Virus Characteristics Could Predict Efficacy of Antibody-Based Treatments in HIV

A new study has identified virus characteristics that may help predict the efficacy of broadly neutralizing antibody (bnAb) treatments in HIV.

Led by researchers at Boston Medical Center (BMC), the study, which was published in the Journal of Virology, used sequence-based methods to determine treatment efficacy with a specific antibody treatment.

Some patients who are diagnosed with HIV are unable to receive antiretroviral therapy (ART) for different reasons, often requiring the use of alternative treatments such as antibody-based treatments. However, it is difficult to predict patients who would be good candidates for these therapies.

Antibody treatments work by binding the HIV-1 envelope protein that protects the virus, helping it avoid the immune system response. These envelope proteins also contain extensive DNA sequence variation that provides virus information, although it is difficult to predict the efficacy of a treatment based on knowing this sequence alone.

For the study, the researchers determined HIV envelope sequence motifs that predict treatment efficacy with a certain type of antibody treatment. The study showed that HIV strains that exclusively use the CXCR4 as compared with the CCR5 receptor are less neutralization susceptible, especially to variable loop 3 (V3) loop bnAbs, in some but not all instances.

Additionally, among pre-treatment envelopes, increased probability using CXCR4 and greater predicted V1 interference is associated with faster virus rebound and lower decrease in plasma virus level respectively after V3 loop bnAb treatment, according to the study.

The researchers concluded that receptor usage information and homology models may be useful in predicting V3 loop bnAb therapy efficacy.

“These findings will allow physicians to make better-informed decisions on treatment plans for patients with HIV-1, ultimately treating the virus to slow it down earlier,” lead author Manish Sagar, MD, an infectious diseases physician at BMC, said in a press release. “Making this process more efficient will only improve patient care, while reducing the time and money spent on finding the right treatment for these patients.”

Reference

Sagar M, Registre L, Moreau Y, et al. HIV-1 co-receptor usage and variable loop contact impact V3 loop bnAb susceptibility. Journal of Virology. 2019. Doi: 10.1128/JVI.01604-19.