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Description: New York State Department of Health (NYSDOH) recommends that all pregnant patients receive human immunodeficiency virus (HIV) screening during pregnancy. This study assessed the prevalence of repeat prenatal HIV testing and factors associated with receipt of the recommended tests. Methods: Data from the NYSDOH newborn screening program were used to randomly select pregnant persons without HIV who delivered a liveborn infant in 2017. Receipt of repeat testing was defined as an initial HIV test in the first or second trimesters and the final in the third trimester (relaxed); or an initial test in the first trimester and the final in the third trimester (strict). Relative risks (RRs) and 95% confidence intervals were calculated in bivariate analyses. Adjusted RRs were calculated to determine associations between demographic and clinical factors and receipt of repeat HIV testing. Results: The cohort included 2,225 individuals. Roughly one quarter (24%) received the recommended tests in the first or second and third trimesters and 17% received them in the first and third trimesters. Individuals who reported Hispanic or Asian race/ethnicities, had government-funded insurance, started prenatal care in the first trimester, delivered in New York City, or received prenatal hepatitis C virus screening were significantly more likely to receive repeat testing using either definition. Conclusions: Despite the benefits and cost-effectiveness, the prevalence of repeat prenatal HIV screening during the third trimester remains persistently low. Improved messaging and targeted education and resources to assist prenatal providers could reinforce the importance of repeat testing and reduce residual perinatal HIV transmission. [ABSTRACT FROM AUTHOR]

We have previously shown accelerated ageing in adolescents perinatally infected with HIV (PHIV +), based on discrepancies between epigenetic and chronological age. The current study examines follow-up longitudinal patterns of epigenetic ageing and the association of epigenetic ageing with cognition as well as whole brain structure changes in PHIV + and healthy controls enrolled in the Cape Town Adolescent Antiretroviral Cohort Study (CTAAC). The Illumina EPIC array was used to generate blood DNA methylation data from 60 PHIV + adolescents and 36 age-matched controls aged 9-12 years old at baseline and again at a 36-month follow-up. Epigenetic clock software estimated two measures of epigenetic age acceleration: extrinsic epigenetic accelerated ageing (EEAA) and age acceleration difference (AAD) at both time points. At follow-up, each participant completed neuropsychological testing, structural magnetic resonance imaging, and diffusion tensor imaging. At follow-up, PHIV infection remains associated with increased EEAA and AAD. Accelerated epigenetic ageing remained positively associated with viral load and negatively associated with CD4 ratio. EEAA was positively associated with whole brain grey matter volume and alterations in whole brain white matter integrity. AAD and EEAA were not associated with cognitive function within the PHIV + group. Measures of epigenetic ageing, as detected in DNA methylation patterns, remain increased in PHIV + adolescents across a 36-month period. Associations between epigenetic ageing measures, viral biomarkers, and alterations in brain micro- and macrostructure also persist at 36-month follow-up. Further study should determine if epigenetic age acceleration is associated with cognitive functional changes due to brain alterations in later life.

Supplemental Digital Content is Available in the Text. Background: With few psychometrically evaluated HIV-related stigma measures for adolescents and young adults living with HIV, we examined the developmental applicability (ie, validity) of 2 subscales of the commonly used stigma measure, the Social Impact Scale, among a cohort of adolescents and young adults with perinatally acquired HIV. Setting: Data were obtained from a New York City longitudinal study (N = 340). This study primarily comprised Black and Latinx adolescents and young adults with either perinatally acquired HIV or those with perinatal exposure but who are uninfected. Data for this analysis were obtained from the population with perinatally acquired HIV and spanned approximately a 15-year survey period (2003–2018). Methods: A confirmatory factor analysis was used at 7 time points to assess whether the Social Rejection and Internalized Shame subscales were consistent in this cohort over time. Overall and individual Cronbach alphas were reported to show the strength of the internal consistency. Results: The mean age from baseline to follow-up 6 ranged from 12 to 23 years over the study period. The Social Rejection subscale was acceptably valid across follow-up periods with strong factor loadings and Cronbach alphas higher than 0.70. However, the Internalized Shame subscale was less valid among younger adolescents. Starting at follow-up 2, we observed better validity with the Internalized Shame subscale performance. Conclusion: Future research must consider mechanisms for developing and adapting measures from a developmental perspective to best measure the experiences of HIV-related stigma among younger populations. [ABSTRACT FROM AUTHOR]

Introduction: Because of privacy and ethical concerns, the data cannot be made available because of the sensitivity of the HIV data and the relatively small sample and ease of identifying people if a few demographics are known. Few studies have examined intimate partner violence (IPV) victimization among adolescents and young adults (AYAs) with perinatally acquired HIV-infection (PHIV) or perinatal HIV exposure without infection (PHEU) in the United States. The purpose of this study was to (1) estimate lifetime and past-year prevalence of IPV victimization and (2) examine correlates of IPV victimization by subtype (physical, psychological, and sexual) and severity (low, moderate, and severe). Methods: Data came from the sixth interview of an ongoing New York City-based longitudinal study of primarily Black and Latinx AYAPHIV and AYAPHEU. We examined 232 participants (142 PHIV; 90 PHEU) who had reported having been in at least 1 romantic relationship. We used logistic regression models to explore the association between IPV victimization outcomes and select sociodemographic, psychiatric, and environmental factors. Models were adjusted for age, gender, race, ethnicity, and HIV status. Results: IPV victimization prevalence was 84% for lifetime and 65% for the past year. There were no differences in IPV victimization prevalence by PHIV status. Having a recent substance use disorder, reporting higher levels of neighborhood stress, and being male were all positively associated with at least 1 IPV outcome; stronger familial relationships exhibited a protective effect. Conclusions: The present study suggests that the prevalence of IPV victimization among AYAPHIV and AYAPHEU is exceedingly high that warrants targeted IPV screening and programming for this population. [ABSTRACT FROM AUTHOR]

Objective This article aims to assess statewide uptake of HIV repeat testing in the first 2 years after the implementation of an amendment to the Illinois Perinatal HIV Prevention Act (IPHPA) mandating universal repeat HIV testing in the third trimester. Study Design This is a retrospective, population-based study of all birthing individuals in Illinois (2018–2019). Data were collected using the state-mandated closed system of perinatal HIV test reporting. We evaluated the incidence of mother–infant pairs with negative early tests and repeat third-trimester tests (RTTTs) performed in adherence with the law, as well as the timing of the performance of the RTTTs (outpatient vs. inpatient). Chi-square tests of trend by quarter were performed to ascertain sustainability. Results Of 138,805 individuals delivered in 2018, 80.6% presented with early test and RTTTs. In 2018, outpatient RTTTs improved from 71.8% (quarter 1) to 85.1% (quarter 4; p < 0.001). In 2018, the proportion of mother–infant dyads who received testing that was adherent to the IPHPA Amendment was 92.1, 95.5, 96.7, and 96.4% in quarters 1 through 4, respectively (p < 0.001). In 2019, outpatient RTTTs performance remained high (87.4%) and stable (p = 0.06). In 2019, 99.9% of mother–infant dyads had testing adherent to the mandate in quarters 1 through 4 (p = 0.39). Of individuals who presented without RTTTs, 93.5% (2018) and 98.8% (2019) underwent inpatient testing before delivery. Conclusion Implementation of RTTTs in Illinois was rapid, successful, and sustained in its first 2 years. Public health methodologies from Illinois may benefit other states implementing RTTT programs. Key Points In 2018, Illinois enacted statewide RTTT for HIV among all parturients. In 2019, over 99% of mother–infant dyads had documentation of both early and repeat HIV testing before hospital discharge. Implementation of repeat third-trimester HIV testing in Illinois was rapid, successful, and sustained in its first 2 years. Public health methodologies from Illinois may benefit other states implementing similar programs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Data on children and adolescents with HIV and coronavirus disease 2019 (COVID-19) co-infection are limited. Clinical and antibody data related to COVID-19 infection in adolescents living with perinatally acquired HIV (ALPHIV) and originally enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) study were collected. We present a descriptive analysis of 53 ALPHIV who were tested for anti-SARS-CoV-2 antibodies. Just over half (53%) of the adolescents tested had positive anti-SARS-CoV-2 antibodies with only one participant describing a prior history of possible symptomatic infection. Contribution: The study contributes to the understanding of SARS-CoV-2 infection and vaccination practices in HIV-positive adolescents.

