Study Confirms Potential HIV Cure Has No Therapeutic Effect

Findings settle a debate sparked by previous promising results

A new study by investigators at the Center for Virology and Vaccine Research (CVVR) at Beth Israel Deaconess Medical Center has helped settle a high-profile debate about a potential strategy for curing HIV. Led by Dan Barouch, MD, PhD, a team of researchers demonstrated that a candidate antibody had no detectible therapeutic effect in non-human primates infected with SIV, an HIV-like virus that causes an AIDS-like disease in monkeys and apes. These findings, together with two other papers from investigators at the National Institute of Allergy and Infectious Diseases (NIAID) and the NIH Vaccine Research Center (VRC) reporting similar results, were published in the journal Science.

Existing antiretroviral therapy (ART) for people with HIV does not cure infection because the virus becomes dormant, remaining present but silent in immune cells, and becoming active again when ART is discontinued. Seeking strategies to achieve ART-free, long-term viral suppression, Barouch and colleagues evaluated the antibody against a cellular protein called α4β7 for its ability to maintain virus suppression after ART has been discontinued.

“The development of strategies that can lead to sustained suppression of the virus in the absence of antiretroviral therapy, known as a functional cure, represents a major goal of HIV research,” said Barouch, who is Director of the CVVR and a Professor of Medicine at Harvard Medical School. “Our data, which are consistent with similar findings that are being reported by other investigators at NIAID and VRC, show that the strategy targeting α4β7 is not effective.”

A prior manuscript from a different group suggested that the antibody against α4β7 led to virologic suppression in SIV-infected rhesus macaques and opened the door to human clinical trials to evaluate this strategy. However, that study used an attenuated strain of SIV, engineered to be less virulent.

In the current study, Barouch and colleagues evaluated the α4β7 antibody against a wildtype, fully pathogenic strain of SIV in 50 nonhuman primates. The animals were infected with the virus, were treated with ART, and then received infusions of the antibody every three weeks for a total of eight infusions. All macaques in all groups rebounded by day 21 after the therapy’s discontinuation.

“In contrast to the previously published study, we observed rapid viral rebound in all α4β7 antibody treated animals that was indistinguishable from controls,” said Barouch. “These findings suggest that this strategy for HIV-1 cure does not have generalizable efficacy.”

Additional authors included Peter Abbink, Noe B. Mercado, Joseph P. Nkolola, Rebecca L. Peterson, Hubert Tuyishime, Katherine McMahan, Edward T. Moseley, Erica N. Borducchi, Abishek Chandrashekar, Esther A. Bondzie and Arshi Agarwal of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center; Aaron J. Belli and Keith A. Reimann of the University of Massachusetts Medical School; Brandon F. Keele of the AIDS and Cancer Virus Program at Frederick National Laboratory; Romas Geleziunas of Gilead Sciences; and Mark G. Lewis of Bioqual.

This work was supported by grants from the National Institutes of Health (AI124377, AI126603, AI126683, AI128751, AI129797, HHSN261200800001E, OD010976), and the Ragon Institute of MGH, MIT, and Harvard. The authors declare no competing interests.