Modern antiretroviral therapies can confer effective suppression of HIV-1 infection. However,
HIV-infected people discontinuing antiretroviral therapy experience a rebound of virus from a
persistent reservoir. Characterizing this reservoir constitutes a crucial step towards developing a
cure, and we hypothesized that assessing the diversity and tropism of rebound virus would
provide insight into the types of cells that likely house the viral reservoir as well as reservoir
diversity. We examined 10 rebound samples from a project within the large-scale AIDS Clinical
Trials Group and used single genome amplification and Primer ID deep sequencing to assess the
genetic diversity of the env gene, which encodes the HIV-1 envelope protein, among rebounding
virus. Samples from the same patients with viral suppression due to antiretroviral therapy were
also available. Most rebound virus populations showed significant diversity. All env genes
examined were isoforms that would require cells to express high surface levels of the CD4
receptor for entry, consistent with the current hypothesis that virus is selectively replicated in
CD4+ T cells. These results indicate that most people discontinuing therapy release a diverse
population of virus, and this released virus targets CD4+ T cells rather than myeloid cells, which
tend to last longer. Research indicates that a small proportion of viruses have evolved to
efficiently enter myeloid cells. Current HIV-1 cure strategies focus on reactivating latent HIV-1
and targeting the resultant virus. It is essential to understand the features of rebound viruses
because they are the first such targets.Bachelor of Science in Public Healt
