Long-term immunologic and virologic follow-up of two HIV-infected individuals who underwent treatment interruption of antiretroviral therapy

Modern antiretroviral therapy (ART) is highly effective in suppressing human immunodeficiency virus (HIV) but cannot eradicate the virus in infected individuals1-4. Therefore, elucidation of the mechanism(s) by which certain infected individuals suppress HIV replication in the absence of ART is of significant interest5,6. We present case reports of two HIV-infected individuals who underwent analytical treatment interruption (ATI) and suppressed plasma viremia for extended periods. Phylogenetic analyses of HIV env sequences in Subject 04 suggested evidence for sequential reactivation of viral reservoirs that led to genetically distinct viral rebound. Subject 04 showed higher frequencies of polyfunctional HIV-specific and lower levels of exhausted CD8+ T cells when compared to those of Subject 30. However, Subject 30 exhibited highly potent plasma-IgG-mediated neutralization activity against the autologous virus. Subject 04 initiated undisclosed self-administration of sub-optimal ART on day 1,030 and Subject 30 experienced sudden plasma viral rebound 1,434 days post ATI due to HIV superinfection. Our data provide insight into highly dichotomous nature of two post-ATI controllers and highlight the importance of frequent monitoring of undisclosed use of ART and superinfection during the treatment interruption phase.