Perinatal HIV Infection Research Articles

B-cell immunity and vaccine induced antibody protection reveal the inefficacy of current vaccination schedule in infants with perinatal HIV-infection in Mozambique, Africa.

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. 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. 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. 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. 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.

Perinatal HIV exposure and infection and caregiver depressive symptoms

ABSTRACT Survival is possible for children perinatally exposed to or infected by HIV in the post-combined antiretroviral therapy era and identifying factors affecting children’s ability to thrive has public health significance. Caregiver mental health is one such factor to consider given its impact on child development, but previous work has not included a full complement of HIV exposure/infection groups within HIV-endemic settings. We compared depressive symptoms among caregivers of 3 groups of 6-10-year-olds in Uganda: children with perinatally acquired HIV infection (CPHIV, n = 102), children with perinatal HIV exposure, but no infection (CPHEU, n = 101), and children without perinatal HIV exposure or infection (CHUU, n = 103). The Hopkins Symptom Checklist was used to assess caregiver depressive symptoms. Generalized linear models were used to estimate group mean differences. Adjusted models included caregiver demographics, social support, and lifetime trauma. Depression symptoms were higher among CPHEU compared to CPHIV caregivers (model coefficient [B] = −3.5, 95%CI −5.3, −1.8). This finding was minimally attenuated following adjustment for covariates (B = −2.2, 95%CI −4.1, −0.4) and among biological mothers. At lower levels of social support and wealth, CPHEU caregivers reported higher levels of depression symptoms than CPHIV caregivers. Our findings point to unmet mental health needs among CPHEU caregivers.

Adoption is not associated with immunological and virological outcomes in children with perinatally acquired HIV infection in the Netherlands.

To provide an overview of the demographics, treatment characteristics and long-term outcomes of children with perinatal HIV-1 infection (PHIV) living in the Netherlands (NL) and to specifically investigate whether outcomes differ by children's adoption status. A prospective population-based open cohort including children with PHIV in NL. We included children with PHIV who had entered HIV care in NL since 2007, in view of a sharp increase in the number of adopted children with PHIV since that year. We compared the proportion with virologic suppression and CD4+T-cell count over time between the following groups of children with PHIV: adopted and born outside NL, non-adopted born in NL, and non-adopted born outside NL, using generalized estimating equations and linear mixed effects models, respectively. To account for the variation in cohort inclusion, we analyzed data of children exposed to at least one year of antiretroviral therapy (ART). We included 148 children (827.5 person-years of follow-up, 72% adopted, age at start care in NL 2.4 (0.5-5.3)). Under-18 mortality was zero. Over the years, a boosted PI-based regimen was most often prescribed. The use of integrase inhibitors increased since 2015. Non-adopted children born in NL were less likely to achieve virological suppression compared to adopted children (OR 0.66, 95%CI 0.51-0.86, p = 0.001), which disappeared after excluding one child with suspected treatment nonadherence (OR 0.85, 95%CI 0.57-1.25, p = 0.400). CD4+T-cell Z-score trajectories were not significantly different between groups. Despite considerable and increasing diversity of the population of children with PHIV in NL, geographical origin and adoption status do not seem to pose important challenges in achieving good immunological and virological outcomes.

Vitamin D and Probability of Developmental Disorders among Perinatally HIV-Affected and Unaffected Ugandan Children.

