|
|
 |
|
Summary
and Conclusions
| •
|
Lactic
acidosis is a life-threatening complication of HAART occurring
with increasing frequency
|
| •
|
The
cause appears to be mitochondrial toxicity from long-term use
of NRTIs
|
| •
|
Offending
agents most often implicated are the d drugs: ddC, ddI, and
d4T
|
| •
|
Diagnosis
is difficult because symptoms are vague and general
|
| •
|
Treatment
includes discontinuing NRTIs, followed by supportive care measures
|
|
|
•
In conclusion, lactic acidosis is a life-threatening and sometimes
fatal complication in patients receiving highly active antiretroviral
therapy (HAART). Cases are occurring with increasing frequency.
• The pathogenesis of this condition appears to be mitochondrial
toxicity brought about by long-term use of NRTIs. These agents have
been found to interfere with DNA polymerase gamma, a cellular enzyme
responsible for mitochondrial DNA replication.
• The most offending agents are those with the most inhibitory
interaction with DNA polymerase gamma, specifically the d drugs ddC,
ddI, and d4T.
• Diagnosing lactic acidosis is often difficult, because patients
complain of vague, generalized symptoms. Anion gap, while often elevated
in these patients, is not a sensitive or specific way to look for
lactic acidosis.
• Treatment options are limited. NRTIs should be discontinued
immediately, followed by supportive care measures designed to correct
the acidosis and assist with respiratory chain function.
• Additional studies are needed to help us understand this complication
more fully.
|
|
|
|
