Hiv and Global Health in a Pandemic Era

Four broad themes run through this year's N'Galy-Mann lecture: clinical medicine, HIV, health security, and global health. Three patterns of disease characterized medicine in East Africa at the time that AIDS was first described in the United States: diseases of poverty, mainly infectious;non-communicable diseases with differing international epidemiology;and classic tropical diseases restricted in distribution by ecologic needs of parasites and vectors. Limited resources did not prevent the practice of good medicine under adverse circumstances, nor application of basic principles of research. The recognition of a second AIDS virus (HIV-2) in West Africa in the mid-late 1980s required applied research to assess implications and potential global impact of this novel infection. CDC established a second collaborative research site in sub-Saharan Africa, Projet RETRO-CI, in Abidjan, Cote d'Ivoire (the first was Projet SIDA in the Democratic Republic of Congo, where N'Galy and Mann made seminal contributions). Controversy around HIV-2 diagnosis, transmission, and pathogenicity was slowly resolved through West African research showing HIV-2 was an AIDS-causing pathogen, slower than HIV-1 in its progression, and less transmissible until late in the course of infection. Mother-to-child transmission was exceptionally rare. Claims that HIV-2 protected against HIV-1 were not substantiated. Projet RETRO-CI clarified the spectrum of HIVassociated disease and the dominant role of tuberculosis. Placebo-controlled trials demonstrated efficacy of short-course zidovudine for prevention of perinatal transmission of HIV-1, and of cotrimoxazole prophylaxis in reducing hospitalization and mortality in persons with HIV. Global health today is dominated by discourse around health security. The West African and Congolese Ebola epidemics since 2014 aroused strong declarations, yet the world was poorly prepared to address the pandemic of COVID-19. Health in the world has changed substantially since AIDS emerged. As 2030, the year for delivery on the Sustainable Development Goals, approaches, development assistance for health remains essential to address traditional, unfinished commitments yet does not match today's global burden of disease. CROI attendees are encouraged to remember colleagues lost to COVID-19 and other challenges;to assess priorities in today's global health, including relating to HIV;and to reflect on what issues? N'Galy and Mann would focus on today.

A RETROSPECTIVE OBSERVATIONAL STUDY TO EVALUATE THE EFFECT OF PULMONARY REHABILITATION IN PATIENTS WITH POST-COVID-19 LUNG DISEASE

SESSION TITLE: Outcomes Across COVID-19 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Pulmonary rehabilitation is an effective intervention in patients with chronic lung disease who have significant dyspnea, poor exercise tolerance and diminished quality of life.This study was undertaken to evaluate the effect of pulmonary rehabilitation in the patients of post-COVID-19 lung disease who had similar disabilities. METHODS: This is a retrospective observational study where data of patients with post covid-19 lung disease, enrolled for Pulmonary rehabilitation was analysed. The details of the patient like demographics, comorbidities, length of illness or hospital stay, oxygen requirements during illness were noted on the first visit. The subjects then underwent an eight week supervised pulmonary rehabilitation protocol consisting of breathing strategies, strength training for upper and lower limb muscle groups, endurance training, balance and coordination training. A 30 second sit to stand test [STST], 30 second wall push up test, St. George's Respiratory Questionnaire (SGRQ), and Modified Borgs Scale were taken as outcome measures at commencement and after the completion of rehabilitation. RESULTS: A total of 57 patients were included in the study and their data analysed. Difference in the Borg 's scale and SGRQ score pre and post pulmonary rehabilitation was calculated. The median (IQR ) difference in Borg's scale pre and post pulmonary rehabilitation was 5 (3). The median ( IQR) difference in SGRQ pre and post pulmonary rehabilitation was 40.04 (22.92). The median( IQR) difference in 30 second STST pre & post pulmonary rehabilitation was 7 (4). The median( IQR) difference in 30 second wall push up test pre & post intervention was 8(5). CONCLUSIONS: Pulmonary rehabilitation is a safe and effective intervention to improve exercise tolerance and quality of life in patients with significant disability following post covid 19 lung disease. CLINICAL IMPLICATIONS: In absence of any proven pharmacotherapy to treat post covid lung disease, pulmonary rehabilitation when implemented appropriately, in a select group of patients with significant residual disability following moderate to severe covid 19 infection, is a safe and effective intervention to hasten return to normalcy. DISCLOSURES: No relevant relationships by Pavanjitsingh Harjitsingh Dumra No relevant relationships by Dr.Aviral Tripathi

