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<jats:p> Since 2001, HIV incidence has declined by 33% worldwide, and more than 9.7 million people with HIV have gained access to treatment. <jats:xref ref-type="fn">*</jats:xref> The Joint United Nations Programme on HIV/AIDS launched the Getting to Zero strategy (2011–2015) that includes zero new infections, zero deaths from HIV, and zero discrimination. Aspirational statements such as “the end of AIDS” have also prevailed. However, do such pronouncements help or hurt? Do they motivate action, or do they risk incredulity, leading to inaction? Do such aspirations epitomize hype or hope? </jats:p>

<jats:p>A vaccine against HIV-1 must prevent infection against genetically diverse virus strains. Two approaches are currently being pursued to elicit antibody-mediated protection: vaccines that induce potent and broadly reactive neutralizing antibodies (bnAbs) or vaccines that induce “conventional antibodies,” which are less potent and broadly neutralizing in comparison. Although bnAbs may provide the greatest level of protection, their structural and genetic characteristics make their elicitation through vaccination a major challenge. In contrast, conventional HIV-1 antibodies have been induced by vaccination and correlated with reduced HIV-1 infection in a phase III vaccine trial. Here, I present evidence that both approaches should be pursued with equal vigor.</jats:p>

<jats:p> Antiretroviral therapy (ART) is able to suppress HIV-1 replication indefinitely in individuals who have access to these medications, are able to tolerate these drugs, and are motivated to take them daily for life. However, ART is not curative. HIV-1 persists indefinitely during ART as quiescent integrated DNA within memory CD4 <jats:sup>+</jats:sup> T cells and perhaps other long-lived cellular reservoirs. In this Review, we discuss the role of the immune system in the establishment and maintenance of the latent HIV-1 reservoir. A detailed understanding of how the host immune system shapes the size and distribution of the viral reservoir should lead to the development of a new generation of immune-based therapeutics, which may eventually contribute to a curative intervention. </jats:p>