Perinatal HIV Research Articles

Early inflammation as a footprint of increased mortality risk in infants living with HIV from three African countries

In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation. Using a propensity score, we selected 40 alive study participants having similar clinical and virological records compared to the deceased group. 13 HIV unexposed (HU) healthy children were additionally used as controls. Baseline plasma samples were analyzed using a targeted proteomic approach, and to assess pathogen-associated and damage-associated molecular patterns (PAMPs, DAMPs) levels. Data from deceased participants were compared to both control groups, with multivariate logistic regression models used to evaluate the association between mortality and plasma proteins. We developed a machine learning model to predict mortality risk, finding that IL-6 and CXCL11 not only were higher in deceased children than Matched-children with HIV (p < 0.001 and p = 0.0034) but also predictive of mortality (accuracy of 77%); levels of PAMPs were higher in deceased children (p = 0.0016). Thus, measuring early inflammatory biomarkers, particularly IL-6, could help mortality risk prediction and potentially guide targeted interventions.

Birth outcomes following bictegravir exposure during pregnancy.

Bictegravir is increasingly prescribed as a co-formulated tablet with tenofovir alafenamide and emtricitabine to pregnant persons with HIV (PWH) despite limited pregnancy and birth outcome data. We sought to provide birth outcome data following exposure to bictegravir during pregnancy. We conducted a descriptive analysis of infants born to pregnant PWH 18-45 years of age enrolled in at least one Pediatric HIV/AIDS Cohort Study (PHACS)-affiliated study who received bictegravir for ≥7 days during pregnancy and completed follow-up through delivery. The outcomes of interest were gestational age at birth, preterm birth (<37 weeks' gestation), gestational-age adjusted birth weight (BWZ) and length (BLZ) z-scores, small for gestational age (SGA, birthweight <10th percentile), congenital anomalies, neonatal deaths in the first 28 days of life, and infant HIV status. A total of 177 infants born to 170 unique PWH were exposed to bictegravir for ≥7 days during gestation; 55% were exposed to bictegravir from the time of conception. Median gestational age at birth was 38.1 weeks. The prevalence of preterm birth was 15.8% and SGA was 9.3%. Mean BWZ and BLZ were -0.48 and 0.03. No neonatal deaths or perinatal HIV transmissions were reported. Among 126 infants exposed to first-trimester bictegravir, 7 (5.6%) had major congenital anomalies with no specific pattern suggestive of a syndrome. These findings provide preliminary data without significant safety concerns for fetal bictegravir exposure in this United States cohort. Comparative data and continued surveillance of outcomes among infants exposed to bictegravir during gestation are warranted.

Increase in Cases of Perinatal HIV Transmission in Maryland in 2022.

The perinatal transmission of HIV is preventable through a regimen that includes testing of all pregnant individuals, antiretroviral treatment (ART) for the pregnant individual, prophylactic or preventative ART for the infant, and cesarean section delivery for mothers with HIV viremia at the time of delivery. Under this protocol, the United States has seen a significant decline in the perinatal transmission of HIV and achieved a perinatal HIV transmission rate of 0.9% in 2019. However, despite this progress nationally and after zero transmissions in 2021, Maryland recorded 6 cases of perinatal HIV diagnoses in 2022. Each of the 3 major referral centers for pediatric HIV patients in Maryland reported 2 new cases in 2022. A root cause analysis of the cases identified risk factors including delayed entry into perinatal and HIV care, premature birth, maternal adherence challenges in the setting of substance use and other adverse social determinants of health, and failure to diagnose maternal HIV infection in a timely way. All patients were successfully linked to care and initiated on ART. Multiple factors contributed to the 2022 increase in cases of perinatal HIV in Maryland. To achieve and then sustain the elimination of perinatal HIV transmission, the constancy of systems that eliminate barriers for all pregnant people to access testing, prevention, and treatment is critical.

Altered Surrogate Markers of Inflammation in Perinatal HIV-Exposed Children with Caries.

