amfAR, The Foundation for AIDS Research

Combination Treatment Cures Mice of HIV

By Marcella Flores, M.P.H., Ph.D.


Antiretroviral therapy (ART) has been extremely effective at reducing HIV in the blood to below levels of detection, but less able to stop viral activity in the tissues. Efforts to achieve a cure for HIV would therefore be aided by stopping this source of virus that continually feeds the HIV reservoir.

Dr. Howard Gendelman of the University of Nebraska Medical Center has developed LASER ART, a slow-release, long-acting nanomedicine version of ART that penetrates deep into tissues to effectively extinguish this source of viral activity. This powerful new technology raises the question: With a newly contained viral reservoir, could the right intervention have a chance to cure HIV?

In a July article in Nature Communications, Dr. Gendelman and Dr. Kamel Khalili, of the School of Medicine at Temple University, demonstrate that it may be possible.

Using humanized mice infected with HIV and treated with LASER ART, Dr. Khalili administered CRISPR, a protein that acts like a molecular scissor, to cut out HIV DNA from infected cells. Sequential treatment with LASER ART followed by CRISPR eliminated viral rebound in two of six mice when ART was stopped—a key measure to determine whether a cure has been achieved.

The research team went a step further, however, transferring cells from these two potentially cured mice into different, uninfected mice and confirming that no HIV infection was transmitted.

These encouraging results are a boon to the field of gene therapy, which is increasingly turning to various types of molecular scissors, including CRISPR, Brec1, and others to eliminate HIV from the body. amfAR’s is currently funding several such innovative gene therapy approaches through its ARCHE-GT collaborative grant initiative.

Dr. Flores is amfAR’s associate director of research.