We tested the hypothesis that vitamin D deficiency (VDD) is associated with higher developmental disorder probability in 604 children with perinatal HIV infection (CPHIV, n = 199), HIV exposed and uninfected (CHEU, n = 196), and HIV unexposed uninfected (CHUU, n = 201). Children at 6-18 years old and their adult caregivers were assessed at enrollment, 6, and 12-month follow-ups. Serum 25-hydroxyvitamin-D (25OHD) levels in children quantified per the NHANES protocol were used to define VD categories as VDD (25OHD < 20 ng/mL), VD insufficient (VDI, 20 ≤ 25OHD ≤ 25 ng/mL), and VD sufficient (VDS = reference group if 25OHD > 25 ng/mL). Perinatal HIV status per DNA polymerase chain reaction/HIV rapid diagnostic tests included: CPHIV, CHEU, and CHUU. Developmental stage was defined as pre-adolescent (age < 11) vs. adolescent (age ≥ 11) years. Caregiver responses to standardized questions from Behavioral Assessment System for Children, Third Edition (BASC-3), were used to calculate probability scores for four disorders, namely: autism (ASD), attention deficit & hyperactivity (ADHD), emotional behavioral disorder (EBD), functional impairment (FI), and resiliency at 0, 6 and 12 months. Multivariable longitudinal models estimated VD-associated standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) in respective probability scores in Statistical Analysis Software (v.9.4). Baseline VDD vs. VDS predicted higher probability scores of moderate clinical importance for ASD, ADHD, EBD, and higher FI among pre-adolescents (SMD = 0.32 to 0.40, 95% CI: 0.00 to 0.74). VDD was not associated with resiliency or any developmental disorders among adolescents. VDD predicted higher developmental disorder and FI scores over 12 months in a developmental stage-dependent manner. This relationship requires further understanding to appropriately target future interventions.

Immune activation and exhaustion marker expression on T-cell subsets in ART-treated adolescents and young adults with perinatal HIV-1 infection as correlates of viral persistence.

HIV-1 infection in memory CD4+ T cells forms a latent reservoir that is a barrier to cure. Identification of immune biomarkers that correlate with HIV-1 reservoir size may aid with evaluating efficacy of HIV-1 eradication strategies, towards ART-free remission and cure. In adults living with non-perinatal HIV-1, the immune exhaustion marker PD-1 on central memory CD4+ T cells (Tcm) correlates with measures of HIV-1 reservoir size. Immune correlates of HIV-1 are less defined in adolescents and young adults with perinatal HIV-1. With multi-parameter flow cytometry, we examined immune activation (CD69, CD25, HLA-DR), and exhaustion (PD-1, TIGIT, TIM-3 and LAG-3) markers on CD4+ T cell subsets (naïve (Tn), central memory (Tcm), and the combination (Ttem) of transitional (Ttm) and effector memory (Tem) cells, in 10 adolescents and young adults living with perinatal HIV-1 (median age 15.9 years; median duration of virologic suppression 7.0 years), in whom HIV-1 reservoir size was measured with the Intact Proviral HIV-1 DNA Assay (IPDA) and an enhanced Tat/Rev limiting dilution assay (TILDA). RNA-seq was also performed on the unstimulated CD4+ T cells. The median total HIV-1 DNA concentration in memory CD4+ T cells was 211.90 copies per million CD4+ T cells. In the 7 participants with subtype B HIV-1 infection, the median intact proviral DNA load was 7.96 copies per million CD4+ T cells. Levels of HLA-DR and TIGIT on the Ttem were correlated with total HIV-1 DNA (r=0.76, p=0.015) and (r=0.72, p=0.023), respectively, but not with intact proviral load or induced reservoir size. HIV-1 DNA load was also positively correlated with transcriptional clusters associated with HLA-DR expression by RNA-seq. In contrast, PD-1 expression on Tcm was inversely correlated with total HIV-1 DNA (r=-0.67, p=0.039). Reservoir size by IPDA and TILDA were correlated (r=0.81, p=0.036). Thus, in this cohort of youths with long-standing treated perinatal infection, HLA-DR and TIGIT on Ttem were the key correlates of HIV-1 infected cell frequencies by total HIV-1 DNA, and not PD-1. Total HIV-1 DNA was negatively correlated with PD-1 expressing Tcm. These differences in longstanding perinatal HIV-1 infection compared with adult infection requires further study in larger cohorts.

Prevalence of neurodevelopmental delays in infants with perinatal HIV infection in comparison with HIV exposure in rural South Africa.

