Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study.

OBJECTIVE: To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment. METHODS: This was a Phase II randomized, double-blind, placebo-controlled, multicenter trial within the Adult AIDS Clinical Trials Group. One-hundred and forty HIV-infected adults with mild to severe AIDS dementia complex receiving stable antiretroviral therapy were enrolled. Memantine was initiated at 10 mg daily escalated to 40 mg daily, or up to the maximum tolerated dose and continued for 16 weeks (primary evaluation visit) followed by a 4-week washout period and re-evaluation at week 20. Changes in cognitive performance were measured as percent change from baseline to week 16 in the average of eight neuropsychological test scores (NPZ-8). Brain metabolism was measured by magnetic resonance spectroscopy in a subgroup of subjects. RESULTS: Sixty-one percent of subjects in the memantine group and 85% in the placebo group reached the 40 mg dose while the reported adverse experiences between the two groups were similar. There were no significant improvements in neuropsychological performance over 16 weeks; however, memantine was associated with a significant increase at week 16 in the N-acetyl aspartate to creatine ratio, in the frontal white matter (P = 0.040) and parietal cortex (P = 0.023). CONCLUSIONS: Memantine was safe and tolerated by HIV-infected subjects with cognitive impairment. Although we observed no significant differences in cognitive performance, the magnetic resonance spectroscopy data suggest that memantine may ameliorate neuronal metabolism, an important step to stabilizing or preventing neuronal injury. These results underscore the need for longer studies to assess the full potential of neuroprotective agents.

Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a cause of major complications in persons who are also infected with the human immunodeficiency virus (HIV). However, the treatment of HCV infection in such persons has been associated with a high rate of intolerance and a low rate of response. We conducted a multicenter, randomized trial comparing peginterferon plus ribavirin with interferon plus ribavirin for the treatment of chronic hepatitis C in persons coinfected with HIV. METHODS: A total of 66 subjects were randomly assigned to receive 180 microg of peginterferon alfa-2a weekly for 48 weeks, and 67 subjects were assigned to receive 6 million IU of interferon alfa-2a three times weekly for 12 weeks followed by 3 million IU three times weekly for 36 weeks. Both groups received ribavirin according to a dose-escalation schedule. At week 24, subjects who did not have a virologic response (those who had an HCV RNA level greater than or equal to 60 IU per milliliter) underwent liver biopsy, and medications were continued in subjects with either a virologic response or histologic improvement. RESULTS: Treatment with peginterferon and ribavirin was associated with a significantly higher rate of sustained virologic response (an HCV RNA level of less than 60 IU per milliliter 24 weeks after completion of therapy) than was treatment with interferon and ribavirin (27 percent vs. 12 percent, P=0.03). In the group given peginterferon and ribavirin, only 14 percent of subjects with HCV genotype 1 infection had a sustained virologic response (7 of 51), as compared with 73 percent of subjects with an HCV genotype other than 1 (11 of 15, P<0.001). Histologic responses were observed in 35 percent of subjects with no virologic response who underwent liver biopsy. CONCLUSIONS: In persons infected with HIV, the combination of peginterferon and ribavirin is superior to the combination of interferon and ribavirin in the treatment of chronic hepatitis C. These regimens may provide clinical benefit even in the absence of virologic clearance. The marked discrepancy in the rates of sustained virologic response between HCV genotypes indicates that strategies are needed to improve the outcome in persons infected with HCV genotype 1.

Correlation of single photon emission computed tomography parameters as a noninvasive alternative to liver biopsies in assessing liver involvement in the setting of HIV and hepatitis C virus coinfection: a multicenter trial of the Adult AIDS Clinical Trials Group.

Performing a liver biopsy in patients infected with HIV and hepatitis C virus (HCV) is considered the standard of practice to assess hepatic involvement but carries risks to patients. This pilot study was designed to identify single photon emission computed tomography (SPECT) parameters that correlate with liver disease stage. HIV-coinfected and HCV-coinfected individuals undergoing a liver biopsy had a SPECT scan performed. The results showed that a number of SPECT parameters were associated with histologic changes in architecture, fibrosis, and cirrhosis, of which two SPECT parameters, the minimum pixel count for spleen region of interest and maximum pixel count for right hepatic lobe, correctly classified 39 of 46 SPECT/biopsy pairs. In conclusion, this pilot trial identified SPECT parameters that correlated with liver histology changes. A larger study is needed to demonstrate whether SPECT parameters alone or with other markers can provide information on fibrosis with the clinical significance obtained through liver biopsy.