We recently demonstrated that adolescents perinatally infected with HIV-1 (PHIV+) have accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock. However, whether epigenetic age acceleration in PHIV+ impacts brain development at the macro- and microstructural levels of brain anatomy has not been studied. We report on a cross-sectional study of PHIV+ enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 180 PHIV+ aged 9 to 12 years. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration (AgeAccelerationResidual) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent T1 structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). In order to investigate the associations of chronological age, sex, epigenetic age acceleration and treatment variables (CNS penetration effectiveness score (CPE)) of antiretroviral regimen on brain structure in PHIV+, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, cortical surface area and DTI measures of white matter microstructural integrity. The mean DNAm age (16.01 years) of the participants was higher than their mean chronological age (10.77 years). Epigenetic age acceleration contributed more to regional alterations of brain volumes, cortical thickness, cortical surface areas and neuronal microstructure than chronological age, in a range of regions. CPE positively contributed to volume of the brain stem. Understanding the drivers of epigenetic age acceleration could lead to valuable insights into structural brain alterations, and the persistence of neurocognitive disorders in seen in PHIV+ .

Abstract Introduction Nigeria has a low uptake of early infant diagnosis (EID) of HIV despite its high pediatric HIV infection rate. Efforts to increase the EID of HIV have been limited by many factors. This research assessed EID uptake and challenges service providers experienced in providing routine care for HIV-exposed infants. Methods This is a mixed-method study at primary health centers (PHCs) in Lagos state, Nigeria. The quantitative component of the research was a review of the PMTCT Infant Follow-up Register at a purposive sample of 22 PHCs of Lagos State. The number of HIV-exposed infants (HEIs) returned for a dried blood sample (DBS) collection, date of collection, and the infant’s EID results for one year preceding the study were captured on Research Electronic Data Capture (RedCap). In-depth interviews were conducted with service providers purposively selected per participating PHC. Electronic transcripts were analyzed using MAXQDA 2020 (VERBI Software, 2019). Results Twenty-two Lagos State primary health centers participated in the research. Fifteen PHCs (68.2%) had PMTCT HIV counseling and Infant follow-up registers. Documentation of DBS sample collection was observed in 12 (54.6%) PHCs. Both DBS sample collection and EID results documentation were observed in only nine (40.9%) PHCs. In-depth interviews revealed both maternal and health systems’ challenges to EID. The denial of HIV status was the only maternal factor reported as a barrier against the use of EID services. Health systems challenges include unavailability of EID services, uncertainty regarding whether EID is performed in a facility, referral to secondary health facilities for EID services (leading to losses to follow-up), and delay in getting results of EID. Task-shifting of DBS collection by nurses was suggested as means to increase access to EID services. Conclusions There is a need to expand EID services and address women’s denial of HIV infection. Counseling women and linkage to available services are emphasized. Re-training of health workers on DBS collection and proper documentation of EID services were noted as key to improving the implementation of early infant diagnosis of HIV in the state.

Introduction: Nigeria has a low uptake of early infant diagnosis (EID) of HIV despite its high pediatric HIV infection rate. Efforts to increase the EID of HIV have been limited by many factors. This research assessed EID uptake and challenges service providers experienced in providing routine care for HIV-exposed infants. Methods: This is a mixed-method study at primary health centers (PHCs) in Lagos state, Nigeria. The quantitative component of the research was a review of the PMTCT Infant Follow-up Register at a purposive sample of 22 PHCs of Lagos State. The number of HIV-exposed infants (HEIs) returned for a dried blood sample (DBS) collection, date of collection, and the infant's EID results for one year preceding the study were captured on Research Electronic Data Capture (RedCap). In-depth interviews were conducted with service providers purposively selected per participating PHC. Electronic transcripts were analyzed using MAXQDA 2020 (VERBI Software, 2019). Results: Twenty-two Lagos State primary health centers participated in the research. Fifteen PHCs (68.2%) had PMTCT HIV counseling and Infant follow-up registers. Documentation of DBS sample collection was observed in 12 (54.6%) PHCs. Both DBS sample collection and EID results documentation were observed in only nine (40.9%) PHCs. In-depth interviews revealed both maternal and health systems' challenges to EID. The denial of HIV status was the only maternal factor reported as a barrier against the use of EID services. Health systems challenges include unavailability of EID services, uncertainty regarding whether EID is performed in a facility, referral to secondary health facilities for EID services (leading to losses to follow-up), and delay in getting results of EID. Task-shifting of DBS collection by nurses was suggested as means to increase access to EID services. Conclusions: There is a need to expand EID services and address women's denial of HIV infection. Counseling women and linkage to available services are emphasized. Re-training of health workers on DBS collection and proper documentation of EID services were noted as key to improving the implementation of early infant diagnosis of HIV in the state. [ABSTRACT FROM AUTHOR]

Given poor adherence to treatment and prevention techniques, condomless sex jeopardizes adolescents and young adults (AYA) with perinatally-acquired HIV-infection (PHIV) or perinatal HIV-exposure who are uninfected (PHEU). We examined condomless sex and its association with PHIV-status, psychiatric disorder, and sociodemographics. Data come from a US-based study of primarily Black and Latinx AYAPHIV and AYAPHEU (N = 340). Linear regression models examined condomless sex longitudinally by PHIV-status, psychiatric trajectories, and sociodemographics. Rates of viremia (AYAPHIV) and PrEP use (AYAPHEU) were assessed. 56% of participants reported recent condomless sex, with higher prevalence among: AYAPHEU vs. AYAPHIV (24% vs. 19%, p = 0.017); Latinx vs. non-Latinx AYA (25% vs. 17%, p = 0.014); and AYA with increasing psychiatric comorbidity (44%) and consistent anxiety (23%) vs. low-level disorder (17%; p < 0.05). AYAPHIV had high rates of unsuppressed viral load and AYAPHEU limited PrEP use. Preventing condomless sex is challenging within AYAPHIV and AYAPHEU. Developing accessible combination HIV/mental health interventions is much-needed. [ABSTRACT FROM AUTHOR]

Katherine Tassiopoulos,1 Yanling Huo,2 Deborah Kacanek,2 Kathleen Malee,3 Sharon Nichols,4 Claude A Mellins,5 Stephan Kohlhoff,6 Russell B Van Dyke7 On behalf of the Pediatric HIV/AIDS Cohort Study1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 2Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 3Departments of Infectious Diseases and Psychiatry and Behavioral Science, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 4Department of Neurosciences, University of California San Diego, La Jolla, CA, USA; 5Psychiatry and Sociomedical Sciences, Columbia University, New York, NY, USA; 6Division of Pediatric Infectious Diseases, SUNY Downstate Medical Center, Brooklyn, NY, USA; 7Pediatric Infectious Diseases, Tulane University School of Medicine, New Orleans, LA, USACorrespondence: Katherine Tassiopoulos, Senior Research Scientist, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Kresge 817B, Boston, MA, 02115, USA, Tel +1 617 432 3265, Fax +1 617 566 7805, Email ktassiop@hsph.harvard.eduPurpose: To determine the relationship between perceived social support and viral suppression among young adults with perinatally-acquired HIV (YAPHIV).Participants and Methods: We included YAPHIV ≥ 18 years enrolled in AMP Up, a study of PHACS (Pediatric HIV/AIDS Cohort Study), with social support evaluations and ≥ 1 HIV viral load (VL) measured over the next year. We evaluated emotional, instrumental, and friendship social support via the NIH Toolbox. We defined social support, measured at study entry and year 3 (if available), as low (T-score ≤ 40), average (41– 59) or high (≥ 60). We defined viral suppression as all VL < 50 copies/mL over the one year after social support measures. We fit multivariable Poisson regression models using generalized estimating equations, and evaluated transition from pediatric to adult care as an effect modifier.Results: Among 444 YAPHIV, low emotional and instrumental support and friendship at entry were reported by 37%, 32% and 36%. Over the next year, 44% were virally suppressed. Of 136 with year 3 data, 45% were suppressed. Average or high levels of all three social support measures were associated with higher likelihood of viral suppression. Instrumental support was associated with viral suppression among those in pediatric (adjusted proportion suppressed among those with average/high vs low support=51.2% vs 28.9%; risk ratio (RR)=1.77, 95% confidence interval (CI)=1.37, 2.29), but not adult care (40.0% vs 40.8%; RR=0.98, 95% CI=0.67, 1.44).Conclusion: Sufficient social support increases likelihood of viral suppression among YAPHIV. Strategies to enhance social support may promote viral suppression as YAPHIV prepare for adult clinical care transition.Keywords: social support, perinatal HIV, young adults, viral suppression, clinical care transition

