Towards an HIV cure: a global scientific strategy

Abstract

Given the limitations of antiretroviral therapy and recent advances in our understanding of HIV persistence during effective treatment, there is a growing recognition that a cure for HIV infection is both needed and feasible. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. Several priorities for basic, translational and clinical research were identified. This Opinion article summarizes the group's recommended key goals for the international community.

Figure 1. The impact of antiretroviral therapy on HIV reservoirs

Most patients who adhere to antiretroviral therapy have dramatic and rapid decreases in plasma levels of HIV RNA. Persistent viraemia largely reflects the release of the virus from stable cellular reservoirs. The source of the virus during effective antiretroviral therapy is primarily defined by the half-life of the cells that were infected before therapy was initiated. After several years of therapy, long-lived populations of resting CD4⁺ central memory T (T_CM) cells become the dominant source of HIV persistence. Some of the data illustrated are based on REF. . HAART, highly active antiretroviral therapy; T_EM, effector memory T; T_TM, transitional memory T.

Figure 2. Mechanisms of HIV persistence during antiretroviral therapy

The left panel illustrates how latent HIV infection can be established in T cell and myeloid cell reservoirs. The primary mechanism is probably infection of activated memory CD4⁺ T cells. Most of these cells die, but a minority revert to a resting state. The centre panel illustrates the fate of these now resting ‘latently infected’ memory CD4⁺ T cells. These cells either die slowly, become a source of new infections, persist as long-lived cells or expand through homeostatic mechanisms. The right panel depicts some immune mechanisms that contribute to persistence. These include mechanisms that maintain cells in a resting state (for example, the upregulation of programmed cell death protein 1 (PD1)). Immune dysfunction during therapy probably reduces the efficient clearance of infected cells.