Evaluation of HIV-1 DNA levels among adolescents living with perinatally acquired HIV-1 in Yaounde, Cameroon: A contribution to paediatric HIV cure research in Sub-Saharan Africa

Background: With the advent of antiretroviral therapy (ART), most children living with HIV in sub-Saharan Africa (SSA) are growing toward adolescence, with scarcity of evidence on the size of viral reservoirs to enhance paediatric cure research strategies. This study aims to compare HIV-1 proviral DNA levels according to virological response among adolescents living with perinatally acquired HIV-1 (ALPHIV) and identify associatedfactors in the Cameroonian context. Methods: In this observational cohort study, HIV-1 RNA viremia and CD4 + T-cell count were assessed through RTPCR and flow cytometry respectively at three time-points over 18 months of observation. At the third time-point, 80 randomly-selected participants were classified as with viremia ( >= 50 HIV-1 copies/mL; n = 40) or without viremia ( <50 HIV-1 copies/mL; n = 40); immune -competent ( >= 500 CD4 + T cells/mm 3 ) or immunocompromised ( <500 CD4 (+) T cells/mm 3 ). Among these participants, total HIV -1 DNA load was quantified through droplet digital PCR using Bio-Rad QX200. Results: Of the 80 randomly -selected adolescents, median [IQR] age was 15 (13-17) years, 56.2% were female, duration on ART was 9.3 [5.4-12.2] years. Among the 40 viremic ones (median viremia 7312 [283-71482]) HIV1 copies/ml, 75.0% (30/40) were in virological failure (>= 1000 HIV -1 copies/ml), while median of CD4 T cells were 494 [360-793] cell/mm 3 with 48.8% (39/80) immunocompromised. No significant variation in HIV -1 RNA viremia and CD4 T cell count was observed between the three time -points, and 13.7% (11/80) adolescents remained aviremic and immune -competent throughout (stable adolescents). A positive and moderate correlation (r = 0.59; p < 0.001) was found between HIV -1 DNA levels and HIV1 RNA viremia. Regarding the CD4 T cell count, a negative and weak correlation (r = -0.28; p = 0.014) was found with HIV -1 DNA loads only among adolescents with viremia. Starting ART within the first year of life, ART for over 9 years and aviremia appear as predictors of low HIV -1 DNA loads. Conclusion: Among ALPHIV, high HIV -1 RNA indicates an elevated viral reservoir size, representing a drawback to cure research. Interestingly, early ART initiation and longer ARTduration lead to sustained viral control and limited HIV -1 reservoir size. As limited size of viral reservoir appears consistent with viral control and immune competence, adolescents with sustained viral control (about 14% of this target population) would be candidates for analytical ART interruptions toward establishing paediatric post -treatment controllers in SSA.