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We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 sociodemographically matched HIV-negative controls), completed a tabletbased neurocognitive test battery. Control-derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T-cell (expression of CD38 and HLA-DR on CD4+ and CD8+) activation and gut markers. Spearman rank correlations and median regressions examined associations between test performance and immune activation. The median [IQR] age was 15 [13-16] years, and 40% were girls. The median time on antiretroviral therapy was 10 years [7-11] for PHIV; 87% had viral load <50 copies/mL. Compared with controls, global z-scores were lower among PHIV (P0.05) and significantly worse on tests of executive functioning and delayed recall (P's ≤ 0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r = 0.21, P=0.04), attention, processing speed, and motor speed (r = 0.2-0.3, P≤0.01). T-cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r=0.2-0.4, P≤ 0.04). In PHIV, after adjusting for age, sex, and antiretroviral therapy duration, activated CD4 T cells remained associated with worse memory (B-0.3, 95% CI: -0.55 to 0.07, P 0.01). PHIV with virologic suppression on antiretroviral therapy shows evidence of worse neurocognitive test performance compared with controls. Monocyte and T-cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV, which has not been previously investigated in this setting. [ABSTRACT FROM AUTHOR]

There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure. In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered. Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9). Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Identifying determinants of longitudinal HIV viral load (VL) trajectories using group-based trajectory modeling (GBTM) can inform clinical strategies and mechanisms of nonadherence among children. Methods: Children under 12 months old who were newly diagnosed with HIV were enrolled in the Optimizing Pediatric HIV therapy cohort (NCT00428116) from 2007 to 2010. Children initiated antiretroviral therapy at enrollment, and VL was assessed every 3 months for 24 months post–antiretroviral therapy and every 6 months thereafter up to 8 years old. VL trajectory groups were defined using GBTM. Fisher's exact and Kruskal–Wallis tests were used to determine the correlates of each trajectory group compared with the sustained-low VL group. Results: Five VL trajectory groups were identified among 89 children with 522 VL visits from 6 to 24 months: sustained-low (63% of children), sustained-very-high (16%), sustained-high (9%), low-to-high (7%), and high-with-periods-of-low (6%). Children in the sustained-high group were more frequently on a first-line protease inhibitor (PI)-based regimen (63% vs 38%; P = 0.03) and had younger caregivers (median: 22 vs 28 years; P = 0.02). Among 54 children with 560 VL visits followed from 48 to 96 months, 5 trajectory groups were identified: sustained-low (74%), mid-range (4%), periods-of-low (7%), high-to-low (7%), and sustained-high (7%). Those in the high-to-low group had younger caregivers (21 vs 29 years; P = 0.01). Conclusions: GBTM identified unique VL patterns among children with unsuppressed VL. Caregiver and regimen-related characteristics were associated with patterns of nonsuppression. Younger caregivers may benefit from tailored counseling to help them support child antiretroviral therapy adherence. Palatable regimens are necessary for viral suppression among children with HIV. [ABSTRACT FROM AUTHOR]

While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early initiation is not always possible in postnatal pediatric HIV infections. The timing of ART initiation is likely to affect the size of the latent viral reservoir established, as well as the development of adaptive immune responses, such as the generation of neutralizing antibody responses against the virus. How these parameters impact the ability of infants to control viremia and the time to viral rebound after ART interruption is unclear and has never been modeled in infants. To investigate this question we used an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT and either given ART at 4-7 days post-infection (early ART condition), at 2 weeks post-infection (intermediate ART condition), or at 8 weeks post-infection (late ART condition). These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. To gain insight into early after analytic treatment interruption (ATI), we constructed mathematical models to investigate the effect of time of ART initiation in delaying viral rebound when treatment is interrupted, focusing on the relative contributions of latent reservoir size and autologous virus neutralizing antibody responses. We developed a stochastic mathematical model to investigate the joint effect of latent reservoir size, the autologous neutralizing antibody potency, and CD4+ T cell levels on the time to viral rebound for RMs rebounding up to 60 days post-ATI. We find that the latent reservoir size is an important determinant in explaining time to viral rebound in infant macaques by affecting the growth rate of the virus. The presence of neutralizing antibodies can also delay rebound, but we find this effect for high potency antibody responses only. Finally, we discuss the therapeutic implications of our findings.

Background: HIV case finding is an essential component for ending AIDS, but there is limited evidence on the effectiveness of such a strategy in the pediatric population. We sought to determine HIV positivity rates among children according to entry points in Cameroon. Methods: A facility-based survey was conducted from January 2015 to December 2019 among mother–child couples at various entry points of health facilities in six regions of Cameroon. A questionnaire was administered to parents/guardians. Children were tested by polymerase chain reaction (PCR). Positivity rates were compared between entry points. Associations were quantified using the unadjusted positivity ratio (PR) for univariate analyses and the adjusted positivity ratio (aPR) for multiple Poisson regression analyses with 95% confidence intervals (CIs). p-values < 0.05 were considered significant. Results: Overall, 24,097 children were enrolled. Among them, 75.91% were tested through the HIV prevention of mother-to-child transmission (PMTCT) program, followed by outpatient (13.27%) and immunization (6.27%) services. In total, PMTCT, immunization, and outpatient services accounted for 95.39% of children. The overall positivity was 5.71%, with significant differences (p < 0.001) between entry points. Univariate analysis showed that inpatient service (PR = 1.45; 95% CI: [1.08, 1.94]; p = 0.014), infant welfare (PR = 0.43; 95% CI: [0.28, 0.66]; p < 0.001), immunization (PR = 0.56; 95% CI: [0.45, 0.70]; p < 0.001), and PMTCT (PR = 0.41; 95% CI: [0.37, 0.46]; p < 0.001) were associated with HIV transmission. After adjusting for other covariates, only PMTCT was associated with transmission (aPR = 0.66; 95% CI: [0.51, 0.86]; p = 0.002). Conclusions: While PMTCT accounts for most tested children, high HIV positivity rates were found among children presenting at inpatient, nutrition, and outpatient services and HIV care units. Thus, systematic HIV testing should be proposed for all sick children presenting at the hospital who have escaped the PMTCT cascade. [ABSTRACT FROM AUTHOR]

