title: Risk factors for symptomatic hyperlactatemia and lactic acidosis among combination antiretroviral therapy-treated adults in Botswana: results from a clinical trial.
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.
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts, USA. william.wester@vanderbilt.edu
authors.forename: C William
authors.initials: CW
authors.lastname: Wester
authors.forename: Svetlana K
authors.initials: SK
authors.lastname: Eden
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: Hermann
authors.initials: H
authors.lastname: Bussmann
authors.forename: Vladimir
authors.initials: V
authors.lastname: Novitsky
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.forename: Sher L
authors.initials: SL
authors.lastname: Hendrickson
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Max
authors.initials: M
authors.lastname: Essex
authors.forename: Richard T
authors.initials: RT
authors.lastname: D'Aquila
authors.forename: Victor
authors.initials: V
authors.lastname: DeGruttola
authors.forename: Richard G
authors.initials: RG
authors.lastname: Marlink
mesh_terms: D000140:Acidosis, Lactic / Q000453:epidemiology / Q000209:etiology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001902:Botswana; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D019344:Lactic Acid