Dental caries is associated with immunologic response, yet its association with hematologic parameters and inflammatory markers is unclear. This study aimed to examine the relationship between some surrogate markers of inflammation and dental caries in the context of perinatal exposure to human immunodeficiency virus (HIV). This cross-sectional study involved 2 groups of children aged 4 to 11 y who were (1) HIV exposed but uninfected (HEU) and (2) HIV unexposed/uninfected (HUU) and recruited from HIV pediatric and child outpatient clinics, respectively, at a tertiary health facility in Nigeria. Medical records were reviewed, and trained dentists conducted oral and dental examinations. Five milliliters of EDTA blood was obtained and used for CD4 and CD8 and complete blood analysis, from which other inflammatory markers such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic inflammatory index (SII), CD4/CD8 ratio were calculated using referenced formulas. In total, 245 (125 HEU and 120 HUU) children with a mean (standard deviation) age of 7 (2) y were included in this study. No differences in caries experience were observed in both groups of children (38 children [16%] were caries affected; 19 [16%] and 19 [15%] from the HEU and HUU groups, respectively). Examining the relationship between studied inflammatory markers and caries showed that leucocyte counts were slightly lower in caries-affected children compared with their caries-free counterparts (P = 0.05). Lower levels of neutrophils (P = 0.04) and higher levels of lymphocytes (P = 0.02) were associated with caries prevalence. Although not significant, NLR, PLR, and SII were lower in caries-affected children. Caries is associated with leucocytes and some of its subsets in both groups of children and independent of perinatal HIV exposure, highlighting the potential of evaluating inflammatory markers in caries prevention, treatment, and research. This study provides evidence that a relationship exists between dental caries, HIV exposure, and inflammation using affordable methods and advocates the inclusion of these markers in caries care in resource-limited settings.

Bridging the gaps in perinatal HIV: treatment and prevention

Bridging the gaps in perinatal HIV: treatment and prevention

Bolstering Access to HIV-Related Health care in Zimbabwe Among Young Mothers Living With HIV: Lessons Learned on HIV Health Promotion From Zvandiri's Young Mentor Mother Program.

HIV disproportionately affects adolescent girls and young women living in Southern Africa. Rates of perinatal HIV transmission are high in this population, emphasizing the need for targeted health promotion and public health programming to improve the health of young mothers living with HIV. Zvandiri, a non-profit organization in Zimbabwe, created the Young Mentor Mother (YMM) program in response to this issue. This health promotion program uses peer-led service delivery conducted by trained young mothers living with HIV, called YMMs. We conducted semi-structured virtual interviews (N = 29) among Zvandiri staff and YMMs to identify benefits and challenges, and to inform future program scaling. We applied thematic analyses to the transcriptions. Participant narratives revealed several themes, including three key benefits from the YMM program: (1) peer support, (2) holistic care, and (3) women's empowerment. Participants also shared barriers to the success of the program, reflecting two overarching dimensions: (1) barriers related to scaling up the YMM program and (2) challenges related to addressing socio-structural factors. Barriers to scale-up included limited funds and resources, and food insecurity. Socio-structural challenges included HIV-related stigma, cultural and geographic differences, and intimate partner violence (IPV). These challenges align with the social-ecological model, whereby structural factors (lack of funding, food insecurity), community factors (HIV-related stigma, socio-cultural differences in accepting HIV care), and interpersonal factors (IPV) affect the implementation and scale-up of the program. We recommend future adopters of the YMM program to tailor the model for their community, prioritize peer supporter's well-being, foster women's empowerment, and adopt a holistic care approach.

Bone Accrual Trajectories in Children and Adolescents with Perinatal HIV Infection.

