A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy

Lynn T. Matthews, Janet Giddy, Musie Ghebremichael, Jane Hampton, Anthony J. Guarino, Aba Ewusi, Emma Carver, Karen Axten, Meghan C. Geary, Rajesh T. Gandhi, David Bangsberg

Research output: Contribution to journalArticle

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Abstract

Background: Stavudine 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. Methods: Antiretroviral-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. Results: Among 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). Conclusions: Stavudine 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.

Original languageEnglish (US)
Article numbere18736
JournalPLoS One
Volume6
Issue number4
DOIs
StatePublished - 2011
Externally publishedYes

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Stavudine
Lactic Acidosis
acidosis
risk factors
Zidovudine
milk
therapeutics
body mass index
Body Mass Index
Therapeutics
creatinine
albumins
gender
CD4 Lymphocyte Count
hazard characterization
Hyperlactatemia
Milk
Albumins
Creatinine
Hazards

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy. / 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.

In: PLoS One, Vol. 6, No. 4, e18736, 2011.

Research output: Contribution to journalArticle

Matthews, LT, Giddy, J, Ghebremichael, M, Hampton, J, Guarino, AJ, Ewusi, A, Carver, E, Axten, K, Geary, MC, Gandhi, RT & Bangsberg, D 2011, 'A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy', PLoS One, vol. 6, no. 4, e18736. https://doi.org/10.1371/journal.pone.0018736
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. / A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy. In: PLoS One. 2011 ; Vol. 6, No. 4.
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title = "A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy",
abstract = "Background: Stavudine 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. Methods: Antiretroviral-na{\"i}ve, 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. Results: Among 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). Conclusions: Stavudine 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.",
author = "Matthews, {Lynn T.} and Janet Giddy and Musie Ghebremichael and Jane Hampton and Guarino, {Anthony J.} and Aba Ewusi and Emma Carver and Karen Axten and Geary, {Meghan C.} and Gandhi, {Rajesh T.} and David Bangsberg",
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T1 - A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy

AU - Matthews, Lynn T.

AU - Giddy, Janet

AU - Ghebremichael, Musie

AU - Hampton, Jane

AU - Guarino, Anthony J.

AU - Ewusi, Aba

AU - Carver, Emma

AU - Axten, Karen

AU - Geary, Meghan C.

AU - Gandhi, Rajesh T.

AU - Bangsberg, David

PY - 2011

Y1 - 2011

N2 - Background: Stavudine 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. Methods: Antiretroviral-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. Results: Among 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). Conclusions: Stavudine 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.

AB - Background: Stavudine 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. Methods: Antiretroviral-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. Results: Among 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). Conclusions: Stavudine 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.

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