BackgroundRecent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after human immunodeficiency virus (HIV) infection compared to adults.MethodsWe evaluated plasma from 212 antiretroviral therapy-naive children with HIV (1-3 years old). Neutralization breadth and potency was assessed using a panel of 10 viruses and compared to adults with chronic HIV. The magnitude, epitope specificity, and immunoglobulin (Ig)G subclass distribution of Env-specific antibodies were assessed using a binding antibody multiplex assay.ResultsOne-year-old children demonstrated neutralization breadth comparable to chronically infected adults, whereas 2- and 3-year-olds exhibited significantly greater neutralization breadth (P = .014). Likewise, binding antibody responses increased with age, with levels in 2- and 3-year-old children comparable to adults. Overall, there was no significant difference in antibody specificities or IgG subclass distribution between the pediatric and adult cohorts. It is interesting to note that the neutralization activity was mapped to a single epitope (CD4 binding site, V2 or V3 glycans) in only 5 of 38 pediatric broadly neutralizing samples, which suggests that most children may develop a polyclonal neutralization response.ConclusionsThese results contribute to a growing body of evidence suggesting that initiating HIV immunization early in life may present advantages for the development of broadly neutralizing antibody responses.

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

A cure for HIV-1 (HIV) remains unrealized due to a reservoir of latently infected cells that persist during antiretroviral therapy (ART), with reservoir size associated with adverse health outcomes and inversely with time to viral rebound upon ART cessation. Once established during ART, the HIV reservoir decays minimally over time; thus, understanding factors that impact the size of the HIV reservoir near its establishment is key to improving the health of people living with HIV and for the development of novel cure strategies. Yet, to date, few correlates of HIV reservoir size have been identified, particularly in pediatric populations. Here, we employed a cross-subtype intact proviral DNA assay (CS-IPDA) to quantify HIV provirus between one- and two-years post-ART initiation in a cohort of Kenyan children (n = 72), which had a median of 99 intact (range: 0–2469), 1340 defective (range: 172–3.84 × 104), and 1729 total (range: 178–5.11 × 104) HIV proviral copies per one million T cells. Additionally, pre-ART plasma was tested for HIV Env-specific antibody-dependent cellular cytotoxicity (ADCC) activity. We found that pre-ART gp120-specific ADCC activity inversely correlated with defective provirus levels (n = 68, r = −0.285, p = 0.0214) but not the intact reservoir (n = 68, r = −0.0321, p-value = 0.800). Pre-ART gp41-specific ADCC did not significantly correlate with either proviral population (n = 68; intact: r = −0.0512, p-value = 0.686; defective: r = −0.109, p-value = 0.389). This suggests specific host immune factors prior to ART initiation can impact proviruses that persist during ART. [ABSTRACT FROM AUTHOR]

Background: HIV case finding is an essential component for ending AIDS, but there is limited evidence on the effectiveness of such a strategy in the pediatric population. We sought to determine HIV positivity rates among children according to entry points in Cameroon. Methods: A facility-based survey was conducted from January 2015 to December 2019 among mother–child couples at various entry points of health facilities in six regions of Cameroon. A questionnaire was administered to parents/guardians. Children were tested by polymerase chain reaction (PCR). Positivity rates were compared between entry points. Associations were quantified using the unadjusted positivity ratio (PR) for univariate analyses and the adjusted positivity ratio (aPR) for multiple Poisson regression analyses with 95% confidence intervals (CIs). p-values < 0.05 were considered significant. Results: Overall, 24,097 children were enrolled. Among them, 75.91% were tested through the HIV prevention of mother-to-child transmission (PMTCT) program, followed by outpatient (13.27%) and immunization (6.27%) services. In total, PMTCT, immunization, and outpatient services accounted for 95.39% of children. The overall positivity was 5.71%, with significant differences (p < 0.001) between entry points. Univariate analysis showed that inpatient service (PR = 1.45; 95% CI: [1.08, 1.94]; p = 0.014), infant welfare (PR = 0.43; 95% CI: [0.28, 0.66]; p < 0.001), immunization (PR = 0.56; 95% CI: [0.45, 0.70]; p < 0.001), and PMTCT (PR = 0.41; 95% CI: [0.37, 0.46]; p < 0.001) were associated with HIV transmission. After adjusting for other covariates, only PMTCT was associated with transmission (aPR = 0.66; 95% CI: [0.51, 0.86]; p = 0.002). Conclusions: While PMTCT accounts for most tested children, high HIV positivity rates were found among children presenting at inpatient, nutrition, and outpatient services and HIV care units. Thus, systematic HIV testing should be proposed for all sick children presenting at the hospital who have escaped the PMTCT cascade.

Summary: Background: Despite antiretroviral treatment (ART), immune dysfunction persists in children with perinatal HIV infection (HEI). Here we investigated the impact of HIV status on maternal antibody (Ab) passage, long-term vaccine induced immunity and B-cell maturation. Methods: 46 HIV Exposed Uninfected (HEU), 43 HEI, and 15 HIV unexposed uninfected (HUU) infants were vaccinated with 3 doses of DTaP-HepB-Hib-PCV10-OP at 2, 3, and 4 months at Matola Provincial Hospital, Maputo, Mozambique. Tetanus toxoid specific (TT) IgG, HIV Ab and B-cell phenotype characteristics were evaluated at entry, pre-ART, 5, 10, and 18 months in this longitudinal cohort study. Findings: Baseline (maternal) plasma TT Ab levels were significantly lower in HEI compared to both HEU and HUU and a faster decay of TT Ab was observed in HEI compared to HEU with significantly lower TT Ab levels at 10 and 18 months of age. TT unprotected (UP) (≤0.1 IU/mL) HEI showed higher HIV-RNA at entry and higher longitudinal HIV viremia (Area Under the Curve) compared to TT protected (P) HEI. A distinct HIV-Ab profile was found at entry in HEI compared to HEU. B-cell phenotype showed a B-cell perturbation in HEI vs HEU infants at entry (mean age 40.8 days) with lower transitional CD10+CD19+ B-cells and IgD+CD27− naive B-cells and an overall higher frequency of IgD−CD27− double negative B-cell subsets in HEI. Interpretation: B-cell perturbation, presenting with higher double negative IgD−CD27− B-cells was observed in neonatal age and may play a major role in the B-cell exhaustion in HEI. The ability to maintain TT protective Ab titers over time is impaired in HEI with uncontrolled viral replication and the current vaccination schedule is insufficient to provide long-term protection against tetanus. Funding: This work was supported by: NIH grant to SP (5R01AI127347-05); Children’s Hospital Bambino Gesú (Ricerca corrente 2019) to NC, and Associazione Volontari Bambino Gesù to PP.

