The Cure for HIV Follows a Long, Uncertain Path

Researchers in the field of HIV have made impressive advances in the development of effective, life-saving antiretroviral therapy (ART). Nevertheless, HIV infection remains an incurable, chronic disease that requires expensive, lifelong treatment. In addition, while current therapies are highly effective, drug side effects, adherence requirements, and the risk of resistance present challenges to the long-term management of HIV. Given these realities, and inspired by recent scientific and clinical advances, research into the development of an effective, affordable cure has taken on a new urgency.

The search for a cure for HIV infection was reinvigorated following a few widely reported individual cases that have pointed to the potential for a cure. In 2007, an HIV-infected man, Timothy Brown (also known as the “Berlin patient”), was treated for leukemia with a transplant of hematopoietic stem cells from a donor with an uncommon genetic mutation that confers resistance to HIV infection. Following his treatment for leukemia, clinicians have been unable to find evidence of HIV infection in his blood or other potential reservoirs, and he remains free of the virus and doesn’t need antiretroviral therapy. More recently, in another widely reported case, an infant born to an HIV-infected mother, and shown to be infected with HIV at birth, appears to have been functionally cured following 18 months of ART initiated immediately following delivery.

Despite the optimism that followed the initial presentation of both of these cases, researchers have acknowledged that the specific circumstances of each case suggest that replicating their results may not be possible on a broader scale. Similarly, the early optimism that greeted the cases of 2 other HIV-infected individuals who developed Hodgkin lymphoma, and who, like Mr. Brown, were treated with bone marrow transplantation, has been short-lived. In both patients, HIV eventually reappeared within months of ART discontinuation. However, the lessons learned from all of these cases are informing new directions in cure research.

Building on these and other advances, in 2012, the International AIDS Society (IAS) Scientific Working Group on HIV Cure issued an ambitious list of priorities for HIV cure research and a call for greater collaboration among researchers. These priorities include5:

Cellular and viral mechanisms that allow HIV to persist
Tissue and cellular sources of persistent SIV/HIV in animal models and long-term ART-treated individuals
Immune activation and dysfunction in the presence of ART
Natural models of SIV/HIV control
Assays to measure persistent infection
Therapeutic and immunological approaches for eliminating persistent HIV infection
Enhancement of immune response to control viral replication