Advances toward a cure for HIV: getting beyond n=2

Abstract

Achieving a cure for HIV remains a priority in HIV research. Two cases of 'sterilizing cure' have been observed-in Timothy Ray Brown and the "London" patient; both patients received allogeneic hematopoietic stem cell transplantation (HSCT) from donors homozygous for the CCR5-delta 32 deletion, which impairs function of an HIV coreceptor on host cells. Other strategies that have been evaluated for achieving sterilizing cure or functional cure--ie, sustained virologic remission in the absence of antiretroviral therapy (ART)-include: HSCT with wild-type CC chemokine receptor (CCR5); early ART to limit size of the HIV latent reservoir; shock and kill strategies using latency reversing agents and/or anti-HIV broadly neutralizing antibodies; and gene therapy, including attempts to modify CCR5 genes, HIV proviruses in autologous host cells, or enhanced T cells. This article summarizes a presentation by Jonathan Li, MD, MMSc, at the International Antiviral Society-USA (IAS-USA) continuing education program held in Atlanta, Georgia, in March 2019.

Figure 1.

Persistence of the HIV reservoir, indicated by levels of HIV DNA in CD4+ cells and peripheral blood mononuclear cells (PBMCs), during antiretroviral therapy (ART). Adapted from Besson, et al.

Figure 2.

HIV remission in Timothy Brown by allogenic hematopoietic skin cell transplant from a donor with the chemokine receptor 5—delta 32 deletion. Abbreviations: AML, acute myeloid leukemia; ART, antiretroviral therapy; SCT, gene for a human hormone secretion. Adapted from Hutter et al.

Figure 3.

HIV remission in the London patient following CC chemokine receptor 5-delta 32/delta 32 deletion hematopoietic stem-cell transplantation. ART indicates antiretroviral therapy Adapted from Gupta et al.

Figure 4.

Delayed viral rebound in the Boston bone marrow transplant (BMT) patients, who received donor cells with wild-type CC chemokine receptor-5 (CCR5). ART indicates antiretroviral therapy (indicated by shaded areas). Adapted from Henrich et al.