Low bone mineral density (BMD) has been reported in children and adolescents living with perinatally-acquired HIV (PHIV). Little is known about their bone accrual through puberty compared to an uninfected healthy cohort. To compare bone accrual in PHIV and healthy children. PHIV children aged 7-16 years had dual energy X-ray absorptiometry (DXA) at entry, 2 years, and then at least 2 years later. Bone accrual was compared to healthy children from the Bone Mineral Density in Childhood Study (BMDCS). United States academic clinical research centers. 172 PHIV; 1321 BMDCS. We calculated height-adjusted whole-body and spine BMD and bone mineral content (BMC) Z-scores in PHIV using BMDCS reference curves. We fit piecewise weighted linear mixed effects models with change points at 11 and 15 years, adjusted for age, sex, race, height Z-score, and Tanner stage, to compare BMD and BMC Z-scores across actual age by cohort.Main Outcome Measure: BMD/BMC Z-scores. Height-adjusted whole-body BMD and BMC Z-scores in PHIV were lower across age compared to BMDCS children. Spine BMD Z-score across age was higher in PHIV after height adjustment. Whole-body and spine bone area tended to be lower in PHIV. PHIV had slower accrual in whole-body and spine bone area before 14 years. After 15 years, bone area accruals were similar, as were height-adjusted spine BMC Z-scores, across age. PHIV had persistent deficits in all measures except height-adjusted spine BMD and BMC Z-scores. Data are needed on PHIV followed to adulthood.

Health-related quality of life in young adults with perinatal HIV after transfer to adult health care in the Netherlands.

Health-related quality of life (HRQoL) in adult people with HIV is lower than that of the general population. Previously, no differences were detected in HRQoL of Dutch children with perinatal HIV (PHIV) compared to norm groups. In this study we compared HRQoL of PHIV young adults (PHIV-YA, aged 18-30) to two norm groups; the healthy Dutch YA population and YA with various chronic conditions. Participants received questionnaires on HRQoL, adherence and demographics. Additional social and healthcare-related variables were collected from patients' medical files. We explored correlations between HRQoL and demographic characteristics. Effect sizes (ES, Hedges' g with confidence intervals) were calculated to quantify the difference between PHIV-YA and norm groups. Of 81 participants, 53 filled out the questionnaires. Compared with the healthy Dutch YA population, PHIV-YA 18-30 had significantly lower HRQoL scores in the school/work subscale. PHIV-YA aged 26-30 had significantly lower total, physical and psychosocial HRQoL scores as well. Participants in the older age category had lower HRQoL scores throughout all subcategories as compared to the younger age group.For PHIV-YA aged 18-25 lower scores on the school/work subscale were correlated with substance use and being born outside the Netherlands. PHIV-YA had low HRQoL scores in school/work functioning compared with the healthy Dutch YA population. The circumstances driving these outcomes are likely to be multi-dimensional, including HIV infection, social background and challenges in growing up with a chronic condition.

Perinatal HIV infection and opportunistic infectious pathology: morphological features of the placenta