Táplálkozási szokások változása a pandémia alatt

The COVID-19 pandemic has had a significant impact on the daily lives of the population, primarily due to the disease control measures. The focus has shifted to health protective factors, with a healthy diet playing a key role in increasing the human body's resistance to pathogens. In addition, being overweight has a negative impact on the course of the disease, making the virus an even greater threat to our society. Our aim was to examine how the pandemic has changed our daily diet, with a particular focus on fruit and vegetable consumption. Data collection included both secondary and primary research. With 242 responses, our primary analysis was conducted using an online questionnaire. The results showed, that half of the respondents had changed their eating habits and one third had gained extra weight during the pandemic. A higher percentage regard their fruit and vegetable consumption as sufficient enough, while only 29.6% think they are eating the daily recommended amount. The results showed that there is a lack of awareness among respondents of the recommended daily intake of fruit and vegetables, which is a fundamental problem in terms of dietary health. JEL Code: I12Alternate : A COVID-19 fertőzés jelentős mértékben hatott a lakosság mindennapi életvitelére, melynek oka elsődlegesen a járványellenes megszorító intézkedések voltak. Előtérbe kerültek az egészséget védő tényezők, melyek közül az egészséges táplálkozásnak kiemelt szerepe van az emberi szervezet kórokozókkal szembeni ellenállás fokozásában. Ezen kívül a túlsúly kedvezőtlenül befolyásolja a betegség lefolyását, így társadalmunkra még nagyobb veszélyt jelent a vírus. Célunk volt vizsgálni, hogy milyen változásokat hozott a pandémia a mindennapi étkezésünkben, kiemelten a zöldség és gyümölcs fogyasztást. Az adatgyűjtés során szekunder és primer kutatást is végeztünk. Primer vizsgálatunkat online kérdőív segítségével végeztük, melyre 242 válasz érkezett. Megállapítottuk, hogy a megkérdezettek felénél változtak a táplálkozási szokások és egy harmada plusz kilókkal küzd a pandémia alatt. Nagyobb százalékban gondolják azt, hogy elegendő zöldség/gyümölcs fogyasztásuk, míg a napi ajánlott mennyiség bevitele már csak 29,6%-ra jellemző. Az eredmények rámutatnak arra, hogy a napi ajánlott zöldség/gyümölcs mennyiségével nincsenek tisztába a megkérdezettek, amely az egészséges táplálkozás szempontjából is alapvető problémaként tekinthető. JEL kód: I12

PREDICTORS of VIRAL SUPPRESSION FOLLOWING ENHANCED ADHERENCE COUNSELING: VISEND TRIAL

Background: The WHO recommends enhanced adherence counseling (EAC) before regimen switch for HIV-positive, antiretroviral therapy (ART)-treated individuals with non-suppressed viral loads (VL). However, there is a paucity of data, especially within a clinical trial setting, on the determinants of viral suppression (VS) following EAC among those failing ART. We thus evaluated predictors of VS among adults failing ART who had undergone EAC in the VISEND clinical trial. Methods: Our trial is a randomized 144 week open label non-inferiority study with adults failing (VL≧ 1000 copies/mL) ART of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) plus efavirenz (EFV) or nevirapine (NVP), switched to 1) TDF,3TC,DTG or 2) tenofovir alafenamide (TAF), emtricitabine (FTC),DTG or 3) lopinavir/ritonavir (LPV/r) or atazanavir/r (ATV/r), zidovudine (ZDV),3TC. Viral loads and other biomarkers were collected at weeks 12, 24, 48, 72, 96 and 144. Adults with VL≧ 1000 copies/mL at each of these time points underwent EAC involving 3 sessions over a period of 3 months according to existing guidelines. We calculated proportions of individuals who achieved VS post EAC and analyzed factors (demographic and clinical) independently associated with VS post EAC. Using multivariable log regression models, associations were analyzed as crude risk ratios (CRR) and adjusted risk ratios (ARR). Results: The overall VS rates following EAC among individuals with virologic failure was 66%;broken down as follows: TAF,FTC,DTG (78%), TDF,3TC,DTG (71%), ZDV,3TC,ATV/r (62%), and ZDV,3TC,LPV/r (53%). Compared to adults with no formal education, those having primary (ARR 1.55 [1.32-1.81], P<0.001) or secondary level education (ARR 1.93 [1.65-2.27], P<0.001) were more likely to achieve VS. Those less likely to suppress post EAC were individuals on ART for > 5 years (ARR 0.75 [0.75-0.75], P<0.001), VL > 10,000 copies/mL at time of failure (0.48 [0.48-0.48], P<0.001), presence of comorbidities (ARR 0.77 [0.66-0.90], P=0.001) and those taking concomitant medications (ARR 0.67 [0.58-0.79], P<0.001). Having suffered from COVID-19 infection had no association with VS post EAC (ARR 0.59 [0.22-1.58], P=0.30). Consistent results are in Table 1. Conclusion: In the VISEND trial, EAC led to VS rates near the WHO target of 70% with disparities in outcomes according to gender, education, and other factors. There is a need to routinely incorporate EAC into clinical trials and practice before regimen switch in order to maximize outcomes.

