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Background Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART). Methods We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months. Results Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22–30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6–2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15–34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16–43%) infants in the POC group vs 7 (19%; 6–32%) in the SOC group (RR: 1.56; .7–3.50). Conclusions POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes. Clinical Trials Registration This trial is registered at https://clinicaltrials.gov (NCT02682810).

Background India lacks epidemiological information on the disease burden of pediatric HIV. The National AIDS Control Program (NACP) estimates the numbers of HIV-positive children as a proportion of adult persons living with HIV. A third of HIV-positive children die before their first birthday and a half before they reach their second birthday. The early detection of HIV is crucial for the prevention of morbidities, growth delays, and death among HIV-positive children. Methods The study aimed to estimate the disease burden of pediatric HIV among children in ‘A’ category district of a high HIV prevalence state. An ‘A’ category district is defined by the presence of > 1% HIV prevalence among the general population, as estimated by HIV Sentinel Surveillance. The study used an innovative three-pronged strategy combining cross-sectional and longitudinal methods. The overall burden of pediatric HIV was calculated as a product of cases detected multiplied by a net inflation factor, for each of three strategies. Results The existing pool of HIV infection in the district is estimated to be 3266 (95% CI: 2621–4197) HIV positive children Conclusions The study estimate of 0.23% HIV prevalence among children (0–14 years of age) is higher than the NACP estimates (0.02) and is 2.5 higher than the Karnataka state estimate (0.09)22. Similarly, the proportion of children among all persons living with HIV in Belgaum district is 10.4% in this study, as against 6.54% for India. The study methodology is replicable for other settings and other diseases.

Background Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART nonadherence is unknown. Methods Peripheral blood total HIV DNA from 164 early treated (day 0–21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART. We evaluated the impact of cART initiation timing on HIV reservoir size and decay, and on the risk of subsequent plasma viremia in cART-suppressed infants. Results Baseline HIV DNA (median 2.8 log10 copies/million peripheral blood mononuclear cells, range 0.7–4.8) did not correlate with age at cART initiation (0–21 days) but instead with maternal antenatal cART use. In 98 infants with plasma viral suppression on cART, HIV DNA half-life was 28 days. However, the probability of maintenance of plasma aviremia was low (0.46 at 12 months) and not influenced by HIV DNA load. Unexpectedly, longer time to viral suppression was associated with protection against subsequent viral rebound. Conclusions With effective prophylaxis against mother-to-child transmission, cART initiation timing in the first 3 weeks of life is not critical to reservoir size., Peripheral blood HIV DNA levels from 164 South African in utero HIV-infected infants showed that with antiretroviral mother-to-child transmission prophylaxis, combination antiretroviral therapy initiation timing in the first 3 weeks of life does not significantly influence latent HIV reservoir size.

Widespread availability of antiretroviral therapy among pregnant women living with HIV has greatly reduced the rate of mother-to-child transmission (MTCT) of HIV across the globe. However, while Joint United Nations Programme on HIV/AIDS has set targets to reduce the annual number of new pediatric HIV infections to fewer than 40,000 in 2018 and fewer than 20,000 in 2020, progress towards these targets has plateaued at an unacceptably high global estimate of greater than 160,000 children newly infected with HIV in 2018. Moreover, it has become clear that expansion of maternal antiretroviral therapy alone will not be sufficient to close the remaining gap and eliminate MTCT of HIV. Additional strategies such as maternal or infant passive and/or active immunization that synergize with maternal antiretroviral therapy will be required to end the pediatric HIV epidemic. In this review, we outline the landscape of existing maternal interventions and emerging maternal immune-based approaches to prevent MTCT of HIV.

ART interruption in children can occur especially in resource-limited settings for reasons including poor adherence, stock-outs, ART intolerance of non-pediatric formulas and pill size, as well as ultimately to test for HIV remission. Although early ART initiation is now standard of care in pediatric HIV management, very little is known on the effect of early ART initiation or subsequent interruption on brain development. This study aimed to investigate the effect of ART interruption on brain cortical thickness (CT) and folding in a subset of children from the Children with HIV Early antiRetroviral therapy (CHER) trial cohort who all started ART before 18 months of age. CHER participants in the neuroimaging follow-up study had magnetic resonance (MRI) scans on a 3T Siemens Allegra brain scanner at age 5.44 ± 0.37 years. MR images were processed using the automated cross-sectional stream in FreeSurfer v6.0 and vertex wise comparisons of CT and local gyrification indices (LGIs) were performed between HIV+ children and HIV- controls, as well as between HIV+ children on interrupted or continuous ART and controls. HIV+ children (n = 46) showed thicker cortex than HIV- children (n = 29) in bilateral frontal and left temporo-insular regions but lower LGIs in left superior and bilateral medial orbitofrontal cortex extending into rostral anterior cingulate. Children on interrupted ART (n = 21) had thicker cortex than HIV- controls in left frontal and right insular regions, but children on continuous treatment (n = 25) showed no difference from controls. Children on both interrupted and continuous ART showed region-specific alterations in LGI relative to controls. Cortical folding appears more sensitive than CT to early life events including early ART and interruption. However, immune health resilience in children can translate to long term preservation of morphometric brain development, especially for those on early and continuous treatment.

In eastern and southern Africa, much is unknown about implementation of nurse-initiated and managed antiretroviral therapy (NIMART). The purpose of this study was to identify perceived barriers and facilitators of NIMART for the prevention of mother-to-child transmission and pediatric HIV services in high-volume, high HIV-burden health facilities across this region. A total of 211 nurses, midwives, and nurse midwives and 62 supervisors from 30 health facilities in 11 countries participated in this mixed-methods evaluation. The findings show that although nurses, midwives, and nurse midwives clearly had the authority to provide NIMART services, they did not necessarily feel that they were well prepared and supported to do so. Deficits in supportive supervision and clinical mentorship were viewed as substantial challenges to effective provision of NIMART for the prevention of mother-to-child transmission and pediatric HIV services—particularly with respect to pediatric HIV services. Health facilities have important opportunities to advance NIMART practice through strengthening these aspects of in-service support.

