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Background It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year. Methods We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P <.05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded. Results We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry–funded trials were more likely to be double-blinded (28.1% vs 10.3%; P =.03) and to describe missing data handling (78.5% vs 59.0%; P =.02). The overall risk of bias was low in 96 of 160 studies (60.0%). Conclusions ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence. [ABSTRACT FROM AUTHOR]

HIV persists in tissues during antiretroviral therapy (ART), but the relative contribution of different anatomical compartments to the viral reservoir in humans remains unknown. We performed an extensive characterization of HIV reservoirs in two men who donated their bodies to HIV cure research and who had been on suppressive ART for years. HIV DNA is detected in all tissues, with large variations across anatomical compartments and between participants. Intact HIV genomes represent 2% and 25% of all proviruses in the two participants and are mainly detected in secondary lymphoid organs, with the spleen and mediastinal lymph nodes harboring intact viral genomes in both individuals. Multiple copies of identical HIV genomes are found in all tissues, indicating that clonal expansions are common in anatomical sites. The majority (>85%) of these expanded clones are shared across multiple tissues. These findings suggest that infected cells expand, migrate, and possibly circulate between anatomical sites. [Display omitted] • In people on ART, half the HIV genomes in tissues are clonally expanded • Genetically intact HIV proviruses are more often found in lymphoid tissues • Identical proviral sequences are frequently found in distant tissues Dufour et al. study viral reservoirs by analyzing multiple samples from two men who donated their bodies for HIV cure research. They show that genetically intact proviruses are more often found in lymphoid organs. Moreover, half of the HIV genomes in tissues are clonally expanded and are frequently located in distant compartments. [ABSTRACT FROM AUTHOR]