Assessing neurodevelopmental functioning in early infancy is essential as this is a critical period for infant development. Infants born to mothers with HIV are at a greater risk of developmental delays than those born to mothers without HIV. In this study, we analyzed differences in early neurodevelopmental functioning for infants with HIV exposure versus HIV infection to inform infant screening and early intervention. Participants were recruited from community health centers in Mpumalanga Province, South Africa. Prenatally, mothers completed baseline demographic assessment at 8 to 24-week gestation periods. Infant neurodevelopment was assessed using the Bayley Infant Neurodevelopmental Screener (BINS) 12 months postnatally. Five areas of development were assessed: cognition, receptive communication, expressive communication, fine motor ability, and gross motor ability. Postnatal infant assessment using the BINS revealed that infants were at risk for neurodevelopmental delays across all domains assessed. Notably, infants exposed to HIV, regardless of HIV status, were 'at emerging risk' or 'at clear risk' for cognitive (43.5%), receptive communication (38.2%), expressive communication (53.1%), fine motor (49.9%), and gross motor delays (55.6%). Differences were noted by HIV status in the cognition domain, such that HIV-exposed infants were more likely to be at emerging or clear risk than HIV-infected infants. There was a different trend with gross motor delays, such that HIV-infected infants were at a greater risk for motor delays than HIV-exposed, uninfected infants. Screening tools for this vulnerable population provide valuable early life assessment to determine infant needs for intervention and treatment planning. Such interventions may mitigate the impact of HIV status on neurodevelopmental health generally and cognition.

How CD4+ T Cells Transcriptional Profile Is Affected by Culture Conditions: Towards the Design of Optimal In Vitro HIV Reactivation Assays.

Unstimulated or stimulated CD4+ T cells of three young adults with perinatal HIV-infection were isolated from PBMCs before or after culture in RPMI medium or autologous plasma. Transcriptomes were sequenced using Oxford Nanopore technologies. Transcriptional profiles revealed the activation of similar pathways upon stimulation in both media with a higher magnitude of TCR cascade activation in CD4+ lymphocytes cultured in RPMI. These results suggest that for studies aiming at quantifying the magnitude of biological mechanisms under T cell activation, the autologous plasma could better approximate the in vivo environment. Conversely, if the study aims at defining qualitative aspects, then RPMI culture could provide more evident results.

Hope for the future protects against suicidal ideation among adolescents and young adults affected by perinatal HIV

ABSTRACT Hope for the future has been found protective against suicidal ideation (SI) in adolescents and young adults (AYA) yet has not been examined in AYA with perinatal HIV-infection (PHIV) or AYA who were perinatally HIV-exposed but uninfected (PHEU), who are at higher risk for SI than general populations. Using data from a New York City-based longitudinal study of AYAPHIV and AYAPHEU enrolled when 9–16 years old, we examined associations between hope for the future, psychiatric disorders, and SI over time using validated measures. Generalized estimating equations were used to estimate differences in mean hope for the future scores by PHIV-status and to estimate adjusted odds ratios for associations between hope for the future and SI. AYA reported high hope for the future scores and low SI across visits, irrespective of PHIV-status. Higher hope for the future scores were associated with lower odds of SI (AOR = 0.48, 95% CI: 0.23, 0.996). Mood disorder was associated with increased odds of SI (AOR = 13.57, 95% CI: 5.11, 36.05) in a model including age, sex, follow-up, PHIV-status, mood disorder, and hope for the future. Understanding how hope can be cultivated and how it protects against SI can help to inform preventive interventions for HIV-affected AYA.