Supplemental Digital Content is Available in the Text., Background: Although the World Health Organization recommends HIV-exposed infants receive a 6-week diagnostic test, few receive results by 12 weeks. Point-of-care (POC) early infant diagnosis (EID) may improve timely diagnosis and treatment. This study assesses the impact of routine POC versus laboratory-based EID on return of results by 12 weeks of age. Methods: This was a cluster-randomized stepped-wedge trial in Kenya and Zimbabwe. In each country, 18 health facilities were randomly selected for inclusion and randomized to timing of POC implementation. Findings: Nine thousand five hundred thirty-nine infants received tests: 5115 laboratory-based and 4424 POC. In Kenya and Zimbabwe, respectively, caregivers were 1.29 times [95% confidence interval (CI): 1.27 to 1.30, P < 0.001] and 4.56 times (95% CI: 4.50 to 4.60, P < 0.001) more likely to receive EID results by 12 weeks of age with POC versus laboratory-based EID. POC significantly reduced the time between sample collection and return of results to caregiver by an average of 23.03 days (95% CI: 4.85 to 21.21, P < 0.001) in Kenya and 62.37 days (95% CI: 58.94 to 65.80, P < 0.001) in Zimbabwe. For HIV-infected infants, POC significantly increased the percentage initiated on treatment, from 43.2% to 79.6% in Zimbabwe, and resulted in a nonsignificant increase in Kenya from 91.7% to 100%. The introduction of POC EID also significantly reduced the time to antiretroviral therapy initiation by an average of 17.01 days (95% CI: 9.38 to 24.64, P < 0.001) in Kenya and 56.00 days (95% CI: 25.13 to 153.76, P < 0.001) in Zimbabwe. Conclusions: POC confers significant advantage on the proportion of caregivers receiving timely EID results, and improves time to results receipt and treatment initiation for infected infants. Where laboratory-based EID systems are unable to deliver results to caregivers rapidly, POC should be implemented as part of an integrated testing system.

The World Health Organization has prioritized integrating tuberculosis (TB) and human immunodeficiency virus (HIV) services. Diagnosis of HIV/TB coinfection in children remains a challenge worldwide for numerous reasons. The care delivery value chain (CDVC) is an effective tool that can be applied as a systemic framework for assessing health care delivery. Our objective was to apply the CDVC framework to improve pediatric HIV/TB care at an HIV center in northern Togo that serves over 130 children and 1000 adults living with HIV. Using the CDVC framework, gaps in HIV/TB care were identified, and services related to screening and diagnosis were prioritized to implement 3 distinct quality improvement cycles. Primary outcomes included percentage of children screened for TB by medical providers and percentage of diagnostic sample results received at the HIV clinic for children and adults. Improvements in the TB diagnostic process were observed, resulting in a change of sputum sample results received for both children and adults from 25% at baseline to >88% at 3 months. Given the relative low associated costs, this QI approach may be applicable and feasible in other settings to target screening and diagnosis of TB for children living with HIV worldwide.

HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV.The study was a retrospective cohort study (study period 2004-2018). Cases of HIV + and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV + controls without SCD (HIV+/SCD-).Thirty-five HIV+/SCD + subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6 years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD + had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P = 0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD + and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD + cohort (P = 0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD + cohort showed a more rapid rise and higher total CD4 count (P = 0.012, regression analysis).The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD + achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.Le VIH et la drépanocytose (SCD) sont des causes importantes de morbidité et de mortalité en Afrique subsaharienne. Compte tenu de leurs rôles distincts dans la dérégulation immunitaire, notre objectif était de caractériser l'impact du SCD sur la présentation et la progression du VIH pédiatrique. MÉTHODES: Etude de cohorte rétrospective (période d'étude 2004-2018). Les cas de patients VIH+ atteints de SCD (VIH+/SCD+) ont été obtenus par analyse des dossiers électroniques dans une clinique pédiatrique du VIH à Kampala, en Ouganda et appariés dans une proportion 1:3 avec des témoins VIH+ sans SCD (VIH+/SCD-). RÉSULTATS: 35 sujets VIH+/SCD+ et 95 témoins VIH+/SCD- ont été analysés (39% de femmes (51/130), 3,6 ans d’âge (SD3,9)). Au départ, le stade clinique de l'OMS (64% de la cohorte totale au stade III/IV) et l'état nutritionnel (9,4% de malnutrition aiguë sévère) étaient similaires pour les deux groupes, tandis que les VIH+/SCD+ avaient un nombre de CD4 de base plus élevé mais non significatif (1036 (DS, 713) vs 849 (DS, 638) cellules/microlitre, p = 0,20, test t bilatéral). Il y a eu 19 décès, 6 (17%) VIH+/SCD+ et 13 (14%) VIH+/SCD-, avec des modèles non ajustés/ajustés ne montrant aucune différence significative. La progression nutritionnelle et la progression du stade clinique n'ont montré aucune différence significative entre les groupes. L'analyse de Kaplan-Meier a montré un taux d'échecs de traitement plus lent dans la cohorte VIH+/SCD+ (p = 0,11, test de survie log-rank). L'analyse de la trajectoire a montré que dans la période analysée, la cohorte VIH+/SCD+ a montré une augmentation plus rapide et un nombre total de CD4 plus élevé (p = 0,012, analyse de régression).L'étude suggère que SCD n'affecte pas négativement la progression du VIH chez les patients sous ART. De plus, les patients VIH+/SCD+ ont atteint un nombre plus élevé de CD4 et moins d'échecs de traitement du VIH, ce qui suggère que les effets physiologiques dus à la SCD pourraient atténuer la progression du VIH.

Purpose of Review Perinatal HIV-1 infection is associated with an increased risk for neurologic impairments. With limited access to clinical specimens, animal models could advance our understanding of pediatric central nervous system (CNS) disease and viral persistence. Here, we summarize current findings on HIV-1 CNS infection from nonhuman primate (NHP) models and discuss their implications for improving pediatric clinical outcomes. Recent Findings SIV/SHIV can be found in the CNS of infant macaques within 48 h of challenge. Recent studies show an impermeable BBB during SIV infection, suggesting neuroinvasion in post-partum infection is likely not wholly attributed to barrier dysfunction. Histopathological findings reveal dramatic reductions in hippocampal neuronal populations and myelination in infected infant macaques, providing a link for cognitive impairments seen in pediatric cases. Evidence from humans and NHPs support the CNS as a functional latent reservoir, harbored in myeloid cells that may require unique eradication strategies. Summary Studies in NHP models are uncovering early events, causes, and therapeutic targets of CNS disease as well as highlighting the importance of age-specific studies that capture the distinct features of pediatric HIV-1 infection.

