Characterising the genetic composition of persistent proviral reservoir cells in adolescents from Botswana living with HIV1-C infection following long-term ART and viral suppression: advancing HIV-1 cure research

Catherine Koofhethile’s current research is setting out to characterise in detail the genetic composition of the proviral reservoir in adolescents from Botswana who acquired HIV-1C perinatally and initiated antiretroviral therapy (ART) within the first year of life, on long-term ART > 15 years and been virally suppressed for nearly two decades. Current research on HIV-1 reservoirs suggests that the quality rather than the quantity of the reservoir can potentially reveal more information on the mechanisms of HIV-1 persistence. While the size of the reservoir in this adolescent population has been previously quantified, what is still understudied in HIV-1C infection is the genetic composition of the reservoir that allows HIV-1 to persist in these adolescents undergoing long-term ART. Koofhethile will determine the frequency and evolution of genome-intact proviruses (potentially infectious virus) as well as determine the chromosomal location sites of those genome-intact proviruses. 

With previous SANTHE collaborative funding, Koofhethile studied this same cohort of adolescents and showed that there were inducible replication competent proviruses present in these adolescents despite early ART initiation, long-term ART and long-standing viral suppression. Out of the 35 adolescents assessed, six adolescents were found to be virally suppressed, while the rest of the individuals experienced viral blips during the treatment. Preliminary data suggest that the size of the reservoir in the six adolescents that are virally suppressed is limited when compared to adult cohorts of Elite controllers and long-term ART treated adults. Additionally, genome-intact proviruses have only been detected in one adolescent. She is therefore hoping to determine where these genome intact proviruses are integrated in the host genome. She also hopes to expand the cohort to assess more cells.

This work has the potential to produce detailed characterisation of the intact reservoir that might reveal possible mechanisms of HIV persistence and therefore enhance HIV cure research. Koofhethile anticipates that the outcomes of this work will enable identification of potential candidates for the analytical treatment interruption protocol that she plans to implement as the next stage of this research.

Koofhethile wants people to stay optimistic about a cure. She says that people living with HIV must remain on ART while the researchers and scientists continue to pursue different avenues to find a more permanent solution. “Governments should put in more money to support researchers and scientists must strengthen collaborations and work together towards advancing HIV cure research,” she says.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.