Florence Cunzolo
07/07/2020 - 16:01
- Clarín.com
- Good Life
In Argentina, almost 8% of the more than 80,000 confirmed Covid-19 cases so far correspond to health personnel. Members of health teams that care for people with coronavirus are exposed to an increased risk of infection, despite the implementation of preventive measures and the use of personal protective equipment (PPE). Given this situation, the Argentine Society of Infectious Diseases (SADI) launched a clinical study to test whether taking a daily tablet of the antiretroviral tenofovir prophylactically can add a protective effect to these non-pharmacological interventions.
The COVIPREP study, presented yesterday during a SADI virtual seminar, seeks to enroll around 1,400 participants between 18 and 70 years of age, including medical, nursing, kinesiologist, laboratory technicians and cleaning personnel in covid areas, among others, who work in the direct assistance of people with coronavirus.
“ One of the most affected subgroups during the current pandemic is represented by health workers. In this sense, (the study) appears as an appropriate strategy that tests the efficacy of PrEP (pre-exposure prophylaxis) pharmacological approaches in addition to the currently recommended control measures, "the researchers highlight in the description of the randomized clinical trial, double blind, placebo controlled.
What do those characteristics imply? That the participants will be randomly divided into two groups: some will receive one Emtricitabine / Tenofovir Alafenamide (TAF / FTC) daily tablet and others will receive a placebo (a pharmacologically inert drug). The pills are indistinguishable from each other, so neither the participants nor the researchers know which branch each volunteer is assigned to. This information is only decrypted at the time of analyzing the results. The use of a blinded placebo is intended to avoid relaxation of non-pharmacological protective measures .
"It is a complementary strategy and we want everyone to continue with adequate protection measures," explained during his presentation Waldo Belloso, a medical specialist in Clinical Pharmacology and Infectology at the Italian Hospital in Buenos Aires. After the 12 weeks of the intervention , "what percentage of participants acquired the infection (symptomatic or asymptomatic) will be evaluated, through the analysis of antibodies in each of the branches (tenofovir vs. placebo)", to see if the drug provided additional protection.
During the presentation, Belloso together with Omar Sued (president of SADI and director of clinical research for Fundación Huierto) and Gustavo Lopardo (infectologist at the Bernardo Houssay hospital and the Stamboulian Centers) pointed out that the incorporation and follow-up of participants will be very simple .
Participation is voluntary, after signing an informed consent. The conditions are that they must not have had previous infection with the new coronavirus, which is confirmed through a PCR study and a serological test to detect IgG antibodies (they will use the Covidar, developed by the team of the virologist Andrea Gamarnik, from the Leloir Institute Foundation); An HIV test and an antigen test for hepatitis B will also be performed, while women of childbearing age will also be required to have a pregnancy test. They only have to attend one visit at the beginning and another at the end, and once a month they will have to withdraw the medication, which is supplied by Richmond Laboratories.
“The idea is to take advantage of this moment of pandemic peak to incorporate the majority of workers. It is an intensive study: we hope to incorporate many people in a short time. The duration is very short, the intervention lasts no more than 12 weeks. It is a study that will be analyzed very quickly. We hope to have results from here to 6 months maximum. Hopefully the situation of the epidemic changes and this type of study turns out to be unnecessary, but in the meantime, one of the best things we can do is generate this type of evidence, ”said Belloso.
He added: “We are currently in an active call for centers . Once we locate the institutions that are interested in participating, the regulatory package will be sent to them so that it can be presented to their ethics committees. We already have the approval of the first institutional ethics committees and we are waiting - between today and tomorrow - to receive the approval of ANMAT in order to formally start the study. ”
Interested institutions can send an email to coviprep@gmail.com . One of the necessary conditions to participate is that at least the week before joining the study they have attended cases of covid.
Healthcare personnel are one of the subgroups most at risk. (AFP / RONALDO SCHEMIDT)
PrEP at Covid-19
Lopardo noted that pre-exposure prophylaxis is used in many circumstances, from surgical interventions to infectious diseases that cannot be prevented through vaccination, such as malaria (antimicrobials are administered to those who travel to areas with circulation). and HIV (as part of the combined prevention strategy in people at high risk of acquiring the infection).
Of the nearly 2,500 clinical trials registered in the United States National Institutes of Health (NIH) database ( clinicaltrials.gov ) linked to Covid-19, 324 aim to test PrEP: 66 prevention or prophylaxis strategies with hydroxychloroquine. , 14 with lopinavir / ritonavir (both strategies already ruled out by the WHO as a treatment scheme, but not for prevention) and 2 with tenofovir, one of them is COVIPREP and another EPICOS, the Spanish study that served as the basis for the site.
Tenofovir is an inhibitor of nucleotide and nucleoside analog RNA synthesis whose action is to inhibit virus replication in the body . Of this family of drugs, remdesivir is the most evaluated against SARS-CoV-2 and has already obtained urgent approval from the FDA and EMA, the regulatory agencies of the United States and Europe, respectively. In Argentina it began to be tested in the framework of the Solidarity trial, of the World Health Organization.
"But there are also drugs (inhibitors of RNA synthesis) like tenofovir, abacavir, lamivudine, which could be an effective alternative for the treatment of SARS-CoV-2 infection. Due to the molecular coupling characteristics that these drugs have, they could be really useful and effective in preventing the replication of the virus . Tenofovir also has some immunomodulatory activity observed in vitro in animal and human cell lines, in addition to its antiviral activity, "added Lopardo.
An additional advantage of the combination is FTC / TAF pointed out by the researchers is that there is already experience of use in PrEP prophylaxis environment in HIV and its safety is widely known .
Lopardo maintained that there is also epidemiological evidence that justifies the choice of the drug. He cited a study carried out in more than 60 Spanish institutions that assist more than 77 thousand people with HIV. Its authors (Julia del Amo, Rosa Polo and Santiago Moreno) observed that 236 of those receiving antiretroviral treatment (ART) acquired Covid infection: of these, 151 were hospitalized, 15 were admitted to intensive care units (ICU), and 20 died. When analyzing which antiretroviral regimen they received, only 10.5% took FTC / TAF, the lowest percentage, and none had died.
The Spanish researchers also found that the mortality in the study population (people with HIV under the ART regimen) was 30 out of 10,000, while in the Spanish general population it was 41.7 out of 10,000 in the same period of time; "Which could be due to the potential protective effect of antiretroviral drugs," said Lopardo.
The existence or not of this potential effect is what COVIPREP will prove, which has the endorsement of the National Ministry of Health. The holder of the portfolio, Ginés González García, and the secretariat of Access to Health, Carla Vizzotti, opened the virtual presentation.