PURPOSE OF REVIEW: In the absence of antiretroviral therapy (ART), more than 50% of perinatally HIV infected children die by two years of age. Early ART from infancy is therefore a global recommendation and significantly improves immune health, child survival and disease outcome. However, even early treatment does not prevent or eradicate the latent reservoir necessitating life-long ART. Adherence to life-long ART is challenging for children and longstanding ART during chronic HIV infection led to higher risks of non-AIDS co-morbidities and virologic failure in infected children. Thus, HIV-infected children are an important population for consideration for immune-based interventions to achieve ART-free remission and functional cure. This review summarizes how the uniqueness of the early life immune system can be harnessed for the development of ART-free remission and functional cure, which means complete virus control in absence of ART. In addition, recent advances in therapeutics in the HIV cure field and their potential for the treatment of pediatric HIV infections are discussed. RECENT FINDINGS: Preclinical studies and clinical trials demonstrated that immune-based interventions target HIV replication, limit size of virus reservoir, maintain virus suppression, and delay time to virus rebound. However, these studies have been performed so far only in carefully selected HIV-infected adults, highlighting the need to evaluate the efficacy of immune-based therapeutics in HIV-infected children and to design interventions tailored to the early life maturing immune system. SUMMARY: Immune-based therapeutics alone or in combination with ART should be actively explored as potential strategies to achieve viral remission and functional cure in HIV-infected pediatric populations.

BACKGROUND There are 170,000 children living with HIV in 2017 in Mozambique. Scaling-up HIV care requires effective retention along the cascade. We sought to evaluate the pediatric cascade in HIV care at the Manhica District Hospital. METHODS A prospective cohort of children

To assess the outcome of HIV-infected individuals attending one of the largest French pediatric HIV centers in 2016-2017 and to compare the rates of antiretroviral coverage and virological suppression with the UNAIDS targets.The clinical and immuno-virological status of 163 HIV-1-infected children and adolescents attending Necker Hospital in Paris, France, were investigated. Virological suppression was defined as an HIV-1 viral load50 copies/mL for at least six months. All genotypic resistance tests performed since birth were analyzed.Most patients were born in Sub-Saharan African countries (41.7%) or in France (38.0%). Their median age was 14 years [IQR 7.3-17.0]. Although 33.7% of individuals had a history of AIDS-defining clinical event(s), 86.5% of children/adolescents were free from HIV-related symptoms at their most recent evaluation. Antiretroviral coverage was high (98.2%; mainly including one integrase inhibitor [42.3%] or one protease inhibitor [23.9%]). At the last visit, most patients (82.8%) had normal CD4T lymphocytes counts (≥25%). Although 61.7% of antiretroviral-experienced children had resistance to≥1 drug class and 9.2% had triple-class resistance, 80.3% of patients receiving antiretrovirals for≥6 months (126/157) were virologically suppressed. International adoptees were more frequently virologically suppressed than other patients (96.0% versus 74.6%, P=0.02).Antiretroviral coverage exceeded the second UNAIDS 90 target aimed at ending the AIDS epidemic. The rate of virological suppression, one of the highest reported in children in high-income countries, is approaching the third UNAIDS 90 target and the rate observed in French HIV-infected adults on antiretrovirals.

Pediatric human immunodeficiency virus post-exposure prophylaxis is frequently indicated, but delays in medication receipt are common. Using plan-do-study-act cycles, we developed a multidisciplinary collaboration to reduce critical process delays in our pediatric emergency department. Interruptions decreased from a median 1 per month pre-intervention to zero per month during the intervention.

PurposeThe purpose of this study was to compare Words-in-Noise (WIN) data between young adults with perinatal HIV (PHIV) infection and those with PHIV exposure but uninfected (PHEU) and to evaluate associations between antiretroviral therapy (ART) exposures and WIN data.MethodThe WIN test and cognitive function were assessed in participants of the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol Up. Impaired WIN (IWIN) performance was defined as a signal-to-babble ratio of > +10 dB. Cognitive function was determined based on fluid cognition composite scores (FCCSs) and crystallized cognition composite scores, and < 70 was considered a fluid or crystallized cognitive impairment. Log binomial models were used to calculate the relative risks of IWIN between PHIV and PHEU.ResultsPHIV (n= 334) and PHEU (n= 52) participants had similar WIN thresholds and IWIN percentages. For young adults with FCCS ≥ 70, participants with PHIV were less likely to have IWIN for the better ear and worse ear as compared to participants with PHEU. For young adults with FCCS < 70, there was no association between HIV status and risk of IWIN for the better ear or worse ear. For those adults with crystallized cognition composite score of ≥ 70, young adults with PHIV were less likely to have IWIN for the better ear than young adults with PHEU; there was no association between HIV status and IWIN for the worse ear. For young adults with PHIV without a Centers for Disease Control and Prevention Class C diagnosis, a longer combination ART duration was associated with a higher risk of IWIN for the better ear.ConclusionsFor those without cognitive impairment, young adults with PHEU had poorer WIN thresholds than those young adults with PHIV. In young adults with PHIV who had no prior Centers for Disease Control and Prevention Class C diagnosis, a longer combination ART duration was associated with IWIN only in the better ear.

Nowadays, it is spreading the false perception that pediatric HIV infection has been almost completely disappeared in Italy, as well as in other Western countries, and it does not deserve the attention of the primary care pediatrician anymore. Hereby, we report the important role still played by the primary care pediatrician in management and prevention of pediatric HIV infection in Western countries.

