Significant progress has been made in the diagnostics and treatment of
AIDS since the discovery of the human immunodeficiency virus type 1 (HIV-1) in 1983. The remarkable effectiveness of combined antiretroviral
therapy (cART) is evidenced by mortality reduction, control of peripheral blood viral load, and in a nearly normal quality of HIV patients' lives. Remaining obstacles in treatment and cure are
drug toxicities and side effects, viral resistance, persistence of HIV-1 reservoirs on termination of cART treatment, the cost of lifelong antiretroviral
therapy, and the stigma associated with taking antiretroviral drugs. As determined by plasma
viral RNA and peripheral blood mononuclear cells (PBMC) proviral
DNA, we show improved suppression of productive
HIV infection in human CD34+ hematopoietic stem cell-engrafted NOD (nonobese diabetic)-SCID (
severe combined immunodeficiency)-il2rg-/- (NSG) mice by combined treatment with cART and CCR5 targeting drugs, compared with cART alone, as well as an increased preservation of human CD4+ T cells (defined as CD45+ CD3+ CD4+ cells) and CD4+/CD8+ cell ratios in infected mice. The data also suggest a possible reduction in viral reservoirs. Our data confirm that this animal model is suitable for detection of productive
HIV infection, replication, and establishment of viral reservoirs. The data also provide proof of principle for the utility of combining CCR5 targeting drugs,
maraviroc and
rapamycin, with traditional cART to improve control of
viremia and reduce viral reservoirs. This study thus serves as a model for future HIV-1 studies that could lead to the clinical development of new generations of antiretroviral drugs.