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Regarding “Persistence of Neuropsychologic Deficits Despite Long-Term Highly Active Antiretroviral Therapy in Patients With HIV-Related Neurocognitive Impairment: Prevalence and Risk Factors”

Biscione, Fernando Martín MD, MSc

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 1st, 2007 - Volume 46 - Issue 4 - p 510
doi: 10.1097/QAI.0b013e318142aba3
Letters to the Editor

Health Sciences Postgraduate Course, Medicine High School, Minas Gerais Federal University, Belo Horizonte, Minas Gerais, Brazil

To the Editor:

Tozzi et al1 are to be commended for their article addressing prevalence and risk factors for persistence of neuropsychologic (NP) deficits in patients with HIV-related neurocognitive impairment (NCI) despite long-term highly active antiretroviral therapy (HAART). One of the main findings of the study was the high proportion of patients with persistent NP deficit (53% over a 65-month period of follow-up on a Kaplan-Meier estimate) despite HAART, leading the authors to conclude that “current HAART regimens are inadequate to treat HIV-related NCI”.1 It seems that the possibility of a survivor bias as an alternative explanation for this observation has not been contemplated by the authors, however.

Among the 94 study participants with NP deficit at study enrollment, 62 (or 66%) were antiretroviral (ARV) naive, whereas 32 (or 34%) were ARV-experienced patients, with a mean of previous ARV exposure of 56.4 months. NP deficits in this latter group likely represent a more selected group of “harder to treat” NCI conditions (eg, as a consequence of more extensive or advanced neuronal/glial damage) as compared with those present in an unselected group of ARV-naive patients. Indeed, a number of studies have found that HAART can actually reverse HIV-related NCI, at least in a subset of patients.2,3 As a consequence, ARV therapy before follow-up initiation may have improved the neurologic performance of some individuals (who thus were not included in the analysis) and selected patients with less responsive disease, who were then enrolled in the study.

Therefore, the inclusion of heavily ARV-experienced patients at baseline may have flawed the reported estimate, resulting in an overestimation of the proportion of patients with persistent NP deficit at follow-up completion. Thus, the question as to whether HAART actually improves (or not) NP outcomes would be better addressed in the group of 62 individuals with newly diagnosed HIV-related NCI who subsequently started HAART. The true proportion of patients with persistent NP impairment at follow-up completion is expected to be less pessimistic than reported.

Fernando Martín Biscione, MD, MSc

Health Sciences Postgraduate Course Medicine High School Minas Gerais Federal University Belo Horizonte, Minas Gerais, Brazil

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1. Tozzi V, Balestra P, Bellagamba R, et al. Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr. 2007;45:174-182.
2. Price RW, Yiannoutsos CT, Clifford DB, et al. Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS Clinical Trial Group and Neurological AIDS Research Consortium Study Team. AIDS. 1999;13:1677-1685.
3. Tozzi V, Balestra P, Galgani S, et al. Positive and sustained effects of highly active antiretroviral therapy on HIV 1-associated neurocognitive impairment. AIDS. 1999;13:1889-1897.
© 2007 Lippincott Williams & Wilkins, Inc.