Original Article: bit.ly/1NqqW4H
HIV infection or inflammatory changes associated with it may be responsible for fat accumulation and body fat redistribution, rather than HIV drugs, the CROI 2105 conference heard last week.
Dr Grace McComsey of Case Western University in Cleveland, Ohio said that although the association of subcutaneous fat loss (lipoatrophy) with mitochondrial damage caused by certain HIV drugs was well-established (and most of the world no longer uses the drugs like stavudine that are most strongly associated with it), two decades of research had failed to establish a cause for the distinctive fat gain (lipohypertrophy), especially in the trunk and within the abdomen, seen in some people on antiretroviral therapy (ART).
Initially these fat gains were associated with protease inhibitors (PIs) but switching from PIs to non-nucleoside reverse transcriptase inhibitors (NNRTIs) or to integrase inhibitors did not reverse fat gains. One study had found greater fat gain in people taking boosted atazanavir rather than efavirenz but a general association with any drug or class of drugs had not been demonstrated. Given that untreated HIV infection usually results in weight loss, fat gains when people started ART, once it became available, may have understandably been associated with ART rather than HIV.
The study McComsey presented, ACTG A5260s, compared changes in limb fat, trunk fat, visceral adipose tissue (central abdominal fat) and lean muscle mass in 1809 ART-naïve patients starting either of the two boosted PIs atazanavir or darunavir, or the integrase inhibitor raltegravir, all combined with tenofovir/emtricitabine (Truvada).
DEXA and CAT scans measured fat and muscle distribution at baseline and nearly two years (96 weeks) later. They were then tested for association with drug regimen, baseline HIV viral load, Framingham risk score (a measure of the likelihood of cardiovascular disease), and a number of hormones, cytokines (cell messenger chemicals) and markers of inflammation: leptin (higher in the obese) adiponectin (lower in the obese), D-dimer and C-reactive protein (inflammation indicators) and the cytokines/cytokine receptors IL-6, CD14 and CD163.
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