A year without HIV
A pair of antibodies suppressed the reproduction of HIV in the blood of patients for a year
Polina Loseva, N+1
Immunologists have tried to achieve remission in HIV-infected patients with a cocktail of two antiviral antibodies. Antibody injections allowed the trial participants to live for 20 weeks without standard antiviral therapy and for several more months without treatment at all. Most of the subjects then had to return to standard therapy, but in two people remission lasted at least a year. The work was published in the journal Nature (Gaebler et al., Prolonged viral suppression with anti-HIV-1 antibody therapy).
Most HIV-infected people — among those who were prescribed treatment on time — manage to restrain the reproduction of the virus. But to do this, you need to take antiretroviral therapy daily. This is inconvenient — the patient is at risk every time he misses a pill for some reason or simply forgets about it. Therefore, scientists are looking for a way to cope with the virus, if not once and for all, then at least for a long time. With HIV prevention, this was partially successful — recently in the United States approved a preventive injection, which is enough to do once every two months. It's not working out that way with medications yet.
A group of doctors and immunologists led by Michel Nussenzweig from Rockefeller University of New York is trying to achieve a long-term effect with the help of antibodies. In 2018, they already reported that three injections of antibodies (a mixture of 3BNC117 and 10-1074 drugs) allowed patients to stay without pills for an average of five months. Now the same group has worked out a new protocol.
The scheme of the experiment. Triangles indicate the time of administration of antibodies. ART is antiretroviral therapy, all participants took it before the experiment, then the first group took a break in it, after injections both groups took a break, and then it was prescribed only to those whose concentration of the virus became critical. Figures from the article by Gaebler et al.
The subjects (26 people in total) had already received seven injections of the same pair of antibodies, the first three at intervals of two weeks, then four more at intervals of four weeks. 18 of them stopped taking antiretroviral drugs shortly after the first injection. And the researchers measured the concentration of viral RNA in their blood from time to time — to resume therapy as soon as the virus begins to multiply again. 76 percent of the participants (13 people) were able to go without pills for at least 20 weeks, and on average 12 weeks without pills and injections.
In two participants, the viral load in the blood did not increase during the whole year of observations. One of them, as the authors of the article note, was a carrier of a gene variant that is associated with a more favorable course of HIV infection. But this participant left the study after the first year, and what happened to him next is unknown. But the second, who did not find any "useful" gene variants, did not need therapy two years after the start of the trial.
Viral load in ten patients from the experimental group. Antiretroviral therapy (gray background) was prescribed after the end of remission. Two patients (5106 and 5120) did not need it a year later.
In addition, the researchers tried to estimate the number of latent (that is, "dormant") viruses in the cells of patients. This reservoir consists of defective copies of HIV genes that are unable to reproduce and form a viral particle, and whole (intact) copies that can turn into infectious particles as soon as therapy stops. It turned out that the number of defective copies in the test participants does not differ significantly from the usual (in people who take regular pills, but do not receive antibodies). But the intact reservoir has decreased — not much, but statistically significantly (p = 0.04).
If it were possible to significantly reduce the intact reservoir, it would be possible to say that the patients were cured of the infection to some extent. In the same experiment, most of them still had to return to antiretroviral therapy within a year. Next, researchers will have to figure out exactly how antibodies affect the intact reservoir and look for a way to reduce it more — perhaps by somehow combining antibodies with antiretroviral therapy.
We have already talked about people who managed to get rid of HIV for years — however, they can still be counted on the fingers. Bone marrow transplantation helped some of them, cord blood transfusion helped another woman, and two more women, apparently, coped with the virus on their own — but it is not yet known how.
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