Brain HIV Reservoir: the stumbling block?
An interview of Bruce Brew, Department of Neurology and HIV Medicine, St. Vincent’s Hospital, Darlinghurst, New South Wales, Australia
Q1: A series of articles have recently emphasized the situation of the brain as a major viral reservoir for HIV in treated patients. What is really known at the tissue level as most studies rely only on CSF?
BB: There is certainly evidence at the brain tissue level for compartmentalisation. The recent papers by Holman et al AIDS Res Ther 2010, Langford et al J Neurovirol 2006, Batmanian and Brew Journal of HIV Therapy 2005, Smit et al J Virol 2004.
Q2: A correlation has been published between antiretroviral drug penetration in CNS and viral expression, or even neuro-cognitive functions. If that is so clear, why this parameter is not included in recommendations about first line choices?
BB: It is puzzling. Presumably formal recommendations require the results of randomised clinical trials.
Q3: If HIV is really on its own in the brain despite ART, are there data that selection of drug-resistant strains can occur first at this level, then reach other body sites?
BB: No but I think this relates to the practical problem of repeated lumbar punctures, the timing of those lumbar punctures in relation to the development of resistant mutations and the detection of resistant quasispecies that may be “swamped” by other more numerous mutant species. .
Q4: Finally, is a good equilibrium possible between brain ART diffusion and ART neural toxicities?
BB: This is an increasingly important concern for which there is no definitive answer at present. ARVs can be toxic to the brain directly albeit that the evidence is still somewhat preliminary, and indirectly through increased cardiovascular risk leading to the possibility of vascular cognitive impairment.
Q5: In a recent Editorial in AIDS, Janice Clement argues that it would be too early to test HIV eradication strategies as we do not master their potent negative/collateral effects on the CNS, could you explain us the concern?
BB: The concern is that eradication strategies at present rely on the efficacy of potent ARV treatments to control the increased viral replication derived from the conversion of the latent to productive pools of infection. Current ARV treatments have varied and relatively limited efficacy in the brain -
Q6: What are the breakthroughs we can expect in the field of HIV persistence in the brain, and how to reach them?
BB: I think HIV brain persistence will be better understood through focus on the importance of astrocyte infection and the molecular basis of neurotropism/neurovirulence as well as the significance of CNS involvement at seroconversion.
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Key words: CNS, HIV reservoir, brain, hiv cure