Human T-cell leukemia virus type 1(HTLV-1) is the etiological agent responsible for the clinical entity of tropical spastic paraparesis/HTLV-1-associated myelitis (TSP/HAM). HTLV-1 and HIV-1, being related retroviruses, coinfection with both is a well-recognized phenomenon but rarely reported in children. We describe a 5-year-old boy with no previously known comorbidity who presented with bilateral lower-limb weakness and calf pain along with urinary retention. Imaging confirmed the presence of myelitis. Investigations showed elevated creatine phosphokinase(CPK) values suggestive of myositis. It was later learned that the parents of the child were on treatment for HIV infection. Antibodies for HIV were positive by ELISA, and in view of the clinical picture, probability of a TSP-like illness as the initial presentation of a hitherto undiagnosed HIV infection was considered. TSP/HAM is an important yet underrecognized cause of spinal disease, especially in HIV-infected individuals. Certain features such as elevated to normal CD4 counts, absence of significant sensory symptoms, and associated myositis may serve as subtle clues to underlying HTLV-1 infection.

BackgroundThe HADITHI study is a cluster-randomized trial of children living with HIV and their caregivers in Kenya that aimed to increase rates of caregiver disclosure of their child's HIV status, encourage earlier status disclosure, and improve pediatric mental health and HIV outcomes. This analysis identified characteristics predicting caregiver non-responsiveness and compared outcomes among children based on disclosure status.MethodsA penalized logistic regression model with lasso regularization identified the most important predictors of disclosure. The two-stage least squares instrumental variable approach was used to assess outcomes accounting for non-compliance to disclosure.ResultsCaregiver non-isolation and shorter time on antiretroviral therapy were predictive of HIV status disclosure. There were no statistically significant differences found in CD4 percentage, depression status, or mental and emotional status based on disclosure status up to 24 months-post intervention.ConclusionThese findings have implications for specialists seeking to tailor disclosure interventions to improve caregiver-child dyad responsiveness.

While the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early initiation is not always possible in postnatal pediatric HIV infections. The timing of ART initiation is likely to affect the size of the latent viral reservoir established, as well as the development of adaptive immune responses, such as the generation of neutralizing antibody responses against the virus. How these parameters impact the ability of infants to control viremia and the time to viral rebound after ART interruption is unclear and has never been modeled in infants. To investigate this question we used an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT and either given ART at 4-7 days post-infection (early ART condition), at 2 weeks post-infection (intermediate ART condition), or at 8 weeks post-infection (late ART condition). These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. To gain insight into early after analytic treatment interruption (ATI), we constructed mathematical models to investigate the effect of time of ART initiation in delaying viral rebound when treatment is interrupted, focusing on the relative contributions of latent reservoir size and autologous virus neutralizing antibody responses. We developed a stochastic mathematical model to investigate the joint effect of latent reservoir size, the autologous neutralizing antibody potency, and CD4+ T cell levels on the time to viral rebound for RMs rebounding up to 60 days post-ATI. We find that the latent reservoir size is an important determinant in explaining time to viral rebound in infant macaques by affecting the growth rate of the virus. The presence of neutralizing antibodies can also delay rebound, but we find this effect for high potency antibody responses only. Finally, we discuss the therapeutic implications of our findings. • Latent reservoir size is an important determinant in explaining time to viral. • Latent reservoir size affects the growth rate of the virus. • Neutralizing antibodies can delay viral rebound for high neutralization potency. [ABSTRACT FROM AUTHOR]

A cure for HIV-1 (HIV) remains unrealized due to a reservoir of latently infected cells that persist during antiretroviral therapy (ART), with reservoir size associated with adverse health outcomes and inversely with time to viral rebound upon ART cessation. Once established during ART, the HIV reservoir decays minimally over time; thus, understanding factors that impact the size of the HIV reservoir near its establishment is key to improving the health of people living with HIV and for the development of novel cure strategies. Yet, to date, few correlates of HIV reservoir size have been identified, particularly in pediatric populations. Here, we employed a cross-subtype intact proviral DNA assay (CS-IPDA) to quantify HIV provirus between one- and two-years post-ART initiation in a cohort of Kenyan children (n = 72), which had a median of 99 intact (range: 0–2469), 1340 defective (range: 172–3.84 × 104), and 1729 total (range: 178–5.11 × 104) HIV proviral copies per one million T cells. Additionally, pre-ART plasma was tested for HIV Env-specific antibody-dependent cellular cytotoxicity (ADCC) activity. We found that pre-ART gp120-specific ADCC activity inversely correlated with defective provirus levels (n = 68, r = −0.285, p = 0.0214) but not the intact reservoir (n = 68, r = −0.0321, p-value = 0.800). Pre-ART gp41-specific ADCC did not significantly correlate with either proviral population (n = 68; intact: r = −0.0512, p-value = 0.686; defective: r = −0.109, p-value = 0.389). This suggests specific host immune factors prior to ART initiation can impact proviruses that persist during ART.

