A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy |
| |
Authors: | Matthews Lynn T Giddy Janet Ghebremichael Musie Hampton Jane Guarino Anthony J Ewusi Aba Carver Emma Axten Karen Geary Meghan C Gandhi Rajesh T Bangsberg David R |
| |
Institution: | Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America. ltmatthe@bidmc.harvard.edu |
| |
Abstract: | BackgroundStavudine continues to be used in antiretroviral treatment (ART) regimens in
many resource-limited settings. The use of zidovudine instead of stavudine
in higher-risk patients to reduce the likelihood of lactic acidosis and
hyperlactatemia (LAHL) has not been examined.MethodsAntiretroviral-naïve, HIV-infected adults initiating ART between 2004
and 2007 were divided into cohorts of those initiated on stavudine- or
zidovudine-containing therapy. We evaluated stavudine or zidovudine use,
age, sex, body mass index (BMI), baseline CD4 cell count, creatinine,
hemoglobin, alanine aminotransferase, and albumin as predictors of time to
LAHL with Cox Proportional Hazards (PH) regression models.ResultsAmong 2062 patients contributing 2747 patient years (PY), the combined
incidence of LAHL was 3.2/100 PY in those initiating stavudine- and 0.34/100
PY in those initiating zidovudine-containing ART (RR 9.26, 95% CI:
1.28–66.93). In multivariable Cox PH analysis, stavudine exposure (HR
14.31, 95% CI: 5.79–35.30), female sex (HR 3.41, 95% CI:
1.89–6.19), higher BMI (HR 3.21, 95% CI: 2.16–4.77),
higher creatinine (1.63, 95% CI: 1.12–2.36), higher albumin (HR
1.04, 95% CI: 1.01–1.07), and lower CD4 cell count (HR 0.96,
95% CI: 0.92–1.0) at baseline were associated with higher LAHL
rates. Among participants who started on stavudine, switching to zidovudine
was associated with lower LAHL rates (HR 0.15, 95% CI:
0.06–0.35). Subgroup analysis limited to women with higher BMI≥25
kg/m2 initiated on stavudine also showed that switch to zidovudine was
protective when controlling for other risk factors (HR 0.21, 95% CI
.07–0.64).ConclusionsStavudine exposure, female sex, and higher BMI are strong, independent
predictors for developing LAHL. Patients with risk factors for lactic
acidosis have less LAHL while on zidovudine- rather than
stavudine-containing ART. Switching patients from stavudine to zidovudine is
protective. Countries continuing to use stavudine should avoid this drug in
women and patients with higher BMI. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|