We assessed the quality of life and HIV adherence self-efficacy of adolescents and young adults (AYA) with perinatal HIV infection (PHIV). This cross-sectional study was conducted in Chiang Mai, Thailand. AYA-PHIV aged between 15 and 25 years were enrolled, who all were initiated on antiretroviral treatment as children. The World Health Organization-quality of life-BREF questionnaire and the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES) were administered. A total of 111 AYA-PHIV were included, including 52 (47%) females. Their median age was 20.2 ± 2.6 years. The overall QOL was rated as favorable (good or very good) by 59.4% of AYA-PHIV. The highest score was seen in the social relationships domain followed by the environmental health domain. Males had a significantly lower score in the psychological health domain than females (p = 0.018). Simple linear regression revealed a negative association between male sex, physical, and psychological health domain scores. The overall mean HIV–ASES score was 7.79 ± 1.96 out of 10, with a trend toward lower scores in males (p = 0.062), and a weak positive correlation with QOL. Our study documented worse QOL and lower HIV adherence self-efficacy in male AYA-PHIV. The findings call for the design of tailored male-focused interventions. [ABSTRACT FROM AUTHOR]

Perinatally acquired HIV (PHIV) has been associated with brain structural and functional deficiencies, and with poorer cognitive performance despite the advent of antiretroviral therapy (ART). However, investigation of brain metabolite levels in PHIV measured by proton magnetic resonance spectroscopy (MRS) methods, is still limited with often inconclusive or contradictory findings. In general, these MRS-based methods have used a single voxel approach that can only evaluate metabolite concentrations in a few select brain anatomical regions. Additionally, most of the published data have been on children perinatally infected with HIV with only a few studies examining adult populations, though not exclusively. Therefore, this prospective and cross-sectional study aims to evaluate metabolite differences at the whole-brain level, using a unique wholebrain proton magnetic resonance spectroscopy imaging (MRSI) method, in a group of PHIV infected young adults (N = 28) compared to age and gender matched control sample (N = 28), and to find associations with HIV clinical factors and neurocognitive scores. MRSI data were acquired on a 3T scanner with a TE of 70 ms. Brain metabolites levels of total N-acetylaspartate (tNAA), total choline (tCho) and total creatine (tCre), as well as ratios of tNAA/tCre, tCho/tCre, and tNAA/tCho, were obtained from the whole brain level and evaluated at the level of gray matter (GM) and white matter (WM) tissue types and anatomical regions of interest (ROI). Our results indicate extensive metabolic abnormalities throughout the brains of PHIV infected subjects with significantly elevated levels of tCre and tCho, notably in GM regions. Decreases in tNAA and ratios of tNAA/tCre and tNAA/tCho were also found mostly in WM regions. These metabolic alterations indicate increased glial activation, inflammation, neuronal dysfunction, and energy metabolism in PHIV infected individuals, which correlated with a reduction in CD4 cell count, and lower cognitive scores. Our findings suggest that significant brain metabolite alterations and associated neurological complications persist in the brains of those with PHIV on long-term ART, and advocates the need for continued monitoring of their brain health. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer burden and prevalence of precursor lesions is unknown among young women living with HIV in high prevalence settings. Current cervical cancer screening guidelines in resource-limited settings with high HIV prevalence typically exclude adolescents and young women. After observing two cases of advanced cervical cancer among young women with perinatally acquired HIV, a pilot screening programme was established in Botswana. Objectives: To compare the prevalence of cervical abnormalities in young women with perinatally acquired HIV with women aged 30–49 years, regardless of HIV status. Method: We conducted a cross-sectional study of 30–49-year-old women who had visual inspection with acetic acid screening through the Botswana public sector programme, and youth (aged 15–24 years) with perinatally acquired HIV, at a single referral site between 2016 and 2018. We describe the prevalence of cervical abnormalities in each group as well as the crude prevalence ratio. Results: The prevalence of cervical abnormalities in women 30–49 years of age was 10.9% (95% confidence interval [CI]: 10.4, 11.4), and 10.1% (95% CI: 4.7, 18.3) for youth. The crude prevalence ratio was 1.07 (95% CI: 0.58, 2.01). Conclusion: Inclusion of youth living with HIV in cervical cancer screening services should be considered in settings with a high prevalence of HIV and cervical cancer.

Perinatally acquired HIV (PHIV) has been associated with brain structural and functional deficiencies, and with poorer cognitive performance despite the advent of antiretroviral therapy (ART). However, investigation of brain metabolite levels in PHIV measured by proton magnetic resonance spectroscopy (MRS) methods, is still limited with often inconclusive or contradictory findings. In general, these MRS-based methods have used a single voxel approach that can only evaluate metabolite concentrations in a few select brain anatomical regions. Additionally, most of the published data have been on children perinatally infected with HIV with only a few studies examining adult populations, though not exclusively. Therefore, this prospective and cross-sectional study aims to evaluate metabolite differences at the whole-brain level, using a unique whole-brain proton magnetic resonance spectroscopy imaging (MRSI) method, in a group of PHIV infected young adults (N = 28) compared to age and gender matched control sample (N = 28), and to find associations with HIV clinical factors and neurocognitive scores. MRSI data were acquired on a 3T scanner with a TE of 70 ms. Brain metabolites levels of total N-acetylaspartate (tNAA), total choline (tCho) and total creatine (tCre), as well as ratios of tNAA/tCre, tCho/tCre, and tNAA/tCho, were obtained from the whole brain level and evaluated at the level of gray matter (GM) and white matter (WM) tissue types and anatomical regions of interest (ROI). Our results indicate extensive metabolic abnormalities throughout the brains of PHIV infected subjects with significantly elevated levels of tCre and tCho, notably in GM regions. Decreases in tNAA and ratios of tNAA/tCre and tNAA/tCho were also found mostly in WM regions. These metabolic alterations indicate increased glial activation, inflammation, neuronal dysfunction, and energy metabolism in PHIV infected individuals, which correlated with a reduction in CD4 cell count, and lower cognitive scores. Our findings suggest that significant brain metabolite alterations and associated neurological complications persist in the brains of those with PHIV on long-term ART, and advocates the need for continued monitoring of their brain health.

