Detection of Inducible Replication-Competent HIV-1 Subtype C Provirus Despite Long-Term Antiretroviral Treatment in Perinatally Infected Adolescents in Botswana

AIDS Res Hum Retroviruses. 2021 Jan;37(1):16-23. doi: 10.1089/AID.2020.0097. Epub 2020 Oct 19.

Abstract

Although antiretroviral therapy (ART) effectively suppresses HIV replication, the latent reservoir remains the barrier to HIV eradication. It remains unknown whether long-term ART impacts levels of inducible replication-competent provirus. To address this knowledge gap, we assessed the proviral reservoir in HIV-1 perinatally infected adolescents having received ART for >13 years. We recruited 15 vertically infected adolescents living with HIV in Botswana. Historical viral load, CD4+ T cell count, and treatment data were retrieved from their outpatient medical records. Inducible replication-competent proviruses from cryopreserved peripheral blood mononuclear cells were quantified using a TZM-bl based assay (TZA). Total proviral DNA copies were quantified using droplet digital PCR. The mean age of study participants was 16 years (standard deviation = 0.7) and median CD4+ T cell count at enrollment was 784 [interquartile range (IQR) = 728.8-1,288] cells/mm3. Median age at ART initiation was 8 (IQR = 6-12) months. Fourteen (93%) participants had HIV-1 RNA <400 copies/mL at the time of enrollment in the study. A median of 19 (IQR = 18-27) HIV-1 RNA measurements were available per participant. Six (40%) participants displayed viral suppression at all clinic visits since initiating ART, whereas the remaining 9 (60%) had one or more clinic visits with detectable HIV-1 RNA. The median inducible replication-competent provirus count was 7.4 infectious units per million cells (IQR = 6.7-19.2), and did not differ significantly by either complete or incomplete viral suppression (7.2 vs. 7.4, p = .86), or by age at ART initiation (7.4 if <12 months, 11.2 if >12 months, p = .85). The median total HIV DNA count was 129.1 copies per million cells (IQR = 18.9-212.3). Our data suggest that long-term ART initiated within the 1st year in perinatally infected infants did not eliminate proviral DNA or inducible replication-competent proviruses.

Keywords: HIV; adolescent; antiretroviral therapy; inducible replication competent; reservoir; viral suppression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Botswana
  • CD4-Positive T-Lymphocytes
  • HIV Infections* / drug therapy
  • HIV-1* / genetics
  • Humans
  • Leukocytes, Mononuclear
  • Proviruses / genetics
  • Viral Load