The use of highly active antiretroviral therapy (HAART) has helped to reduce complications from AIDS in North America and Western Europe. Unfortunately, however, HAART-users can experience a range of side effects, including the following — which collectively is called the lipodystrophy syndrome:
Hampering efforts to understand why these side effects occur is the fact that people with HIV/AIDS (PHAs) are often taking combination therapy made up of treatments from at least two of the following groups of drugs:
PHAs who are also co-infected with hepatitis C virus (HCV) may also be using interferon-alpha and the anti-HCV nuke ribavirin (Virazole).
Even though treatment regimens can be complex, researchers around the world are beginning to develop ideas about some of the causes of drug side effects. Below are some brief explanations.
Nukes can damage the energy-producing parts — called mitochondria (Mt) — of a cell, including fat cells. Over time, with continued exposure to nukes, damaged Mt become dysfunctional and dwindle in number. The end result is that a cell has less energy with which to do its work. Cells experiencing this kind of energy shortage don't work properly and can die. Here are some examples of what can happen in cases of Mt damage:
In the time before lipodystrophy became a common problem for PHAs, Mt damage also appeared in other, HIV negative people, particularly those with neurologic problems. In such cases, doctors used the following substances to treat Mt damage:
Use of another group of anti-HIV drugs called protease inhibitors (PI) appears to increase the risk of type 2 diabetes and possibly heart disease by increasing levels of fatty substances in the blood. The role that non-nukes play in the HIV-lipodystrophy syndrome is not clear.
REFERENCES
1. Spellberg B, Carroll RM, Robinson E and Brass E. mtDNA disease in the primary care setting. Archives of Internal Medicine 2001;161:2497-2500.
2. Côté HCF, Brumme ZL, Craib KJP et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. New England Journal of Medicine 2002;346:811-820.
3. Walker UA, Bickel M, Volksbeck SIL, et al. Evidence of nucleoside analogue reverse transcriptase inhibitor-associated genetic and structural defects of mitochondria in adipose tissue of HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes 2002;29(2):117-121.
4. Lim SE and Copeland WC. Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase . Journal of Biological Chemistry 2001;26:23616-23623.
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