We don't really know what causes lipodystrophy. All we know is that a large number of HIV-positive people are experiencing one or more of the symptoms discussed in the first section of this lesson. We also know that most patients who have lipodystrophy started noticing these symptoms while taking combination anti-HIV drug therapy. Lipodystrophy was first reported among patients taking combinations of drugs that included a protease inhibitor (PI).
Since 1996, when lipodystrophy was first reported by researchers and health-care providers, several patients who have never taken a protease inhibitor (PI)—but have taken either non-nucleoside reverse transcriptase inhibitors (NNRTIs) and/or nucleoside reverse transcriptase inhibitors (NRTIs) in combination with each other—have been diagnosed with lipodystrophy. There are also some patients who have experienced one or more symptoms of lipodystrophy without taking any anti-HIV drugs at all. It's still not clear what role these anti-HIV drugs play in the development of lipodystrophy. Similarly, it's not known which drugs will most likely cause this problem.
Here is a review of what we do and don't know about the possible causes of lipodystrophy:
Protease inhibitors (PIs): Some researchers believe that protease inhibitors can impair the ability of certain enzymes responsible for mopping up excess fat and keeping fat cells functional. This, in turn, would account for the high levels of lipids being seen in some people living with HIV. This might also explain why fat accumulates around the gut, breasts, or neck. It's still not clear which protease inhibitors are most likely to cause lipodystrophy. One protease inhibitor, Reyataz (atazanavir), is believed to be the least likely to cause increased lipid levels in the blood (the risk of raised lipid levels may increase slightly when Reyataz is combined with low-dose Norvir). It is not yet clear if Reyataz is associated with fat accumulation, although some clinical trial data suggest that it is not.
Nucleoside reverse transcriptase inhibitors (NRTIs): Some NRTIs can impair the "power generators" of human cells called mitochondria. A growing number of researchers say that this might explain many of the side effects seen in people taking NRTIs, including peripheral neuropathy, pancreatitis, decreased white blood cell counts (leukopenia), and possibly lipodystrophy (particularly lipoatrophy).
It is believed that many of the "d" NRTIs—d4T (Zerit), ddI (Videx), and ddC (Hivid)—are the most likely to damage mitochondria, particularly if they are used for long periods of time. There have also been a number studies linking Zerit to fat loss in the face, arms, and legs (lipoatrophy). While other NRTIs [including AZT (Retrovir)] have also been linked to lipoatrophy, the risk appears to be highest in people who are taking Zerit. In turn, the U.S. Department of Health and Human Services (DHHS) no longer lists Zerit as a "preferred" NRTI choice in its HIV treatment guidelines. If fewer HIV-positive people use Zerit, experts argue, there will be fewer cases of lipoatrophy.
Other factors: Not everyone taking PIs or NRTIs develops lipodystrophy or problems with fat or sugar levels in the blood. In turn, researchers have been looking into other factors that may increase the risk of these side effects while on anti-HIV drug treatment. For example, people who start HIV treatment with lower CD4 cell counts may be at a higher risk of developing lipodystrophy than those who start treatment with higher CD4 cell counts. People who are older when they start treatment may also be at a higher risk, compared to those who are younger when treatment is started. And the longer a person has been on an anti-HIV drug regimen that contains certain PIs and/or NRTIs, the greater the risk of lipodystrophy or fat/sugar-related problems.
HIV itself may be a factor to consider. Long before people started taking anti-HIV drug combinations, people living with HIV were more likely to have higher levels of triglycerides in their blood and to experience body-shape changes, compared to HIV-negative people. And because many HIV-positive people are living longer while on combination anti-HIV drug therapy, the HIV-related fat problems continue to get worse. Researchers are still looking into the effects of HIV (and problems with the immune system) on the way our bodies store and utilize lipids.
Researchers have also been looking into genetic factors that may increase or decrease the risk of lipodystrophy and problems with fat or sugar levels in the blood. Some people may have genetic mutations—scientifically known as "polymorphisms"—that may affect the way cells in the body (including fat cells) work. People with these polymorphisms taking certain HIV medications may be at an increased risk for body-shape changes and problems with fat or sugar levels in the blood. More research is needed to better understand our genetic differences and the role they may play in the side effects of HIV drug treatment.
Search for news stories about this topic