Opportunistic infections account for more than 90% of all deaths associated with immunosuppression resulting from exposure to the human immunodeficiency virus (HIV). Fatal opportunistic infections include Pneumocystis pneumonia, cryptococcosis, cytomegalovirus infection, and viral hepatitis B and/or C. HIV-infected pregnant women have a high incidence of cytomegalovirus infection, which increases the risk of transplacental transmission of HIV from mother to fetus. In addition, an important factor in perinatal transmission of HIV is a genital infection caused by herpes simplex virus type 2 detected during pregnancy in HIV-infected women. Also, at present, there is no doubt about the possibility of damage to placental cells by the SARS-CoV-2 virus and its transplacental transmission.The aim of this study was to study the morphological features of the placenta in the presence of opportunistic infections caused by viruses of the herpes family (herpes simplex viruses types 1/2, cytomegalovirus, Epstein-Barr virus), as well as SARS-CoV2 in HIV-infected pregnant women.Materials and methods. A study was conducted of 21 placentas with various pregnancy outcomes in HIV-infected women, including 12 placentas obtained as a result of term birth, 1 placenta from premature birth at 29 weeks, and 8 observations of failed miscarriages (non-developing pregnancy).Results and discussion. Viral lesions were represented by the action of HIV with giant cell metamorphosis of trophoblast cells and placental macrophages, as well as infiltration by immunocompetent cells and fibrosis of the villous stroma. In addition, groups of immature villi were identified, the edematous stroma of which contained an increased number of large cells with light nuclei. In HIV-infected pregnant women with immunosuppression, the outcome of pregnancy in 8 cases was a miscarriage with a morphologically detected and immunohistochemically confirmed infection caused by herpes simplex virus types 1/2 (3 observations), cytomegalovirus (2 observations), and SARS-CoV-2 (3 observations), in 1 case the outcome of pregnancy was premature birth with morphologically identified and immunohistochemically confirmed infection caused by the Epstein-Barr virus.Conclusion. The placentas of HIV-infected pregnant women are characterized by impaired villous maturation with stromal fibrosis, which is the morphological substrate of chronic placental insufficiency with varying degrees of compensation. If HIVinfected pregnant women have opportunistic infections caused by viruses of the herpes family (herpes simplex viruses types 1/2, cytomegalovirus, Epstein-Barr virus), as well as SARS-CoV-2, pronounced involutive-dystrophic changes are observed in the placentas — perivillous deposition fibrinoid, petrification, which increases the likelihood of an unfavorable pregnancy outcome in the form of miscarriage or premature birth.

Longitudinal controlled attenuation parameter and liver stiffness in children with and without perinatal HIV infection in South Africa.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging cause of liver disease in HIV. Transient elastography (TE) with controlled attenuation parameter (CAP) measures liver stiffness as a marker of liver fibrosis and CAP as a measure of hepatic steatosis. Our aim was to evaluate longitudinal CAP and liver stiffness in children with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) from early life compared to children without HIV (HU). Prospective cohort study. PHIV and HU were followed annually for two years. During the study, 60% of PHIV switched from older ART regimens to tenofovir disoproxil, lamivudine and dolutegravir (TLD). Longitudinal evolution of CAP and liver stiffness were investigated in two PHIV groups - on older ART and on TLD - compared to HU children using linear mixed effects models. 263 children and adolescents (112 PHIV, 151 HU) aged 7-20 years were followed. PHIV on older ART had CAP 8.61% (95% CI 4.42-12.97, P < 0.001) greater than HU and no significant difference in CAP between PHIV on TLD and HU. No significant difference in liver stiffness was found between PHIV on older ART regimens and PHIV on TLD compared to HU. PHIV on older ART had higher CAP than HU, whereas in PHIV switched to TLD there was no difference in CAP compared to HU. There was no difference in liver stiffness between either PHIV group and HU. This suggests starting ART early in life might protect PHIV from developing hepatic fibrosis.

Neurocognitive Functioning is Impaired in Perinatally HIV-Infected Youth.

The present study examined neurocognitive differences between Perinatally HIV (PHIV)-infected-youth and age and gender matched healthy controls. Despite early, long-term anti-viral treatment (ART), significant neurocognitive deficiencies remain for PHIV-infected-youth reaching adulthood compared to controls. Participants were assessed with a comprehensive neuropsychological battery. An Overall Neurocognitive Composite Score and a Global Deficit Score (GDS) were created. Sleep, depression, and developmental level of intellectual functioning were also examined. PHIV-youth performed more poorly than controls in all neurocognitive domains. Very large effect sizes were observed for the Overall Neurocognitive Composite Score and GDS. PHIV-infected-youth appear to be significantly more depressed compared to controls, but there were no differences in amount or type of sleep observed. Despite early, long-term anti-viral treatment (ART), neurocognitive deficiencies remain for PHIV-infected-young-adults. The verbal learning domain was significantly impaired with implications for functioning. The PHIV-infected-youth were also depressed and not receiving treatment for depression.

Perinatal HIV transmission in the Philippines: current status, prevention and future prospects.

Perinatal HIV transmission in the Philippines: current status, prevention and future prospects.

Preventing perinatal HIV acquisition; current gaps and future perspectives.

