What causes lipoatrophy?

It's not yet clear why or how lipoatrophy occurs in HIV-positive people. However, it is believed to be a side effect of ARV therapy.

Two Nucleoside reverse transcriptase inhibitors (NRTIs) have been singled out as the most likely cause of lipoatrophy. While it is not entirely clear why these particular drugs cause this side effect, it is probably related to the ability of these drugs to damage cellular mitochondria.

Mitochondria are considered to be the "powerhouses" of cells in the body. All cells in the body, with the exception of red blood cells, contain mitochondria. They are primarily responsible for converting nutrients, such as sugar and fats, into energy that can be used by the cells. If something goes wrong with the mitochondria, the cell isn't able to get the energy it needs, which can prevent the cell from doing what it is supposed to do. If the cells in question are fat cells (adipocytes), responsible for storing and exporting fat for when it is needed, significant mitochondrial damage can cause these cells to loose both their function and shape, or to die altogether. And if enough fat cells are affected, it can cause noticeable wasting of fat tissue in the face and other parts of the body.

Zerit (d4T, stavudine) is the NRTI most frequently tied to lipoatrophy. In test tube studies, Zerit has been shown to cause mitochondrial damage and to alter the function of adipocytes as well. Clinical trials also suggest have confirmed that HIV-positive people taking drug regimens that contain Zerit are more likely to experience lipoatrophy than those taking drug regimens that do not contain Zerit. However, drug regimens that contain Retrovir (AZT; zidovudine) have also been shown to cause lipoatrophy, although not to the same degree as drug regimens containing Zerit. Experts reckon that the NRTIs Viread (tenofovir), Epivir (3TC; lamivudine), Emtriva (emtricitabine), and Ziagen (abacavir) are the least likely to cause lipoatrophy.

Protease inhibitors (PIs) may cause lipoatrophy as well. Researchers have found that while the drugs do not interfere with cellular mitochondria, they can affect other components of fat cells that affect the way adipocytes work. Some data from clinical trials involving HIV-positive people taking protease inhibitors also suggest that these drugs may be partly to blame for lipoatrophy.

Other factors that may increase (or decrease) the risk of lipoatrophy include age, gender, genetic predisposition, the CD4 cell count at the time therapy is started (the lower the CD4 cell count, the more likely it is the lipoatrophy will occur), and the length of time on antiretroviral therapy (the longer the time on therapy, the more likely that lipoatrophy will occur).

There is evidence that fat cells affected by lipoatrophy can become dysfunctional and may die as well. Research has found that fat cells in people with lipoatrophy have very high levels of mitochondrial damage, inflammation, and reduced ability to function. Scientists have also found elevated levels of proteins associated with fat cell death in people with HIV. No one has yet proven which problem is most prominent, however, and the answer to this question may help determine the degree to which the condition is reversible. If cells are merely dysfunctional, then they can hopefully be replaced over time, though studies where people switch off of the most offending drugs suggest that recovery is slow. If cells die, however, the body might not be able to replace them, or may only be able to partially replace them.

Search for news stories about this topic