| Post date: 2023/09/25 |
Patients recently diagnosed with HIV have previously been observed to produce stronger immune responses and lower levels of the virus in their blood when administered monoclonal antibodies and regular medical treatment. In a new study published in Nature Medicine, investigators found that this treatment approach also benefited patients who had been on treatment for years.1
The study showed that the monoclonal antibody treatment resulted in the suppression of the virus for more than 3 months, with some continuing to suppress HIV for more than 18 months after their regular HIV treatment stopped.1
"The study is one of the first placebo-controlled trials conducted on humans, where we have shown a way to boost the body's own ability to fight HIV, even when standard treatment is paused. We, therefore, see the study as an important step towards a cure," lead study author Ole Schmeltz Søgaard, MD, PhD, from Department of Clinical Medicine at Aarhus University, said in a statement.1
In the study (NCT03837756), individuals from Denmark, Norway, and Australia were randomly divided into 4 groups: 1 received MGN-1703 (Lefitolimod; Gilead Sciences) designed to enhance immune cell response against HIV; 1 received 2 monoclonal antibodies, 3BNC117 and 10-107 designed to eliminate the virus and strengthen cell immunity; 1 received both types of experimental medicine; and 1 received the standard of care treatment.1 There were 43 patients included, with recruitment starting from April 12, 2019, through November 4, 2021, and the follow-up concluding June 9, 2022.2 Approximately 72% of individuals had HIV subtype B while the remaining had other HIV subtypes.2
Individuals underwent 25 weeks of antiretroviral therapy (ART) interruptions. The primary endpoint included the “time from stopping ART to the date of meeting the criteria for loss of virologic control (defined as 4 weeks with sustained plasma HIV-1 RNA ≥1,000 copies per milliliter or two consecutive measurements >100,000 copies per milliliter),” according to the study authors.2
Investigators found that there was no extra benefit from MGN-1703, however, those who received the monoclonal antibodies before pausing their regular HIV medication did have a benefit for 3 months before the virus reappeared.1 Additionally, the immune system in about one-third of individuals receiving the monoclonal antibodies partially or completely suppressed the virus, even after discontinuing the antibodies.1
Overall, investigators determined that both experimental treatment options were safe. There was a total of 253 adverse events (AEs), 94 of which were not determined to be related to any of the investigational drugs. The most common AEs for MGN-1703 included injection site reaction and fatigue. For the broadly neutralizing anti-HIV-1 antibodies, fatigue was the most commonly reported AE.2
The investigators added that they are putting together more trials to further optimize the treatment and enhance the benefits.1
"The hope is that we will gradually improve our experimental treatment strategy to a level where the effect of our treatment is that up to 50%, 70%, or even 100% of patients become medication-free and neither relapse nor can infect others. If we can achieve that, we will have developed a cure for HIV that will change the lives of approximately 38 million [individuals] living with the disease today,” Søgaard said in the statement.1
References
The study showed that the monoclonal antibody treatment resulted in the suppression of the virus for more than 3 months, with some continuing to suppress HIV for more than 18 months after their regular HIV treatment stopped.1
"The study is one of the first placebo-controlled trials conducted on humans, where we have shown a way to boost the body's own ability to fight HIV, even when standard treatment is paused. We, therefore, see the study as an important step towards a cure," lead study author Ole Schmeltz Søgaard, MD, PhD, from Department of Clinical Medicine at Aarhus University, said in a statement.1
In the study (NCT03837756), individuals from Denmark, Norway, and Australia were randomly divided into 4 groups: 1 received MGN-1703 (Lefitolimod; Gilead Sciences) designed to enhance immune cell response against HIV; 1 received 2 monoclonal antibodies, 3BNC117 and 10-107 designed to eliminate the virus and strengthen cell immunity; 1 received both types of experimental medicine; and 1 received the standard of care treatment.1 There were 43 patients included, with recruitment starting from April 12, 2019, through November 4, 2021, and the follow-up concluding June 9, 2022.2 Approximately 72% of individuals had HIV subtype B while the remaining had other HIV subtypes.2
Individuals underwent 25 weeks of antiretroviral therapy (ART) interruptions. The primary endpoint included the “time from stopping ART to the date of meeting the criteria for loss of virologic control (defined as 4 weeks with sustained plasma HIV-1 RNA ≥1,000 copies per milliliter or two consecutive measurements >100,000 copies per milliliter),” according to the study authors.2
Investigators found that there was no extra benefit from MGN-1703, however, those who received the monoclonal antibodies before pausing their regular HIV medication did have a benefit for 3 months before the virus reappeared.1 Additionally, the immune system in about one-third of individuals receiving the monoclonal antibodies partially or completely suppressed the virus, even after discontinuing the antibodies.1
Overall, investigators determined that both experimental treatment options were safe. There was a total of 253 adverse events (AEs), 94 of which were not determined to be related to any of the investigational drugs. The most common AEs for MGN-1703 included injection site reaction and fatigue. For the broadly neutralizing anti-HIV-1 antibodies, fatigue was the most commonly reported AE.2
The investigators added that they are putting together more trials to further optimize the treatment and enhance the benefits.1
"The hope is that we will gradually improve our experimental treatment strategy to a level where the effect of our treatment is that up to 50%, 70%, or even 100% of patients become medication-free and neither relapse nor can infect others. If we can achieve that, we will have developed a cure for HIV that will change the lives of approximately 38 million [individuals] living with the disease today,” Søgaard said in the statement.1
References
- Danish researchers take another big step toward HIV cure. Mews release. Aarhus University. September 12, 2023. Accessed September 21, 2023. https://health.au.dk/en/display/artikel/danske-forskere-tager-endnu-et-stort-skridt-mod-hiv-kur
- Gunst JD, Højen JF, Pahus MH, Rosás-Umbert M, et al. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial. Nat Med. 2023;10.1038/s41591-023-02547-6. doi:10.1038/s41591-023-02547-6
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