RIO DE JANEIRO, BRAZIL – Researchers from the Federal University of São Paulo (UNIFESP) conducted a global scale study with people infected with HIV and succeeded in eradicating the virus from the body of a 35-year-old Brazilian patient diagnosed in 2012.
The strategy consisted in enhancing treatment, and the research was to be introduced on Tuesday, July 7th, at the 23rd International AIDS Conference, the largest gathering on the subject in the world. Despite the promising result, it is not yet possible to speak about a cure for AIDS.
According to the university, the results represent a further breakthrough in research that may one day lead to the discovery of a cure for AIDS. Worldwide, three cases are now considered an eradication cure, in which HIV has been completely eliminated: a patient in Berlin, another in London and one in Düsseldorf, also in Germany. They all underwent bone marrow transplants, so this Brazilian case would be the first to achieve a successful result with drug treatment alone.
Coordinated by infectologist Ricardo Sobhie Diaz, director of the Retrovirology Laboratory of the institution’s Department of Medicine, the UNIFESP research initially included 30 volunteers who presented an undetectable HIV viral load in the organism and underwent standard treatment with antiretroviral cocktails. They were divided into six groups and each was administered a drug combination in addition to the standard treatment.
The group with the best results was administered two extra antiretrovirals: a stronger drug called dolutegravir and maraviroc, which “forces” the virus to surface, bringing it out of its latent state, a kind of hiding place in the body. By doing so, it can be destroyed by the drugs. Still according to UNIFESP, two other prescribed substances enhanced the effects of the substances – nicotinamide and auranofine. Diaz found that tests on cells, animals and humans confirm the greater efficacy of nicotinamide against latency than two other drugs used for this purpose and tested jointly.
The Brazilian patient began treatment with antiretroviral drugs two months after being diagnosed with HIV in 2012. Four years later, he joined the UNIFESP research and underwent treatment for 48 weeks. After 14 months, the virus remains undetected in his body. “This case is extremely interesting, and I really hope it can encourage more research into curing HIV,” said Andrea Savarino, a physician at the Italian Institute of Health who co-led the study.
Infectologist José Valdez Ramalho Madruga, coordinator of the SBI’s AIDS Committee, said the major advantage of this study is that the result was achieved using only oral drugs. The other cases known to science had marrow transplants as a basis. “It is a very interesting research and an extremely promising data. The chance to reproduce it on a large scale is much greater,” says the researcher at the STD/AIDS Reference and Treatment Center.
However, he considers that this was a concept-proof study, i.e. with a small number of participants to determine if the methodology works. “A larger study is needed. The perspective now is to reproduce this study with a larger number of patients.”
Andrea Savarino also cautioned that the other four patients in the group who were administered the same drug combination did not have the virus eliminated from their bodies. “It may be that the result is not reproducible. This is a first study, which will need to be extended.” At the conference where the study was introduced, doctors discussed the results and urged caution, according to The New York Times.
Steve Deeks, an HIV researcher at the University of California, San Francisco (UCSF) said it is too early to tell if the patient is indeed free of the virus until other independent laboratories confirm the results. Nevertheless, he said it is unclear if the patient’s condition is a result of the treatment combination he was administered. “These are exciting discoveries, but they are very preliminary,” said Monica Gandhi, an HIV specialist at UCSF.
According to her, nicotinamide has been used in other studies without these results and no drug “has worked so far in terms of long-term remission.” The fact that this is the only case raises doubts, albeit promising. Researchers in the study are expected to test the patient’s blood to determine whether or not he maintained the antiretroviral drugs, which could have compromised the results.
Research into effective treatment for HIV also included the development of a kind of vaccine with dendritic cells (immune cells), which succeeded in “teaching” the body to locate the infected cells and destroy them.
The challenges to curing AIDS
Infectologist Tania Vergara, of the Brazilian Society of Infectious Diseases (SBI), explains that, currently, two types of AIDS cure are being considered: an eradication or sterilization, in which HIV is completely removed, and a functional one termed HIV remission, which aims to achieve an infection control that sustains itself even in the absence of antiretroviral therapy (ART). This treatment acts to prevent the virus from replicating in active cells.
However, the greatest challenge for a cure is to reach the inactive cell pool where the virus is dormant, or latent, where current drugs are unable to act. However, it is known that viral latency is a reversible process and that HIV multiplies in the absence of effective antiretroviral therapy.
“In ART use time, this latent cell pool slowly decreases, but it can take about 70 years to become extinct, although there is evidence of a reduction in four years followed by a plateau, which may be related to the ability of the infected cells to proliferate,” says Tania.
She says that another obstacle is that the latent pool can form in compartments of the human body where neither the immune system nor the treatment are able to recognize it because of physical and cellular obstacles. “To contemplate a cure, the path seems to be one of multiple approaches. The earlier the onset of ART and the control of viral replication, the smaller the latent pool of HIV may be, the better the innate immunity and the better the immune response,” says the SBI expert. According to her, the protocol presented at the event by infectologist Ricardo Sobhie Diaz “seems to represent a great step towards a cure.”
The International AIDS Conference is organized by the International AIDS Society (IAS) every two years and is sponsored by the Joint United Nations Programme on HIV/AIDS (UNAIDS). The event, which discusses worldwide scientific findings on HIV, was to take place this year in San Francisco, USA, but will be held virtually due to the pandemic.
The coronavirus pandemic is also affecting the distribution of drugs to HIV patients around the world. On Monday, July 6th, the World Health Organization reported that 73 countries have alerted that they are at risk of running out of antiretrovirals. Twenty-four countries reported that their stocks are low and are suffering from interruptions in the supply of these life-saving drugs.
By the end of 2018, the world counted 37.9 million people living with HIV, according to UNAIDS. Brazil’s Ministry of Health’s HIV/AIDS 2019 Epidemiological Report said the country’s AIDS detection rate has been dropping in recent years. In 2012, the rate was 21.7 cases per 100,000 residents, falling to 20.6 in 2014 and 18.9 in 2016. In 2018, the rate reached 17.8. The document also states that between 1980 and June 2019, 966,058 AIDS cases were reported in Brazil, with an annual average of 39,000 new cases over the past five years.
Cases described in science
Tania Vergara says that there are three cases considered to be an eradication cure. The pioneer was American Timothy Ray Brown, now 54, who in addition to HIV also had leukemia. To overcome the disease, after chemotherapy sessions with no significant effects, the medical team performed a bone marrow transplant. HIV needs a protein present in the blood to reproduce and some people do not produce it as a result of a rare genetic mutation that renders them immune to the virus.
The strategy – unprecedented and accurate – was to find a donor that fits these parameters in order to destroy the original immune system and create a new defense mechanism to eliminate the virus. After beating HIV in 2007, Brown became known as the “Berlin patient”, as he lived in the German city. To fight leukemia, the American needed a new bone marrow transplant from the same donor.
About 12 years later, the marrow donation strategy worked again, this time in a London patient. Scientists described the case as “long term remission”.
The third case is that of a person known as the “Düsseldorf patient”, who is still under follow-up after undergoing treatment for acute myeloid leukemia. He also received a bone marrow transplant in February 2013 from a donor who lacked the recipient to which HIV binds to penetrate the cells. The person had antiretroviral treatment suspended in November 2018 and remains with an undetectable HIV viral load.