The absence of a cure for HIV-1 despite highly effective antiretroviral therapy creates multiple burdens that impact the lives of each individual and up to society as a whole. Without a cure, HIV-1 can impact not only the infected individuals who face stigma, require lifelong therapy, and suffer the effects of drug toxicity, but U.S. society as a whole, the drug companies pressed with developing new therapies, and overall global resource governance are all adversely affected by a lack of a cure for HIV-1.
The BEAT-HIV Delaney Collaboratory to Cure HIV-1 by Combination Immunotherapy has three central objectives.
Objective 1Identify the best approach to target immunotherapy against replication-competent reservoirs by defining the relationship between plasma and tissue clonal expansion, characterize integration sites within blood and tissue, and determine how to maximize viral reactivation of distinct reservoir compartments. |
Objective 2Test clinical strategy combining IFN-α immunotherapy to activate intrinsic/innate responses and antibody-dependent cell-mediated cytotoxicity (ADCC) with broadly neutralizing anti-HIV antibodies (both strategies shown to have an effect in humans when used singly); advance preclinical studies on IFN-α response, ex vivo combinations with added T-cell mediated strategies, and develop innovate DNA vaccine delivery systems for sustaining neutralizing antibodies in vivo. |
Objective 3Test clinical strategy that combines two gene therapy vectors to intrinsically protect HIV-specific killer cells by a ΔCCR5 zinc nuclease given together with a CAR delivery HIV-specificity to CD8 T-cells, and advance the preclinical humanized mice platform to test novel combinations of immunotherapy (with/without novel delivery) when administered jointly or in sequence with the objective to recruit maximal intrinsic, innate, and/or adaptive anti-HIV effects. |
The objectives are supported by four teams addressing clinical, HIV reservoir measures, HIV evasion analysis, and biostatistics and data management. Community engagement takes advantage of a more than 20-year relationship with the local HIV community, the Center For AIDS Research (CFAR), and AIDS Clinical Trials Group (ACTG) activity ensuring partnership with target populations. This group brings diverse expertise and innovation, representing the first time that distinct immunotherapy strategies with initial promising results in human trials focused on intrinsic/innate, humoral, and adaptive arms of the immune response are actively joined to advance an HIV cure and/or remission under a single common multi-investigator, multi-industry team. The entire team is committed to advance the best outcomes from our collective effort to ultimately develop a strategy to eradicate HIV.