Purpose of Review: In the context of the opioid epidemic, hepatitis C virus (HCV) infection prevalence is increasing among women of reproductive age. Pregnant people with HIV/HCV coinfection may be at increased risk of adverse pregnancy and neonatal outcomes, although research in this key population is lacking. Recent Findings: Treatment with directly acting antivirals (DAAs) has transformed the clinical care for most patients with HCV. However, pregnant people were excluded from trials of these medications. A recent phase I study has shown promise with excellent safety profile for ledipasvir-sofosbuvir; demonstrating no episodes of perinatal transmission, 100% sustained virologic response, and no safety concerns. Summary: Pregnancy represents a time of maximal interaction with the healthcare system and therefore an ideal window of opportunity to cure HCV. Current observational data regarding pregnant people who are co-infected with HCV and HIV suggest poor outcomes such as increased risk of preterm birth; however, there are no prospective and well-controlled studies to fully understand the impact of HIV/HCV coinfection on pregnancy. Phase 1 studies suggest that DAAs are well-tolerated and effective during pregnancy. Only through large, prospective clinical trials will we be able to understand the interaction of HCV and HIV during pregnancy and to evaluate safety and efficacy of DAAs in this key population. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer burden and prevalence of precursor lesions is unknown among young women living with HIV in high prevalence settings. Current cervical cancer screening guidelines in resource-limited settings with high HIV prevalence typically exclude adolescents and young women. After observing two cases of advanced cervical cancer among young women with perinatally acquired HIV, a pilot screening programme was established in Botswana. Objectives: To compare the prevalence of cervical abnormalities in young women with perinatally acquired HIV with women aged 30–49 years, regardless of HIV status. Method: We conducted a cross-sectional study of 30–49-year-old women who had visual inspection with acetic acid screening through the Botswana public sector programme, and youth (aged 15–24 years) with perinatally acquired HIV, at a single referral site between 2016 and 2018. We describe the prevalence of cervical abnormalities in each group as well as the crude prevalence ratio. Results: The prevalence of cervical abnormalities in women 30–49 years of age was 10.9% (95% confidence interval [CI]: 10.4, 11.4), and 10.1% (95% CI: 4.7, 18.3) for youth. The crude prevalence ratio was 1.07 (95% CI: 0.58, 2.01). Conclusion: Inclusion of youth living with HIV in cervical cancer screening services should be considered in settings with a high prevalence of HIV and cervical cancer. [ABSTRACT FROM AUTHOR]

HIV infection and its treatment are associated with mitochondrial dysfunction and metabolic derangement. However, longitudinal changes in oxidative phosphorylation activities [Complex I (C1) and Complex IV (C4)], or venous lactate/pyruvate ratios (LPR), and their relationships with insulin resistance (IR), remain unclear in youth living with perinatally-acquired HIV (YPHIV). We measured venous LPR, C1, and C4 activities in blood cells and homeostatic model assessment for IR (HOMA-IR) over two years. Limited longitudinal differences in mitochondrial-related measures and IR were observed in YPHIV vs youth perinatally HIV-exposed but uninfected. There were no systematic differences in C1, C4, or HOMA-IR between the groups. [ABSTRACT FROM AUTHOR]

OBJECTIVE:Recent studies demonstrate that infection with the HIV-1 is associated with accelerated aging effects in adults according to a highly accurate epigenetic biomarker of aging known as epigenetic clock. However, it is not yet known whether epigenetic age acceleration occurs as early as adolescence in perinatally HIV-infected (PHIV+) youth. DESIGN:Observational study of PHIV and HIV-uninfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study. METHODS:The Illumina EPIC array was used to generate blood DNA methylation data from 204 PHIV and 44 age-matched, uninfected (HIV-) adolescents aged 9-12 years old. The epigenetic clock software and method was used to estimate two measures of epigenetic age acceleration. Each participant completed a comprehensive neuropsychological test battery upon enrollment to Cape Town Adolescent Antiretroviral Cohort. RESULTS:HIV is associated with biologically older blood in PHIV+ adolescents according to both measures of epigenetic age acceleration. One of the measures, extrinsic epigenetic age acceleration, is negatively correlated with measures of cognitive functioning (executive functioning, working memory, processing speed). CONCLUSION:Overall, our results indicate that epigenetic age acceleration in blood can be observed in PHIV+ adolescents and that these epigenetic changes accompany poorer cognitive functioning.

ABSTRACT: Background: Similar to other young people with a chronic health condition, perinatally HIV-infected (PHIV) adolescents may have an impacted sexual development. Objectives: This paper aims to compare sexual milestones of PHIV to HIV uninfected peers, through a systematic review (SR) and explorative study. Methods: 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. Results: 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). Strengths and Limitations: 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. Conclusion: 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.

Abstract Background Fatigue is common among adults living with human immunodeficiency virus (HIV) as well as children with a chronic disease (CCD). Fatigue can have disastrous effects on health status, including health related quality of life (HRQOL). Even so, fatigue is underexplored in children and adolescents perinatally infected with HIV (PHIV+) in the Netherlands. The objective of this observational study is to explore fatigue in PHIV+ and its association with their HRQOL. Methods We measured HRQOL and fatigue using the Pediatric Quality of Life Inventory™ (PedsQL 4.0) and the PedsQL Multidimensional Fatigue Scale (MFS). The PedsQL MFS encompasses three subscales: general fatigue, sleep/rest fatigue and cognitive fatigue, and a total fatigue score. We compared outcomes of PHIV+ children and adolescents in the Amsterdam University Medical Centre with three groups: 1) HIV-uninfected controls (HIV-) matched for age, sex, region of birth, socioeconomic status and adoption status, 2) CCD, and 3) the general Dutch population. Within the PHIV+ group we explored associations between fatigue and HRQOL. Results We enrolled 14 PHIV+ (median age 10.2 years [IQR 9.2–11.4]) and 14 HIV-. Compared to CCD, PHIV+ significantly reported less general fatigue (mean difference 13.0, 95% CI 1.3 to 24.8). PHIV+ did not score significantly different on any of the other PedsQL MFS scales compared to HIV-, CCD or the general Dutch population. PHIV children scored relatively low on the cognitive fatigue scale in comparison to HIV-uninfected matched controls, CCD and the general population, although these differences did not reach significance. Among PHIV+, a lower score on total fatigue, general fatigue and cognitive fatigue was associated with a lower HRQOL score. Conclusions The results of this study suggest that PHIV children and adolescents do not experience more symptoms of fatigue than their healthy peers. However, PHIV children and adolescents may be more likely to experience cognitive fatigue. Fatigue in PHIV also appears to be associated with children’s HRQOL. Further research should confirm these exploratory findings.

Perinatal HIV infection (PHIV) and prolonged use of antiretroviral therapy (ART) may increase the likelihood of developing subclinical vascular dysfunction at an early age. We conducted a systematic review to assess the effect of PHIV and ART on intima-media thickness (IMT), arterial stiffness and endothelial function in individuals aged 6–25 years. Medline, Embase and Web of Science were searched, and studies screened by two independent reviewers. We performed a meta-analysis on selected studies reporting on IMT. A total of 680 studies were retrieved from the databases, with 21 studies deemed eligible for qualitative analysis. There were few studies assessing IMT, arterial stiffness and endothelial function. More than half of the studies found either increased IMT, stiffer arteries or impaired endothelial function in PHIV compared to uninfected controls. A minority of the studies reported that the two groups had similar vascular parameters, a conflicting finding. There was a lack of standardisation for IMT assessment and reporting in numerous studies. In a meta-analysis of seven studies with matching methodologies, IMT was higher in PHIV compared to uninfected controls, (mean difference, 0.05 (0.01–0.09; p = 0.01) but heterogeneity between the studies was substantial (I2, 96.7%; p < 0.001). PHIV may affect vascular structure and function. Existing studies are generally small, often contradictory, and predominantly cross-sectional in design. Further studies are required to understand vascular health in PHIV to identify cardiovascular disease risk and improve interventional strategies aimed at prevention and treatment of early vascular changes in this population. [Display omitted] • HIV infection and antiretroviral therapy (ART) may accelerate subclinical vascular damage and atherogenesis. • Young people with perinatal HIV have altered vascular structure and function. • Presently, data on perinatal HIV (PHIV) and atherogenesis are limited and sometimes contradictory, hence further studies are warranted. • The role of ART in vascular dysfunction remains unclear. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Youth with perinatal HIV exposure have demonstrated high rates of emotional–behavioral problems. Few studies have longitudinally examined racial/ethnic disparities in such functioning across adolescence, a critical time for targeting prevention/intervention efforts. Setting: The Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol is one of the largest US-based cohort studies of youth with perinatal HIV (YPHIV) infection or HIV exposed but uninfected (YPHEU). Methods: Youth and caregivers individually completed the Behavior Assessment System for Children, second edition, every 2 years between ages 7 and 19 years. We used adjusted mixed-effects models to evaluate whether mean youth-reported emotional concerns and caregiver-reported behavioral concerns differed by race/ethnicity. We used group-based trajectory models to identify groups having similar emotional–behavioral trajectories, followed by multinomial models to determine which factors predicted group membership. Results: Three hundred ninety-one YPHIV and 209 YPHEU (7% White non-Hispanic, 21% White Hispanic, 66% Black non-Hispanic, and 6% Black Hispanic) completed a median of 4 assessments over follow-up. Adjusted models showed more caregiver-reported behavioral concerns for Black non-Hispanic YPHEU than for Black non-Hispanic YPHIV, White Hispanic YPHIV, and White Hispanic YPHEU, particularly later in adolescence. Race/ethnicity did not predict membership in subgroups of youth-reported emotional or caregiver-reported behavioral functioning identified using group-based trajectory models. However, factors predicting membership in vulnerable youth-reported emotional and caregiver-reported behavioral groups included experiencing a stressful life event and living with a caregiver who was married or screened positive for a psychiatric condition. Conclusions: Our study revealed that Black non-Hispanic YPHEU are a vulnerable subgroup. Contributing factors that could inform interventions include the caregiver's health, household characteristics, and psychiatric status. [ABSTRACT FROM AUTHOR]