The Role of Nanotechnology in Antiviral Regime: An Overview

Nanomedicine or nanotechnology exhibits outstanding features to challenge severe health issues including pathogenic viral infections, the most culpable invaders in the present situation. The perpetual mutational pattern in viruses topped with raising resistance to drug epitomizes the current situation as a trigger to explore nanotech platforms in antiviral therapies. Referring to novel physicochemical features of nanomaterials associated with effective drug delivery, it is viewed as an ideal strategy for treatment of viral infections. The coronavirus induced pathogenesis, including MERS, SARS and SARS-CoV-2 infections, has triggered alarming and highly dangerous precedents against existence of humans. Applications of nanotechnology can serve a new direction for disinfection or treatment of viruses. Presently, various types of nanomaterials, such as nanogels, nanospheres, nanocapsules, liposomes, nanoparticles and many others, that have been investigated in vivo and in vitro for successful drug delivery, vaccination, diagnostic assay and device development with anticipation to be translated in advanced clinical practices, need a collective relook. This paper intents to contribute insightful critique of current studies on the efficacy of nanoplatforms as drug transporter, diagnostic tool and vaccine candidate against pathogenic viruses counting the highly pathogenic and incurable "coronaviruses".

A Review on the New Indication of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in the Treatment of Coronavirus Disease 2019.

BACKGROUND: In December 2019, a new coronavirus (nCoV) emerged as a public health concern spreading all around the world. Several attempts have been made to discover effective drugs and vaccines. Up to now, multiple COVID-19 vaccines have been developed against this mysterious virus, and a lot of individuals have already got vaccinated. OBJECTIVE: Anti-viral drugs are effective in treating and managing COVID-19. Nucleoside reverse transcriptase inhibitors (NRTIs) are a collection of antiviral drugs for treating HIV and HBV infections. These drugs prevent virus replication by blocking reverse transcriptase (RT). In this review, we discuss the interaction of this class of anti- HIV drugs with specific functional proteins and enzymes of SARSCoV- 2. METHODS: A search of the databases, including Web of Science, Embase, PubMed, Scopus, and Google Scholar, was conducted from commencement to September 2020. The relevant articles on the potential effects of NRTIs on COVID-19 were collected. Finally, twenty-three articles were selected, including all in vitro, in vivo, and clinical studies. RESULTS: It was observed that RdRp, spike, ACE2, PNP, inflammatory cytokines, and nucleocapsid protein participate in the pathogenesis of SARS-CoV-2. NRTIs target these proteins by binding to them. CONCLUSION: This review is focused on the mechanisms of NRTIs to introduce them as potential therapies for COVID-19. However, further in vitro and in vivo investigations will provide helpful information for the identification of drug candidates as a part of COVID-19 management.

A németországi termelői boltok online marketing tevékenysége

The importance of digital marketing is increasing significantly. During the current pandemic situation, its shortcomings are even more easily noticeable. Due to the German consumers' green purchasing behaviour, the poor online performance of German farmer shops appeared. The aim of this paper was to analyse the usage of digital marketing tools in this field. A representative database was applied for the descriptive statistics and the principal component analysis as well. Five clusters were defined by the K-mean method. The research of 375 farmer shops highlighted shortcomings in the usage of the website and social media. More than 70% of the farmer shops did not operate any website or did not provide on it all the required information, while only 20% of the shops were available online as a webshop. The low share of digitally well-managed farmer shops (less than 3%) was revealed by the clustering method. These focus mostly on the sale of alcoholic beverages. The social media surfaces meant in the case of many shops the only contact to the consumers, however, the application of these platforms was not common according to the applied method. For the farmer shops, the lack of digital marketing could mean a disadvantage in a short period, however, the increasing importance of online appearance could cause the decrease of interest and sales for a longer period. JEL Codes: M31, O13, E21Alternate : A digitális marketing jelentősége folyamatosan nő, a pandémiás helyzetben pedig az alkalmazásának a hiánya még szembetűnőbb. A német fogyasztók környezettudatos vásárlási preferenciáinak, valamint a COVID-19 okozta helyzetnek köszönhetően a németországi termelői boltok alacsony online jelenlétére hamar fény derült. A kutatás célja éppen ezért, az elsődleges termelői élelmiszerboltok által használt digitális marketing eszközök elemzése. A reprezentatív mintán végzett főkomponens elemzéssel és a K-közép módszer alkalmazásával öt csoportot azonosítottunk. A vizsgálat alapját képező 375 termelői bolt adatai nyomán kijelenthetjük, hogy ezek az üzletek a weboldalaik és a közösségi média felületeik használatára csekély figyelmet fordítanak. Az elemzett boltok több, mint kétharmada nem üzemeltetett semmilyen honlapot, vagy nem tűntette fel azon a törvényileg előírt információkat, és csupán minden ötödik biztosított lehetőséget online vásárlásra (webshop). A digitális marketing nyújtotta lehetőségeket jól kihasználó (leginkább alkoholos termékek értékesítésére fókuszáló) üzletek alacsony száma a klaszterezés során vált igazán jól láthatóvá. A vizsgálati módszerek segítségével azt is megállapították a szerzők, hogy sok üzlet esetében a közösségi média használata jelentette az egyetlen online kapcsolatot a vásárlókkal, viszont még ezen felületek alkalmazása sem nevezhető általánosan bevett gyakorlatnak a német termelői boltok vonatkozásában. A digitális marketing hiánya rövid távon hátrányt, hosszabb távon akár a vevők számának és ezáltal a bevétel nagyságának csökkenését is eredményezheti. JEL-kódok: M31, O13, E21