P1093 is a multicenter, open-label, phase I/II study of pharmacokinetics, safety, and tolerability of dolutegravir plus an optimized background regimen in pediatric participants aged 4 weeks to

BACKGROUND Children living with HIV and taking antiretroviral therapy (ART) are a priority group for routine viral load (VL) monitoring. As per Lesotho guidelines, a VL ≥1000 copies/mL ("unsuppressed") should trigger adherence counseling and a follow-up VL; 2 consecutive unsuppressed VLs ("virologic failure") qualify for switching to second-line ART, with some exceptions. Here, we describe the pediatric VL cascade in Lesotho. METHODS In a prospective open cohort study comprising routine VL results from 22 clinics in Lesotho, we assessed outcomes along the VL cascade for children who had at least 1 VL test from January 2016 through June 2020. Data were censored on February 10, 2021. RESULTS In total, 1215 children received 5443 VL tests. The median age was 10 years (interquartile range 7-13) and 627/1215 (52%) were female; 362/1215 (30%) had at least 1 unsuppressed VL. A follow-up VL was available for 325/362 (90%), although only for 159/362 (44%) within 6 months of the first unsuppressed VL. Of those with a follow-up VL, 172/329 (53%) had virologic failure and 123/329 (37%) qualified for switching to second-line ART. Of these, 55/123 (45%) were ever switched, although only 9/123 (7%) were switched within 12 weeks of the follow-up VL. Delays were more pronounced in rural facilities. Overall, 100/362 (28%) children with an unsuppressed VL received a timely follow-up VL and, if required, a timely regimen switch. CONCLUSIONS Despite access to VL monitoring, clinical management was suboptimal. HIV programs should prioritize timely clinical action to maximize the benefits of VL monitoring.

Transitioning from pediatric to adult services is known to be associated with worsening of health outcomes and decreased retention in care among adolescents and youth living with HIV (AYLHIV). We aimed to identify factors associated with HIV care transition readiness among AYLHIV in care at a pediatric HIV clinic in Washington, DC. This retrospective cohort study from June 2019 through January 2021 collected demographic and clinical characteristics from the clinic database. We adapted the Transition Readiness Assessment Questionnaire (TRAQ; scored 1-4; 1 being the lowest level of preparedness) to evaluate transition readiness over time. We analyzed data using two-sided unadjusted two-sample and paired t-tests and adjusted analysis of variance (ANOVA). We included 103 AYLHIV (50.49% female; 100% non-Hispanic Black/African American; mean age = 19.54 ± 2.78 years; 81.55% virally suppressed). Mean baseline TRAQ score (2.32 ± 0.78) was associated with age (p 10 years (p = 0.013). Adjusted for covariates, older age (p < 0.0001), undetectable viral load (p = 0.0008), and presence of mental health condition(s) (p = 0.020) were associated with higher TRAQ scores. Lower improvement in transition readiness among youth with a longer history of HIV suggests that AYLHIV with perinatally acquired HIV might require additional support than those with horizontally acquired HIV.

Background Advanced HIV infection is associated with an inflammatory arthritis, however few reports have described this disorder in children. This study aimed to describe the clinical features of HIV arthropathy in a case series of children in South Africa and compare these with features of JIA. Methods Retrospective data were collected from HIV-infected children with HIV arthropathy enrolled in a Paediatric Rheumatology clinic in Cape Town, South Africa. Data from a recently described, published cohort of children with JIA enrolled in the same clinic were included for comparison. Ethical approval was granted by the Human Research Ethics Committee of the University of Cape Town, with a waiver for consent. Results Eleven cases of HIV arthropathy were identified. Cases predominantly affected boys (8/11), and the median age of onset was 10.3 years (IQR 6.9–11.6). Most cases presented in the setting of advanced immunosuppression, with a median absolute CD4+ count of 389 cells/uL (IQR 322–449) and median CD4+ proportion of 19.5% (IQR 14.8–25.0) at presentation. The clinical presentation was variable, with both oligoarthritis (6/11) and polyarthritis (5/11) being prevalent. All cases exhibited large joint involvement, which was usually asymmetrical. In addition, four children had asymmetrical small joint involvement. Associated features included enthesitis (4/11) and dactylitis (1/11). The most consistent laboratory feature was elevated acute phase reactants, and typical ultrasonographic findings were joint effusions and synovial hypertrophy. JIA and HIV arthropathy presented at a similar age, with median age at HIV arthritis onset of 10.3 years (IQR 6.9–11.6) versus 9.25 years (IQR 4.5–12.3) at arthritis onset in the JIA subgroup. HIV arthropathy cases were predominantly male (M/F ratio 3.0), whereas JIA cases had an equal sex distribution (M/F ratio 0.9). Oligo-articular disease was more frequently described in children with HIV arthropathy (55%), compared to those with JIA (38%). Conclusion In this series, most cases of HIV arthropathy exhibited asymmetrical large joint oligoarthritis or polyarthritis, and presented in older boys with advanced immunosuppression. HIV arthropathy appears to present at a similar age to JIA, with a comparable pattern of joint involvement to oligo-articular and poly-articular JIA subtypes.

PURPOSE OF REVIEW: Antiretroviral therapy (ART) scale-up has dramatically reduced rates of pediatric HIV mortality and morbidity. Children living with perinatally acquired HIV (PHIV) are now expected to live through adolescence and well into adulthood, such that adolescents now represent the largest growing population living with HIV. This review aims to discuss the prevalence and mechanisms for cardiometabolic co-morbidities in the setting of newer ART regimens and the research gaps that remain. RECENT FINDINGS: Data highlight the continued risks of subclinical cardiometabolic complications in PHIV in the setting of newer ART. Novel techniques in imaging and omics may help identify early cardiometabolic abnormalities in this young population and potentially identify early changes in the mechanistic pathways related to these changes. SUMMARY: Further studies to determine risk and management strategies of the cardiometabolic effects in PHIV adolescents, beyond ART, are warranted. Focus should be on prevention of these complications in youth to avoid new epidemic of diabetes and cardiovascular disease when these youth become aging adults.

