AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 31, Number 1, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/aid.2014.0358
COMMENTARIES
How to Cure AIDS: Feeling the Elephant David Margolis
T
its tools are now light-years ahead of nitrogen mustard. Similarly, we should expect that the fight to eradicate HIV infection may continue to use some of the principals and tools discussed in this issue, but that although efforts toward a cure will be less often marked by breakthroughs than by incremental advances, eventually therapies may bear little resemblance to what is currently being tested or considered. The persistence of HIV infection despite the durable suppression of viral replication by ART is a difficult problem to study, and the development of latency reversing agents and reservoir depletion strategies is challenging given the extraordinary health benefits of ART. Lest we end up bickering pointlessly like the blind men who attempt to describe an elephant following a limited examination with imperfect tools, we will need to work together with a diversity of approaches, improving measurements, and creativity, hoping for breakthroughs but seeking carefully measured progress. No one can be certain that a cure for AIDS is unachievable, and the efforts such as those illustrated in this issue show that we have started on the road toward a cure.
his issue of AIDS Research and Human Retroviruses manifests the rapid growth in research ‘‘toward an HIV cure.’’ This phrase, coined as a rallying cry by the International AIDS Society, invokes the penultimate goal of HIV treatment, and implies the durable effort that will be needed to achieve that aspiration. The breadth and diversity of reports found in the issue reflect the many domains of investigation that must be brought to bear to solve challenges of persistent HIV infection, and provide one of the critical missing tools needed to end the worldwide AIDS pandemic. Timothy Brown, the ‘‘Berlin patient’’ and the only person who fits the practical definition of a cure of HIV infection, provides a personal reflection on his experience as an inspirational invocation for this journal and the field. It is important to note his altruistic motivations, as research toward a cure cannot move very far forward without the participation of HIV-infected patients who have almost nothing to gain by their contribution. Overviews on emerging approaches to disrupt latency and on distinct efforts to clear persistent infection are followed by a discussion of the issues and challenges of low-level viremia that persists despite antiretroviral therapy (ART), and a proposal to reinvigorate the testing of therapeutic HIV vaccines. The issue is rounded out by diverse primary reports on clinical studies issues of consent and inclusion of patient populations, studies of novel molecular therapies and immune strategies to overcome persistent infection, and basic molecular studies of cellular mechanisms related to HIV latency. Although cancer chemotherapy first appeared as a gas warfare agent in World War I, 75 years later some of these primitive therapeutic modalities and principles are still in use. However, although the war to cure cancer is still raging,
Author Disclosure Statement
No competing financial interests exist. Address correspondence to: David Margolis 2060 Genetic Medicine Building, CB#7042 120 Mason Farm Road University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599-7042 E-mail: [email protected]
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
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COMMENTARIES
How to Cure AIDS: Feeling the Elephant David Margolis
T
its tools are now light-years ahead of nitrogen mustard. Similarly, we should expect that the fight to eradicate HIV infection may continue to use some of the principals and tools discussed in this issue, but that although efforts toward a cure will be less often marked by breakthroughs than by incremental advances, eventually therapies may bear little resemblance to what is currently being tested or considered. The persistence of HIV infection despite the durable suppression of viral replication by ART is a difficult problem to study, and the development of latency reversing agents and reservoir depletion strategies is challenging given the extraordinary health benefits of ART. Lest we end up bickering pointlessly like the blind men who attempt to describe an elephant following a limited examination with imperfect tools, we will need to work together with a diversity of approaches, improving measurements, and creativity, hoping for breakthroughs but seeking carefully measured progress. No one can be certain that a cure for AIDS is unachievable, and the efforts such as those illustrated in this issue show that we have started on the road toward a cure.
his issue of AIDS Research and Human Retroviruses manifests the rapid growth in research ‘‘toward an HIV cure.’’ This phrase, coined as a rallying cry by the International AIDS Society, invokes the penultimate goal of HIV treatment, and implies the durable effort that will be needed to achieve that aspiration. The breadth and diversity of reports found in the issue reflect the many domains of investigation that must be brought to bear to solve challenges of persistent HIV infection, and provide one of the critical missing tools needed to end the worldwide AIDS pandemic. Timothy Brown, the ‘‘Berlin patient’’ and the only person who fits the practical definition of a cure of HIV infection, provides a personal reflection on his experience as an inspirational invocation for this journal and the field. It is important to note his altruistic motivations, as research toward a cure cannot move very far forward without the participation of HIV-infected patients who have almost nothing to gain by their contribution. Overviews on emerging approaches to disrupt latency and on distinct efforts to clear persistent infection are followed by a discussion of the issues and challenges of low-level viremia that persists despite antiretroviral therapy (ART), and a proposal to reinvigorate the testing of therapeutic HIV vaccines. The issue is rounded out by diverse primary reports on clinical studies issues of consent and inclusion of patient populations, studies of novel molecular therapies and immune strategies to overcome persistent infection, and basic molecular studies of cellular mechanisms related to HIV latency. Although cancer chemotherapy first appeared as a gas warfare agent in World War I, 75 years later some of these primitive therapeutic modalities and principles are still in use. However, although the war to cure cancer is still raging,
Author Disclosure Statement
No competing financial interests exist. Address correspondence to: David Margolis 2060 Genetic Medicine Building, CB#7042 120 Mason Farm Road University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599-7042 E-mail: [email protected]
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
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