Title

Risk Factors for Symptomatic Hyperlactatemia and Lactic Acidosis Among Combination Antiretroviral Therapy-Treated Adults in Botswana: Results from a Clinical Trial

Authors

C. William Wester, Harvard University; Vanderbilt University
Svetlana K. Eden, Vanderbilt University
Bryan E. Shepherd, Vanderbilt University
Herman Bussmann, Harvard University; Botswana-Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education - Gaborone, Botswana
Vladimir Novitsky, Harvard University; Botswana-Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education - Gaborone, Botswana
David C. Samuels, Vanderbilt University
Sher L. Hendrickson, National Cancer Institute at Frederick
Cheryl Winkler, National Cancer Institute at Frederick
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
Max Essex, Harvard University; Botswana-Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education - Gaborone, Botswana
Richard T. D'Aquila, Vanderbilt University
Victor deGruttola, Harvard University
Richard G. Marlink, Harvard University; Botswana-Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education - Gaborone, Botswana

Document Type

Article

Publication Date

8-2012

Publication Title

AIDS Research and Human Retroviruses

ISSN

0889-2229

Volume

28

Issue/No.

8

First Page

759

Last Page

765

Abstract

Nucleoside analogue reverse transcriptase inhibitors are an integral component of combination antiretroviral treatment regimens. However, their ability to inhibit polymerase-γ has been associated with several mitochondrial toxicities, including potentially life-threatening lactic acidosis. A total of 650 antiretroviral-naive adults (69% female) initiated combination antiretroviral therapy (cART) and were intensively screened for toxicities including lactic acidosis as part of a 3-year clinical trial in Botswana. Patients were categorized as no lactic acidosis symptoms, minor symptoms but lactate <4.4 mmol/liter, and symptoms with lactate ≥4.4 mmol/liter [moderate to severe symptomatic hyperlactatemia (SH) or lactic acidosis (LA)]. Of 650 participants 111 (17.1%) developed symptoms and/or laboratory results suggestive of lactic acidosis and had a serum lactate drawn; 97 (87.4%) of these were female. There were 20 events, 13 having SH and 7 with LA; all 20 (100%) were female (p<0.001). Cox proportional hazard analysis limited to the 451 females revealed that having a higher baseline BMI was predictive for the development of SH/LA [aHR=1.17 per one-unit increase (1.08–1.25), p<0.0001]. Ordered logistic regression performed among all 650 patients revealed that having a lower baseline hemoglobin [aOR=1.28 per one-unit decrease (1.1–1.49), p=0.002] and being randomized to d4T/3TC-based cART [aOR=1.76 relative to ZDV/3TC (1.03–3.01), p=0.04] were predictive of the symptoms and/or the development of SH/LA. cART-treated women in sub-Saharan Africa, especially those having higher body mass indices, should receive additional monitoring for SH/LA. Women presently receiving d4T/3TC-based cART in such settings also warrant more intensive monitoring.

NSUWorks Citation

Wester, C. William; Svetlana K. Eden; Bryan E. Shepherd; Herman Bussmann; Vladimir Novitsky; David C. Samuels; Sher L. Hendrickson; Cheryl Winkler; Stephen J. O'Brien; Max Essex; Richard T. D'Aquila; Victor deGruttola; and Richard G. Marlink. 2012. "Risk Factors for Symptomatic Hyperlactatemia and Lactic Acidosis Among Combination Antiretroviral Therapy-Treated Adults in Botswana: Results from a Clinical Trial." AIDS Research and Human Retroviruses 28, (8): 759-765. https://nsuworks.nova.edu/cnso_bio_facarticles/436

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015