Towards a drug-free remission of HIV/AIDS: A collection of good news from 2010 for the World AIDS Day.
The year 2010 has been rich in terms of publications and events tackling the issue of HIV 'functional' cure and drug-free remission. On this World AIDS Day, Doctor Andrea Savarino from the Istituto Superiore di Sanita in Rome recaps these 'hot' 2010 moments and shows us that there are many reasons for hope.
A report published in the journal AIDS has recently furnished new evidence for the possibility to obtain a long-term remission of HIV infection [Hocqueloux L, Prazuck T, Avettand-Fenoel V, Lafeuillade A, Cardon B, Viard JP, Rouzioux C. AIDS. 2010 Jun 19;24(10):1598-601]. Hocqueloux et al. showed· that, five out of 32 human subjects treated with antiretroviral therapy (ART; mean duration: 77 months) in temporal vicinity of primary infection displayed, following therapy suspension, no detectable viral load rebounds for approx. three years and maintained stable but low levels of viral DNA. As emphasised by the study co-coordinator Christine Rouzioux in conclusion of the meeting: “Towards a Cure: HIV Reservoirs and Strategies to Control Them” (held in Vienna, July 17-18, 2010),
a thorough analysis of these “post-therapy HIV controllers” will be of pivotal importance for the understanding of the mechanisms leading to a drug-free remission of the infection.
The idea to “Hit hard, hit early” has long been sustained by part of the medical community, and is supported by data recently collected from the pre-exposure prophylaxis (PrEP) trial showing that 47% of people under Truvada did not become infected despite risky behaviour. However, only a minority of people may take advantage from these early/very early interventions, and the majority of patients usually come to clinical attention only when they are already in the chronic phase of the disease. Therefore, novel strategies are badly needed to favour regression of chronic HIV disease to a stage in which there is still a window of opportunity for the aforementioned early pharmacological interventions.
At the Istituto Superiore di Sanità in Rome, Italy, we are trying to develop this type of intervention. Data presented last July at the International Conference on AIDS in Vienna, showed that the disease shifted backward in the monkey model when the viral DNA reservoir was abated by a novel pharmacological intervention using the gold compound auranofin, in the presence of intensified ART (see slides). Following suspension of all drugs, the macaques that had been treated with auranofin, but not those treated with iART alone, experienced delayed viral load rebounds that consisted in a peak reminiscent of a novel acute infection, followed by a progressive viral load reduction with a viral set point significantly lower than pre-therapy values. Of note, CD4 counts remained high in the auranofin group but not in the iART-only group. In the absence of effective therapeutic vaccines on the horizon, the aforementioned ART-based pharmacological strategies, and maybe other new strategies might thus graft during the onset of the novel “acute infection” induced by auranofin, thus giving similar opportunities to both acutely and chronically infected subjects. Of course, a drug-free remission of HIV infection is not yet possible, at least for all of the patients, but these results allow catching a glimpse of a light at the end of the tunnel.
Andrea Savarino, M.D.
Dept. of Infectious, Parasitic and Immune-mediated Diseases
Istituto Superiore di Sanità
Viale Regina Elena, 299
00161 Rome, Italy.
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Key words: HIV cure, acute, acute hiv infection, auranofin, cure, hiv eradication, hiv reservoirs, pre-exposure prophylaxis, prep, primary HIV infection, reservoirs, world aids day