Antiretroviral treatment has undergone major changes in the last 20 years, from monotherapy, to dual therapy and finally to triple therapy. Lately, more focus has been placed on better, more well-tolerated combinations and formulations. As in most other disciplines in medicine, the development of paediatric HIV dosages and formulations always tends to lag behind adult research. Twenty years ago, it could take several years before data were available to enable the use of life-saving antiretrovirals in children. Paediatricians, being ever resourceful, were not prepared to let their paediatric patients suffer despite the lack of data or formulations and so made a plan. This article describes some of the trials and tribulations that we went through trying to make sure that our paediatric HIV patients not only survived but thrived. Clinicians treating paediatric patients today have it so much easier because of what our colleagues and their patients went through in those early days.

From April to June 2019, a total of 909 new HIV infections were identified in Larkana, Pakistan; 86% was children younger than 15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019.For cases, we selected a systematic random sample of 100 HIV-positive children from the screening list. We chose 2 age-matched and sex-matched controls from the neighborhood of each HIV-positive case. All selected children were tested using the World Health Organization-approved rapid diagnosis test algorithm. We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression.The ages of the selected children ranged from 1 month to 10 years. More than 90% of both HIV+ and HIV- children had received outpatient health care from MBBS-qualified private physicians. Eighty-three percent of HIV+ children versus 46% of HIV- children had received health care from one private physician [adjusted odds ratio (aOR) = 29, 95% confidence interval (95% CI): 10 to 79]. Intravenous infusions during the last outpatient visit were reported by 29% of case versus 7% of controls (aOR 57, 95% CI: 2.9 to1000), whereas no case children and 17% of control children had received only intramuscular injections (aOR 0, 95% CI: 0 to 41). Among cases, 94% had been given infusions through a drip set compared with 85% of control children (aOR = 7.7, 95% CI: 2.3 to 26). Infusions had been administered with reused IV drip sets in 70% of cases compared with 8% of controls (aOR = 197, 95% CI: 16 to 2400).Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners were suggested.

Objective Objective assessment of neurocognitive lags in pediatric HIV patients and its correlation with various clinical, social and familial factors. Methods Ninety-eight school-aged children living with HIV (CLHIV) (age 7-18 years) attending regional pediatric HIV clinic were observed for neurocognitive lag using Raven's Standard Progressive Matrices by the same trained instructor. Sociodemographic data, mode of transmission, clinical staging, CD4 count, highly active antiretroviral therapy (HAART) duration were recorded and analyzed in the well-performing group and under-performing group. Results 29.6% of children had definitive neurocognitive lag. The proportion of older children (11-18 years) in the under-performing group was significantly high (P = 0.007). The mean CD4 counts were low in the under-performing group (P = 0.001). Other socioeconomic factors could not be specifically correlated with neurocognitive lag in either of the groups. Conclusion CLHIV has a significant neurocognitive lag, which is accentuated in the upper age group. Findings point toward declining intellectual gains with increasing age in CLHIV.

Background: Suicidal behavior and HIV/AIDS are vital public health challenges especially in low and middle-income countries. As suicide in adults is perturbing for those closest to them, this sentiment is much more intense and generalized in the case of a child or adolescent. Knowledge of factors associated with suicidal ideation in HIV infected children and adolescents may inform suicide prevention strategies needed to improve their quality of life. This study aimed to assess the prevalence and factors associated with suicidal ideation among HIV infected children and adolescents attending a pediatric HIV clinic in Uganda.Methods: Data from a sample of 271 children and adolescents aged 6–18 years living with HIV/AIDS attending a pediatric HIV clinic was analyzed. Child characteristics and clinical variables were assessed using a socio-demographic questionnaire and medical records respectively. Suicidal ideation and depression were assessed using the Child Depression Inventory. The types of behavioral problems and the parent–child relationship were assessed using Child Behavioral Check List (6–18 years) and the Parent Child Relationship Scale respectively. Child exposure to different stressful life events was assessed with a series of standardized questions. Logistic regression models were used to explore factors independently associated with suicidal ideation.Results: The prevalence of suicidal ideation was 17%. In the multivariate analysis; Child exposure to family or friend’s death (prevalence rate ratio (PRR = 2.02; 95% CI, 1.01–4.03), p = 0.046), HIV wasting syndrome (PRR = 0.39; 95% CI, 0.21–0.75, p = 0.04), Depression (PRR = 1.08; 95% CI, 1.03–1.12, p = 0.001), Anxiety symptoms (PRR = 1.10; 95% CI, 1.01–1.20, p = 0.024) and Rule breaking behavior (PRR = 1.06; 95% CI, 0.99–1.13, p = 0.051) were independently associated with suicidal ideations.Conclusion: The prevalence of suicidal ideation among children and adolescents living with HIV/AIDS is substantial. Children and adolescents with exposure to family or friend’s death, those with higher depression scores, anxiety symptoms and rule breaking behavior are more likely to report suicidal ideation. Those with HIV wasting syndrome were less likely to report suicidal ideation. There is urgent need for HIV care providers to screen for suicide and link to mental health services.

There are about 2.1 million children infected with HIV globally and about 120,000 deaths annually. Nigeria has one of the highest rates of pediatric HIV infection globally. Pretreatment HIV drug resistance data inform the choice of first- and second-line antiretroviral therapy (ART) regimens. This study investigated the prevalence of HIV drug-resistant strains among ART-naive children in Ibadan, Nigeria. A total of 20 children aged15 years were enrolled. Demographic, clinical, and laboratory data were documented. Total nucleic acid was extracted from blood samples after which amplification of HIV-1 pol gene was done using polymerase chain reaction. Amplified gene was sequenced using big dye sequencing method. The sequenced HIV-1 pol gene was typed and analyzed for identification of mutations indicative of drug resistance across the different classes of ART. HIV-1 RNA pol gene was successfully amplified in 12/20 (60%) children. All were identified as HIV-1 and the subtypes were G and CRF 02AG, recombinant of 02_AG/G and recombinant of 02_AG/A1. Drug-resistant mutations (DRMs) were identified in 4/12 (33%). Three out of the four mutations were identified as non-nucleoside reverse transcriptase inhibitors DRM (K103N), whereas the fourth had nucleoside reverse transcriptase inhibitors DRM (M184V). Results from this preliminary study show that drug resistance among ART-naive children is a problem in Ibadan. Pretreatment drug resistance testing is desirable in children before initiation of ART to guide effective treatment.

