New Insights From Perinatal HIV: A Way Forward for HIV Cure Research

(See the Major Article by Khetan et al on pages e1396–406.) Of the 41 million people living with HIV-1, about 2.4 million are children and adolescents. Many children and adolescents with perinatal HIV infection struggle to adhere to antiretroviral therapy (ART) and rates of sustained virologic suppression are lower than in adults. As a result, there is a critical need for research into how to achieve ART-free remission or HIV cure in children with perinatal infection. In both children and adults with HIV, a long-lived reservoir of infected cells prevents ART from curing the infection. Immediately after acquisition, HIV integrates into the host genome and persists in cells as proviral DNA. Initial studies of the HIV reservoir focused on measuring total HIV DNA in people on ART. However, almost all of that DNA is defective; only the small fraction of proviruses that are intact can replicate and cause viral rebound when ART is withdrawn. In recent years, multiplex PCR assays have been developed that differentiate intact from defective proviruses [1]. New insights into HIV persistence have come from studies of the intact and defective proviral landscape in people with HIV.