RESUMEN
The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, consistency, and validity, and the safety of the clinical research or trial participants and laboratory staff, as well as ensures adherence to regulatory requirements. This article describes the application of the DAIDS GCLP Guidelines, the DAIDS Integrated Laboratory Oversight Framework, and the coordinated efforts of the collaborative oversight team of laboratory experts to support and monitor the performance of over 175 participating laboratories worldwide. Data from two self-administered online surveys conducted in 2017 and 2023 assessed the laboratory staff's experience implementing the GCLP Guidelines. The results of the 2017 survey were instrumental in informing changes to GCLP audit activities and promoting harmonization in the approach to laboratory oversight. A key finding from the 2023 survey results is the preference for hybrid GCLP training, encompassing face-to-face and online modules. Overall, both surveys acknowledged satisfaction with applying and implementing GCLP Guidelines. The need to effectively disseminate information about DAIDS laboratory oversight requirements to support the improved implementation of GCLP Guidelines was notable from both survey results. The collaborative team of laboratory experts and the integrated oversight approach promote knowledge-sharing and accountability to support the application of the GCLP Guidelines and compliance monitoring. The systematic implementation of the integrated laboratory oversight activities helped identify valuable lessons for improving laboratory performance and opportunities to strengthen quality oversight for laboratories participating in clinical research or trials.
RESUMEN
It is unclear why discordant immunologic and virologic responses occur during therapy for human immunodeficiency virus (HIV) infection. This study examined whether markers of immune activation and naive/memory lymphocyte subsets at study baseline could predict discordance between HIV type 1 (HIV-1) RNA and CD4+ lymphocyte responses at week 24 of antiretroviral therapy. Ten diverse, prospective antiretroviral studies with 1007 evaluable subjects were included. Subsets of subjects at increased risk for discordance were identified by recursive partitioning. The strongest predictor of more-favorable immunologic than virologic responses was a lower baseline CD4+ lymphocyte count. Weaker predictors in small subsets of subjects were fewer activated CD4+ lymphocytes and fewer CD8+ lymphocytes. Conversely, the strongest predictors of more-favorable virologic than immunologic responses were higher baseline CD4+ lymphocyte count and percentage. Additional predictors in some analyses were higher CD8+ lymphocyte count or percentage and lower HIV-1 RNA concentrations. Baseline markers of immune activation and naive/memory lymphocyte subsets had limited ability to predict subsequent discordance.