Evolution of Experimental Design and Research Techniques in HIV-1 Reservoir Studies: A Systematic Review

Although HIV-1 has evolved from a deadly to a chronic disease over the past 20 years, an HIV-1 cure is still lacking due to the presence of persisting cellular viral reservoirs which are spread throughout the body in different anatomical compartments. Hence, the identification and characterization of these HIV-1 reservoirs were the focus of many studies during the past decades. In this review, a systematic literature screening and text mining approach were implemented to assess the evolution in experimental design of these HIV-1 reservoir studies. For this purpose, the online databases PubMed, Web of Science, and ClinicalTrials.gov were consulted and 1768 articles were identified, of which 106 are included in this review. We observed several evolutions that indicate a more structured approach of recent HIV-1 reservoir studies. This includes the use of well-characterized patient cohorts, tissue sampling at several time points and anatomical compartments, the inclusion of patients with different treatment status (on and off antiretroviral therapy), and the implementation of state-of-the-art research techniques such as single genome sequencing. In addition, there is an increased interest and sampling of lymphoid tissues and cerebrospinal fluid together with methods to investigate cellular subsets and HIV-1 sequences. Overall, this review describes an observed shift from detecting and quantifying HIV-1 toward a qualitative in-depth assessment of anatomical reservoirs and cellular subsets playing a role in HIV-1 persistence/latency. These trends coincide with the evolution in focus from controlling HIV-1 replication by currently available antiretroviral therapy toward HIV-1 curative strategies.