Background: To address the problem of poor adherence among adolescents with perinatal HIV (PHIV), all clinics in Lesotho offer adolescent-friendly services and psychosocial support to improve their overall health outcomes and adherence. As a result, most adolescents with PHIV attend Teen Clubs as part of the package of youth-friendly HIV services. This study set out to determine whether attending Teen Clubs facilitates treatment adherence among adolescents with PHIV. Methods: In this cross-sectional study, data were collected from 130 adolescents aged 10–19 years who were aware of their HIV status and had attended three or more Teen Club sessions in selected clinics in rural district in Lesotho. Adherence was measured through self-report of last pills missed, based on the 7-days recall of pills taken. Descriptive statistics were used to analyse the data. Results: The median age of adolescents was 15 years, 56% were female, 37.7% were orphans, 41% were being cared for by their grandparents, 6.9% were living with siblings with no adult figure, and two were living on their own. The majority (93%) reported optimal adherence, 92% had not missed a clinic appointment in the past 30 days, and 74.4% knew that if they skipped doses, the viral load would increase and they would get sick. Over half (56%) had been reminded by their caregivers to take their medication and 96% talked to their caregivers regularly about their medication. Conclusion: A supportive environment provided through the Teen Clubs and in the home were the main facilitators for adherence. Strategies to improve adherence among adolescents should consider the importance of the involvement of caregivers in the adolescents' visits to their clinic.

Objectives: Although the risk of AIDS‐associated diseases has declined dramatically with combination antiretroviral therapy (cART), the incidence rates of chronic non‐AIDS‐associated diseases in perinatally HIV‐infected adults have risen and have not been well characterized. Both traditional and HIV‐associated risk factors have been found to contribute to hypertension in non‐perinatally HIV‐infected adults; whether these same factors contribute to hypertension in perinatally infected adults is not known. The purpose of this study was to determine the socio‐demographic, clinical, virological and immunological factors associated with systemic hypertension among a cohort of perinatally HIV‐infected adolescents and young adults. Methods: We conducted a case–control study among a population of adults aged 18–35 years with perinatally acquired HIV infection receiving care at the University of Maryland Medical Center. Covariates assessed included traditional risk factors such as age, family history of hypertension, and smoking, as well as numerous HIV‐ and antiretroviral‐associated covariates, including CD4 nadir. Results: Approximately 31% of the cohort met criteria for hypertension. There were no significant differences in the odds of most traditional or HIV‐associated risk factors among perinatally HIV‐infected adults with hypertension compared with those with no diagnosis of hypertension. Exposure to lopinavir/ritonavir was associated with greater odds of not having hypertension, while a concurrent diagnosis of chronic kidney disease (CKD) was associated with greater odds of having hypertension. Conclusions: The results of this study suggest that most traditional and HIV‐related risk factors do not appear to increase the odds of having hypertension in this cohort of individuals. The aetiology of hypertension in this population remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Perinatally HIV-acquired infants benefit from an early antiretroviral treatment initiation. Thanks to a short viral exposure time, their immune system can be maintained or reconstituted, allowing a "normal" immune development. Methods: In this study, we mathematically modeled and quantified individual CD4+ T-cell reconstitution of a subset of 276 children who started treatment within 6 months of age and achieved sustained viral suppression. Considering natural age differences in CD4+ T-cell dynamics, we fitted distances to age-matched healthy reference values with a linear model approaching an asymptote. Results: Depleted CD4+ percentages (CD4%) and CD4+ counts (CD4ct) restored healthy levels during treatment. CD4ct recovered with a median rate of 4 cells/ [micro]L /d, and individual recovery rates were correlated negatively with their initial CD4ct. CD4 values at onset of treatment decrease with age, whereas recovery times and levels seem to be age-independent. CD4 recovery correlates positively with viral suppression, and the stabilization of CD4 levels usually occurs after viral suppression. CD4 levels stabilize within 3-13 months after treatment initiation. The recovery dynamics of the CD4% is comparable with those of the CD4ct. Conclusions: In early-treated children with successful viral suppression, the CD4 depletion is typically mild and CD4+ T cells tend to "fully" recover in numbers. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV) is a global public health issue. HIV has been nationally notifiable in Canada since 1985. The Public Health Agency of Canada (PHAC) monitors trends in new HIV diagnoses. Objectives: The objective of this surveillance report is to provide an overview of the epidemiology of reported HIV cases in 2019 in Canada. The report highlights 10-year trends (2010–2019). Data on HIV diagnosed through Immigration Medical Exams (IME) and trends in perinatal transmission of HIV are also presented. Methods: PHAC monitors HIV through the HIV/AIDS Surveillance System, a passive, case-based system that collates non-nominal data submitted voluntarily by all Canadian provinces and territories. Descriptive analyses were conducted on national data. IME data were obtained from Immigration, Refugees and Citizenship Canada (IRCC), and data on HIV-exposed pregnancies were obtained through the Canadian Perinatal HIV Surveillance Program. Results: In 2019, a total of 2,122 HIV diagnoses were reported in Canada (5.6 per 100,000 population). Saskatchewan reported the highest provincial diagnosis rate at 16.9 per 100,000 population. The 30 to 39-year age group had the highest HIV diagnosis rate at 12.7 per 100,000 population. While the rates for both males and females fluctuated in the past decade, since 2010 the rates among males decreased overall, while the rate among females increased slightly. As in previous years, the diagnosis rate for males in 2019 was higher than that for females (7.9 versus 3.4 per 100,000 population, respectively). The highest proportion of all reported adult cases with known exposure were gay, bisexual and other men who have sex with men (gbMSM, 39.7%), followed by cases attributed to heterosexual contact (28.3%) and among people who inject drugs (PWID, 21.5%). The number of migrants who tested positive for HIV during an IME conducted in Canada was 626. The one documented perinatal HIV transmission related to a mother who had not received antepartum or intrapartum antiretroviral therapy prophylaxis. Conclusion: The number and rate of reported HIV cases in Canada has remained relatively stable over the last decade, with minor year-to-year variations. As in previous years, the gbMSM and PWID populations represent a high proportion of HIV diagnoses, although a sizable number of cases were attributed to heterosexual contact. It is important to routinely monitor trends in HIV in light of pan-Canadian commitments to reduce the health impact of sexually transmitted and blood-borne infections by 2030.