Although current treatment could eradicate vertical transmission, in 2022, 130 000 infants acquired HIV globally. HIV suppression with antiretroviral therapy (ART) transforms survival for people living with HIV (PLWH), and prevents transmission, including vertical. International guidelines recommend lifelong ART for PLWH, consequently perinatal HIV acquisition reflects implementation gaps in the HIV care cascade. We summarize these gaps, exploring potential novel approaches and therapeutic innovations towards eliminating vertical HIV transmission. Multifactorial challenges continue to underpin gaps in the HIV care cascade, including accessibility, availability and sustainability of HIV testing, prevention and treatment, alongside stigma, gender-based violence and poverty. Long-acting ART may be important in preventing perinatal HIV acquisition, with early data demonstrating tolerability and efficacy of injectable ART throughout pregnancy, both as HIV treatment and prevention. Carefully selected long-acting broadly neutralizing antibodies (bNAbs) matching circulating, exposing viral envelope sequences have demonstrated safety, clinical trials are ongoing to demonstrate efficacy. Emerging clinical studies should prioritize pregnant/lactating people and infants to ensure such therapies are well tolerated and efficacious. Alongside therapeutic innovation, programmatic strategies must address social and economic challenges, ensuring sustainable HIV treatment/prevention programmes and facilitating global elimination of blood-borne viruses.

Evaluation of person-centered interventions to eliminate perinatal HIV transmission in Kisumu County, Kenya: A repeated cross-sectional study using aggregated registry data.

Following a decline in perinatal HIV transmission from 20% to 10% between 2010 and 2017 in Kenya, rates have since plateaued with an estimated 8% transmission rate in 2021. Between October 2016 and September 2021, Family AIDS Care & Education Services (FACES) supported HIV care and treatment services across 61 facilities in Kisumu County, Kenya with an emphasis on service strengthening for pregnant and postpartum women living with HIV to reduce perinatal HIV transmission. This included rigorous implementation of national HIV guidelines and implementation of 3 locally adapted evidence-based interventions targeted to the unique needs of women and their infants. We examined whether these person-centered program enhancements were associated with changes in perinatal HIV transmission at FACES-supported sites over time. We conducted a repeated cross-sectional study of annually aggregated routinely collected documentation of perinatal HIV transmission risk through the end of breastfeeding at FACES-supported facilities between October 2016 and September 2021. Data included 12,599 women living with HIV with baseline antenatal care metrics, and, a separate data set of 11,879 mother-infant pairs who were followed from birth through the end of breastfeeding (overlapping with those in antenatal care 2 years prior). FACES implemented 3 interventions for pregnant and postpartum women living with HIV in 2019: (1) high-risk clinics; (2) case management; and (3) a mobile app to support treatment engagement. Our primary outcome was infant HIV acquisition by the end of breastfeeding (18 to 24 months). We compared infant HIV acquisition risk in the final year of the FACES program (2021) to the year before intervention scale-up and following implementation of the "Treat All" policy (2018). Mother-infant pair loss to follow-up was a secondary outcome. Program data were aggregated by year and site, thus in multivariable regression, we adjusted for site-level characteristics, including facility type, urban versus rural, number of women with HIV in antenatal care each year, and the proportion among them under 25 years of age. Between October 2016 and September 2021, 81,172 pregnant women received HIV testing at the initiation of antenatal care, among whom 12,599 (15.5%) were living with HIV, with little variation in HIV prevalence over time. The risk of infant HIV acquisition by 24 months of age declined from 4.9% (101/2,072) in 2018 to 2.2% (48/2,156) in 2021 (adjusted risk difference -2.6% [95% confidence interval (CI): -3.7, -1.6]; p < 0.001). Loss to follow-up declined from 9.9% (253/2,556) in 2018 to 2.5% (59/2,393) in 2021 (risk difference -7.5% [95% CI: -8.8, -6.2]; p < 0.001). During the same period, UNAIDS estimated rates of perinatal transmission in the broader Nyanza region and in Kenya as a whole did not decline. The main limitation of this study is that we lacked a comparable control group. These findings suggest that implementation of person-centered interventions was associated with significant declines in perinatal HIV transmission and loss to follow-up of pregnant and postpartum women.