Objective: To analyze perspectives on health care transitions among parents who have internationally adopted children living with HIV (IACH)The transition of youth with living with HIV from pediatric to adult care is associated with adverse health outcomes, including poor medication adherence and appointment attendance. However, little is known about the experiences of IACH. Methods: This qualitative project explores the perspectives of 17 parents of 24 IACH in the United States through hour-long semi-structured phone interviews focused on healthcare transition. The purposive sample was recruited from two pediatric infectious disease clinics and private social media sites. Drawing on analytic principles of constant comparison, transcripts were analyzed for emergent themes. Results: Most parents identified as white (n = 16), female (n = 16). Median age of IACH was 16 years. Two had transitioned to adult care. Fourteen did not have a transition plan with their provider. Many parents expressed apprehension regarding the transition to adult care. Anxiety over the ability to communicate with their child’s health provider and lack of comprehensive planning were expressed. Parents also felt their child may feel out of place in the adult infectious disease clinic and emphasized the trusting, long standing relationship with pediatric providers. Participants acknowledged that transition to another provider could be challenging for their child as adult providers may be less aware of adoption-related trauma. Conclusion: It is vital that physicians consider trauma-informed care throughout the transition process with IACH. Providers should support health management-related independence of both IACH and their parents prior to transition. Coordination with adult care providers is key to a successful health care transition.

Early initiation of antiretroviral therapy and adherence to achieve viral load suppression (VLS) are crucial for reducing morbidity and mortality of perinatally HIV-infected infants. In this descriptive cohort study of 39 HIV perinatally infected infants, who started treatment at one month of life in Mozambique, we aimed to describe the viral response over 2 years of follow up. VLS ≤ 400 copies/mL, sustained VLS and viral rebound were described using a Kaplan–Meier estimator. Antiretroviral drug transmitted resistance was assessed for a sub-group of non-VLS infants. In total, 61% of infants reached VLS, and 50% had a rebound. Cumulative probability of VLS was 36%, 51%, and 69% at 6, 12 and 24 months of treatment, respectively. The median duration of VLS was 7.4 months (IQR 12.6) and the cumulative probability of rebound at 6 months was 30%. Two infants had resistance biomarkers to drugs included in their treatment regimen. Our findings point to a low rate of VLS and high rate of viral rebound. More frequent viral response monitoring is advisable to identify infants with rebound and offer timely adherence support. It is urgent to tailor the psychosocial support model of care to this specific age group and offer differentiated service delivery to mother–baby pairs. [ABSTRACT FROM AUTHOR]

Background: Based on recent World Health Organization recommendations, there has been a large-scale transition in Sub-Saharan Africa to integrase inhibitor (II)-based antiretroviral therapy (ART) regimens., Setting: This study was conducted at an urban referral center in Lusaka, Zambia., Methods: This study included 297 children and adolescents with HIV (CAWH) on ART for one year prior to enrollment and followed for 1-4 years after enrollment. ART adherence, ART regimen, and viral load were assessed periodically. Structured interviews were conducted with a subset of 95 children to assess adherence barriers and side effects., Results: Children on protease inhibitor (PI)-based regimens were more likely to report adherence problems than children taking II- or Efavirenz-based regimens (10% vs. 28%, p=0.03) and noted more days with missed doses (median 1 vs. 0, p=0.02). In interviews, the most common reasons given for poor adherence included bad medication taste, not being home when medications were due, and perceived side effects. The PI group was more likely to report that taste was a problem affecting adherence (22% vs. 4%, p=0.05) and headache as an ART side effect (17% vs. 4%, p=0.05). Switching from a PI- to an II-based regimen was associated with improved adherence (72% vs. 92%, p=0.01) and an undetectable viral load (67% vs. 78%)., Conclusions: Switching CAWH from PI-based to II-based regimens has many advantages including superior side effect profiles, adherence, and viral suppression. PI taste aversion may be a significant contributor to pediatric adherence issues. Palatability should be considered in pediatric HIV drug development., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to disclose.

Background: Chronic kidney disease (CKD) remains an important comorbid condition in people living with HIV. However, data in children living with HIV/AIDS (CLWHA) in sub-Saharan Africa is limited. We sought to establish the prevalence and identify risk factors of CKD among CLWHA in SSA. Methods: This was a retrospective chart review across five SSA countries HIV/AIDS care sites, March 2000 and June 2016. Results: 4,859 children with at least two clinic visits were enrolled in the study. The median age at the first clinic visit was 5.7 (IQR; 2.5, 9.5) years, and median follow-up time was 22.6 (IQR 9.8, 46.1) months. 11.2% CLWHA had an eGFR of

Early initiation of antiretroviral therapy (ART) significantly improves clinical outcomes and reduces mortality of infants/children living with HIV. However, the ability of infected cells to establish latent viral reservoirs shortly after infection and to persist during long-term ART remains a major barrier to cure. In addition, while early ART treatment of infants living with HIV can limit the size of the virus reservoir, it can also blunt HIV-specific immune responses and does not mediate clearance of latently infected viral reservoirs. Thus, adjunctive immune-based therapies that are geared towards limiting the establishment of the virus reservoir and/or mediating the clearance of persistent reservoirs are of interest for their potential to achieve viral remission in the setting of pediatric HIV. Because of the differences between the early life and adult immune systems, these interventions may need to be tailored to the pediatric settings. Understanding the attributes and specificities of the early life immune milieu that are likely to impact the virus reservoir is important to guide the development of pediatric-specific immune-based interventions towards viral remission and cure. In this review, we compare the immune profiles of pediatric and adult HIV elite controllers, discuss the characteristics of cellular and anatomic HIV reservoirs in pediatric populations, and highlight the potential values of current cure strategies using immune-based therapies for long-term viral remission in the absence of ART in children living with HIV. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus type 1(HTLV-1) is the etiological agent responsible for the clinical entity of tropical spastic paraparesis/HTLV-1-associated myelitis (TSP/HAM). HTLV-1 and HIV-1, being related retroviruses, coinfection with both is a well-recognized phenomenon but rarely reported in children. We describe a 5-year-old boy with no previously known comorbidity who presented with bilateral lower-limb weakness and calf pain along with urinary retention. Imaging confirmed the presence of myelitis. Investigations showed elevated creatine phosphokinase(CPK) values suggestive of myositis. It was later learned that the parents of the child were on treatment for HIV infection. Antibodies for HIV were positive by ELISA, and in view of the clinical picture, probability of a TSP-like illness as the initial presentation of a hitherto undiagnosed HIV infection was considered. TSP/HAM is an important yet underrecognized cause of spinal disease, especially in HIV-infected individuals. Certain features such as elevated to normal CD4 counts, absence of significant sensory symptoms, and associated myositis may serve as subtle clues to underlying HTLV-1 infection. [ABSTRACT FROM AUTHOR]

