OLA-Simple : a software-guided HIV-1 drug resistance test for low-resource laboratories

Background: HIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels. Methods: The oligonucleotide ligation assay (OLA)-Simple kit was developed for detection of HIVDR against first-line non-nucleoside/nucleoside reverse transcriptase inhibitors and validated on 672 codons (168 spedmens) from subtypes A, B, C, D, and AE. The kit uses dry reagents to facilitate assay setup, lateral flow devices for visual HIVDR detections, and in-house software with an interface for guiding users and analyzing results. Findings: HIVDR analysis of specimens by OLA-Simple compared to Sanger sequencing revealed 99.6 +/- 0.3% specificity and 98.2 +/- 0.9% sensitivity, and compared to high-sensitivity assays, 99.6 +/- 0.6% specificity and 86.2 +/- 2.5% sensitivity, with 2.6 +/- 0.9% indeterminate results. OLA-Simple was performed more rapidly compared to Sanger sequencing (<4 h vs. 35-72 h). Forty-one untrained volunteers blindly tested two specimens each with 96.8 +/- 0.8% accuracy. Interpretation: OLA-Simple compares favorably with HIVDR genotyping by Sanger and sensitive comparators. Instructional software enabled inexperienced, first-time users to perform the assay with high accuracy. The reduced complexity, cost, and training requirements of OLA-Simple could improve access to HIVDR testing in low-resource settings and potentially allow same-day selection of appropriate antiretroviral therapy

Profiles of mortality among Chinese hypertensive patients in Hong Kong: a cohort study

We studied the profiles of all-cause and cardiovascular (CVS) mortality among users of different antihypertensive classes in a Chinese population. From electronic patient records, a cohort study was conducted among 18,338 patients who ever newly prescribed an alpha-blocker, thiazide diuretic, beta-blocker, calcium channel blocker (CCB) or agents acting on the renin-angiotensin system (RAS) without drug discontinuation or switching in the public primary-care sector in a large Territory of Hong Kong during January 2004-June 2007. The odds ratios of mortality (all-cause and CVS) were evaluated according to the prescribed antihypertensive drug classes by Cox proportional hazards regression analyses. A total of 823 deaths (4.5%) were reported during the study period. The crude proportions of all-cause mortality were highest in alpha-blockers (6.2%) and CCB (5.7%), but lowest in beta-blockers (2.8%). Compared with CCB, patients on thiazide diuretics were shown to have statistically significantly lower all-cause (adjusted hazard ratios (aHRs) 0.75, 95% CI 0.60, 0.93, P=0.010) and CVS mortality (aHR 0.40, 95% CI 0.21, 0.78, P=0.007), but the 95% CI of the odds ratios of the major drug classes overlapped. When each drug class was used as a reference group, or when patients with only uncomplicated hypertension were included, their respective 95% CI similarly overlapped. Antihypertensive drug classes were associated with statistically comparable odds of all-cause and CVS mortality. This finding from real-life clinical practice further supports the position statements from international guidelines, which recommend that the major antihypertensive drug classes are suitable for initiating pharmacotherapy for the management of hypertension