Growth and the pubertal growth spurt in South African adolescents living with perinatally-acquired HIV infection.

BACKGROUND: The majority children living with HIV infection now survive into adulthood because of effective antiretroviral therapy (ART), but few data exist on their growth during adolescent years. This study investigated growth patterns and evaluated factors associated with suboptimal growth in adolescents with perinatally-acquired HIV infection. METHODS: This retrospective cohort study included HIV-infected adolescents, aged 13 to 18 years, with at least 5 years of ART follow-up at a large HIV clinic in the Gauteng Province, South Africa. Weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores were calculated using World Health Organization (WHO) growth standards. Growth velocity graphs were generated utilising the mean height change calculated at 6-monthly intervals, using all available data after ART initiation, to calculate the annual change. Other collected data included WHO HIV disease staging, CD4%, HIV viral loads (VLs), ART regimens and tuberculosis co-infection. RESULTS: Included were 288 children with a median age of 6.5 years (IQR 4.2;8.6 years) at ART initiation, and 51.7% were male. At baseline the majority of children had severe disease (92% WHO stages 3&4) and were started on non-nucleoside reverse transcriptase inhibitor-based regimens (79.2%). The median CD4% was 13.5% (IQR 7.9;18.9) and median HIV viral load log 5.0 (IQR 4.4;5.5). Baseline stunting (HAZ <-2) was prevalent (55.9%), with a median HAZ of -2.2 (IQR -3.1;-1.3). The median WAZ was -1.5 (IQR -2.5;-0.8), with 29.2% being underweight-for-age (WAZ <-2). The peak height velocity (PHV) in adolescents with baseline stage 3 disease was higher than for those with stage 4 disease. Being older at ART start (p<0.001) and baseline stunting (p<0.001) were associated with poorer growth, resulting in a lower HAZ at study exit, with boys more significantly affected than girls (p<0.001). CONCLUSIONS: Suboptimal growth in adolescents with perinatally-acquired HIV infection is a significant health concern, especially in children who started ART later in terms of age and who had baseline stunting and is more pronounced in boys than in girls.

Ethical considerations for research involving pregnant women living with HIV and their young children: a systematic review of the empiric literature and discussion.

BACKGROUND: The proper and ethical inclusion of PWLHIV and their young children in research is paramount to ensure valid evidence is generated to optimize treatment and care. Little empirical data exists to inform ethical considerations deemed most critical to these populations. Our study aimed to systematically review the empiric literature regarding ethical considerations for research participation of PWLHIV and their young children. METHODS: We conducted this systematic review in partnership with a medical librarian. A search strategy was designed and performed within the following electronic databases: Ovid MEDLINE, Embase and CINAHL. We screened titles and abstracts using the following inclusion criteria: (1) a study population of PWLHIV or children under 5 years of age; and (2) collection of qualitative or quantitative data regarding ethics of research participation. Excluded were reviews, commentaries, policy statements, clinical care-related ethics concerns, abstracts, case studies, or studies unrelated to HIV research. Studies were appraised for quality, data were extracted, and studies were qualitatively analyzed using a principle-based ethical framework within the Belmont Report. RESULTS: Of the 7470 titles identified, 538 full-text articles were reviewed for eligibility and only three articles met full criteria for inclusion within this review. While we allowed for inclusion of studies involving young children born to mothers with HIV, only articles focused on PWLHIV were identified. Within the results of these studies, four themes emerged: (1) adequacy of informed consent; (2) consideration of paternal involvement; (3) balancing risks; and (4) access to research and treatment. A strength of this review is that it included perspectives of international research investigators, community leaders, and male partners. However, only two studies collected empiric data from PWLHIV regarding their experiences participating in research CONCLUSION: Researchers and funding agencies should be aware of these considerations and appreciate the value of and critical need for formative research to ensure clinical trials involving PWLHIV promote ethical, well-informed research participation and, ultimately, improve care outcomes. More research is needed to create a comprehensive ethical framework for researchers when conducting studies with PWLHIV.

