Combination antibody treatment for HIV

Colorized scanning electron micrograph of an HIV-infected T cell. NIAID

Antiretroviral therapy (ART) can almost completely suppress levels of human immunodeficiency virus (HIV)—the virus that causes acquired immunodeficiency syndrome (AIDS)—in the blood. But ART often requires taking medication every day for a lifetime. It also carries risks of long-term side effects and developing drug-resistant virus. A long-acting therapy that could suppress HIV levels without needing to be taken daily would thus be a welcome alternative.

Broadly neutralizing antibodies (bNAbs) could potentially provide longer-term HIV suppression. But individual bNAbs have only had limited success in previous studies. This is in part because antibody-resistant virus either already existed in the patient or emerged soon after treatment began. To get around this problem, a team of researchers led by Dr. Tae-Wook Chun at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) conducted a clinical trial of two bNAbs in combination that targeted different parts of the virus. Results appeared in Nature on June 1, 2022.

In the first part of the trial, 14 people with HIV were assigned at random to receive infusions of either both bNAbs or an inactive placebo. All participants had started ART early in their infections. Participants received up to 8 infusions over a period of 24 weeks. ART was suspended after the first infusion. The bNAbs were well tolerated, with no serious adverse events that could be attributed to the treatments.

Six of the seven participants who received the placebo had to resume ART within 28 weeks of the first infusion. In contrast, none of the participants who received the antibodies had to do so. Virus levels in the blood rebounded within 8 weeks in all patients receiving placebo. Virus levels also rebounded quickly in two participants who received the antibodies. Both participants harbored virus resistant to at least one of the antibodies before the treatment began. The bNAbs suppressed blood virus levels for 32-43 weeks in the remaining participants.

In the second part of the trial, the researchers gave bNAb infusions to five people who had not received ART but still maintained low virus levels. Only two of these participants harbored virus that was sensitive to both antibodies. In these two, antibody treatment completely suppressed the virus for an average of 42 weeks.

The results suggest that combination bNAb therapy can suppress HIV for long periods of time without ART. But it only works if resistant virus is not already present, which may pose a challenge for treatment on a large scale. The researchers note that larger studies will be needed to confirm these findings.

“Administration of such antibodies as infrequently as twice a year, possibly along with a long-acting injectable antiretroviral drug, could potentially lead to ART-free HIV suppression for years in infected individuals,” Chun says.

—by Brian Doctrow, Ph.D.