BackgroundThe International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1104s study evaluated neuropsychological outcomes over 96 weeks in children living with HIV (CLHIV) aged 5–11 years at 6 Sub-Saharan African sites to explore associations between HIV-illness related biomarkers and neuropsychological outcomes.MethodsChildren living with HIV had participated in IMPAACT P1060, which compared efficacy of nevirapine versus lopinavir/ritonavir in children initiating ART at

Early initiation of antiretroviral therapy (ART) significantly improves clinical outcomes and reduces mortality of infants/children living with HIV. However, the ability of infected cells to establish latent viral reservoirs shortly after infection and to persist during long-term ART remains a major barrier to cure. In addition, while early ART treatment of infants living with HIV can limit the size of the virus reservoir, it can also blunt HIV-specific immune responses and does not mediate clearance of latently infected viral reservoirs. Thus, adjunctive immune-based therapies that are geared towards limiting the establishment of the virus reservoir and/or mediating the clearance of persistent reservoirs are of interest for their potential to achieve viral remission in the setting of pediatric HIV. Because of the differences between the early life and adult immune systems, these interventions may need to be tailored to the pediatric settings. Understanding the attributes and specificities of the early life immune milieu that are likely to impact the virus reservoir is important to guide the development of pediatric-specific immune-based interventions towards viral remission and cure. In this review, we compare the immune profiles of pediatric and adult HIV elite controllers, discuss the characteristics of cellular and anatomic HIV reservoirs in pediatric populations, and highlight the potential values of current cure strategies using immune-based therapies for long-term viral remission in the absence of ART in children living with HIV.

The “shock and kill” strategy for HIV-1 cure incorporates latency-reversing agents (LRA) in combination with interventions that aid the host immune system in clearing virally reactivated cells. LRAs have not yet been investigated in pediatric clinical or preclinical studies. Here, we evaluated an inhibitor of apoptosis protein (IAP) inhibitor (IAPi), AZD5582, that activates the noncanonical NF-k B (ncNF-k B) signaling pathway to reverse latency. Ten weekly doses of AZD5582 were intravenously administered at 0.1 mg/kg to rhesus macaque (RM) infants orally infected with SIVmac251 at 4 weeks of age and treated with a triple ART regimen for over 1 year. During AZD5582 treatment, on-ART viremia above the limit of detection (LOD, 60 copies/mL) was observed in 5/8 infant RMs starting at 3 days post-dose 4 and peaking at 771 copies/mL. Of the 135 measurements during AZD5582 treatment in these 5 RM infants, only 8 were above the LOD (6%), lower than the 46% we have previously reported in adult RMs. Pharmacokinetic analysis of plasma AZD5582 levels revealed a lower Cmax in treated infants compared to adults (294 ng/mL versus 802 ng/mL). RNA-Sequencing of CD41 T cells comparing pre- and post-AZD5582 dosing showed many genes that were similarly upregulated in infants and adults, but the expression of key ncNF-k B genes, including NFKB2 and RELB, was significantly higher in adult RMs. Our results suggest that dosing modifications for this latency reversal approach may be necessary to maximize virus reactivation in the pediatric setting for successful “shock and kill” strategies. IMPORTANCE While antiretroviral therapy (ART) has improved HIV-1 disease outcome and reduced transmission, interruption of ART results in rapid viral rebound due to the persistent latent reservoir. Interventions to reduce the viral reservoir are of critical importance, especially for children who must adhere to lifelong ART to prevent disease progression. Here, we used our previously established pediatric nonhuman primate model of oral SIV infection to evaluate AZD5582, identified as a potent latency-reversing agent in adult macaques, in the controlled setting of daily ART. We demonstrated the safety of the IAPi AZD5582 and evaluate the pharmacokinetics and pharmacodynamics of repeated dosing. The response to AZD5582 in macaque infants differed from what we previously showed in adult macaques with weaker latency reversal in infants, likely due to altered pharmacokinetics and less inducibility of infant CD41 T cells. These data supported the contention that HIV-1 cure strategies for children are best evaluated using pediatric model systems. [ABSTRACT FROM AUTHOR]

Introduction: mixed feeding practices among HIV positive mothers increases the risk of HIV transmission by 3-4 folds. Approximately 37.7 million people globally live with HIV, of these, 1.7 were children aged from 0-14 years. Globally, about 1.5 million people captured the new HIV in 2020. Nearly 90% of HIV infection among pediatrics is due to vertical transmission. However, there is no data regarding the feeding practices of HIV-positive mothers in the study area. Therefore, this study aimed to assess the magnitude of infant feeding practices among HIV-infected mothers in Wolaita, Ethiopia. Methods: an institution-based cross-sectional study design was conducted among 146 HIV positive in selected hospitals of Wolaita from February to June 2021. A simple random sampling was employed to select health facilities. Data were collected by face to face interviewer who administered a structured questionnaire with document review. Data entry was done by Epi data version 3.1 and analyzed by SPSS version 25. Descriptive statistics were used to show the results. Results: out of 146 HIV-positive mothers were involved in the study. The prevalence of exclusive breastfeeding, exclusive replacement feeding, and mixed feeding practices among mothers with HIV in the present study was found to be 49.3%, 19.9%, and 30.8% respectively in Wolaita. Conclusion: exclusive breastfeeding and exclusive replacement feeding in the current study area was found to be significantly low when compared to global recommendations for feeding options for HIV-positive mothers. Therefore, all stakeholders are recommended to put an extraordinary effort to fill the gap. [ABSTRACT FROM AUTHOR]