Disability, fatigue and peripheral neuropathy in adolescents with perinatal HIV infection

ABSTRACT Perinatally HIV-infected adolescents (PHIVA) experience many physical sequelae, but little is known about their levels of disability, fatigue or peripheral neuropathy. This study aimed to determine these sequelae through a cross-sectional analysis in a population of PHIVA and HIV-negative adolescents, based in Johannesburg, South Africa. Outcome measures used were the HIV-related Fatigue Scale, World Health Organization Disability Assessment Schedule 2.0 and the Brief Peripheral Neuropathy Screen, to measure fatigue, level of disability and peripheral neuropathy, respectively. Of the 249 participants assessed, 59% (n = 147) were PHIVA, and the mean age of the participants was 12 years. Clinical data for the PHIVA group showed that the majority (87.1%) were virally suppressed. When compared to the HIV-negative group, PHIVA presented with significantly greater levels of fatigue intensity [1.2(SD±0.5) vs. 1.5(SD±0.9) p = 0.022] and disability [9.2(±6.8) vs. 11.5(±8.9) p = 0.023], with specific limitations in mobility, self-care and participation. No significant differences in peripheral neuropathy were found. In conclusion, PHIVA face challenges with disability and fatigue highlighting the necessity of comprehensive management for this population.

Pulse wave velocity in early-treated children living with perinatal HIV infection is similar to uninfected children.

HIV is associated with accelerated cardiovascular disease, due to HIV-associated metabolic abnormalities, antiretroviral therapy (ART), and HIV itself. Carotid-femoral pulse wave velocity (PWV) is the noninvasive gold standard measurement of arterial stiffness, and associated with incident vascular events in adults. It is unclear if arterial stiffness is accelerated in children living with perinatal HIV (CHIV) who initiate ART early in life. We compared the longitudinal trajectory of PWV in CHIV to children unexposed to HIV. A secondary comparison compared HIV exposed uninfected children (CHEU) to unexposed children. Four hundred and sixty-five children (141 CHIV, 160 CHEU, 164 unexposed) previously in the children with HIV early antiretroviral therapy (ART) (CHER) and P1060 trials were followed annually at Tygerberg Children's Hospital, South Africa between 2014 and 2020. CHIV initiated ART in infancy or early childhood, with excellent ART adherence and largely sustained viral suppression. The primary outcome was PWV, measured using the Vicorder system, and evaluated using linear mixed effects models. Median (interquartile range) age at first PWV measurement was 8.64 (7.7-9.1) years, and median follow-up time 2.9 (1.6-4.0) years. Adjusted analyses showed no significant mean difference in PWV in CHIV and CHEU compared to unexposed [CHIV: 0.101 m/s, 95% confidence interval (CI) -0.012 to 0.214; CHEU: 0.068 m/s, 95% CI -0.047 to 0.183], after adjusting for gender, age, ethnicity, mean arterial pressure, resting average heart rate and family history of cardiovascular disease. Early-treated CHIV with sustained viral suppression have similar PWV to unexposed children. Excellent adherence and early ART initiation may protect against cardiovascular disease.

Integrase Strand Transfer Inhibitor Use in Children with Perinatal HIV-1 Infection: A Narrative Review.

Integrase strand transfer inhibitors (INSTIs), including raltegravir (RAL), dolutegravir (DTG), elvitegravir (EVG), bictegravir (BIC), and cabotegravir (CAB), are increasingly used, given excellent data on their efficacy, effectiveness, and tolerability profile in adults, while data in children are accumulating. To review the most recent evidence on the efficacy, effectiveness, safety, and resistance of INSTIs in children, a quick narrative review of the available literature data was performed using the MEDLINE/PubMed and Scopus databases, including only English-language studies, published between 2009 and 2022. Six studies (259 children) on RAL use, 17 studies (3,448 children) on DTG, 2 studies (73 children) on EVG, and 1 study (102 children) on BIC were retrieved. Results on efficacy and effectiveness were close to those reported in adult studies, suggesting similarities between children and adult population. Resistance to RAL was detected in four studies, ranging between 5.0% to 35.3% of participants. In four studies resistance to DTG occurred in 12.4% to 22% of children. Adverse events to RAL have been uncommon reported. In studies on EVG, 8% to 74% of children developed uveitis, nausea, or abdominal pain. In DTG studies, the proportion of weight gain ranged from 10% to 87%, and neuropsychiatric effects ranged 1% to 16% of participants. One BIC study reported adverse events >10% of participants. The evidence supports high efficacy and low toxicity of INSTIs in pediatric and adolescent populations.

