Efforts to cure HIV-1 infections are hampered by the latent viral reservoir, which can lead to viral rebound in infected individuals following discontinuation of antiretroviral therapy. The development of strategies to eliminate the persistent HIV-1 reservoir is challenging, partly owing to a lack of accurate and scalable reservoir assays, with current assays possibly underestimating the reservoir size. Siliciano and colleagues report the development of a method to detect infected cells and to distinguish intact proviruses (defined by the authors as proviruses that lack overt fatal genetic defects such as large deletions and hypermutations) from the vast excess of defective proviruses. Moreover, the assay revealed differential dynamics of intact and defective proviruses, emphasizing the importance of direct measurement of intact proviruses.