Safety of Antiretroviral Exposure During Pregnancy: Opportunities to Close Data Gaps.

Pregnant persons with chronic health conditions often require pharmacotherapy to remain healthy. The Antiretroviral Pregnancy Registry is a prospective, international, voluntary, and exposure registry that collects information on antiretroviral (ARV) exposure; however, a minority of providers use the registry, leaving critical gaps to guide prescribing in this population. The Task Force for the Elimination of Perinatal HIV Transmission in the United States, funded by the Centers for Disease Control and Prevention, has identified the monitoring of ARV safety as a paramount concern in the ongoing mission to eliminate perinatal human immunodeficiency virus (HIV) transmission. As active members of this task force, we urge all healthcare providers who care for pregnant individuals to prioritize reporting all ARV exposures to the registry.

Drug monitoring of antiretroviral drugs in children with perinatal HIV infection

Therapeutic drug monitoring is the practice of measuring the concentration of a drug in patient’s biological fluids to assess the effectiveness and safety of drug therapy. The results of determining the drug level in biological fluids can also indicate noncompliance of therapy regimen and low adherence to therapy.The aim. To compare the concentrations of some antiretroviral drugs (lopinavir, ritonavir, lamivudine, abacavir, zidovudine) in children living with HIV infection of different age groups.Methods. We examined 184 children with perinatal HIV infection who underwent therapeutic drug monitoring of nucleoside reverse transcriptase inhibitors (lamivudine, abacavir, zidovudine) and protease inhibitors (lopinavir, ritonavir). Children were divided into four age groups. Group 1 included children 1–2 years old (n = 7); group 2 – children 3–5 years old (n = 14); group 3 – children 6–11 years old (n = 78); group 4 – children 12–17 years old (n = 85). The concentration of antiretroviral drugs in blood plasma was determined using high-performance liquid chromatography with mass selective detection.Results. The lowest lopinavir concentration was found in children 12–17 years old (3782 [2117–5046] ng/ml), which was statistically significantly different from the similar values in children 6–11 years old (5614 [3521–7264] ng/ml; p = 0.011). For other antiretroviral drugs, no statistically significant differences in blood plasma concentrations were found in children of different age groups.Conclusion. The lowest lopinavir concentrations are detected in children older than 11 years. For the other studied antiretroviral drugs, this pattern was not revealed

Late Identification of Perinatal Transmission of HIV in an Infant at High Risk.

The focus of this case study is the delayed diagnosis of a perinatal HIV transmission, which was identified when the infant reached 4months of age, and the social conditions and structural determinants that contributed to the increased transmission risk. Despite adhering to the diagnostic testing protocols and neonatal antiretroviral (ARV) guidelines of the New York State Department of Health, this transmission still occurred. This transmission event prompted strategies to address criminalization of substance use during pregnancy and a reevaluation of the HIV testing and treatment protocols, including the timing of testing. Obtaining a diagnostic specimen at birth before initiating prophylactic or presumptive therapy, without causing delays in therapy, and incorporating HIV-1 DNA or RNA testing 2 to 6weeks after discontinuing ARV therapy might have facilitated earlier detection and a quicker resumption of ARV therapy for this high-risk infant. Subsequently, the New York State HIV perinatal testing guidelines were updated. These changes included the recommendation to obtain a diagnostic specimen at birth before initiating ARV medications, whenever feasible, without causing delays in ARV initiation. Additionally, an extra virologic diagnostic test is recommended at 2 to 6weeks after discontinuing ARVs for infants at high risk of perinatal HIV transmission, especially those with possible DNA or RNA suppression due to ARV prophylaxis or presumptive HIV therapy.