Background: Due to the successful antiretroviral therapy (ART) programme in Botswana, large numbers of perinatally HIV-infected adolescents are emerging into young adulthood. Young adulthood is a critical period of human development. However, there is lack of information on the factors affecting the health-related quality of life (HRQOL) of young adults living with perinatally acquired HIV (YALPH) in Botswana. Objectives: The objective of this study was to assess the HRQOL and its determinants among YALPH who were enrolled on ART at Botswana-Baylor Children’s Clinical Centre of Excellence in Gaborone, Botswana. Method: A cross-sectional study assessed the HRQOL of 509 YALPH aged 18–30 years using the WHOQOL-HIV BREF. Data about other variables of interest were abstracted from medical records. Bivariate analyses were performed using t and Chi-square tests to determine the associations between demographic and clinical variables and general HRQOL. The variables that were associated with the general HRQOL at P-value 0.1 were included in the multivariable analysis using the logistic regression approach. Results: The majority of participants had good general HRQOL (78.4%). The highest mean HRQOL score was in the Physical domain (5.4 [± 2.9]) and the lowest in the Environment domain (13.8 [± 2.7]). The factors that were significantly associated with the general HRQOL included: level of education attained (P = 0.012), employment status (P = 0.069), viral load suppression (P = 0.073) and self-reported illness (P = 0.001). Conclusion: Interventions that effectively increase educational attainment, employment opportunities, ART adherence, and prevention or management of illness are needed to promote good HRQOL among YALPH in Botswana.

The Penta Network has made significant strides in pediatric human immunodeficiency virus (HIV) research, initially focusing on clinical trials for children in Europe, before expanding globally to countries with high HIV prevalence. Key contributions include the ODYSSEY trial, which established dolutegravir as a superior treatment for children and the Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies consortium, aimed at developing strategies for HIV remission. The ongoing empirical and thrive projects address advanced HIV disease, particularly severe pneumonia and postdischarge mortality in children. Going beyond clinical trials, the Penta Network also plays a key role in bringing stakeholders and industry together to achieve better antiretroviral formulations for children., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Since the first reported cases of perinatally acquired human immunodeficiency virus (HIV) in 1982, a generation born with HIV has reached adulthood. The authors conducted a scoping review of PubMed and Google Scholar for articles published between January 2000 and June 2023 to assess the long-term, multisystem health outcomes of this population. Long-term health outcomes studied in this population pertain to the effects of perinatal HIV (PHIV) infection and life-long antiretroviral therapy on the endocrine, reproductive, psychosocial, neurobehavioral, immunologic, and cardiovascular systems. Holistic health of all body systems should be considered in the long-term care of people with PHIV., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Supplemental Digital Content is Available in the Text. Background: Little is known regarding the long-term effects of antiretroviral (ARV) exposure on body composition for people living with HIV (PLWH) since early childhood. This study explores changes in body fat distribution in relation to ARV exposure. Methods: We conducted a prospective study of adults with perinatal HIV (n = 70) using dual-energy X-ray absorptiometry and standard anthropometrics. Trunk to limb fat ratio and waist to hip ratio were compared cross-sectionally to 47 matched controls. Furthermore, changes in body composition and ARV exposure were evaluated longitudinally in a subset of 40 PLWH with a median follow-up of 7 years. Results: Cross-sectional comparisons of PLWH with controls revealed significantly higher waist to hip ratio, trunk to limb fat ratio, HOMA-IR, and triglycerides, whereas BMI did not differ. Among PLWH with longitudinal follow-up, the prevalence of overweight increased from 27.5% to 52.5% and obesity from 12.5% to 25%; waist to hip and trunk to limb fat ratios also increased (P < 0.0001). Changes in waist to hip ratio were positively correlated with longer exposure during follow-up to darunavir (r = 0.36; P = 0.02), whereas increases in trunk to limb fat ratio were positively correlated with longer exposure to stavudine (r = 0.39; P = 0.01) and didanosine (r = 0.39; P = 0.01) but inversely associated with emtricitabine (r = −0.33; P = 0.04). Increases in waist to hip ratio were correlated with increases in triglyceride levels (r = 0.35; P = 0.03). Conclusion: This study presents strong evidence for persistent and worsening central adiposity in young adults with lifelong HIV and extensive ARV exposure. As this cohort ages, continued evaluation of the body composition and metabolic impact of lifelong ARV therapy is warranted to optimize long-term health. [ABSTRACT FROM AUTHOR]

Background: Due to the successful antiretroviral therapy (ART) programme in Botswana, large numbers of perinatally HIV-infected adolescents are emerging into young adulthood. Young adulthood is a critical period of human development. However, there is lack of information on the factors affecting the health-related quality of life (HRQOL) of young adults living with perinatally acquired HIV (YALPH) in Botswana. Objectives: The objective of this study was to assess the HRQOL and its determinants among YALPH who were enrolled on ART at Botswana-Baylor Children’s Clinical Centre of Excellence in Gaborone, Botswana. Method: A cross-sectional study assessed the HRQOL of 509 YALPH aged 18–30 years using the WHOQOL-HIV BREF. Data about other variables of interest were abstracted from medical records. Bivariate analyses were performed using t and Chi-square tests to determine the associations between demographic and clinical variables and general HRQOL. The variables that were associated with the general HRQOL at P-value < 0.1 were included in the multivariable analysis using the logistic regression approach. Results: The majority of participants had good general HRQOL (78.4%). The highest mean HRQOL score was in the Physical domain (5.4 [± 2.9]) and the lowest in the Environment domain (13.8 [± 2.7]). The factors that were significantly associated with the general HRQOL included: level of education attained (P = 0.012), employment status (P = 0.069), viral load suppression (P = 0.073) and self-reported illness (P = 0.001). Conclusion: Interventions that effectively increase educational attainment, employment opportunities, ART adherence, and prevention or management of illness are needed to promote good HRQOL among YALPH in Botswana. [ABSTRACT FROM AUTHOR]

This article summarizes the updated guidelines on breastfeeding with HIV with an emphasis on using relational decision-making and intellectual humility to support the conversation around infant feeding choices. The complex cultural experiences and historical disparities that influence these decisions are highlighted, along with an overview of the recent changes to recommendations for breastfeeding in people with HIV. The article describes individualized clinical scenarios that consider infant feeding decisions, outlines communication and support strategies for health care providers, and proposes a relational decision-making model to guide discussions on infant feeding options., Competing Interests: Disclosures The authors report no real or perceived vested interests related to this article that could be construed as a conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Fatigue is common among adults living with human immunodeficiency virus (HIV) as well as children with a chronic disease (CCD). Fatigue can have disastrous effects on health status, including health related quality of life (HRQOL). Even so, fatigue is underexplored in children and adolescents perinatally infected with HIV (PHIV+) in the Netherlands. The objective of this observational study is to explore fatigue in PHIV+ and its association with their HRQOL. Methods: We measured HRQOL and fatigue using the Pediatric Quality of Life Inventory™ (PedsQL 4.0) and the PedsQL Multidimensional Fatigue Scale (MFS). The PedsQL MFS encompasses three subscales: general fatigue, sleep/rest fatigue and cognitive fatigue, and a total fatigue score. We compared outcomes of PHIV+ children and adolescents in the Amsterdam University Medical Centre with three groups: 1) HIV-uninfected controls (HIV-) matched for age, sex, region of birth, socioeconomic status and adoption status, 2) CCD, and 3) the general Dutch population. Within the PHIV+ group we explored associations between fatigue and HRQOL. Results: We enrolled 14 PHIV+ (median age 10.2 years [IQR 9.2-11.4]) and 14 HIV-. Compared to CCD, PHIV+ significantly reported less general fatigue (mean difference 13.0, 95% CI 1.3 to 24.8). PHIV+ did not score significantly different on any of the other PedsQL MFS scales compared to HIV-, CCD or the general Dutch population. PHIV children scored relatively low on the cognitive fatigue scale in comparison to HIV-uninfected matched controls, CCD and the general population, although these differences did not reach significance. Among PHIV+, a lower score on total fatigue, general fatigue and cognitive fatigue was associated with a lower HRQOL score. Conclusions: The results of this study suggest that PHIV children and adolescents do not experience more symptoms of fatigue than their healthy peers. However, PHIV children and adolescents may be more likely to experience cognitive fatigue. Fatigue in PHIV also appears to be associated with children's HRQOL. Further research should confirm these exploratory findings. [ABSTRACT FROM AUTHOR]