Background: Impaired lung function is common among older children with perinatally acquired HIV (PHIV) who initiated antiretroviral therapy (ART) late in childhood. We determined the prevalence of abnormal spirometry and cofactors for impaired lung function among school-age children with PHIV who initiated ART when aged 12 months or younger. Setting: Children who received early ART in the Optimizing Pediatric HIV-1 Therapy study in Kenya and underwent spirometry at school age. Methods: Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured. Abnormal spirometry was defined as follows: obstructive (FEV1/FVC <1.64 z score [ z FEV1/FVC]) and restricted (z FVC <1.64 with z FEV1/FVC ≥1.64). Characteristics, including anthropometric and HIV-related data, were ascertained in infancy and at school age. Caregiver carbon monoxide exposure served as a proxy for school-age child exposure. Linear regression determined associations of cofactors with lung function. Results: Among 40 children, the median age was 5 months at ART initiation and 8.5 years at spirometry. The mean zFEV1, zFVC, and zFEV1/FVC (SD) were 0.21 (1.35), 0.31 (1.22), and −0.24 (0.82), respectively. Five (13%) children had abnormal spirometry. Spirometry z scores were significantly lower among children with pre-ART pneumonia, WHO HIV stage 3/4, higher HIV RNA at 6 months after ART initiation, low anthropometric z scores, and higher carbon monoxide exposure. Conclusions: Most of the children with PHIV who initiated ART at age 12 months or younger had normal spirometry, suggesting that ART in infancy preserved lung function. However, 13% had abnormal spirometry despite early ART. Modifiable factors were associated with impaired lung function, providing potential targets for interventions to prevent chronic lung disease. [ABSTRACT FROM AUTHOR]

Pediatric HIV infection remains a global health crisis with an estimated 150,000 new mother-to-child (MTCT) infections each year. Antiretroviral therapy (ART) has improved childhood survival, but only an estimated 53% of children worldwide have access to treatment. Adding to the health crisis is the neurological impact of HIV on the developing brain, in particular cognitive and executive function, which persists even when ART is available. Imaging studies suggest structural, connectivity, and functional alterations in perinatally HIV-infected youth. However, the paucity of histological data limits our ability to identify specific cortical regions that may underlie the clinical manifestations. Utilizing the pediatric simian immunodeficiency virus (SIV) infection model in infant macaques, we have previously shown that early-life SIV infection depletes the neuronal population in the hippocampus. Here, we expand on these previous studies to investigate the dorsolateral prefrontal cortex (dlPFC). A total of 11 ART-naïve infant rhesus macaques (Macaca mulatta) from previous studies were retrospectively analyzed. Infant macaques were either intravenously (IV) inoculated with highly virulent SIVmac251 at ~1 week of age and monitored for 6–10 weeks or orally challenged with SIVmac251 from week 9 of age onwards with a monitoring period of 10–23 weeks post-infection (19–34 weeks of age), and SIV-uninfected controls were euthanized at 16–17 weeks of age. Both SIV-infected groups show a significant loss of neurons along with evidence of ongoing neuronal death. Oral- and IV-infected animals showed a similar neuronal loss which was negatively correlated to chronic viremia levels as assessed by an area under the curve (AUC) analysis. The loss of dlPFC neurons may contribute to the rapid neurocognitive decline associated with pediatric HIV infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pediatric HIV is a significant contributor to childhood morbidity and mortality. As HIV infects bone marrow CD34-positive progenitor cells, the hematological abnormalities are well-expected. The viral load is much higher in children predisposing them to opportunistic infections and hematopoietic malignancies. The present study aimed to determine the spectrum of hematological abnormalities that may yield clinically useful information in HIV-infected children. This was a retrospective study of 19 HIV-infected children who underwent bone marrow examination. Overall, 20 peripheral blood and bone marrow samples were analyzed for morphological changes in all hematopoietic lineages. Immunohistochemistry was performed on trephine biopsy sections for evaluation of B and T cells and cytomegalovirus inclusions. Anemia was the most common cytopenia (95%), followed by thrombocytopenia (45%) and leukopenia (40%). Myelodysplasia was noted in 70% of cases. Dysmegakaryopoiesis was predominant in 65% of cases, while dyserythropoiesis was noted in 25% of cases. Hemophagocytosis and reactive cellular changes were noted in 20% of cases each. Benign lymphoid aggregates and granulomatous inflammation were observed in 15% and 10% of cases, respectively. Significant myelofibrosis was found in 35% of cases. One case showed infiltration by Burkitt lymphoma. Parvoviral inclusions were identified in 1 case. An interstitial increase and aggregates of CD8 + T cells and reduced CD4 + T cells were noted. CD20 + B cells were normal to mildly increased in the bone marrow. Bone marrow examination provides clinically significant information in pediatric HIV revealing the underlying cause of hematopoietic abnormalities and allows the exclusion of major hematological neoplasms. [ABSTRACT FROM AUTHOR]

Objectives: UNAIDS estimates 152,984 children under 15 years living with HIV (C/ALHIV) by 2022 in South Africa. Monitoring the continuity of antiretroviral treatment remains challenging without electronic health records. We explored treatment cohort growth and interruption trends in 14-USAID-PEPFAR-supported districts., Methods: We reviewed data from 2018 to 2023. We triangulated this data with NAOMI HIV estimates. We used Tableau version 2023.2 for analysis to understand heterogeneity in outcomes., Results: HIV incidence halved from 4.3 per 1000 in 2017 to 2.5 per 1000 in 2022. HIV testing doubled: 188,371 in FY19Q1 to 399,708 in FY23Q4 while testing positivity declined from 3.3% to 0.7%. Linkage to treatment increased from 67% to 102%, viral suppression increased from 79% to 84%. C/ALHIV treatment cohort started at 82,897 in FY19Q1 and increased to 105,107 in FY20Q2. Subsequently, the cohort decreased to 79,288 in FY23Q4 despite 42,498 initiations and 62,256 returns., Conclusions: The C/ALHIV treatment and viral suppression increased substantially commensurate with expected trends. Subsequent cohort decline was aligned to vertical transmission reduction, HIV incidence decline, and expected aging. We highlight the inadequacy of the information systems to quantify losses. We underscore a need for resources to enhance program monitoring and interventions to address this gap., Competing Interests: The authors have no competing interests to declare.