To assess the prevalence of psychiatric problems among adolescents living with HIV (ALHIV).Questionnaire-based cross-sectional study conducted at pediatric HIV clinic of a tertiary care hospital. Participants: 101 ALHIV between 10-18 years of age.Of the 101 ALHIV, 12 (11.88%) met criteria for psychiatric disorders, of which dysthymi (5,41.6%) and oppositional defiant disorder (6,50%) were the commonest. Father of 7 (58.34%) and mother of 8 (66.6%) screen positive patients were dead as compared to 22 (24.7%) and 13 (14.6%) of screen negative patients (P=0.016 and P=0.0003, respectively).Psychiatric problems are common in ALHIV in the age group more than 15 years.

Nigeria has high rate of pediatric HIV but there is a dearth of empirical data on the mode of HIV transmission. Association for Reproductive and Family Health (ARFH), with the support of USAID, is implementing a project to mitigate the impact of HIV on Orphans and Vulnerable Children (OVC) affected/infected with HIV/AIDS in Akwa-Ibom, Lagos, and Rivers states, Nigeria. The mode of HIV transmission among their OVC was examined. A retrospective study of enrolled OVC was done in the three states. HIV OVC whose mothers are HIV positive were classified under those who got HIV through vertical transmission, otherwise horizontal. The data was summarized using descriptive statistics. Significance of association between qualitative variables and mode of transmission was determined using Chi-square test. Among the 387 OVC HIV positives who enrolled, there was a slight preponderance of males (50.6%); and about 42% were aged 10 - 17 years and 26%

In South Africa, prevention of mother to child transmission (PMTCT) has reduced MTCT from 3.6% in 2011 to 1.3% in 2017. However, there are challenges in reaching vulnerable HIV-positive children; t...

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations. Issues relating to drug optimisation for neonatal prophylaxis and paediatric treatment, and those relating to the investigation of novel antiretrovirals in adolescents and pregnant and lactating women were also discussed. Continued focus on identifying, prioritising, and providing access to optimal antiretroviral formulations suitable for infants, children, and adolescents is key to ensuring that global HIV treatment targets can be met.

Objective Dolutegravir is recommended worldwide as a first-line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants of dolutegravir-treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada. Design The Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies. Setting Paediatric HIV clinics. Population Live-born infants born in Canada to WLWH between 2007 and 2017. Methods Data on mother-infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites. Main outcome measures Congenital anomalies. Results Of the 2423 WLWH, 85 (3.5%, 95% CI 2.85-4.36%) had non-chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women who were on ART in their first trimester (3.9%, CI 1.7-7.6%) or later in the pregnancy (3.9%, 95% CI 2.6-5.6%). Four of the 80 (5.0%, 95% CI 1.4-12.3%) neonates born to WLWH on dolutegravir during the first trimester had congenital anomalies, none were neural tube defects (95% CI 0.00-3.10%). Conclusion Despite recent evidence raising a safety concern, this analysis found no signal for increased congenital anomalies. Tweetable abstract Five percent of the infants of Canadian women living with HIV on dolutegravir at conception had congenital anomalies; none had neural tube defects.

Metabolic perturbations in HIV-exposed uninfected (HEU) obese youth may differ from those in the general obese pediatric population.Metabolic parameters of obese (body mass index Z-score95th percentile) HEU youth in the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study were compared with a matched sample of obese youth from the US National Health and Nutrition Examination Survey (NHANES). We evaluated systolic and diastolic hypertension (blood pressure ≥90th percentile for age, sex, and height), total cholesterol200 mg/dL, high-density lipoprotein cholesterol35 mg/dL, low-density lipoprotein cholesterol130 mg/dL, triglycerides (TGs)150 mg/dL, and Homeostatic Model Assessment-Insulin Resistance4.0. Modified Poisson regression models were fit to quantify the prevalence ratio (PR) of each outcome comparing the 2 cohorts, adjusting for confounders.The blood pressure outcome analytic subgroup included 1096 participants (n = 304 HEU), the total cholesterol and high-density lipoprotein cholesterol subgroup 1301 participants (n = 385 HEU), and the low-density lipoprotein cholesterol, TG, and Homeostatic Model Assessment-Insulin Resistance subgroup 271 (n = 83 HEU). After adjustment, obese HEU youth had a higher prevalence of systolic and diastolic hypertension [PR = 3.34, 95% confidence interval (CI): 2.48 to 4.50; PR = 2.04, 95% CI: 1.18 to 3.52, respectively], but lower prevalence of insulin resistance (PR = 0.67, 95% CI: 0.54 to 0.85) and hypercholesterolemia (PR = 0.67, 95% CI: 0.44 to 1.01) compared with obese NHANES youth.In the United States, obese HEU youth seem to have an increased risk of hypertension, but lower risk of insulin resistance and hypercholesterolemia, compared with a general obese pediatric population. Monitoring for cardiovascular morbidity in adulthood may be warranted in HEU children.

With the success of evolving cART, HIV has become a chronic condition, however, children vertically infected with HIV have been shown to have developmental difficulties and disabilities. This study aimed to investigate the prevalence of disabilities among a group of HIV infected children in South Africa and whether they are being referred to and accessing support services. A cross-sectional study was conducted at a paediatric HIV clinic in Johannesburg. Parents were interviewed about their child using the Ten Question Screen for Disability questionnaire along with a follow-up questionnaire. Data from the child’s clinic file were recorded. Of the 200 children whose parents were interviewed, 50.5% experienced disabilities, where 58.4% of those had more than one co-existing disability. The most commonly reported disabilities were, developmental delay (27%), cognitive and behaviour difficulties (21%), communication difficulties (17%) and physical disabilities (13%). Of the children who reported disabi...

