Antonio Fuchs and Bárbara Clara (INI/Fiocruz)
The Evandro Chagas National Institute of Infectious Diseases (INI/Fiocruz) participated in a study that assessed cases of Monkeypox in people with advanced HIV infection. Presented at the 30th Conference on Retroviruses and Opportunistic Infections (CROI 2023) and published (2/21) in the scientific journal The Lancet, the study had researchers from 19 countries such as the United States, Spain, Mexico, the United Kingdom and Brazil, who provided data from confirmed cases of Monkeypox (between May 11th, 2022 and January 18th, 2023). INI/Fiocruz is a reference in the treatment of cases of monkeypox in Rio de Janeiro and develops different research that contribute to the fight against this disease.
With the collaboration of Mayara Secco Torres Silva, Infectologist at the Laboratory of Clinical Research on STDs and AIDS at INI/Fiocruz, the study Mpox in people with advanced HIV infection: a global case series gathered 382 cases, 349 (91%) of which were cases in individuals living with HIV. Overall, 107 patients (28%) were hospitalized and 27 deaths (25%) occurred, all cases of people with advanced HIV immunosuppression. One of the highlights of the work was the description of a severe form of Monkeypox, characterized by necrotizing skin and mucosal lesions, with a high prevalence of fulminant dermatological and systemic manifestations and death in patients with advanced HIV disease, characterized by CD4+T lymphocyte counts below 200 cells/mm3.
According to the researchers, it is important to assess the inclusion of these severe forms of monkeypox with a new AIDS-defining condition in the classifications of HIV diseases by the Centers for Disease Control and Prevention (CDC) of the United States and the World Health Organization (WHO). Another important finding of the study was the fatal outcome of patients with suspected clinical deterioration due to immune reconstitution inflammatory syndrome (Iris). Of a total of 85 patients who started or restarted the use of antiretrovirals, it was suspected, in 25% of the cases, that the clinical deterioration could have occurred as a result of the Iris, 57% of which died.
This data brought great concern to the researchers. “As far as prevention is concerned, people with HIV and at high risk of monkeypox infection should be prioritized for a preventive vaccine. Moreover, two-thirds of the registered deaths occurred in Latin America. Findings are particularly relevant for countries with low levels of HIV diagnosis or with no free universal access to antiretroviral therapy or intensive care units, where the interaction of uncontrolled HIV infection and Monkeypox is more prevalent. In these countries, a concerted effort to provide urgent access to Monkeypox antivirals and vaccines is of critical importance”, the study authors reported.
Fight against monkeypox
The work of INI/Fiocruz in the fight against monkeypox goes beyond healthcare. Among the research, two multicentric studies coordinated by INI/Fiocruz stand out, scheduled to start in March 2023. The first is to assess the MVA-BN Jynneos vaccine, produced by the company Bavarian Nordic, as post-exposure prophylaxis, that is, the administration of the vaccine is carried out after the person has contact with a high degree of potential exposure to the virus through intimate contact with a person who is a confirmed case of monkeypox or who has had an accident when handling material contaminated by the virus in the collection of clinical material or in the processing of material in a laboratory.
“These people will attend the research centers and will be vaccinated with two doses of the vaccine, with an interval of 28 days between doses, if the exposure has occurred in the interval of up to 14 days. People whose exposure has occurred after 14 days will be able to participate in the study and will be followed up, but will not be vaccinated. The study foresees the participation of at least 746 individuals. Our expectation is that this immunizer, applied within this time interval, can block the process of infection by the virus or attenuate the development of the disease”, explained Valdiléa Veloso, study coordinator and director of INI/Fiocruz.
The second study is Unity, a multicenter, international, randomized double-blind clinical trial that will assess the safety and efficacy of the antiviral Tecovirimat in the treatment of patients with monkeypox. Coordinated by Beatriz Grinsztejn, researcher and head of the Laboratory of Clinical Research on STDs and AIDS at INI/Fiocruz, in partnership with Alexandra Calmy, from the University Hospital of Geneva - Switzerland and the French National Agency for Research on AIDS and Viral Hepatitis (ANRS). In Brazil, the participating centers will be coordinated by INI/Fiocruz.
Tecovirimat was developed for the treatment of smallpox, licensed by the European Medicines Agency (EMA) for monkeypox in 2022, based on data from limited animal and human studies. However, so far there have been no clinical trials to confirm whether the drug can help monkeypox patients recover from the disease. Results from the Unity clinical trial will be instrumental in filling this knowledge gap.
Monkeypox at Croi 2023
Monkeypox was one of the highlights of the 30th Conference on Retroviruses and Opportunistic Infections (CROI 2023), an event organized by the Croi Foundation in partnership with the International Antiviral Society (IAS-USA), held between February 19th and 22nd in Seattle (USA). Three researchers from the Laboratory of Clinical Research on STDs and AIDS of INI/Fiocruz, present at the event, presented unpublished studies relating to monkeypox and HIV.