Development of retinal structure in perinatally HIV-infected children and adolescents: A longitudinal and cross-sectional assessment.

In perinatally HIV-infected (PHIV) children, cross-sectional studies reported on subtle structural retinal differences and found associations between the retina and structural brain changes. Our objective is to investigate whether neuroretinal development in PHIV children is similar to the development in healthy matched controls and to explore associations with the brain structure. We measured RT using optical coherence tomography (OCT) on two occasions in 21 PHIV children or adolescents and 23 matched controls-all with good visual acuity-with a mean interval of 4.6 years (SD 0.3). We also included 22 participants (11 PHIV children and 11 controls) together with the follow-up group for a cross-sectional assessment using a different OCT device. Magnetic resonance imaging (MRI) was used to assess the white matter microstructure. We used linear (mixed) models to assess changes in RT and its determinants (over time), adjusting for age and sex. The development of the retina was similar between the PHIV adolescents and controls. In our cohort, we found that changes in the peripapillary RNFL was significantly associated with changes in WM microstructural makers: fractional anisotropy (coefficient = 0.030, p = 0.022) and radial diffusivity (coefficient = -0.568, p = 0.025). We found comparable RT between groups. A thinner pRNFL was associated with lower WM volume (coefficient = 0.117, p = 0.030). PHIV children or adolescents appear to have a similar development of the retinal structure. In our cohort, the associations between RT and MRI biomarkers underscore the relation between retina and brain.

Virological failure of antiretroviral therapy and associated social and clinical factors in children and adolescents living with HIV

According to the World Health Organization, sustained virological suppression of 90 % should be achieved among children and adolescents living with HIV / AIDS, which makes it important to assess the prevalence of virological failure of antiretroviral therapy. The aim of this study was to determine the prevalence of virological failure and the clinical factors associated with it, as well as therapeutic drug monitoring in groups divided by the viral load level among children and adolescents with HIV. Materials and Methods: A retrospective analysis of the medical records of 184 children and adolescents receiving antiretroviral therapy and registered at the Irkutsk Regional Center for the Prevention and Control of AIDS and Infectious Diseases, Irkutsk, was carried out. The study included 172 children aged 1-18 years with perinatal HIV infection. Patients were divided into groups depending on the level of viral load: group 1 – 21 patients with viral load &gt; 1000 copies/ml of plasma, group 2 – 42 patients with viral load 50– 1000 copies/ml of plasma, group 3 – 109 patients with undetectable viral load (&lt; 50 copies/ml). All patients underwent standard tests in accordance with clinical guidelines for the treatment of HIV infection in children, as well as therapeutic drug monitoring. Results. Against the background of ongoing antiretroviral therapy, a significant number of patients 21 / 172 (12,2 %) experienced virological failure. The proportion of children and adolescents with incomplete suppression of HIV replication is 42 / 172 (24,4 %). Statistically significant differences were obtained by changing the ART regimen (p = 0,031). In the first group, the proportion of patients who changed the therapy regimen is 7 / 21 (33,3 %), which is two times less than in the group with a zero viral load of 70 / 109 (64,2 %). There are differences in the proportion of children and adolescents with zero concentrations of ritonavir and lopinavir (p = 0,020 and p = 0,012) in the three compared groups. The distribution of patients with zero concentrations was as follows: for ritonavir in the first group 3 / 17 (17,6 %), in the second – 8/37 (21,6 %), in the third group – 4/80 (5 %); for lopinavir – 4/17 (23,5 %), 6/36 (16,7 %), 3/80 (3,8 %), respectively. Conclusion. This study demonstrates that the prevalence of virological failure among children and adolescents receiving ART remains high. To achieve sustained virological suppression in children and adolescents taking a protease inhibitor regimen, adherence to therapy must be increased. As one of the methods for assessing adherence, therapeutic drug monitoring can be used.

