Browsing by Author "Veldsman, Kirsten Abigail"
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- ItemInvestigating HIV-1 DNA and HIV-1 RNA kinetics with ultrasensitive assays in very early treated infants and determining predictors associated with kinetics in older treated children(Stellenbosch : Stellenbosch University, 2019-12) Veldsman, Kirsten Abigail; Van Zyl, Gert Uves; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.Background The impact of early initiation of antiretroviral therapy (ART) on HIV-1 persistence has been characterised in adult cohorts and in well-suppressed children on continuous therapy. These studies have shown that early ART initiation may limit the size of the latent HIV reservoir that is established early in infection. Early initiation of therapy causes a more rapid decay of infected cells and may increase the probability of post-treatment control which is valuable for HIV-1 remission strategies. However, there remains limited information from longitudinal studies from resource limited settings especially investigating the effects of therapy initiation within days of birth on HIV-1 DNA and viral decay kinetics. Our aims were to investigate total HIV-1 DNA and HIV-1 RNA decay in very early treated infants and in older treated children who underwent therapy interruption and to determine potential predictors influencing decay. Methods Participants were selected from two cohorts; eleven infants from a public health sector birth diagnosis program who initiated ART at median of four days and 31 children from a clinical trial study where children were randomised to elective time-limited therapy or delayed continuous therapy. Peripheral blood mononuclear cells (PBMCs) were processed at scheduled study visits and plasma viral load measured using commercial diagnostic assays. Following DNA extraction from PBMCs, total HIV-1 DNA was quantified using a sensitive real-time PCR assay adapted for HIV-1 subtype C targeting a conserved region in the HIV-1 genome (integrase gene). Generalised linear and mixed effect regression models; and Spearman rank correlations were used to study decay and associating predictors. Statistical tests were implemented in R software version 3.4.3. Results In our study we observed that infants who initiated therapy at around five days had a faster decay rate than children who initiated ART at around five months of age, the half-life (t ½) HIV-1 DNA was 2.7 months and 9.2 months, respectively. In the multivariate model, high pre-treatment HIV-1 DNA level (p<0.001) and an increase in HIV-1 DNA concentration during the period of therapy interruption (p<0.01) were independent significant predictors of slower subsequent HIV-1 DNA decay. In contrast, children who received prolonged initial treatment for 96 weeks had a faster decay after reinitiating on therapy (p=0.02). Conclusion This study provided some of the first longitudinal data of HIV-1 DNA decay in children from a resource limited setting. We suggest early treatment as an important modifiable factor in determining HIV-1 DNA decay. Furthermore, we show that very early diagnosis and subsequent therapy initiation, when achieving adequate virological suppression, in the early stages of infection may be valuable in limiting the persistence of long-lived HIV-1 infected cells.