Master of Public Health - MPH / Background: According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 340 000 children between 0-14years of age are living with HIV in South Africa as of 2019. Decentralization of HIV services was included in South Africa’s paediatric guidelines since 2010 in a bid to improve access to care. The current study sought to address the paucity of Eastern Cape (EC) data on the outcomes of down-referred paediatric antiretroviral therapy (ART) patients. These outcomes included retention in care (RIC) and virological suppression after 12 months Methodology: This retrospective analysis was conducted in the Buffalo City Municipality (BCM) district of the EC. The study population included HIV positive males and females, 0-14 years of age at transfer, who were initiated on ART at a tertiary or a regional hospital and subsequently down-referred, between June 2013 and June 2017. Data were collected from electronic databases at the facilities (Tier.net), patient files and patient registers. A descriptive analysis was performed using SPSS Statistics software version 26. Results: In total, 80.1% of patients successfully down-referred to a primary healthcare (PHC) facility, in a median of 42 days. Of those, 95.4% of patients were retained in care at 6 months and 93.1% at 12 months after arrival, with a median of 4 scheduled monthly visits missed. For those with results, virological suppression was maintained in 96.7% of patients at 6 months, 92.2% at 12 months and 96.2% for the entire post-transfer period of 2-14 months. In the 2-14 months post down-referral only 76.9% of patients had at least one viral load (VL) result and 50.3% had one CD4 result. For those with results, immune response (IR) to ART was maintained in 100% of patients at 6 months, 94.3% at 12 months and 97.7% in the 2-14 month period post successful down-referral. Conclusions: This study confirmed that loss to follow-up (LTFU) and treatment interruption at the point of transfer are significant risk factors for paediatric ART patients. This study also demonstrated high levels of RIC once patients had successfully down-referred. However, missed clinic visits suggest possible treatment interruptions for many patients post down-referral. While good virological and immunological responses to ART were maintained at the PHC facilities, suboptimal VL and CD4 monitoring was highlighted by the low proportion of available results. Therefore, while there are a number of issues to address, this study confirms that down-referral is a feasible option for up-scaling paediatric HIV care in the EC.

L’obstacle majeur à l’éradication du VIH est l’existence de réservoirs cellulaires du VIH, qui échappent au traitement et à la réponse immunitaire de l’hôte. Ce réservoir s’établit très tôt dans l’infection, menant typiquement à la destruction d’un grand nombre de lymphocytes T CD4+. Cependant, une faible proportion de ces cellules retourne à l’état quiescent en ayant intégré le génome viral. La taille et l’évolution du réservoir chez l’adulte ont été bien élucidées. Cependant, on en sait moins sur la taille et la distribution du réservoir du VIH, et sur l’impact de l’initiation précoce de la thérapie antirétrovirale combinée (TARc) sur ces dernières dans la population infantile. Cet essai s’inscrit dans le cadre de l’étude prospective multicentrique EPIC4 (Early Pediatric Initiation, Canada Child Cure Cohort Study), qui a recruté 221 enfants infectés par la voie verticale dans neuf centres pédiatriques canadiens. Nous soumettons l’hypothèse que l'initiation très précoce de la TARc chez l’enfant infecté par le VIH permettrait de réduire le réservoir à ses plus bas niveaux, menant à un meilleur contrôle de la réplication virale suite à une éventuelle interruption de traitement. Nous avons obtenu des corrélations positives entre la taille du réservoir viral lymphocytaire sanguin du VIH-1 et l'âge de l’initiation de la TARc et l'âge à la suppression virale soutenue (SVS). Les niveaux des réservoirs sont négativement corrélés à la proportion de la vie sous TARc efficace et à la proportion de la vie sous SVS et au compte de lymphocytes T CD4+. Nous avons montré également qu’un traitement initié précocement dans les premiers six mois de vie serait un facteur de prédictions d’une suppression virale plus rapide et plus soutenue. Nos résultats confirment que l’initiation précoce de la TARc et le maintien à long terme de la suppression virale stable sont des facteurs clés conduisant à une taille limitée du réservoir viral. Par ailleurs, nous démontrons pour la première fois que la taille du réservoir inductible du VIH-1 mesurée dans les lymphocytes T CD4+ du sang périphérique après stimulation avec un analogue de prostratine corrèle significativement avec celle mesurée en ADN proviral. Ainsi, nous avons validé une nouvelle technique de mesure de réservoir inductible qui est rapide et moins coûteuse et surtout requiert un faible volume de sang donc semble très prometteuse pour des études sur le VIH-1 pédiatrique. / The major barrier to eradicating HIV is the existence of cellular reservoirs of HIV, which escape the treatment and immune response of the host. This reservoir is established very early in the infection, typically leading to the destruction of a large number of CD4+ T cells. However, a small proportion of these cells return to quiescent state after integrating the viral genome. The size and evolution of the reservoir in adults have been well understood. However, we know less about the size and distribution of the HIV reservoir, and the impact of early initiation of combination antiretroviral therapy (cART) on it in the infant population. Our study is a part of the Early Pediatric Initiation Canada, Child Cure Cohort (EPIC4); a prospective, multicenter study, which enrolled 221 vertically HIV-1 infected children in nine Canadian pediatric centers. We hypothesize that very early initiation of cART in HIV-infected children would reduce the reservoir to its lowest levels, leading to better control of viral replication following a possible interruption of treatment. A strong positive correlation was observed between reservoir size in peripheral blood and both the age at initiation of cART and the age at which sustained viral suppression (SVS) was achieved. We found a strong negative correlation between the size of the viral reservoir and the proportion of life spent on effective cART or the proportion of life with SVS and CD4+ T lymphocytes count. This study shows that starting cART within 6 months from birth is a predictor of faster and more sustained virological suppression in infants. Our findings suggest that early cART initiation in infants and long-term viral suppression are key factors leading to limited viral reservoir size. Furthermore, we established for the first time that the size of the inducible HIV-1 reservoir in peripheral blood CD4+ T lymphocytes of children, quantified by the prostratin analogue stimulation test, correlates with the size obtained using proviral DNA measurement. Thus, we have validated a new inducible reservoir measurement technique that is fast, less expensive, and, importantly requires a lower blood volume. This assay could be very promissing for evaluating inducible HIV-1 reservoirs in pediatric HIV-1 studies.