, naive from HAART, were randomly assigned to HAART with dietary intervention (diet group, n = 43) or HAART without dietary intervention (control group, n = 40) for 12 months. Diet, according to the National Cholesterol Education Program, was given every 3 months. Before and after intervention, 24-h food records and lipid profile were obtained. Data were analyzed by intention to treat, using mixed-effects models. Results Diet resulted in reduction of percentage of fat intake (from 31 ± 7% to 21 ± 3% of calories), while controls presented no change in percentage of fat intake. Plasma cholesterol (from 151 ± 29 mg/dl to 190 ± 33 mg/dl) and low-density lipoprotein cholesterol (from 85 ± 24 mg/dl to 106 ± 31 mg/dl) increased in the control group and were unchanged in the diet group. Plasma triglycerides were reduced by diet (from 135 ± 67 mg/dl to 101 ± 42 mg/dl) and increased in the control group (from 134 ± 70 mg/dl to 160 ± 76 mg/dl). After 1-year follow-up, 21% of patients who received diet had lipid profile compatible with dyslipidemia compared with 68% (p Conclusions Among HIV-1–positive individuals naive of previous treatment, diet prevents dyslipidemia associated with HAART. (Effect of Nutritional Intervention on the Lipid Profile of HIV-Positive Patients Who Start HAART: a Randomized Trial; NCT00429845)

Metabolic complications continue to play a major role in the management of HIV infection. Dyslipidemia associated with HIV infection and with the use of combined antiretroviral therapy includes elevations in triglycerides, reduced high-density cholesterol, and variable increases in low-density and total cholesterol. The association between dyslipidemia and specific antiretroviral agents has been underscored. Multiple pathogenic mechanisms by which HIV and antiretroviral agents lead to dyslipidemia have been hypothesized, but they are still controversial. The potential clinical and pathological consequences of HIV-associated hyperlipidemia are not completely known, but several studies reported an increased risk of coronary artery disease in HIV-positive individuals receiving combined antiretroviral therapy. HIV-infected persons who have hyperlipidemia should be managed similarly to those without HIV infection in accordance with the National Cholesterol Education Program. Life style changes are the primary target. Statins and fibrates and/or modification in antiretroviral therapy are possible approaches to this problem. Keywords: HIV/AIDS, dyslipidemia, combined antiretroviral therapy, nutrition, Public Health

Kaposi's sarcoma (KS) is the most frequent type of cancer in patients with Acquired Immune Deficiency Syndrome (AIDS). In the western world, its incidence decreased dramatically in the era of highly active anti-retroviral therapy (HAART). In contrast, the incidence of KS has been steadily climbing in parallel with the AIDS epidemic in Africa over the past 10-15 years, being the most common cancer in adult men in countries like Uganda and Zimbabwe. AIDS-KS can be diagnosed at any stage of HIV infection, although it more commonly occurs in the setting of severe immune suppression, especially with an elevated viral load. Up to now, AIDS-KS is still an incurable disease. Its clinical course is variable, ranging from very indolent cases, requiring no or minimal therapy, to a rapidly progressive disease. Various local therapies are available to control small and asymptomatic lesions, while cytotoxic, immunological and biological therapies can be considered for more aggressive disease. The primary goal of therapy in most of the cases is to provide safe and effective palliation, in order to quality of life. Optimal anti-retroviral therapy is a key component of AIDS-KS management. There are still many questions to be answered in the management of patients with AIDS-KS, such as (1) What are the therapeutic agents that should be used in this disease, and in which sequence? and (2) What are the benefits and risks expected with each treatment option? The aim of this review is to discuss the systemic management of AIDS-KS, with special focus on the above mentioned questions.

Antitumour activity of cytotoxic agents, evaluated in patients with AIDS-related Kaposi's sarcoma (KS), is about 30–80%. However, responses are mostly partial and short. Experience with etoposide is similar. Teniposide has a longer elimination half-life and superior antitumour activity compared with etoposide in some experimental models. Thus a phase II trial was done in 25 patients with AIDS-related KS. Teniposide was given by 60-min infusion at 360 mg/m 2 every 3 weeks. 10 (40%) showed a partial response, median duration of 9 (6–20) weeks. The main side-effects were leukopenia, thrombocytopenia, nausea and vomiting, alopecia and mucositis.

A 41-year-old woman with advanced HIV infection (CD4 cell count of 4 cells per μL) was admitted at our hospital with an ulcer on the central area of the tongue’s dorsal surface that started 1 week before (fi gure, A). She had fever, weight loss, and a recent diagnosis of histoplasmosis of the lymph nodes that was being treated with oral itraconazole. At the examination, the tongue was tender and the ulceration was involved by atrophy and elongated fi liform papillae that are typical of a hairy tongue, with a dark colour secondary to porphyrin pigment deposition by bacterial metabolism. A biopsy of the ulcer showed minimal epidermal changes and an “owl’s eye” appearance of the endothelial cells, which is pathognomonic for cytomegalovirus infection. The biopsy was negative for Histoplasma capsulatum organisms. No other site was aff ected by cytomegalovirus. Intravenous ganciclovir for 14 days was started with complete regression of the tongue ulcer (fi gure, B). The patient was started on antiretroviral treatment (stavudine, lamivudine, and efavirenz) and, as of February, 2006, she was asymptomatic, with a CD4 cell count of 208 cells per μL and a viral load of less than 50 copies per mL. She has had no further cytomegalovirusrelated complications. In patients with advanced AIDS, cytomegalovirus is a frequent cause of chorioretinitis, oesophagitis, pneumonitis, and chronic perineal ulcerations. It has also been involved in endocrine, bone marrow, central nervous system, and kidney abnormalities. Cutaneous manifestations are often atypical and range from vesicles to nodules and chronic ulcerations, but rarely aff ect the tongue. However, tongue involvement in advanced AIDS is common. The tongue is aff ected by local rather than systemic pathologies and a large number of concomitant lesions are often present. The most common lesions are candidosis, hairy leucoplakia, non-specifi c chronic glossitis, melanotic pigmentation, and herpes simplex infection. Fortunately, mucocutaneous lesions associated with cytomegalovirus or other herpesvirus infection respond well to systemic antiviral therapy but are diffi cult to diff erentiate from other ulcerogenic diseases—eg, aphthous major, necrotising stomatitis, and other unspecifi ed ulcerations—without biopsy and histopathological examination. Cytomegalovirus in an AIDS patient