Antiviral drugs suppress infection of 2019-nCoV spike pseudotyped virus by interacting with ACE2 protein.

The outbreak of coronavirus disease 2019 (COVID-19) has induced a large number of deaths worldwide. Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for the 2019 novel coronavirus (2019-nCoV) to infect the host cells. Therefore, ACE2 may be an important target for the prevention and treatment of COVID-19. The aim of this study was to investigate the inhibition effect of valaciclovir hydrochloride (VACV), zidovudine (ZDV), saquinavir (SQV), and efavirenz (EFV) on 2019-nCoV infection. The results of molecule docking and surface plasmon resonance showed that VACV, ZDV, SQV, and EFV could bind to ACE2 protein, with the KD value of (4.33 ± 0.09) e-8 , (6.29 ± 1.12) e-6 , (2.37 ± 0.59) e-5 , and (4.85 ± 1.57) e-5 M, respectively. But only ZDV and EFV prevent the 2019-nCoV spike pseudotyped virus to enter ACE2-HEK293T cells with an EC50 value of 4.30 ± 1.46 and 3.92 ± 1.36 µM, respectively. ZDV and EFV also have a synergistic effect on preventing entry of virus into cells. In conclusion, ZDV and EFV suppress 2019-nCoV infection of ACE2-HEK293T cells by interacting with ACE2.

Drug Repurposing Approaches to Combating Viral Infections.

Development of novel antiviral molecules from the beginning costs an average of $350 million to $2 billion per drug, and the journey from the laboratory to the clinic takes about 10-15 years. Utilization of drug repurposing approaches has generated substantial interest in order to overcome these drawbacks. A drastic reduction in the failure rate, which otherwise is ~92%, is achieved with the drug repurposing approach. The recent exploration of the drug repurposing approach to combat the COVID-19 pandemic has further validated the fact that it is more beneficial to reinvestigate the in-practice drugs for a new application instead of designing novel drugs. The first successful example of drug repurposing is zidovudine (AZT), which was developed as an anti-cancer agent in the 1960s and was later approved by the US FDA as an anti-HIV therapeutic drug in the late 1980s after fast track clinical trials. Since that time, the drug repurposing approach has been successfully utilized to develop effective therapeutic strategies against a plethora of diseases. Hence, an extensive application of the drug repurposing approach will not only help to fight the current pandemics more efficiently but also predict and prepare for newly emerging viral infections. In this review, we discuss in detail the drug repurposing approach and its advancements related to viral infections such as Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Targeting the SARS-CoV2 nucleocapsid protein for potential therapeutics using immuno-informatics and structure-based drug discovery techniques.

The occurrence of the SARS-CoV2 infection has become a worldwide threat and the urgent need to discover therapeutic interventions remains paramount. The primary roles of the coronavirus nucleocapsid (N) protein are to interact with the viral genome and pack them into ribonucleoprotein complex. It also plays critical roles at many stages of the viral life cycle. Herein, we explore the N protein of SARS-CoV2 to identify promising epitope-based vaccine candidates and target the N-terminal domain of SARS-CoV2 N-protein for potential inhibitors using an integrative bioinformatics approach. We identified B-cell epitopes and T-cell epitopes that are non-toxic, non-allergenic, capable of inducing IFN-γ and structurally stable with high global population coverage of response. The 404SKQLQQSMSSADS416 and 92RRIRGGDGKMKDL104 sequences of N-protein were identified to induce B-cell immunity. We also identified 79SSPDDQIGY87 and 305AQFAPSASAFFGMSR319 as potential T-cell epitopes that form stable structures with human leucocyte antigens. We have also identified zidovudine triphosphate, an anti-HIV agent, as a potential inhibitor of the N-terminal domain of SARS-CoV2 N-protein based on docking and simulation analysis and should be considered for experimental validations. The findings of this study can help fast-track the discovery of therapeutic options to combat COVID-19.