



In the U.S. alone, there are over one million individuals living with HIV and 1 in 7 of them don’t know they are infected. As antimicrobial resistance is a growing global public health threat, researchers are actively taking steps to minimize the emergence and spread of HIV drug resistance—as well as treating current HIV therapy-resistant patients. Now, a new collaborative study led by investigators at the Yale School of Medicine describes how the biologic drug ibalizumab, a humanized IgG4 monoclonal antibody, was found to block the entry of HIV-1 through noncompetitive binding to CD4 in individuals with advanced, drug-resistant HIV infection.

Findings from the new study—published recently in the New England Journal of Medicine through an article titled “Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1”—showed that when used in combination with existing HIV medications, ibalizumab use is a promising strategy for patients who have run out of effective treatment options.

For some individuals with HIV, existing drug therapies fail to suppress the virus, leading to drug resistance and worsening disease. While several HIV drugs target the virus effectively, there has not been a new class of HIV drugs approved to combat the disease in a decade. This past March, the FDA approved ibalizumab, a drug that targets the primary receptor for HIV entry into immune cells known as CD4 T cells. This novel mechanism of action prevents HIV from entering target cells.

Results from this study were notable in how effectively it treated the drug-resistant population of patients studied. “These patients had extremely advanced HIV and resistant virus with limited options,” explains lead study investigator Brinda Emu, M.D., assistant professor of medicine at Yale University. “To see viral suppression in a significant percentage of these patients at six months is heartening. The result represents a much-needed new mechanism of action for patients who have highly resistant HIV.”

In the current analysis, patients received a dose of ibalizumab, which is delivered intravenously, in addition to their failing regimen, for one week. After that period, they received ibalizumab in combination with optimized treatment regimens for six months.

The research team found that after one week on ibalizumab, the majority of the 40 patients (83%) enrolled in the study experienced a decrease in viral load, which refers to the amount of HIV detected in the blood. After 25 weeks, nearly half of patients saw viral load suppression dip below the level of detection. The researchers also reported an increase in CD4 T cells, which are a marker for immune strength. A single individual experienced an adverse event, which was felt to be ibalizumab-related and resulted in withdrawal from the study,

As the first monoclonal antibody approved to treat HIV, ibalizumab is a promising option for individuals who have tried several other drug therapies. “It should be considered for patients that have multi-drug resistance given the efficacy seen in this study,” Dr. Emu notes.

Because of its novel mechanism, ibalizumab will not interact negatively with other medications. Moreover, it is delivered intravenously every two weeks and lasts longer than current HIV drugs, which are taken daily by mouth.

“It's ushering in a whole class of medicine and a new mode of delivery for the treatment of HIV. I look forward to discussions in the community about how such therapy will fit into the current treatment paradigm for HIV infection,” Dr. Emu concludes. “We must also keep in mind that ibalizumab was approved with a smaller number of patients treated than other medications due to the rarity of patients with multi-drug resistant HIV. As such, patients and providers must remain vigilant for side effects and adverse events.”



