Supplemental Digital Content is Available in the Text. Introduction: Because of low pediatric HIV prevalence, more tests are needed to find 1 HIV-positive child compared with adults. In Uganda, the number needed to test (NNT) to find 1 new HIV-positive child was 64 in outpatient departments (OPDs) and 31 through index testing. We aimed to develop and validate a pediatric (1.5–14 years) screening tool to optimize testing approaches. Methods: Phase 1 evaluated the performance of 10 screening questions in 14 OPDs using a variable selection algorithm to evaluate combinations of screening questions. Using logistic regression, we identified the number of screening questions with the best predictive accuracy using the receiver operation characteristic curve. Phase 2 validated the proposed tool in 15 OPDs and 7 orphan and vulnerable children programs. We estimated sensitivity, specificity, and NNT accounting for intercluster correlations. Results: A total of 3482 children were enrolled. The optimal model included reported HIV-positive maternal status or 2/5 symptoms (sickly in the last 3 months, recurring skin problems, weight loss, not growing well, and history of tuberculosis). The proposed tool had sensitivity of 83.6% [95% confidence interval (CI): 68.1 to 92.4] and specificity of 62.5% (95% CI: 55.0 to 69.4). The tool was validated in a sample of 11,342 children; sensitivity was 87.8% (95% CI: 80.9 to 92.5) and specificity 62.6% (95% CI: 54.8 to 69.7) across OPDs and community sites. In OPDs, sensitivity was 88.1% (95% CI: 80.8 to 92.8) and specificity 69.0% (95% CI: 61.9 to 75.3). The NNT was 43 (95% CI: 28 to 67) across settings and 28 (95% CI: 20 to 38) for OPD. Conclusions: This HIV screening tool has high sensitivity and reasonable specificity, increasing testing efficiency and yield for children and adolescents. [ABSTRACT FROM AUTHOR]

Early initiation of antiretroviral therapy and adherence to achieve viral load suppression (VLS) are crucial for reducing morbidity and mortality of perinatally HIV-infected infants. In this descriptive cohort study of 39 HIV perinatally infected infants, who started treatment at one month of life in Mozambique, we aimed to describe the viral response over 2 years of follow up. VLS ≤ 400 copies/mL, sustained VLS and viral rebound were described using a Kaplan–Meier estimator. Antiretroviral drug transmitted resistance was assessed for a sub-group of non-VLS infants. In total, 61% of infants reached VLS, and 50% had a rebound. Cumulative probability of VLS was 36%, 51%, and 69% at 6, 12 and 24 months of treatment, respectively. The median duration of VLS was 7.4 months (IQR 12.6) and the cumulative probability of rebound at 6 months was 30%. Two infants had resistance biomarkers to drugs included in their treatment regimen. Our findings point to a low rate of VLS and high rate of viral rebound. More frequent viral response monitoring is advisable to identify infants with rebound and offer timely adherence support. It is urgent to tailor the psychosocial support model of care to this specific age group and offer differentiated service delivery to mother–baby pairs.

HIV-1 is known for its complex interaction with the dysregulated immune system and is responsible for the development of neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. Considering that HIV-1-induced immune dysregulation and its association with neurodevelopmental and neurocognitive impairments in pediatric populations are not well understood, we conducted a scoping review on this topic. The study aimed to systematically review the association of blood and cerebrospinal fluid (CSF) immune markers with neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. PubMed, Scopus, and Web of Science databases were searched using a search protocol designed specifically for this study. Studies were selected based on a set eligibility criterion. Titles, abstracts, and full texts were assessed by two independent reviewers. Data from the selected studies were extracted and analyzed by two independent reviewers. Seven studies were considered eligible for use in this context, which included four cross-sectional and three longitudinal studies. An average of 130 (±70.61) children living with HIV, 138 (±65.37) children exposed to HIV but uninfected and 90 (±86.66) HIV-negative participants were included across the seven studies. Results indicate that blood and CSF immune markers are associated with neurocognitive development/performance in pediatric HIV populations. Only seven studies met the inclusion criteria, therefore, these limited the number of significant conclusions which could have been made by using such an approach. All considered, the evidence suggests that immune dysregulation, as in the case of adult HIV populations, also has a significant association with neurocognitive performance in pediatric HIV populations.

