An analysis of the HIV testing cascade of a group of HIV-exposed infants from birth to 18 months in peri-urban Khayelitsha, South Africa.

BACKGROUND: Despite the reduction of HIV mother-to-child transmission, there are concerns regarding transmission rate in the breastfeeding period. We describe the routine uptake of 6 or 10 (6/10) weeks, 9 months and 18 months testing, with and without tracing, in a cohort of infants who received HIV PCR testing at birth (birth PCR) (with and without point of care (POC) testing) in a peri-urban primary health care setting in Khayelitsha, South Africa. METHODS: In this cohort study conducted between November 2014 and February 2018, HIV-positive mothers and their HIV-exposed babies were recruited at birth and all babies were tested with birth PCR. Results of routine 6/10 weeks PCR, 9 months and 18 months testing were followed up by a patient tracer. We compared testing at 6/10 weeks with a subgroup from historical cohort who was not tested with birth PCR. RESULTS: We found that the uptake of 6/10 weeks testing was 77%, compared to 82% with tracing. When including all infants in the cascade and comparing to a historical cohort without birth testing, we found that infants who tested a birth were 22% more likely to have a 6/10 weeks test compared to those not tested at birth. There was no significant difference between the uptake of 6/10 weeks testing after birth PCR POC versus birth PCR testing without POC. Uptake of 9 months and 18 months testing was 39% and 24% respectively. With intense tracing efforts, uptake increased to 45% and 34% respectively. CONCLUSION: Uptake of HIV testing for HIV-exposed uninfected infants in the first 18 months of life shows good completion of the 6/10 weeks PCR but suboptimal uptake of HIV testing at 9 months and 18 months, despite tracing efforts. Birth PCR testing did not negatively affect uptake of the 6/10 weeks HIV test compared to no birth PCR testing.

Characterizing the double-sided cascade of care for adolescents living with HIV transitioning to adulthood across Southern Africa.

INTRODUCTION: As adolescents and young people living with HIV (AYLH) age, they face a "transition cascade," a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where "transition" may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when "transition" to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. METHODS: We included AYLH aged <16 years at enrolment, receiving antiretroviral therapy (ART) within International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) sites (2004 to 2017) with no history of transferring care. Using the ages of 16, 18, 20 and 22 years as proxies for "transition to autonomy," we compared the outcomes: no gap in care (≥2 clinic visits) and viral suppression (HIV-RNA <400 copies/mL) in the 12 months before and after each age threshold. Using log-binomial regression, we examined factors associated with no gap in care (retention) in the 12 months post-transition. RESULTS: A total of 5516 AYLH from 16 sites were included at "transition" age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y, in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y: adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). CONCLUSIONS: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood.

Lamivudine monotherapy as a holding regimen for HIV-positive children.

BACKGROUND: In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes. METHODS: We describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART. FINDINGS: We included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3-14.6), duration on cART was 3.6 years (IQR 2.0-5.9) and median CD4 count was 605.5 cells/µL (IQR 427-901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/µL (95% CI 37.7-55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/µL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3-73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART. INTERPRETATION: Most patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available.

New and Repurposed Drugs for Pediatric Multidrug-Resistant Tuberculosis. Practice-based Recommendations.

It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.

Paediatric HIV treatment failure: a silent epidemic.

Paediatric antiretroviral treatment (ART) failure is an under-recognized issue that receives inadequate attention in the field of paediatrics and within HIV treatment programmes. With paediatric ART failure rates ranging from 19.3% to over 32% in resource limited settings, a comprehensive evaluation of the causes of failure along with approaches to address barriers to treatment adherence are urgently needed. In partnership with the local Department of Health, a pilot programme has been established by Medecins Sans Frontieres (MSF) in Khayelitsha, South Africa, to identify and support paediatric HIV patients with high viral loads and potential treatment failure. Through detailed clinical and psychosocial evaluations and adherence support with an innovative counselling model, treatment barriers are identified and addressed. Demographic and clinical characteristics from the cohort show a delayed median start date for ART, prolonged viraemia including a large number of patients who have never achieved viral load (VL) suppression, a low rate of regimen changes despite failure, and a high percentage of pre-adolescent and adolescent patients who have not gone through the disclosure process. Stemming this epidemic of paediatric treatment failure requires programmatic responses to high viral loads in children, starting with improved "case finding" of previously undiagnosed HIV-infected children and adolescents. Viral load testing needs to be prioritized over CD4 count monitoring, and flagging systems to identify high VL results should be developed in clinics. Clinicians must understand that successful treatment begins with good adherence, and that simple adherence support strategies can often dramatically improve adherence. Moreover, appropriate adherence counselling should begin not when the child fails to respond to treatment. Establishing good adherence from the beginning of treatment, and supporting ongoing adherence during the milestones in these children's lives is key to sustaining treatment success in this vulnerable HIV-infected patient population.

Echocardiographic diagnosis of persistent fifth aortic arch.

We describe echocardiography and computerized tomographic imaging findings in the two subtypes of fifth aortic arch in infants. In the first form, the fifth aortic arch creates a systemic to systemic connection extending from the ascending to the descending aorta. When this form appears in isolation, it does not cause hemodynamic disturbance, although associated cardiac lesions, such as aortic coarctation or interruption and patent ductus arteriosus, may influence the clinical presentation. In the second form the fifth aortic arch connects the systemic and pulmonary circulations from persistent connections between the embryological fifth and sixth arches, which may cause significant hemodynamic disturbance from left to right shunting. Although this form has been associated with a wide array of congenital cardiac lesions, this is the first description of 5th aortic arch in association with atrioventricular septal defect and double outlet right ventricle.