Risk factors for and clinical characteristics of severe hyperlactataemia in patients receiving antiretroviral therapy: a case-control study.
BACKGROUND
Symptomatic hyperlactataemia and lactic acidosis (SHLA) are potentially life-threatening complications associated with stavudine (d4T), an antiretroviral therapy (ART) drug widely used in developing countries.


METHODS
Cases comprised all symptomatic patients with measured lactates >or= 5 mmol/L referred to a South African hospital between August 2003 and November 2005. Matched controls were selected according to facility and duration on ART.


RESULTS
Seventy-one cases and 142 controls were included in the study. The majority of cases presented between 6 and 18 months on ART. Female sex [adjusted odds ratio (AOR) 23.4; 95% confidence interval (CI) 4.0-136.6], a baseline weight between 60 and 75 kg (AOR 4.5; 95% CI 1.4-14.1) or, in particular, >or= 75 kg (AOR 19.4; 95% CI 4.1-82.5) at ART initiation and gaining >or= 6 kg in the first 3 months on therapy (AOR 3.5; 95% CI 1.3-9.5) were independent risk factors identifying patients who may subsequently develop SHLA. Weight loss of >or= 2 kg (AOR 6.1; 95% CI 2.0-18.3), a rise in alanine aminotransferase (ALT) >or= 10 U/L (AOR 3.1; 95% CI 1.1-8.9), the presence of at least one of three major symptoms (vomiting, nausea and abdominal pains) of SHLA (AOR 12.6; 95% CI 3.3-47.2) and peripheral neuropathy (AOR 3.4; 95% CI 1.1-9.8) were the clinical parameters that were most able to identify patients with early manifestations of SHLA.


CONCLUSIONS
This is the first case-control study for SHLA in Southern Africa. Given these findings, we advise that stavudine is avoided in overweight women. Weight loss, a rise in ALT, peripheral neuropathy and/or gastrointestinal symptoms should prompt healthcare workers to assess for SHLA, especially at between 6 and 18 months on ART.
Osler
Meg
M
Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. megosler@gmail.com
Stead
D
D
Rebe
K
K
Meintjes
G
G
Boulle
A
A
D000140:Acidosis, Lactic / Q000097:blood / Q000139:chemically induced*; D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003906:Developing Countries; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D050177:Overweight / Q000150:complications; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011247:Pregnancy; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D013019:South Africa; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects*; D015431:Weight Loss
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019344:Lactic Acid; D018119:Stavudine; D000410:Alanine Transaminase