Pediatric HIV remains a significant global concern, with 160,000 new infections annually. Accelerating Children's HIV/AIDS Treatment (ACT) provided a strategic response to the "treatment gap" for children. We examined whether activities under ACT increased testing and identification of youth living with HIV (YLWH). Family AIDS CareEducation Services implemented ACT across 130 health facilities in western Kenya between October 2015 and September 2016, providing: HIV-testing counselors and space; training on the Family Information Table (FIT) and chart audits; community outreach testing; and text message reminders for pregnant women. We analyzed the number of youths tested and identified with HIV over time and between intervention and control sites using interrupted time series analysis. We tested 268,312 youths (7,183 infants18 months; 145,833 children 18 months to 9 years; and 115,296 adolescents 10-14 years). Mean monthly number tested per health facility increased from 2.8 to 7.2 (

The increased coverage of antiretroviral therapy has resulted in a decrease in the positive predictive value (PPV) and diagnostic sensitivity of early infant diagnosis assays. To evaluate the diagnostic performance of the Aptima HIV-1 Quant DX assay (Aptima) in detecting HIV infection at birth. The study was a cross-sectional laboratory based evaluation using whole blood DBS specimens. Samples were collected from HIV-exposed neonates at birth at two paediatric facilities in Gauteng between 1st March 2018 – 31st January 2020. Performance of the Aptima compared to the Cobas® AmpliPrep/Cobas® TaqMan HIV-1 Qualitative Test v2.0 was calculated using a two-by-two table and reported as proportions with 95% confidence intervals. A total of 363 infants met the inclusion criteria of which 4 (1.1%) had an Aptima result discordant with CAP/CTM HIV status: two (50%) negative and two (50%) positive. The Aptima assay had a sensitivity of 93.75% (95% CI: 79.19%-99.23%), specificity of 99.4% (95% CI: 97.83%-99.93%), PPV of 93.75% (95% CI: 78.98%-98.36%), negative predictive value of 99.4% (95% CI: 97.73%-99.84%), and overall accuracy of 98.9% (95% CI: 97.2%-99.7%). The Aptima yielded an error code on 37 (10.19%) results, of which 35 (94.59%) were resolved on repeat testing. Of the 32 HIV-detected specimens, 20 had a plasma VL result available (18 on Abbott and 2 on Cobas). The absolute median difference was 0.66 log10 (IQR: 0.36-1.71). The Aptima demonstrated good EID performance and can be considered as a qualitative EID assay.

Background Early infant diagnosis of HIV infection is challenging in sub-Saharan Africa, particularly in rural areas, leading to delays in diagnosis and treatment. Use of a point-of-care test would overcome many challenges. This study evaluated the validity of a novel point-of-care p24 antigen detection test (LYNX) in rural and urban settings in southern Zambia. Methods Two studies were conducted: a cross-sectional study from 2014 to 2015 at Macha Hospital (LYNX Hospital study) and a longitudinal study from 2016 to 2018 at 12 health facilities in Southern Province, Zambia (NSEBA study). In both studies, children attending the facilities for early infant diagnosis were enrolled and a blood sample was collected for routine testing at the central lab and immediate on-site testing with the LYNX test. The performance of the LYNX test was measured in comparison to nucleic acid-based testing at the central lab. Results In the LYNX Hospital study, 210 tests were performed at a median age of 23.5 weeks (IQR: 8.9, 29.0). The sensitivity and specificity of the test were 70.0 and 100.0%, respectively. In the NSEBA study, 2608 tests were performed, including 1305 at birth and 1222 on children ≥4 weeks of age. For samples tested at birth, sensitivity was 13.6% (95% CI: 2.9, 34.9) and specificity was 99.6% (95% CI: 99.1, 99.9). While specificity was high for all ages, sensitivity increased with age and was higher for participants tested at ≥4 weeks of age (80.6%; 95% CI: 67.4, 93.7). Children with positive nucleic acid tests were more likely to be negative by the LYNX test if their mother received antiretroviral therapy during pregnancy (60.7% vs. 24.2%; p = 004). Conclusions Considering the high specificity and moderate sensitivity that increased with age, the LYNX test could be of value for early infant diagnosis for infants ≥4 weeks of age, particularly in rural areas where centralized testing leads to long delays. Point-of-care tests with moderate sensitivity and high specificity that are affordable, easy-to-use, and easily implemented and maintained should be developed to expand access to testing and deliver same-day results to infants in areas where it is not feasible to implement nucleic acid-based point-of-care assays.

The lack of sufficient knowledge of mother to child transmission (MTCT) of human immunodeficiency virus (HIV) among pregnant women is considered a major contributor to new pediatric HIV infections globally, and increasing HIV related infant mortality especially in developing countries. Nigeria has the highest number of new HIV infections among children in the world. This study was designed to examine the spatial pattern and determinants of acquisition of sufficient knowledge of MTCT and prevention of mother to child transmission (PMTCT) in Nigeria. The data used in the study were extracted from the 2018 Nigeria Democratic Health Survey. The spatial modeling was through a Bayesian approach with appropriate prior distributions assigned to the different parameters of the model and inference was through the integrated nested Laplace approximation technique (INLA). Results show considerable spatial variability in the acquisition of sufficient knowledge of MTCT and its prevention with women in the southwestern and southeastern part of the country having higher likelihood. The nonlinear effects findings show that acquisition of sufficient knowledge of MTCT and PMTCT increased with age of women and peaked at around age 35yearswhere it thereafter dropped drastically among the older women. Furthermore, sufficient knowledge of MTCT and PMTCT was found to be driven by ethnicity, respondents’ education and wealth status.

This review aimed to determine: whether EF is affected in children and adolescents (2–24-years-old) with perinatal HIV infection, perinatal HIV exposure without infection, and behaviourally acquired HIV. A systematic review (PROSPERO number: CRD42017067813) was conducted using 11 electronic databases (01.01.1981–09.07.2019) and 8 conference websites. Primary quantitative studies with EF scores on cognitive tasks and/or behavioural report measures were included. Meta-analyses were performed by EF subtype and subpopulations compared. 1789 records were found. Sixty-one studies were included in the narrative synthesis; 32 (N = 7884 participants) were included in meta-analyses. There was a distinct pattern of reduced EF in those with perinatal HIV infection on antiretroviral therapy compared to controls: pooled effect sizes were largest for verbal and visuospatial working memory, with smaller effects on planning, inhibitory control and set-shifting. Data were limited for other HIV-affected subpopulations. Perinatal HIV infection is associated with reduced EF with varying effect sizes for the different EF subtypes.

