No evidence of HIV replication in children on antiretroviral therapy

• Published in: The Journal of clinical investigation Vol. 127; no. 10; pp. 3827 - 3834
• Main Authors: Van Zyl, Gert U, Katusiime, Mary Grace, Wiegand, Ann, McManus, William R, Bale, Michael J, Halvas, Elias K, Luke, Brian, Boltz, Valerie F, Spindler, Jonathan, Laughton, Barbara, Engelbrecht, Susan, Coffin, John M, Cotton, Mark F, Shao, Wei, Mellors, John W, Kearney, Mary F
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.10.2017
• Subjects: Acquired immune deficiency syndrome; AIDS; Anti-Retroviral Agents - administration & dosage; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biomedical research; Child; Child, Preschool; Children; Dosage and administration; Drug resistance; Drug therapy; Evolution; Female; Genetic aspects; Health aspects; HIV; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - metabolism; HIV-1 - physiology; Human immunodeficiency virus; Humans; Infant; Infant, Newborn; Lymph nodes; Male; Pediatric HIV infections; Phylogeny; Replication; Viremia; Viremia - drug therapy; Viremia - genetics; Viremia - metabolism; Virus replication; Virus Replication - drug effects
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI94582

It remains controversial whether current antiretroviral therapy (ART) fully suppresses the cycles of HIV replication and viral evolution in vivo. If replication persists in sanctuary sites such as the lymph nodes, a high priority should be placed on improving ART regimes to target these sites. To investigate the question of ongoing viral replication on current ART regimens, we analyzed HIV populations in longitudinal samples from 10 HIV-1-infected children who initiated ART when viral diversity was low. Eight children started ART at less than ten months of age and showed suppression of plasma viremia for seven to nine years. Two children had uncontrolled viremia for fifteen and thirty months, respectively, before viremia suppression, and served as positive controls for HIV replication and evolution. These latter 2 children showed clear evidence of virus evolution, whereas multiple methods of analysis bore no evidence of virus evolution in any of the 8 children with viremia suppression on ART. Phylogenetic trees simulated with the recently reported evolutionary rate of HIV-1 on ART of 6 × 10-4 substitutions/site/month bore no resemblance to the observed data. Taken together, these data refute the concept that ongoing HIV replication is common with ART and is the major barrier to curing HIV-1 infection.