Background: PD-1 marks exhausted T cells, with weak effector functions. Adults living with human immunodeficiency virus (HIV) have increased levels of PD-1+ CD8 T cells that correlate with HIV disease progression, yet little is known about the role of PD-1+ CD8 T cells in children with perinatal HIV.Methods: We enrolled 76 Kenyan children with perinatal HIV and 43 children who were HIV unexposed and quantified PD-1 levels on CD8 T cells; their coexpression with immune checkpoints (ICs) 2B4, CD160, and TIM3; correlates with immune activation and HIV disease progression; and HIV-specific and -nonspecific proliferative responses.Results: PD-1+ CD8 T-cell frequencies are elevated in children with perinatal HIV and associated with disease progression. The majority of PD-1+ CD8 T cells coexpress additional ICs. ART initiation lowers total PD-1 levels and coexpression of multiple ICs. The frequency of PD-1+2B4+CD160+TIM3- in PD-1+ CD8 T cells predicts weaker HIV-specific proliferative responses, suggesting that this subset is functionally exhausted.Conclusions: Children with perinatal HIV have high levels of PD-1+ CD8 T cells that are a heterogeneous population differentially coexpressing multiple ICs. Understanding the complex interplay of ICs is essential to guide the development of PD-1-directed immunotherapies for pediatric HIV remission and cure. [ABSTRACT FROM AUTHOR]

Perceived HIV stigma and mental health are fluid across the lifespan for people living with perinatally-acquired HIV (PHIV). The process of navigating discredited identities over time in the context of other life demands potentially exerts a toll on the mental health of adolescents and young adults living with PHIV (AYAPHIV). Based on data from a longitudinal study in New York City examining mental health and health risk behaviors among 182 AYAPHIV, we examined if increased perceived HIV stigma predicted mental health, future orientation, HIV-disclosure, and healthcare transition over time (2003–2018). Findings from linear mixed-effects modeling indicated that older age predicted poorer mental health, less future orientation, more HIV-serostatus disclosure, and adult medical services utilization. Perceived stigma was the only significant predictor of mental health and mediated the association between age and mental health—highlighting the importance of addressing stigma across development for AYAPHIV while addressing systems that perpetuate them. [ABSTRACT FROM AUTHOR]

Background: Breastfeeding mothers with HIV infection not qualifying for antiretroviral therapy (ART) based on country-specific guidelines at the time of the Promoting Maternal-Infant Survival Everywhere trial and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) postpartum. HIV transmission proportions were similar (<1%) in the 2 arms. We assessed whether maternal viral load (MVL) and CD4 cell counts were associated with breastfeeding HIV transmission. Methods: MVL was collected at entry (7-14 days postpartum) and at weeks 6, 14, 26, and 50 postpartum. CD4 cell counts were collected at entry and weeks 14, 26, 38, and 50 postpartum. Infant HIV-1 nucleic acid test was performed at weeks 1 and 6, every 4 weeks until week 26, and then every 12 weeks. The associations of baseline and time-varying MVL and CD4 cell counts with transmission risk were assessed using time-to-event analyses by randomized treatment arm. Results: Two thousand four hundred thirty-one mother-infant pairs were enrolled in the study. Baseline MVL (P = 0.11) and CD4 cell counts (P = 0.51) were not significantly associated with infant HIV-1 infection. Time-varying MVL was significantly associated with infant HIV-1 infection {hazard ratio [95% confidence interval (CI)]: 13.96 (3.12 to 62.45)} in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 1.04 (0.20 to 5.39)]. Time-varying CD4 cell counts were also significantly associated with infant HIV-1 infection [hazard ratio (95% CI): 0.18 (0.03 to 0.93)] in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 0.38 (0.08 to 1.77)]. Conclusions: In women receiving mART, increased MVL and decreased CD4 cell counts during breastfeeding were associated with increased risk of infant HIV-1 infection. [ABSTRACT FROM AUTHOR]

We examined reporting agreement of oral, vaginal, and anal sex in adolescents and young adults living with perinatally-acquired HIV and those perinatally HIV-exposed and uninfected in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) and AMP Up studies. Agreement between fixed constructs (e.g., age at first sex) and prevalence of logical inconsistencies (e.g., reclaimed virginity status) over time were assessed. Internal consistency was also examined using an attention check question and questions regarding condom use in the prior three months. Those who reported having anal sex in adolescence had a higher proportion of inconsistent responses compared to vaginal and oral sex measures. At their most recent survey, 84% of young adults correctly answered an attention check question and 74% agreed within the survey on condom use in the prior three months. In bivariate analyses, HIV status was not associated with responding inconsistently. Increased time between surveys, male sex, and younger age at first survey were associated with multiple measures of inconsistency over time, while lower cognitive scores, having less than a high school diploma, and negatively answering post-survey acceptability questions were associated with incorrectly answering an attention check question. [ABSTRACT FROM AUTHOR]

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Background: Prior studies have measured accelerated aging in people with HIV using a DNA methylation (DNAm)-based biomarker of aging, "epigenetic age," but data are limited in African American (AA) young adults with perinatally acquired HIV infection (PHIV). Methods: We performed a cross-sectional study of AA young adults aged 20-35 years with PHIV (N = 31) and seronegative controls (N = 30) using DNAm measured in whole blood and cognitive function measured by the NIH Toolbox. Illumina EPIC array was used to measure DNAm age and accelerated aging markers including epigenetic age acceleration (EAA), as well as extrinsic (EEAA) and intrinsic (IEAA) EAA. Results: PHIV and controls did not differ by sex (45 vs. 43% male), chronological age (26.2 vs. 28.0 years), or ethnicity. Chronological age and DNAm age were correlated (r = 0.56, P<0.01). PHIV had a higher mean EAA (2.86±6.5 vs. -2.96±3.9, P<0.01) and EEAA (4.57±13.0 vs. -4.72±6.0, P<0.01) than controls; however, IEAA was not different between groups. Among PHIV, EAA and EEAA were higher in those with HIV viral load $50 copies/mL than ,50 copies/mL (EEA: 8.1±5.2 vs. 0.11±5.5, P = 0<0.01 and EEAA: 16.1±10.6 vs. 21.83±9.7, P<0.01). We observed negative correlations (r = 20.36 to 20.31) between EEAA and executive function, attention, and language scores. Conclusions: In conclusion, EAA in blood was observed in AA young adults with PHIV on ART using 2 measures, including EEAA which upweights the contribution of immunosenescent cell types. However, there was no evidence of age acceleration with a measure independent of cell type composition. [ABSTRACT FROM AUTHOR]

Background: Youth with perinatal HIV exposure have demonstrated high rates of emotional-behavioral problems. Few studies have longitudinally examined racial/ethnic disparities in such functioning across adolescence, a critical time for targeting prevention/intervention efforts. Setting: The Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol is one of the largest US-based cohort studies of youth with perinatal HIV (YPHIV) infection or HIV exposed but uninfected (YPHEU). Methods: Youth and caregivers individually completed the Behavior Assessment System for Children, second edition, every 2 years between ages 7 and 19 years. We used adjusted mixed-effects models to evaluate whether mean youth-reported emotional concerns and caregiverreported behavioral concerns differed by race/ethnicity. We used group-based trajectory models to identify groups having similar emotional-behavioral trajectories, followed by multinomial models to determine which factors predicted group membership. Results: Three hundred ninety-one YPHIV and 209 YPHEU (7% White non-Hispanic, 21% White Hispanic, 66% Black non-Hispanic, and 6% Black Hispanic) completed a median of 4 assessments over follow-up. Adjusted models showed more caregiver-reported behavioral concerns for Black non-Hispanic YPHEU than for Black non-Hispanic YPHIV, White Hispanic YPHIV, and White Hispanic YPHEU, particularly later in adolescence. Race/ethnicity did not predict membership in subgroups of youth-reported emotional or caregiver-reported behavioral functioning identified using group-based trajectory models. However, factors predicting membership in vulnerable youth-reported emotional and caregiver-reported behavioral groups included experiencing a stressful life event and living with a caregiver who was married or screened positive for a psychiatric condition. Conclusions: Our study revealed that Black non-Hispanic YPHEU are a vulnerable subgroup. Contributing factors that could inform interventions include the caregiver's health, household characteristics, and psychiatric status. [ABSTRACT FROM AUTHOR]