1266. Effects of Rapid Initiation of Antiretroviral Therapy in an Urban Clinic Setting

Abstract Background Rapid initiation of antiretroviral therapy (ART), i.e. within 72 hours of diagnosis, in people living with HIV (PLWH) has shown improved viral suppression, medication adherence, and retention in care, compared to deferral until initial labs have resulted. More real-world experience with rapid ART programs is needed, however, particularly among clinics in resource-limited settings that serve a complex and largely uninsured or underinsured population, such as the HIV clinic at SUNY Downstate Medical Center. In 2017, the clinic implemented rapid ART in select PLWH. Methods This was a single-center retrospective chart review of patients seen at our HIV clinic between January 2015 and June 2021. Patients were included if they were ART-naïve or off ART for &amp;gt; 3 months. Exclusion criteria included baseline undetectable viral load (VL) and perinatal HIV infection. Patients were assigned to standard or rapid start groups based on time from intake to initiation of ART. The primary outcome was proportion of patients with VL &amp;lt; 50 copies/mL at week 52. Secondary outcomes were proportion of patients with VL &amp;lt; 200 copies/mL, retention in care, and mean weight change from baseline, all at week 52; time from intake to ART; and time to viral suppression. Results As shown in Table 1, of the 190 patients that were included, 133 were rapid start while 77 were standard start. 103 patients had baseline resistance data; only 1 had integrase stand inhibitor resistance. Median time to ART was 0 days and 2.5 weeks in the rapid and standard groups, respectively. The most common initial regimen was BIC/FTC/TAF in both groups (49.6%, 31.2%). As described in Tables 2 and 3, 62.1% and 73.7% of patients had VL &amp;lt; 50 and &amp;lt; 200 copies/mL at week 52, respectively. Nearly 73% of patients remained in care at week 52, with similar rates between groups. Time from ART to viral suppression was similar between groups. Conclusion Rapid ART was well-tolerated but resulted in similar viral suppression and retention in care at week 52 compared to standard ART. However, rapid ART resulted in quicker viral suppression, although further evaluation of the clinical impact of this finding is needed. This study highlights the need for a multifaceted approach to engaging patients with HIV throughout the care continuum to ensure retention in care. Disclosures All Authors: No reported disclosures.

Comorbid disease in children and adolescents with perinatal HIV infection: A pilot study

Background. With the increased use of combination antiretroviral therapy, the mortality of people living with HIV has decreased significantly, which has led to an increase of comorbidity and secondary HIV-related pathology in both adults and also in children and adolescents living with HIV infection. The incidence of children and adolescents with HIV infection and those in the general population varies significantly.The aim. To assess the frequency and range of chronic comorbidities in children and adolescents with perinatal HIV infection Methods. We carried out an observational study. Data on the incidence of 161 children with perinatal HIV infection registered in the Irkutsk Regional AIDS Center were copied.Results. Overall incidence of tuberculosis (18633.5 per 100 000 children), diseases of the digestive system (24844.7 per 100 000 children), diseases of the eye and adnexa (28571.4 per 100 000 children), diseases of the nervous system (18012.4 per 100 000 children), mental and behavioral disorders (13,664.6 per 100 000 children) in children with perinatal HIV infection is the higher than in children of comparable age. The overall incidence values of the endocrine system diseases, eating and metabolic disorders, diseases of the ear and mastoid process, diseases of the circulatory system, diseases of the genitourinary system, as well as congenital disorders and chromosomal disorders in children and adolescents with and without perinatal HIV infection are comparable.Conclusion. The prevalence of diseases of the circulatory, respiratory and genitourinary systems in children with perinatal HIV infection is comparable to that in the corresponding population. Prevalence of tuberculosis, anemia, diseases of the gastrointestinal tract, diseases of the eye and adnexa, diseases of the nervous system, mental and behavioral disorders is higher compared to children not exposed to HIV.

Longitudinal comparison of insulin resistance and dyslipidemia in children with and without perinatal HIV infection in South Africa.

