Finding a pathway to HIV cure among adolescents on long-standing ART in Botswana through reservoir analysis, analytic treatment interruption, and biomarker assessment

Abstract Adolescents living with HIV-1, many of whom began antiretroviral treatment (ART) in early life, are an ideal group to benefit from novel HIV-1 treatment approaches and curative strategies. However, a better understanding of HIV-1 persistence into adolescence following continuous ART in childhood is critical for the development of effective cure strategies. In this K43 application, I propose to develop and get trained on laboratory techniques and next generation sequencing techniques to advance an HIV-1 cure research program in Botswana with specific aims to 1) first identify adolescents with low reservoir without detectable intact virus (Type I controllers) or those with a blocked and locked reservoir profile (with detectable intact proviruses with non-genic chromosomal integration (Type II controllers) from a cohort of adolescents who were perinatally infected with HIV-1 and having been on ART since the first 2 years of life. 2) Evaluate how the reservoir changes over time in the same adolescent cohort living with HIV-1C while for those with ‘blocked and locked’ reservoir profile, if they agree, I will enroll them into the Tatelo Plus ATI study (U01AI179561) to test the hypothesis that those with a ‘blocked and locked’ reservoir profile (Type II) may be post-treatment controllers and evaluate how their reservoir evolves pre and post ATI; and 3) identify biomarkers associated with the potential for Type I or Type II control. I am originally from Botswana and I hold a PhD in Immunology and Virology, Master’s degree in Immunology, and a Bachelor’s degree in Medical Microbiology. I completed my postdoctoral fellowship at Harvard T H Chan School of Public Health and the Ragon Institute in 2022 and have now returned to my home country Botswana, where I am in the process of setting up an adolescent HIV-1 cure research program and planning to become an independent investigator at the Botswana Harvard Health Partnership. This proposal will most importantly support my mentored career development and assist me advance the HIV cure research in Botswana.