2023 amfAR Research Grants Total $5.5 Million

BROADLY NEUTRALIZING ANTIBODIES (bNAbs)

Rachel Rutishauser, MD, PhD

University of California,
San Francisco
$622, 272

Several studies have demonstrated that post-treatment control of HIV is possible, at least for a while. In some individuals with HIV on ART, administering a cocktail of bNAbs at the time of temporarily stopping ART—as part of a clinical cure study—improves control of HIV, though the virus eventually reappears despite absence of detectable levels of ART or bNAbs. Dr. Rutishauser and a team of co-investigators from the U.S. and Denmark, including Drs. Steven Deeks and Michael Peluso of the amfAR Institute for HIV Cure Research at UCSF, will study possible mechanisms that mediate this control.

Dr. Rutishauser’s work is based on the concept of an antibody-mediated “vaccinal effect,” by which bNAbs facilitate HIV-specific T cell killing. Her group plans to interrogate data and clinical samples from five clinical trials involving over 100 participants who were administered bNAbs when ART was stopped. One of these trials at UCSF was funded by amfAR and involved Dr. Rutishauser. Her group will perform cross-trial comparisons of specific immune responses and the genetics of rebounding to see if delivering bNAbs at the time of ART interruption leads to boosting of immune responses in at least a subset of participants to promote post-treatment control. This should enable a better understanding of how to augment these responses in future cure studies

James Termini, PhD

University of Miami, Coral Gables, FL
$480,000

Anti-HIV bNAbs, delivered by a variety of harmless viral vectors such as AAV (adeno-associated virus), can control HIV replication in the absence of antiretrovirals in animal models, but they have not been able to eradicate HIV reservoirs. Dr. Termini will study if using such antibodies with greatly enhanced ability to promote a form of anti-virus immunity known as ADCC, or antibody-dependent cellular cytotoxicity—those that are over 100-fold more potent than existing antibodies—might overcome this roadblock.

POST-TREATMENT CONTROL

Xu Yu, PhD

Massachusetts General Hospital, Boston, MA
$1,273,483

Dr. Yu received this extension grant to continue her study aimed at understanding why some people living with HIV are seemingly able to clear replication-competent HIV.

Researchers know of two individuals, Loreen Willenberg and an Argentinian woman known as the Esperanza patient, who appear to have eradicated their HIV infection without benefit of ART or other medical interventions. Several lines of evidence point to their immune systems having cleared replication-competent HIV, while leaving other forms of the virus including defective viruses and HIV integrated into so-called “gene deserts”—regions of their chromosomes with very low or no gene activity—in place. Dr. Yu speculated that similar cases of natural control of HIV may be hidden among individuals taking ART and fully suppressing their virus for prolonged periods of time.

With amfAR support, this group undertook a deep exploration of the trajectory of loss of repli­cation-competent HIV vs. accumulation of HIV in gene deserts in 66 individuals who have been on ART for at least 15 years. The additional funding will support high-resolution reservoir evaluations in these individuals and, most importantly, a clin­ical study. The study will interrupt ART in those among the 66 whose “signatures” of immune selection against HIV reservoirs are particularly ro­bust, to see if time and immunity have led to cures like those that occurred in the two women men­tioned above.

NATURAL KILLER CELLS