Important note: Information in this article was accurate in September 2000. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, September 4, 2000
Prepared by AIDS Weekly editors from staff and other reports
NewsRx -- Nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy contributes to subcutaneous fat wasting in HIV patients, according to researchers in Australia.
"Progressive subcutaneous fat wasting, fat accumulation, dyslipidemia, and insulin resistance in HIV infected patients on antiretroviral therapy have been attributed to the long-term toxicity of HIV protease inhibitors (PI)," stated S.A. Mallal and colleagues, Royal Perth Hospital, Australia. "More recently, fat wasting has been observed in patients who have never taken a PI, implicating an independent effect of nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy."
The researchers set out to determine the relative contribution of NRTI, PI, and any other factors, to fat wasting in HIV infected patients. They conducted a longitudinal cohort study that included 277 patients from the Western Australian HIV Cohort Study ("Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection," AIDS 2000 Jul 7;14(10):1309-16.
They compared the time to onset of clinically apparent fat wasting in patients receiving different antiretroviral regimens. Standardized clinical criteria were used to make the diagnosis. They also compared regional fat which was measured by dual energy X-ray absorptiometry (DEXA). This was done in 161 of the participating patients.
"The average rate of percentage fat reduction was estimated in 70 patients who had consecutive DEXA scans at approximately six monthly intervals," continued Mallal et al. "Multiple confounding factors were considered in the analyses."
The researchers observed that progressive subcutaneous fat wasting, which was indistinguishable from that described in PI-treated patients, could be found in PI-naive, NRTI-treated patients. They found increased risk of fat wasting in patients falling under the following criteria: those taking triple combination antiretroviral therapy, those who were older in age (relative risk = 1.052 per year; P<0.0001), those who were of the white race (relative risk = 3.9; P=0.023), those who had a longer duration of dual NRTI therapy prior to addition of PI (relative risk = 1.021 per month; P=0.0046), and those who had increased cumulative time on stavudine-containing regimens compared with time on zidovudine-containing regimens (relative risk = 1.085 per month; P<0.0001).
The researchers reported the risk of fat wasting increased by 265% per year if the patient used stavudine as compared with zidovudine. The data showed, however, that PI therapy was associated with faster progression to clinically apparent wasting than was dual NRTI therapy without PI.
"The results of DEXA scanning supports these clinical data and suggest a non-linear decline in fat over time," Mallal et al. concluded. "NRTIs do have an independent contribution to fat wasting, but PI are the predominant influence and may act synergistically with NRTIs.
"NRTIs appear to predispose individuals to slowly progressive fat loss, which is markedly accelerated when a PI and NRTIs are combined. Of the NRTIs, stavudine leads to an earlier onset of clinically apparent fat wasting compared with zidovudine. Fat wasting associated with NRTI use may be a manifestation of mitochondrial toxicity, which may be exacerbated by PI use."
The corresponding author for this report is S.A. Mallal, Royal Perth Hospital, Department of Clinical Immunology, Wellington St, Perth, WA 6000, Australia.
A search of the www.NewsRx.com online database using the terms "HIV" and "fat" generated 86 articles.
Key points reported in this study are:
This article was prepared by AIDS Weekly editors from staff and other reports.
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