Background: Despite antiretroviral treatment (ART), immune dysfunction persists in children with perinatal HIV infection (HEI). Here we investigated the impact of HIV status on maternal antibody (Ab) passage, long-term vaccine induced immunity and B-cell maturation., Methods: 46 HIV Exposed Uninfected (HEU), 43 HEI, and 15 HIV unexposed uninfected (HUU) infants were vaccinated with 3 doses of DTaP-HepB-Hib-PCV10-OP at 2, 3, and 4 months at Matola Provincial Hospital, Maputo, Mozambique. Tetanus toxoid specific (TT) IgG, HIV Ab and B-cell phenotype characteristics were evaluated at entry, pre-ART, 5, 10, and 18 months in this longitudinal cohort study., Findings: Baseline (maternal) plasma TT Ab levels were significantly lower in HEI compared to both HEU and HUU and a faster decay of TT Ab was observed in HEI compared to HEU with significantly lower TT Ab levels at 10 and 18 months of age. TT unprotected (UP) (≤0.1 IU/mL) HEI showed higher HIV-RNA at entry and higher longitudinal HIV viremia (Area Under the Curve) compared to TT protected (P) HEI. A distinct HIV-Ab profile was found at entry in HEI compared to HEU. B-cell phenotype showed a B-cell perturbation in HEI vs HEU infants at entry (mean age 40.8 days) with lower transitional CD10+CD19+ B-cells and IgD+CD27- naive B-cells and an overall higher frequency of IgD-CD27- double negative B-cell subsets in HEI., Interpretation: B-cell perturbation, presenting with higher double negative IgD-CD27- B-cells was observed in neonatal age and may play a major role in the B-cell exhaustion in HEI. The ability to maintain TT protective Ab titers over time is impaired in HEI with uncontrolled viral replication and the current vaccination schedule is insufficient to provide long-term protection against tetanus., Funding: This work was supported by: NIH grant to SP (5R01AI127347-05); Children's Hospital Bambino Gesú (Ricerca corrente 2019) to NC, and Associazione Volontari Bambino Gesù to PP., Competing Interests: Declaration of interests All authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: The HADITHI study is a cluster-randomized trial of children living with HIV and their caregivers in Kenya that aimed to increase rates of caregiver disclosure of their child's HIV status, encourage earlier status disclosure, and improve pediatric mental health and HIV outcomes. This analysis identified characteristics predicting caregiver non-responsiveness and compared outcomes among children based on disclosure status., Methods: A penalized logistic regression model with lasso regularization identified the most important predictors of disclosure. The two-stage least squares instrumental variable approach was used to assess outcomes accounting for non-compliance to disclosure., Results: Caregiver non-isolation and shorter time on antiretroviral therapy were predictive of HIV status disclosure. There were no statistically significant differences found in CD4 percentage, depression status, or mental and emotional status based on disclosure status up to 24 months-post intervention., Conclusion: These findings have implications for specialists seeking to tailor disclosure interventions to improve caregiver-child dyad responsiveness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Magill, Nyandiko, Baum, Aluoch, Chory, Ashimoshi, Lidweye, Njoroge, Sang, Nyagaya, Scanlon, Hogan and Vreeman.)

Background: The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1104s study evaluated neuropsychological outcomes over 96 weeks in children living with HIV (CLHIV) aged 5-11 years at 6 Sub-Saharan African sites to explore associations between HIV-illness related biomarkers and neuropsychological outcomes., Methods: Children living with HIV had participated in IMPAACT P1060, which compared efficacy of nevirapine versus lopinavir/ritonavir in children initiating ART at <3 years of age. At age 5-11, neuropsychological evaluations of KABC cognitive ability, TOVA attention-impulsivity and BOT-2 motor domains were assessed and repeated after 48 and 96 weeks. Clinical, antiretroviral therapy (ART) and laboratory (immunological and virological) parameters were used to predict neuropsychological outcomes using linear mixed-effects multivariable regression models, controlling for child and caregiver characteristics., Results: 246 CLHIV (45% male, mean age at initial neuropsychological evaluation 7.1 yrs [SD 1.2]) began ART at a median age 14.9 months (IQR 8.2, 25.2). Nadir CD4 percentage was 14.7% (IQR 11.0, 19.5); the median peak viral load (VL) was 750 000 copies/ml (IQR 366 000, 750 000) and 63% had ≥WHO stage 3 clinical disease; 164 (67%) were on lopinavir/ritonavir, 71 (29%) were on nevirapine and 7 (3%) were on efavirenz. Other antiretrovirals were similar. Nevirapine at P1104s study start or later was associated with poorer neuropsychological scores across all domains except Global Executive Composite, even when controlling for nadir CD4 percent and time-varying HIV VL. Other predictors of poorer scores in KABC domains included low birth weight, WHO stage 4 disease and serious illness history and elevated VL was associated with worse BOT-2 scores., Conclusion: Children receiving nevirapine had poorer neuropsychological scores than those on lopinavir/ritonavir. Antiretroviral choice might adversely impact neuropsychological performance. In addition, low birth weight and markers of severe HIV disease: advanced WHO clinical HIV disease, history of serious illness and an elevated VL, were associated with lower neuropsychological scores., Competing Interests: LB-M was employed by MU-JHU Care Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fairlie, Chernoff, Cotton, Bwakura-Dangarembizi, Violari, Familiar-Lopez, Barlow-Mosha, Kamthunzi, McCarthy, Jean-Philippe, Laughton, Palumbo and Boivin.)

HIV-1 is known for its complex interaction with the dysregulated immune system and is responsible for the development of neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. Considering that HIV-1-induced immune dysregulation and its association with neurodevelopmental and neurocognitive impairments in pediatric populations are not well understood, we conducted a scoping review on this topic. The study aimed to systematically review the association of blood and cerebrospinal fluid (CSF) immune markers with neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. PubMed, Scopus, and Web of Science databases were searched using a search protocol designed specifically for this study. Studies were selected based on a set eligibility criterion. Titles, abstracts, and full texts were assessed by two independent reviewers. Data from the selected studies were extracted and analyzed by two independent reviewers. Seven studies were considered eligible for use in this context, which included four cross-sectional and three longitudinal studies. An average of 130 (±70.61) children living with HIV, 138 (±65.37) children exposed to HIV but uninfected and 90 (±86.66) HIV-negative participants were included across the seven studies. Results indicate that blood and CSF immune markers are associated with neurocognitive development/performance in pediatric HIV populations. Only seven studies met the inclusion criteria, therefore, these limited the number of significant conclusions which could have been made by using such an approach. All considered, the evidence suggests that immune dysregulation, as in the case of adult HIV populations, also has a significant association with neurocognitive performance in pediatric HIV populations. [ABSTRACT FROM AUTHOR]