HIV infection is associated with insulin resistance and dyslipidaemia driven by HIV-associated immune dysregulation and antiretroviral therapy (ART). Children living with perinatally acquired HIV (CHIV) face many decades of exposure to these factors. We evaluated the longitudinal trajectory of insulin resistance and dyslipidaemia in CHIV and HIV-exposed uninfected children (CHEU), compared with children HIV-unexposed (CHU). Four hundred and eighty-five children (141 CHIV, 169 CHEU, 175 CHU) aged 5-16 years, previously part of CHER and P1060 trials, were followed annually at Tygerberg Children's Hospital, South Africa. The primary outcome was Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Secondary outcomes included low-density lipoprotein (LDL) cholesterol, triglyceride-to-HDL ratio, android fat mass and SBP. Outcomes were evaluated using linear mixed effects models, adjusting for potential confounders. CHIV had 73% greater HOMA-IR than CHU in ages 6-8 years (95% CI 15.9-158.2%, P < 0.001), and 24.7% greater HOMA-IR than CHU in ages 9-10 years (0.3-55.1%, P = 0.04). By 10-11 years, the difference was not significant (P = 0.161). Longitudinally, triglyceride-to-HDL was 47.94% (34.50-62.73%, P < 0.001) higher in CHIV vs. CHU; LDL was 0.25 mmol/l (0.10-0.39, P = 0.001) higher in CHIV vs. CHU; android fat mass was 11.57% (-21.11 to -0.87%, P = 0.035) lower in CHIV than CHU. No significant difference in SBP was found. CHEU and CHU had similar outcomes. Early-treated CHIV have elevated insulin resistance, which resolves with time. Triglyceride-to-HDL ratio and LDL cholesterol were elevated into puberty. CHIV should be monitored for insulin resistance, dyslipidaemia and subclinical cardiovascular disease.

PP 4.26 – 00201 Study of reservoir size and telomere length in children with perinatal HIV-1 infection who achieved late viral suppression

PP 4.26 – 00201 Study of reservoir size and telomere length in children with perinatal HIV-1 infection who achieved late viral suppression

Zaburzenia poznawcze u dzieci i młodzieży z wrodzonym zakażeniem HIV w Polsce

The aim of the study was to assess the presence of cognitive impairments in children and adolescents with vertically transmitted HIV infection and to determine possible relationships with clinical and socio-demographic variables. Fifty children with perinatal HIV infection aged 6-18 years were included in the experimental group (PHIV+). Two sex- and age-matched groups were recruited as reference groups: (1) a PHEU group that included 24 healthy children perinatally HIV-exposed but uninfected, and (2) an HIV-nA group that included 43 healthy children of uninfected parents. CANTAB Research Suite was used to assess cognitive functioning. In comparison with the HIV-nA group, the PHIV+ group scored worse in movement execution, shifting and flexibility of attention, reversal learning and working memory. In comparison with the PHEU group, the PHIV+ group had significantly longer planning time in the memory task. The analysis of results for the 12-18 year-old age group revealed deterioration of cognitive functions in all tests of the PHIV+ children in comparison with the HIV-nA group. A higher logarithm of viral load at the start of the ARV treatment was associated with worse results in the use of feedback, shifting of attention, cognitive flexibility and worse information processing. Results of the research indicate deterioration of executive functioning in the PHIV+ group associated with longer duration of HIV neuroinfection and severity of infection before treatment.

Sexual Development in Perinatally HIV-Infected Young People: A Systematic Review and Explorative Study.

