|
More
on Lactic Acidosis
Severe
Nucleoside-Associated Lactic Acidosis in Human Immunodeficiency
Virus-Infected Patients: Report of 12 Cases and Review of the Literature
[Falco V et al. CID 2002:34:838]: This is a report from
Spain concerning 12 patients with lactic acidosis found by screening
records for unexplained metabolic acidosis among 5,400 patients
treated with NRTIs during the period 1997-2000. Symptoms in these
12 patients included GI complaints (10), cough and dyspnea (6),
weight loss (4), and paresthesias or extremity pain (4). Laboratory
tests showed the following median levels: pH-7.2; bicarbonate-11.45
mM, and lactate levels-6.5 mM. There were five patients admitted
to ICU and 4 deaths (33%) due to this complication. The literature
review was based on a Medline search with the following criteria:
adult patients treated with ART, confirmed metabolic acidosis, and
exclusion of other known causes of lactic acidosis. This resulted
in 60 cases of severe lactic acidosis. The mortality in the literature
review series was 55% and correlated directly with the lactic acid
level as shown in the following table:
| |
|
Lactic
acid level
(mM)
|
#
|
Mortality |
5-10
|
15
|
7% |
| 10-15 |
14 |
43% |
| 15-20 |
9 |
67% |
| 20-25 |
7 |
71% |
| >
25 |
8 |
88% |
With regard to
nucleoside analogs, the number of cases associated with specific
NRTIs was highly dependent on the period of reporting. The most
commonly used agent prior to 1996 was AZT; there was a mixture for
1997-99; and since 2000, d4T has accounted for the great majority.
These data are shown in the following table:
| |
|
Reporting
Period
|
#
|
AZT |
ddI |
d4T |
3TC |
| 1991-96 |
23 |
22 |
2 |
- |
- |
| 1997-99 |
13 |
6 |
4 |
7 |
4 |
| 2000-01 |
34 |
2 |
11 |
33 |
15 |
Comment: There
are several important observations in this review: 1) Women accounted
for a disproportionate 50% of the reported cases; 2) this complication
appears to be unrelated to the CD4 cell count; 3) multivariate analysis
showed that serum lactic acid levels greater than 10 mM were associated
with higher mortality; 4) abacavir and tenofovir may be attractive
treatment options for continued NRTI use due to the low frequency
with which these drugs have been implicated, a clinical observation
that is supported by evidence of low affinity for mitochondrial
DNA polymerase-?; 5) there are anecdotal case reports showing treatment
benefit with thiamine, riboflavin, L-carnitine, vitamin C, and antioxidants.
(In this series, seven of the twelve were treated with riboflavin
and/or thiamine, and only one died.)
|
|
back
to news table of contents