Prevalence, risk factors and outcome of hyperlactataemia in HIV‐infected patients*

Abstract

ObjectiveWe describe the prevalence, risk factors and outcome of hyperlactataemia (HL) in a cohort of 140 HIV-infected patients. Patients and methodsPatients were enrolled consecutively within a 3-month period (July to September 1999) and followed until 31 October 2000. One hundred and forty HIV-infected patients had venous plasma lactate levels measured. HL was de®ned at baseline by two consecutive lactate levels > 2.1 mmol/L (upper limit of normal). We compared baseline demographic characteristics, immuno-virological parameters, antiretroviral therapy and outcome between patients with HL (cases) or without HL (controls). We described the clinical features of patients with HL. ResultsAmong 129 patients included in the analysis, HL was found in 11 patients (8.5%), all of whom were receiving nucleoside reverse transcriptase inhibitors (NRTIs). Cases were more likely than controls to receive didanosine or stavudine (82% vs. 19%, P 2.7 Â 10 À6 and 82% vs. 48%, P 0.03, respectively). Only 4/11 cases (36%) had symptoms consistent with HL. After a median follow-up of 15 months, lactate level returned to normal in all three patients who discontinued NRTIs, but in only 2/8 patients who did not (P 0.06). Only one case experienced lactic acidosis and died during followup. Mortality rate was similar in cases and controls. ConclusionHL is associated with NRTI use, in particular didanosine and stavudine, and discontinuation of NRTIs seems to be associated with rapid resolution of HL. Lactic acidosis remains rare and the long-term outcome of patients with HL does not seem to be poorer than controls.

Mitochondrial Genomics and Antiretroviral Therapy-Associated Metabolic Complications in HIV-Infected Black South Africans: A Pilot Study

“…Hyperlactatemia is a recognized consequence of mitochondrial dysfunction associated with d-drug use. 35 We found no association between African mtDNA haplogroups and hyperlactatemia, which is similar to the finding from another South African study. 36 There are inconsistent data regarding the influence of specific European mtDNA haplogroups on lipoatrophy.…”

Severe Lactic Acidosis in Association with Reverse Transcriptase Inhibitors with Potential Response to L-Carnitine in a Pediatric HIV-Positive Patient

“…2,7 The majority of cases appear to be associated with regimens containing didanosine and stavudine, but there have also been reports in association with zidovudine, and lamivudine. 1,11,15,16 Acidosis results most frequently when they are used in combination, but may also occur when only one of these medications is included in a therapeutic regime. This observation is supported by in vitro evidence that suggests additive or synergistic long-term mitochondrial toxicity in some NRTI combinations.…”

Risk factors for and clinical characteristics of severe hyperlactataemia in patients receiving antiretroviral therapy: a case–control study

“…The associations between SHLA and exposure to d4T and ddI were initially described in a number of small crosssectional and cohort studies [10][11][12][13][14][15]. Recently, 110 cases of SHLA were pooled across multiple countries to conduct a case-control study, which identified advanced age, low nadir CD4 cell count, exposure to d4I and ddI and female gender as additional associations [16].…”

“…Although hyperlactataemia and lactic acidosis have become rare in developed world settings, they are still considered significant challenges to large-scale ART provision in developing countries. A better understanding of the risk factors for SHLA is important in combating the morbidity and mortality associated with such an adverse event.Although the World Health Organization (WHO) now recommends tenofovir (TDF) or zidovudine (ZDV) as the preferred NRTIs for combination with lamivudine (3TC) or emtricitabine (FTC) in standard first-line regimens [8], d4T-based regimens continue to be widely used in developing countries, for reasons of cost, availability, and ease of administration [9].The associations between SHLA and exposure to d4T and ddI were initially described in a number of small crosssectional and cohort studies [10][11][12][13][14][15]. Recently, 110 cases of SHLA were pooled across multiple countries to conduct a case-control study, which identified advanced age, low nadir CD4 cell count, exposure to d4I and ddI and female gender as additional associations [16].…”