Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.

BACKGROUND: HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. METHODS: In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per microL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. FINDINGS: Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). INTERPRETATION: ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment. FUNDING: UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories

The ASOS Surgical Risk Calculator: development and validation of a tool for identifying African surgical patients at risk of severe postoperative complications

Background: The African Surgical Outcomes Study (ASOS) showed that surgical patients in Africa have a mortality twice the global average. Existing risk assessment tools are not valid for use in this population because the pattern of risk for poor outcomes differs from high-income countries. The objective of this study was to derive and validate a simple, preoperative risk stratification tool to identify African surgical patients at risk for in-hospital postoperative mortality and severe complications. Methods: ASOS was a 7-day prospective cohort study of adult patients undergoing surgery in Africa. The ASOS Surgical Risk Calculator was constructed with a multivariable logistic regression model for the outcome of in-hospital mortality and severe postoperative complications. The following preoperative risk factors were entered into the model; age, sex, smoking status, ASA physical status, preoperative chronic comorbid conditions, indication for surgery, urgency, severity, and type of surgery. Results: The model was derived from 8799 patients from 168 African hospitals. The composite outcome of severe postoperative complications and death occurred in 423/8799 (4.8%) patients. The ASOS Surgical Risk Calculator includes the following risk factors: age, ASA physical status, indication for surgery, urgency, severity, and type of surgery. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.805 and good calibration with c-statistic corrected for optimism of 0.784. Conclusions: This simple preoperative risk calculator could be used to identify high-risk surgical patients in African hospitals and facilitate increased postoperative surveillance. © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.Medical Research Council of South Africa gran

Maternal and neonatal outcomes after caesarean delivery in the African Surgical Outcomes Study: a 7-day prospective observational cohort study.

BACKGROUND: Maternal and neonatal mortality is high in Africa, but few large, prospective studies have been done to investigate the risk factors associated with these poor maternal and neonatal outcomes. METHODS: A 7-day, international, prospective, observational cohort study was done in patients having caesarean delivery in 183 hospitals across 22 countries in Africa. The inclusion criteria were all consecutive patients (aged ≥18 years) admitted to participating centres having elective and non-elective caesarean delivery during the 7-day study cohort period. To ensure a representative sample, each hospital had to provide data for 90% of the eligible patients during the recruitment week. The primary outcome was in-hospital maternal mortality and complications, which were assessed by local investigators. The study was registered on the South African National Health Research Database, number KZ_2015RP7_22, and on ClinicalTrials.gov, number NCT03044899. FINDINGS: Between February, 2016, and May, 2016, 3792 patients were recruited from hospitals across Africa. 3685 were included in the postoperative complications analysis (107 missing data) and 3684 were included in the maternal mortality analysis (108 missing data). These hospitals had a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0·7 per 100 000 population (IQR 0·2-2·0). Maternal mortality was 20 (0·5%) of 3684 patients (95% CI 0·3-0·8). Complications occurred in 633 (17·4%) of 3636 mothers (16·2-18·6), which were predominantly severe intraoperative and postoperative bleeding (136 [3·8%] of 3612 mothers). Maternal mortality was independently associated with a preoperative presentation of placenta praevia, placental abruption, ruptured uterus, antepartum haemorrhage (odds ratio 4·47 [95% CI 1·46-13·65]), and perioperative severe obstetric haemorrhage (5·87 [1·99-17·34]) or anaesthesia complications (11·47 (1·20-109·20]). Neonatal mortality was 153 (4·4%) of 3506 infants (95% CI 3·7-5·0). INTERPRETATION: Maternal mortality after caesarean delivery in Africa is 50 times higher than that of high-income countries and is driven by peripartum haemorrhage and anaesthesia complications. Neonatal mortality is double the global average. Early identification and appropriate management of mothers at risk of peripartum haemorrhage might improve maternal and neonatal outcomes in Africa. FUNDING: Medical Research Council of South Africa.Medical Research Council of South Africa