Worldwide, children who acquired human immunodeficiency virus (HIV) at an early age, either perinatally or through blood transfusion, are reaching adolescence and adulthood due to successful antiretroviral treatment (ART). While many are thriving, a significant proportion face unprecedented multilevel challenges that can affect their long-term outcomes. Specifically, longstanding and poorly controlled HIV resulting from inadequate early regimens and nonadherence, along with the toxicities of some ART agents, can predispose them to sequelae including HIV-associated complications and other comorbidities. This paper reviews and summarizes the unique issues facing adolescents and young adults with early acquired HIV (AYA-EAHIV), including ART challenges, emerging comorbidities, and complications, including mental health comorbidities, secondary prevention, and transition from pediatric/adolescent to adult care. AYA-EAHIV are a special population that have lived their entire lives with the physical and psychological toll of HIV mandating targeted and purposeful approaches to optimize their management and outcomes. Multifaceted inclusive and context-specific approaches focusing on heightened research, risk reduction interventions, and 'outside the box' thinking will be required to optimize treatment and reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopmental stimulation programmes can improve developmental outcomes. Antiretroviral therapy (ART) started soon after birth potentially limits the invasion of HIV into the central nervous system. A combination of developmental stimulation and early ART initiation may reduce developmental delays in children with perinatally acquired HIV infection. Methods: At a single site in Johannesburg, South Africa, we enrolled 36 HIV‐infected neonates on ART into an intervention group (IG) participating in a yearlong home‐based, neurodevelopmental stimulation programme. Bayley Scales of Infant and Toddler Development‐3rd Edition (BSID‐III) assessments were conducted at 12 months. Scores were compared with 24 early treated HIV‐infected infants in an observational group (OG). BSID‐III assessments were also conducted for older children in an OG at 24 or 36 months. Cognitive, language and motor scaled and composite scores were analysed. Results: BSID‐III scaled and composite scores were all higher in the IG apart from the gross motor scaled score (9.25 vs. 10, p = 0.1954). Receptive communication scaled score was significantly higher in the IG (10.96 vs. 9, p = 0.0331). IG composite scores were all higher than OG scores. OG children assessed at 24 or 36 months had lower composite scores in all subscales than 12‐month OG scores. Conclusions: Early treated HIV‐infected children participating in a neurodevelopmental stimulation programme achieved higher BSID‐III scores at 12 months compared with early treated HIV‐infected children who did not receive the programme. [ABSTRACT FROM AUTHOR]

Abstract Background Cognitive and behavioral impairment are common in children living with perinatally acquired HIV (pHIV) and children exposed to HIV in utero but uninfected (HEU). Methods We sought to determine the prevalence of adverse behavioral symptomatology using a Thai-translated and validated version of the SNAP-IV questionnaire and assess cognitive function utilizing the Children's Color Trails Test, Delis-Kaplan Executive Function System, and the Wechsler Intelligence Scales, in our cohort of Thai adolescents (10–20 years old) with well-controlled pHIV compared to HEU and HIV-unexposed, uninfected youth. We then evaluated the interaction between HIV status, behavioral impairment, and executive function outcomes independent of demographic variables. Results After controlling for demographic factors of age and household income, adolescents with pHIV had higher inattentive symptomatology and poorer neuropsychological test scores compared to uninfected controls. Significant interactions were found between inattention and executive function across multiple neurocognitive tests. Conclusions Behavioral impairment and poor executive functioning are present in adolescents with well-controlled pHIV compared to HIV-uninfected matched peers. The SNAP-IV questionnaire may be a useful tool to identify those with attentional impairment who may benefit from further cognitive testing in resource-limited settings.

Background: Cognitive and behavioral impairment are common in children living with perinatally acquired HIV (pHIV) and children exposed to HIV in utero but uninfected (HEU). Methods: We sought to determine the prevalence of adverse behavioral symptomatology using a Thai-translated and validated version of the SNAP-IV questionnaire and assess cognitive function utilizing the Children's Color Trails Test, Delis-Kaplan Executive Function System, and the Wechsler Intelligence Scales, in our cohort of Thai adolescents (10–20 years old) with well-controlled pHIV compared to HEU and HIV-unexposed, uninfected youth. We then evaluated the interaction between HIV status, behavioral impairment, and executive function outcomes independent of demographic variables. Results: After controlling for demographic factors of age and household income, adolescents with pHIV had higher inattentive symptomatology and poorer neuropsychological test scores compared to uninfected controls. Significant interactions were found between inattention and executive function across multiple neurocognitive tests. Conclusions: Behavioral impairment and poor executive functioning are present in adolescents with well-controlled pHIV compared to HIV-uninfected matched peers. The SNAP-IV questionnaire may be a useful tool to identify those with attentional impairment who may benefit from further cognitive testing in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV) is a global public health issue. HIV has been nationally notifiable in Canada since 1985. The Public Health Agency of Canada (PHAC) monitors trends in new HIV diagnoses.Objectives: The objective of this surveillance report is to provide an overview of the epidemiology of reported HIV cases in 2019 in Canada. The report highlights 10-year trends (2010-2019). Data on HIV diagnosed through Immigration Medical Exams (IME) and trends in perinatal transmission of HIV are also presented.Methods: PHAC monitors HIV through the HIV/AIDS Surveillance System, a passive, case-based system that collates non-nominal data submitted voluntarily by all Canadian provinces and territories. Descriptive analyses were conducted on national data. IME data were obtained from Immigration, Refugees and Citizenship Canada (IRCC), and data on HIV-exposed pregnancies were obtained through the Canadian Perinatal HIV Surveillance Program.Results: In 2019, a total of 2,122 HIV diagnoses were reported in Canada (5.6 per 100,000 population). Saskatchewan reported the highest provincial diagnosis rate at 16.9 per 100,000 population. The 30 to 39-year age group had the highest HIV diagnosis rate at 12.7 per 100,000 population. While the rates for both males and females fluctuated in the past decade, since 2010 the rates among males decreased overall, while the rate among females increased slightly. As in previous years, the diagnosis rate for males in 2019 was higher than that for females (7.9 versus 3.4 per 100,000 population, respectively). The highest proportion of all reported adult cases with known exposure were gay, bisexual and other men who have sex with men (gbMSM, 39.7%), followed by cases attributed to heterosexual contact (28.3%) and among people who inject drugs (PWID, 21.5%). The number of migrants who tested positive for HIV during an IME conducted in Canada was 626. The one documented perinatal HIV transmission related to a mother who had not received antepartum or intrapartum antiretroviral therapy prophylaxis.Conclusion: The number and rate of reported HIV cases in Canada has remained relatively stable over the last decade, with minor year-to-year variations. As in previous years, the gbMSM and PWID populations represent a high proportion of HIV diagnoses, although a sizable number of cases were attributed to heterosexual contact. It is important to routinely monitor trends in HIV in light of pan-Canadian commitments to reduce the health impact of sexually transmitted and blood-borne infections by 2030. [ABSTRACT FROM AUTHOR]

Data on children and adolescents with HIV and coronavirus disease 2019 (COVID-19) co-infection are limited. Clinical and antibody data related to COVID-19 infection in adolescents living with perinatally acquired HIV (ALPHIV) and originally enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) study were collected. We present a descriptive analysis of 53 ALPHIV who were tested for anti-SARS-CoV-2 antibodies. Just over half (53%) of the adolescents tested had positive anti-SARS-CoV-2 antibodies with only one participant describing a prior history of possible symptomatic infection., Contribution: The study contributes to the understanding of SARS-CoV-2 infection and vaccination practices in HIV-positive adolescents., Competing Interests: The authors have declared that no competing interests exists., (© 2024. The Authors.)