Researchers have succeeded in leading a group of monkeys infected with SIV, the simian version of HIV, into a state of sustained viral remission for as long as 23 months following an experimental antibody treatment. The treatment has also led the monkeys to experience an almost-total rebound of key immune cells that the virus destroyed.
These findings are a good sign, albeit very preliminary, for the quest to develop a functional HIV cure in humans—in which their immune systems control the virus without the need for daily antiretrovirals (ARVs). Enrollment into a small, early-phase human trial of a similar treatment that will primarily look at safety measures has already begun.
Speaking about the monkey trial, Anthony S. Fauci, MD, who co-led the study as chief of the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases (NIAID), said in a press release, “Our data suggest that the immune systems of these animals are controlling SIV replication in the absence of antiretroviral therapy. The experimental treatment regimen appears to have given the immune systems of the monkeys the necessary boost to put the virus into sustained remission.”
In an interview with POZ, Fauci, who is also the head of NIAID, cautioned about reading too much into the success of the experimental treatment at this time, saying, “We don’t know if it’s applicable to humans. This is too early to make any dramatic statements about anything.”
Publishing their findings in the journal Science, NIAID-funded researchers infected 18 rhesus macaques with SIV. Five weeks later, they started the animals on 90 days of ARVs. Nine weeks after infection, 11 of the monkeys were put on infusions of an investigational treatment antibody every three weeks for 23 weeks while the seven other monkeys received a placebo under this protocol. The monkeys stopped receiving all treatments 32 weeks after being infected with the virus.
The antibody treatment, which is similar to the ulcerative colitis and Crohn’s disease drug Entyvio (vedolizumab), was designed to work against a receptor on immune cells known as α4β7 integrin. One function of the α4β7 integrin antibody is to prevent the sort of immune cells that HIV and SIV targets from seeking out and nestling into gastrointestinal tissues. Such tissues are a major site for the virus’s replication and a place where the viral reservoir develops early in infection.
The HIV reservoir is composed at least in part of latently infected immune cells that, because they are not replicating, remain out of reach of standard ARV treatment.
By their third week on ARVs, all 18 monkeys had a fully suppressed virus. While receiving the antibody treatment, three of them developed antibodies against the treatment; they were then excluded from the study.
Once the other 15 monkeys stopped receiving ARVs, the seven control animals saw their virus rebound within two weeks and remain at high levels. As for the eight monkeys that received the antibody treatment, SIV rebounded temporarily in six of them. However, within four weeks, their immune systems had controlled the virus. The other two monkeys in the antibody treatment group never experienced viral rebound.
So far, the eight monkeys that received α4β7 integrin have maintained a fully suppressed virus for as long as 23 months after ending all treatment.
Researchers are not certain why the antibody treatment prompted the monkeys’ immune systems to wrest control of their SIV infections but hope to develop answers in subsequent research.
A small, early phase clinical trial of short-term treatment with Entyvio among humans has already begun enrollment in Bethesda, Maryland.
Unlike the monkeys, who were all very newly infected, the human trial participants will have long-established HIV infections and must already be on stable ARV treatment. While the trial will indeed test whether the treatment is effective at controlling HIV after the participants interrupt ARV treatment, it is primarily concerned with safety. Researchers expect to have preliminary results by the end of 2017 and further data in 2018.
According to Fauci, subsequent trials would enroll people recently infected with HIV.
Because the monkeys were all recently infected, whether similar success would be seen in humans not also recently infected remains a key question.
To read a press release about the study, click here.
To read the study abstract, click here.
For information on participating in the clinical trial, click here.
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