Similar to other young people with a chronic health condition, perinatally HIV-infected (PHIV) adolescents may have an impacted sexual development. This paper aims to compare sexual milestones of PHIV to HIV uninfected peers, through a systematic review (SR) and explorative study. We performed a systematic search in 4 electronic databases (Medline, Embase, Web of Science, and Scopus), according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Last search in all databases was performed in May 2021. We included studies that reported on quantitative data of any of the main outcomes and compared PHIV to HIV uninfected control groups. Main outcomes were defined as the occurrence and/or debut age of sexual milestones (falling in love, having been in a romantic relationship, masturbation, kissing, non-genital caressing (feeling or petting, touching), genital caressing (fingering, handjob), giving or receiving oral sex, and penetrative sex (vaginal or anal). We excluded case reports, audits, guidelines, editorials, abstracts, studies that reported on behaviorally infected HIV patients, studies that did not include an HIV uninfected control group and studies that could not be translated to English or Dutch. We used the Agency for Health Care Research and Quality (AHRQ) Checklist for quality assessment. We performed qualitative synthesis of the data. In the explorative study, we compared sexual milestones of PHIV and HIV uninfected controls matched for age, sex, ethnicity and educational level, using a subset of questions of a validated questionnaire. We included eighteen studies in the SR, describing outcomes of an estimated 1,963 participants. Seventeen studies compared the occurrence and/or debut age of intercourse in PHIV and HIV uninfected controls and 4 studies reported on any of the other sexual milestones. The majority of studies found no difference in occurrence (12 of 16 studies) or debut age (6 of 8 studies) of intercourse in PHIV compared to controls. Two of 4 studies reporting on any of the other milestones found no significant differences between PHIV and HIV uninfected controls. In the explorative study, we included ten PHIV participants and 16 HIV uninfected, matched controls. PHIV tended to report a later debut age of sexual milestones than controls (not significant). The SR includes only a small number of studies and few studies report on non-penetrative milestones. The explorative study adds to this review by including non-penetrative milestones and comparing PHIV to HIV-uninfected, well-matched controls. However, the sample size was small. PHIV seem to engage in sexual activities and achieve sexual milestones at a similar rate as their HIV uninfected peers, with a tendency of a later start in well treated PHIV. The review was registered in the PROSPERO database (CRD42021252103) and funded by AIDSfonds. AIDSfonds had no role in the study design or interpretations of this study. ter Haar AM, Fieten A, Van den Hof M, et al. Sexual Development in Perinatally HIV-Infected Young People: A Systematic Review and Explorative Study. Sex Med 2022;10:100578.

Real-world experience with weight gain among pregnant women living with HIV who are using integrase inhibitors.

We assessed real-world weight change and pregnancy outcomes among pregnant women living with HIV who used integrase strand transferase inhibitor (INSTI)-based combined antiretroviral therapy (cART). In a retrospective cohort study from 2014 to 2021 for prevention of perinatal HIV infection, we evaluated changes in weight from the first prenatal visit to near delivery for two groups. The categories of change were: low (< 0.18 kg/week), normal (0.18-0.59 kg/week), and high (> 0.59 kg/week). The backbones were lamivudine + tenofovir disoproxil or lamivudine + zidovudine. The comparison groups were women with body mass index (BMI) < 25 kg/m2 versus BMI ≥ 25 kg/m2 and INSTI-naïve versus INSTI-experienced. Continuous variables were analysed with a Kruskal-Wallis test and count or categorical data with χ2 tests. We enrolled 198 pregnant women. At study entry, 74 had BMI < 25 kg/m2 and 124 had BMI ≥ 25 kg/m2 . Excess gestational weight gain was more frequent among women who were INSTI-naïve among both BMI groups (< 25 and ≥ 25). However, the proportion of participants per weight change category was only significantly different between INSTI-naïve women with baseline BMI < 25 kg/m2 and INSTI-experienced women with BMI < 25 kg/m2 . In particular, INSTI-naïve women with BMI < 25 kg/m2 had significantly higher rates of excess gestational weight gain (31.6%) compared with participants with BMI < 25 kg/m2 who conceived while on INSTIs (11.8%, p=0.004). Rates of unfavourable pregnancy outcomes were low and did not differ significantly between groups. INSTI-naïve participants with BMI < 25 kg/m2 gained more weight during pregnancy than participants with BMI ≥ 25 kg/m2 who conceived while using INSTIs. Rates of adverse pregnancy outcomes did not differ between the groups.