Background and Objective: Over the past 15 years, there have been three major updates to the South African national guidelines for the management of human immunodeficiency virus (HIV) in children. The purpose of this study is to describe the clinical characteristics of children who were initiated on antiretroviral therapy (ART) in Bloemfontein, South Africa, following these national treatment guidelines. Methods: Clinical information during initiation of ART in children aged 0-13 years was obtained from five HIV clinics in Bloemfontein from 2004 to 2019 as part of the establishment of an antiretroviral (ARV) pediatric registry at the University of the Free State. Data were analyzed for patient demographics, clinical presentation (World Health Organization (WHO) HIV-staging, growth rate and comorbid conditions), types of investigations done, and medicines prescribed. Results: The number of children initiated on ART increased from 168 in the period 2004-2009 to 349 (107.8%) in 2010-2014, and then dropped to 162 in the period 2015-2019. The increase in 2010-2014 was mainly in the 1000 copies/ml). There was increased use of ABC/3TC/LPVr in the < 3-year age group and ABC/3TC/EFV in the > 3-year age group. There was reduced use of the stavudine and other regimens. Conclusion and Global Health Implications: More children were started on ART and safer ARV drugs. Children under 2 years were the most debilitated by HIV, and there was an increase in HIV prevalence among children > 5 years. New strategies for the prevention and management of HIV among children in these two age groups are needed. Copyright © 2021 Walubo et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in this journal, is properly cited.

Background A large number of HIV-infected children continue to die despite reported scale-up of paediatric HIV services. Aim The trend in attrition among children enrolled in an anti-retroviral therapy (ART) programme was evaluated. Methods This was a retrospective review of children enrolled into NAUTH ART programme between 2003 and 2019. Results 1114 children 50% of attrition was recorded within 6 months of care. Advanced WHO stage, young age, non-initiation on ART or period of enrolment (P p = 0.026) were associated with attrition in bivariate analysis. Apart from caregiver category, these factors remained significant in multivariate analysis. Most LTFU could not be reached on phone. Among those contacted, common reasons for being lost to follow-up were financial constraints, caregiver loss, claim to divine healing, family disharmony/child custody issues and relocation of family/child. Conclusion/recommendation Attrition rate was high and was mostly due to LTFU. Predictors of attrition were late presentation, young age, delay in ART initiation and financial constraints. Efforts should be intensified at early diagnosis, linkage to care and implementation of “test and treat” strategy. Innovative child centered approaches should be adopted to enable the HIV-infected children remain in care despite challenges which can truncate treatment.

BACKGROUND: Financial incentives (FI) can motivate desirable health behaviors, including adult HIV testing. Data regarding the effectiveness of FI for HIV testing in children, who require urgent testing to prevent mortality, are lacking. METHODS: In a 5-arm unblinded randomized controlled trial, adults living with HIV attending 19 HIV clinics in Western Kenya, with children 0-12 years of unknown HIV status, were randomized with equal allocation to $0, $1.25, $2.50, $5 or $10. Payment was conditional on child HIV testing within 2 months. Block randomization with fixed block sizes was used; participants and study staff were unblinded at randomization. Primary analysis was intent-to-treat, with predefined primary outcomes of completing child HIV testing and time to testing. RESULTS: Of 452 caregivers, 90, 89, 93, 92 and 88 were randomized to $0, $1.25, $2.50, $5.00, and $10.00, respectively. Of those, 31 (34%), 31 (35%), 44 (47%), 51 (55%), and 54 (61%) in the $0, $1.25, $2.50, $5.00, and $10.00 arms, respectively, completed child testing. Compared to the $0 arm, and adjusted for site, caregivers in the $10.00 arm had significantly higher uptake of testing (Relative risk: 1.80 [95%CI 1.15, 2.80] p=0.010). Compared to the $0 arm, and adjusted for site, time to testing was significantly faster in the $5.00 and $10.00 arms (Hazard ratio: 1.95 [95%CI 1.24, 3.07] p=0.004, 2.42 [95%CI 1.55, 3.79] p

This study developed a novel child-friendly drug delivery system for pediatric HIV treatment: a liquid, taste-masked, and solvent-free monoolein-based nanoparticles formulation containing indinavir (0.1%).Adherence to antiretroviral therapy by pediatric patients is difficult because of the lack of dosage forms adequate for children.Monoolein-based nanoparticles were developed. The particle size, zeta potential, pH, drug content, small angle X-ray scattering, stability,Monoolein-based formulations containing indinavir had nanosized particles with 155 ± 7 nm, unimodal particle size distribution, and polydispersity index of 0.16 ± 0.03. The zeta potential was negative (-31.3 ± 0.3 mV) and pH was neutral (7.78 ± 0.01). A 96% drug incorporation efficiency was achieved, and the indinavir concentration remained constant for 30 days. Polarized light microscopy revealed isotropic characteristics. Transmission electron microscopy images showed spherical shaped morphology. Small-angle X-ray scattering displayed a form factor broad peak. Indinavir had a sustained release from the nanoparticles. The system was nonirritant and was able to mask drug bitter taste.Monoolein-based nanoparticles represent a suitable therapeutic strategy for antiretroviral treatment with the potential to reduce the frequency of drug administration and promote pediatric adherence.

An amendment to this paper has been published and can be accessed via the original article.

Background: As many as 40% of the 1 million children living with HIV (CLHIV) receiving antiretroviral treatment (ART) in resource limited settings have not achieved viral suppression (VS). Kenya has a large burden of pediatric HIV with nearly 140,000 CLHIV. Feasible, scalable, and cost-effective approaches to ensure VS in CLHIV are urgently needed. The goal of this study is to determine the feasibility and impact of point-of-care (POC) viral load (VL) and targeted drug resistance mutation (DRM) testing to improve VS in children on ART in Kenya. Methods: We are conducting a randomized controlled study to evaluate the use of POC VL and targeted DRM testing among 704 children aged 1–14 years on ART at health facilities in western Kenya. Children are randomized 1:1 to intervention (higher frequency POC VL and targeted DRM testing) vs. control (standard-of-care) arms and followed for 12 months. Our primary outcome is VS (VL