Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

BACKGROUND: Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p=0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary

Delayed recognition of Judah Folkman’s hypothesis on tumor angiogenesis: when a Prince awakens a Sleeping Beauty by self-citation

Judah Folkman is considered the father of angiogenesis research. However, his hypothesis on tumor angiogenesis initially met with considerable skepticism. Scientific resistance has been described in the sociology of science, and leads to delayed recognition of pioneering work. In bibliometrics, delayed recognition is characterized by papers referred to as “sleeping beauties”. Sleeping beauties do not achieve recognition in terms of citations until they are awakened a few years after their original publication. The study of sleeping beauties is necessary to understand scientific knowledge better. The present paper explores the extent to which the phenomenon of delayed recognition affected Folkman’s body of work by analyzing his scientific production and the citation life of his publications. Citation analysis shows that Folkman’s landmark paper published in 1971 is a sleeping beauty. Scientometric analysis was combined with a qualitative analysis of the Folkman case in order to shed light on the reasons behind this delayed recognition, and the awakening of the “Sleeping Beauty” by a “Prince”, thus attracting a lot of attention in terms of citations. Interestingly, the fact that Judah Folkman was one of the co-authors of the Prince paper challenges the practice of excluding self-citations when conducting bibliometric analysis. By continuously citing his own paper after years of sleep, Folkman demonstrated his persistence and belief in the importance of his theory. Constancy and continuity in research are important components in ensuring the acceptance of unpopular hypotheses and the development of new research fields