DOI: 10.1097/01.qai.0000195609.32885.71
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Issn Print: 1525-4135
Publication Date: 2006/02/01
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Excerpt
The authors thank Dr. Milazzo and her colleagues for their interest in our paper, which was recently published in this journal.1 In their letter, Milazzo and her colleagues point to some differences regarding the results of their own study2 and our study.
The study by Milazzo et al2 and our study had different 13C-methionine breath-test outcomes in the “asymptomatic” patient group, which could be explained by different baseline characteristics. The subgroup rated as “asymptomatic” by Milazzo et al2 had longer disease duration and a higher proportion of D-drug-experienced patients compared with our study, which makes them better comparable to our subgroup of lipoatrophic patients.
In contrast to our results, Milazzo et al2 could not find any functional mitochondrial impairment in therapy-naive patients compared with healthy controls. There is no obvious explanation for these differences in the reports, because demographic and biochemical patient characteristics are comparable in both studies. In their letter, Milazzo and her colleagues presented new longitudinal data on therapy-naive patients, which confirms their previous findings: 19 previously treatment-naive patients starting on highly active antiretroviral therapy (HAART) were monitored by the 13C-methionine breath test (MeBT) at baseline and at 6 and 12 months after treatment initiation with no significant alteration in breath-test performance at any time point. In the ongoing longitudinal trial of our research group, 55 therapy-naive patients have been enrolled and we currently have complete results from 21 patients starting antiretroviral therapy. Although breath test results are more variable in this larger cohort (compared with the pilot trial), we still found a significant decay of cumulative 13CO2 exhalation (cPDR) in therapy-naive patients compared with healthy controls (cPDR = 1.5 hours, controls: 5.7 ± 1.1% [n = 15] vs. HIV-positive therapy-naive patients: 3.4 ± 1.6% [n = 55]; P < 0.001 by the Mann-Whitney U test). Moreover, the 21 patients starting antiretroviral therapy with successful suppression of their HIV viral load (n = 17) demonstrated rapid amelioration of breath test performance at 3 months after initiating HAART (Fig. 1). Four patients with treatment failure (2 with primary resistance and 2 with noncompliance; dashed lines in Fig. 1) remained unchanged or worsened. The ongoing study should demonstrate whether this significant treatment effect after 3 months of therapy on mitochondrial function is maintained.
These contrary observations indicate the need for further validation of this new and interesting method with a greater number of well-defined patients and observations beyond 12 months in combination with histologic studies to clarify the development, extension, and progression of mitochondrial dysfunction in therapy-naive patients as well as in patients on antiretroviral therapies. Finally, the use of the 13C-methionine breath test could be a promising tool for noninvasive assessment of hepatic-mitochondrial function in chronic HIV disease, because hepatic disorders caused by current treatment options are a major source of HIV-related morbidity and mortality.
