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Author's Response to “Persistence of Neuropsychologic Deficits Despite Long-Term Highly Active Antiretroviral Therapy in Patients With HIV-Related Neurocognitive Impairment”

Tozzi, Valerio MD; Balestra, Pietro PsyD; Vlassi, Chrysoula MD; Salvatori, Maria Flora DSc

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15th, 2007 - Volume 46 - Issue 5 - p 657-658
doi: 10.1097/QAI.0b013e318157b0f0
Letters to the Editor

National Institute for Infectious Diseases, Rome, Italy

In Reply:

This letter is in response to Dr. Garvey and colleagues' concerns regarding our article,1 in which we describe prevalence and risk factors for persistent neuropsychologic (NP) deficits despite long-term highly active antiretroviral therapy (HAART) in a cohort of 94 patients with HIV-related neurocognitive impairment (NCI) treated with potent antiretroviral therapy. We found, at univariate analyses, an association of persistent NP deficits with positive hepatitis C virus (HCV) serology. However, this difference was no longer significant at Cox model. Dr. Garvey and colleagues' concern was that we could have underestimated the potential role of HCV in contributing to the persistence of NP deficits.

The association of positive HCV serology with cognitive impairment in HIV-infected patients has been well documented in the literature. HCV, as well as HIV, has been associated with significant deficits in sustained attention and psychomotor speed.2,3 HCV in association with HIV may lead to more profound neurocognitive impairment than either virus alone.4,5 Given the high prevalence of patients with positive HCV serology in our cohort, Dr. Garvey and colleagues correctly ask for detailed information on serum HCV RNA levels, liver function tests, and HCV therapy in the patients studied.

Among the 43 patients with positive HCV serology, the prevalence of patients with abnormal liver enzymes did not differ between patients with persistent and reversible NP deficits. Four patients had evidence of cirrhosis at liver biopsy. Moreover, 5 patients received pegylated interferon plus ribavirin during the study, and 2 of them cleared HCV. However, no conclusion was possible with this limited set of patients. Twenty-nine patients had detectable plasma HCV RNA. Notably, we found that 24 of 59 (40.7%) patients with persistent NP deficits were HCV RNA positive, compared to 5 of 35 (14.3%) patients with reversible NP deficits. This difference was statistically significant (P = 0.014). However, after including the HCV RNA results (either detectable or not detectable) in the multivariable model, this difference did not remain independently associated with persistent NP deficits (odds ratio [OR] = 0.9; 95% confidence interval [CI]: 0.4 to 2.8).

Although the results of the multivariable model seem to preclude the involvement of HCV in persistent NP deficits, we agree that further studies on this topic are needed. Our study was not aimed to assess the contribution of HCV infection on changes in NP performance over time. To our knowledge, whether HCV-coinfected patients during HAART might respond neurocognitively worse than patients infected solely with HIV is unknown. We agree that studies on this topic are needed, and we appreciate Dr. Garvey and colleagues' insights.

Valerio Tozzi, MD

Pietro Balestra, PsyD

Chrysoula Vlassi, MD

Maria Flora Salvatori, DSc

National Institute for Infectious Diseases Rome, Italy

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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. Hilsabeck RC, Perry W, Hassanein TI. Neuropsychological impairment in patients with chronic hepatitis C. Hepatology. 2002;35:440-446.
3. Forton DM, Thomas HC, Murphy CA, et al. Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. Hepatology. 2002;35:433-439.
4. Tozzi V, Balestra P, Lorenzini P, et al. Prevalence and risk factors for HIV-associated neurocognitive impairment, 1996 to 2002: results from an urban observational cohort. J Neurovirol. 2005;11:265-273.
5. Letendre SL, Cherner M, Ellis RJ, et al. The effects of hepatitis C, HIV, and methamphetamine dependence on neuropsychological performance: biological correlates of disease. AIDS. 2005;19(Suppl 3):S72-S78.
© 2007 Lippincott Williams & Wilkins, Inc.