An international Phase 3 study is being conducted in Brazil to test an injectable drug for HIV that could potentially reduce the number of injections to three cycles per year. The goal is to maintain viral control for a longer period between doses while preserving safety and efficacy.
Among the study participants is anthropologist and activist Pisi Bruza, who became the first volunteer in the country to begin the four-month interval assessment phase. Before potential approval is granted, the study must demonstrate the viability of the new formulation.
The study, named CUATRO, investigates new formulations of cabotegravir and rilpivirine, two antiretroviral drugs used in the fight against HIV. Approximately 564 volunteers are planned to be recruited from different countries, with monitoring extending until 2029. In Brazil, 65 participants have already been enrolled, and five more are undergoing screening, according to infectious disease specialist Jose Valdes Ramalho Madruga, a researcher at the Center for STD/AIDS Reference Centers and Training (CRT) in São Paulo.
Each cycle involves two intramuscular injections—one of each drug. Pisi, a public health graduate student at the USP Faculty of Medicine, has already received the first dose. The protocol includes laboratory tests, electrocardiograms, and periodic check-ups to detect possible side effects and monitor viral control.
The active components are not new; long-acting injectable versions have already been approved in other countries, albeit with shorter intervals between doses. CUATRO is testing ultra-long-acting formulations to extend this period to four months.
The possibility of reducing the frequency of drug administration is significant for people who struggle with daily treatment. Forgetfulness and side effects can disrupt routines, and the fear of diagnosis disclosure causes some individuals to hide their medication.
Pisi personally knows this problem and emphasizes the impact of prejudice on the lives of people living with HIV. In an interview with g1, she stated: 'Taking medication every day is not easy, especially because of the stigma associated with HIV.'
Madruga also pointed out social barriers affecting treatment adherence. The infectious disease specialist noted: 'Therefore, the longer the interval between doses, the better for the patient.'
The study will evaluate fundamental aspects to determine whether the new formulation can become a safe alternative. Volunteers are already entering the study with suppressed viral loads, meaning they have controlled HIV. One indicator will be the proportion of participants with a viral load equal to or exceeding 50 copies per milliliter. Therefore, the results cannot be automatically applied to all people living with HIV.
Injectable versions of cabotegravir and rilpivirine have already received Anvisa approval in Brazil for certain patients, but they are not yet provided through the Universal Health System (SUS). Currently, the public network mainly offers daily antiretroviral regimens. When treatment sustains an undetectable viral load, the person does not transmit HIV sexually. This principle is known as I=I (Undetectable = Untransmittable).
The potential implementation of the new formulation into SUS will depend on positive study results, regulatory evaluation, and analysis by the National Commission for Inclusion of Technologies in SUS (Conitec), after which a decision will be made by the Ministry of Health. Until then, the four-month regimen remains experimental.