"I want to be healthy and move on": A qualitative study of barriers and facilitators to antiretroviral treatment adherence among young adult survivors with perinatal HIV in Thailand.

We know that HIV treatment outcome depends on antiretroviral treatment (ART) adherence. Young adults with perinatal HIV (YPHIV) who survived have endured various adherence challenges in their adolescent years. While some of them could maintain perfect adherence with sustainable virologic suppression, many experienced one or more episodes of virologic failure. We explored factors affecting ART adherence from real-life experiences of YPHIV. A qualitative study was conducted between June and November 2022. Twenty YPHIV aged 21-29 years with a history of virologic failure and resumed virologic suppression during adolescent years were invited to share their experiences through individual in-depth interviews. Audio records were transcribed verbatim and analyzed using deductive thematic analysis. We divided excerpts into two themes: barriers and facilitators to ART adherence. The socio-ecological model was used to frame subthemes at personal, societal, and healthcare system levels. Most barriers to adherence were concentrated at the personal level, including work/study-related conditions, personal entertainment, medication issues, mental health problems, thought, and belief. At the societal level, social activities and fear of HIV disclosure were frequently mentioned as barriers. Medical care cost was the only identified barrier at the healthcare system level. The facilitators to adherence at the personal level included perceiving health deterioration, being afraid of hospitalization and medical procedures, and wishing to be healthy and move on. At the same time, perceived family support and determination to complete family without HIV transmission were identified as facilitators at the societal level. Service behaviors of healthcare providers were mentioned as facilitators to adherence at the healthcare system level. From this study, most factors associated with non-adherence in adolescents were at the personal level, and the fear of HIV disclosure was critical at the societal level. The key facilitator to adherence was the determination to be healthy and have a promising future. Our findings reinforce the importance of establishing youth-friendly services in the existing HIV care setting. More time allocation for tailored individual counseling, using other novel approaches like mHealth, online media, and involvement of social support from different sectors might be beneficial to maximize adherence self-efficacy during the transitional period of YPHIV.

Associations Between Fatty Acid Levels and Perinatal HIV Status and In-Utero/Peripartum Antiretroviral Therapy (IPA) Exposure Among Ugandan Children and Adolescents

Associations Between Fatty Acid Levels and Perinatal HIV Status and In-Utero/Peripartum Antiretroviral Therapy (IPA) Exposure Among Ugandan Children and Adolescents

Subcortical Brain Volumes and Neurocognitive Function in Children With Perinatal HIV Exposure: A Population-Based Cohort Study in South Africa.

Children who are HIV-exposed and uninfected (HEU) are at risk for early neurodevelopmental impairment. Smaller basal ganglia nuclei have been reported in neonates who are HEU compared to HIV-unexposed (HU); however, neuroimaging studies outside infancy are scarce. We examined subcortical brain structures and associations with neurocognition in children who are HEU. This neuroimaging study was nested within the Drakenstein Child Health Study birth cohort in South Africa. We compared (T1-weighted) magnetic resonance imaging-derived subcortical brain volumes between children who were HEU (n = 70) and HU (n = 92) at age 2-3 years using linear regression. Brain volumes were correlated with neurodevelopmental outcomes measured with the Bayley Scales of Infant and Toddler Development III. Compared to HU children, on average children who were HEU had 3% lower subcortical grey matter volumes. Analyses of individual structures found smaller volume of the putamen nucleus in the basal ganglia (-5% difference, P = .016) and the hippocampus (-3% difference, P = .044), which held on adjustment for potential confounders (P < .05). Maternal viremia and lower CD4 count in pregnancy were associated with smaller child putamen volumes. Children who were HEU had lower language scores than HU; putamen and hippocampus volumes were positively correlated with language outcomes. Overall, children who are HEU had a pattern of smaller subcortical volumes in the basal ganglia and hippocampal regions compared to HU children, which correlated with language function. Findings suggest that optimizing maternal perinatal HIV care is important for child brain development. Further studies are needed to investigate underlying mechanisms and long-term outcomes.