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Muscle Damage with HAART
HAART often causes muscle damage (myopathy) which often manifests itself as weakness and wasting. This is often caused by damage to the mitochondria, energy-regulating organelles, that have their own DNA. Nucleoside analogs, the backbone of AIDS drug 'cocktails' are notorious for damage to DNA.
“Bristol Myers Squibb (BMS) has chosen to inform doctors of rapidly ascending muscular weakness as new symptom of nucleoside-related lactic acidosis and hyperlactataemia...A review by the EMEA of nucleoside analogue-related LA [lactic acidosis] and HL [hyperlactataemia] has highlighted seven cases of rapidly ascending muscular weakness, similar to that symptoms seen with Guillain-Barré Syndrome [a form of paralysis], and a further seven cases of muscular weakness or pain which preceded the development of LA and HL...Early symptoms of LA and HL include nausea, vomiting, diarrhoea, rapid and deep breathing, stomach cramp, myalgia [muscle pain] and paresthesia [numbness]. Ascending neuromuscular weakness should now be added to this list. Severe complications which currently include pancreatitis [pancreas failure] and liver failure should now be broadened to include motor paralysis”
Rapidly ascending neuromuscular weakness associated with nucleoside analogues. HIV Treatment Bulletin. 2001 Oct;2(8).
“7 HIV patients presenting LD [Lipodystrophy, all taking antiretroviral therapy] and 5 HIV non-LD controls participated in the study…Structural muscle abnormalities, mitochondrial respiratory chain dysfunction or mtDNA deletions were detected in all HIV lipodystrophic patients”
Zaera MG et al. Mitochondrial involvement in antiretroviral therapy-related lipodystrophy. AIDS. 2001 Sep 7;15(13):1643-51.
“Patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy [muscle damage] or neuropathy [nerve damage] after long-term therapy. Zidovudine (AZT) causes myopathy…stavudine (d4T) and fialuridine (FIAU) cause neuropathy or myopathy and lactic acidosis. The tissue distribution of phosphorylases responsible for phosphorylation of NRTIs relates to their selective tissue toxicity. The myopathy is characterized by muscle wasting, myalgia, fatigue, weakness and elevation of CK…patients treated with AZT, the best studied NRTI, develop a mitochondrial myopathy [muscle damaged as a result of mitochondrial damage]…Animals or cultured cells treated with NRTIs develop neuropathy, myopathy, or cell destruction with similar changes in the mitochondria. There is evidence that the NRTI-related neuropathy is also due to mitochondrial toxicity”
Dalakas MC. Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst. 2001 Mar;6(1):14-20.
“There was a marked decrease in complex IV activity in muscle biopsies from four of five patients, consistent with a mitochondrial dysfunction”
Gerard Y et al. Symptomatic hyperlactataemia: an emerging complication of antiretroviral therapy. AIDS. 2000 Dec 1;14(17):2723-30.
“drugs that have been shown to induce mitochondrial toxicity are nucleoside analogues used in chemotherapy and antiretroviral therapy, such as HIV RTI [reverse transcriptase inhibitors]…Since these nucleoside analogues elicit complete mtDNA replication deficits, clinical features can be regarded as a compilation of those seen in the genetic mitochondriocytopathies. These features include myopathy [muscle damage, including wasting], cardiomyopathy [heart muscle damage]…[and other non-muscle-related side effects]”
Brinkman K et al. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as a common pathway. AIDS. 1998 Oct 1;12(14):1735-44.
“typical mitochondrial myopathy [muscle damage] has been reported to be expressed among many patients with AIDS treated with long-term azidothymidine (AZT) therapy…for AIDS patients, it is urgently necessary to develop a remedy substituting this toxic substance, AZT [yet, more than a decade later, it is still one of the most commonly used AIDS medications, including as one of two drugs in Combivir pills (along with 3TC)]”
Hayakawa M et al. Massive conversion of guanosine to 8-hydroxy-guanosine in mouse liver mitochondrial DNA by administration of azidothymidine. Biochem Biophys Res Commun. 1991;176:87-93.
Courtesy Alberta Reappraising AIDS Society, October 24, 2008.