Patients starting d4T on the lower dose who gained weight to above 60 kg were changed to the higher dose. As per clinical guidelines, lactate

measurements are requested in symptomatic patients only. The existing case series from which the cases were drawn describes the clinical management of SHLA in this setting, as well as the referral rates, characteristics and outcomes of referred patients with SHLA [18]. In the published case series the referral rate was 17.5 [95% confidence interval (CI) 13.7–21.9] per 1000 patient-years for SHLA, and 12.1 (95% CI 9.2–16.1) per 1000 patient-years for lactic acidosis (53 of the 75 cases in the full series were acidotic, and the median lactate value was 7.6 mmol/L [interquartile range Lorlatinib chemical structure (IQR) 5.9–9.8]). Acute mortality was 16% for SHLA and 21% for lactic acidosis. A matched case–control study was conducted using incidence density sampling and builds on the case series reported by Stead et al. [18] This case–control study was nested within the larger cohort of ART patients attending public sector ART services in the province [19]. All patients with lactate ≥5 mmol/L referred to GF Jooste Hospital between 1 August 2003 and 15 November 2005 were considered. Potential cases with alternative aetiology to explain a raised lactate, including hepatitis, severe dehydration and sepsis, were excluded from the study. The resulting sample size of selleck chemicals llc 71 cases provided 80% power to detect a 3-fold

difference in the risk of SHLA for women compared with men and for weight above 70 kg, assuming two controls for each case. These effect sizes were well within those described in a smaller cohort study in the same setting [17]. Two systematically selected controls were matched to their respective cases by primary health care facility and duration on ART. Matching by facility

was necessary because of the nature of the information system, during while matching by duration was by design, to avoid over-representing patients who had recently started ART. Controls were considered eligible if they were still in care at the facility at the time of the SHLA diagnosis of their matched case. Selected controls had to be treatment-naïve and not have a determined lactate ≥5 mmol/L between ART initiation and the SHLA presentation date of their matched case. Nonreplacement selection was used; however, because of the small numbers initiating therapy per facility at the beginning of the national ART roll-out, four controls were selected twice. All baseline and longitudinal data were collected retrospectively from each participant’s primary care folder. Follow-up data were collected from ART initiation to either case presentation for the cases or the date of presentation for each control’s matched case. Variables at baseline included demographic information, WHO stage-defining illnesses, concomitant chronic medical conditions, tuberculosis history, baseline laboratory results and clinical assessment details.