Alteration of the gut fecal microbiome in children living with HIV on antiretroviral therapy in Yaounde, Cameroon.

Multiple factors, such as immune disruption, prophylactic co-trimoxazole, and antiretroviral therapy, may influence the structure and function of the gut microbiome of children infected with HIV from birth. In order to understand whether HIV infection altered gut microbiome and to relate changes in microbiome structure and function to immune status, virological response and pediatric ART regimens, we characterized the gut microbiome of 87 HIV-infected and 82 non-exposed HIV-negative children from Yaounde, a cosmopolitan city in Cameroon. We found that children living with HIV had significantly lower alpha diversity in their gut microbiome and altered beta diversity that may not be related to CD4+ T cell count or viral load. There was an increased level of Akkermansia and Faecalibacterium genera and decreased level of Escherichia and other Gamma proteobacteria in children infected with HIV, among other differences. We noted an effect of ethnicity/geography on observed gut microbiome composition and that children on ritonavir-boosted protease inhibitor (PI/r)-based ART had gut microbiome composition that diverged more from HIV-negative controls compared to those on non-nucleoside reverse-transcriptase inhibitors-based ART. Further studies investigating the role of this altered gut microbiome in increased disease susceptibility are warranted for individuals who acquired HIV via mother-to-child transmission.

Point-of-care p24 antigen detection for early infant diagnosis of HIV infection: cross-sectional and longitudinal studies in Zambia.

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

Evaluating Neurodevelopmental Consequences of Perinatal Exposure to Antiretroviral Drugs: Current Challenges and New Approaches.

As antiretroviral therapy (ART) becomes increasingly affordable and accessible to women of childbearing age across the globe, the number of children who are exposed to Human Immunodeficiency Viruses (HIV) but remain uninfected is on the rise, almost all of whom were also exposed to ART perinatally. Although ART has successfully aided in the decline of mother-to-child-transmission of HIV, the long-term effects of in utero exposure to ART on fetal and postnatal neurodevelopment remain unclear. Evaluating the safety and efficacy of therapeutic drugs for pregnant women is a challenge due to the historic limitations on their inclusion in clinical trials and the dynamic physiological states during pregnancy that can alter the pharmacokinetics of drug metabolism and fetal drug exposure. Thus, much of our data on the potential consequences of ART drugs on the developing nervous system comes from preclinical animal models and clinical observational studies. In this review, we will discuss the current state of knowledge and existing approaches to investigate whether ART affects fetal brain development, and describe novel human stem cell-based strategies that may provide additional information to better predict the impact of specific drugs on the human central nervous system. Graphical Abstract Approaches to evaluate the impact of drugs on the developing brain. Dysregulation of the developing nervous system can lead to long-lasting changes. Integration of data from animal models, clinical observations, and cell culture studies is needed to predict the safety of therapeutic antiretroviral drugs during pregnancy. New approaches include human induced pluripotent stem cell (iPSC)-based 2D and 3D models of neuronal networks and brain regions, as well as single cell profiling in response to drug exposure.

HIV-related enacted stigma and increase frequency of depressive symptoms among Thai and Cambodian adolescents and young adults with perinatal HIV.

HIV-related enacted stigma and social problems may increase risk for depression and/or behavioral problems among adolescents and young adults with perinatal HIV(AYA-PHIV), yet few studies have explored stigma in AYA-PHIV residing in low-to-middle income regions, including Southeast Asia. We assessed HIV-related enacted stigma and social problems in AYA-PHIV who participated in the RESILIENCE study (clinicaltrials.gov identification: U19AI53741) in Thailand and Cambodia using specific questions during structured in-person interviews. Depression was measured by the Child Depression Inventory for children <15 years, or the Center for Epidemiologic Studies Depression Scales for youth ≥15 years); behavioral problems were measured by the Child Behavior Checklist (CBCL-caregiver report). Among 195 AYA-PHIV (median age 16.9 years), 25.6% reported a lifetime experience of enacted stigma, while 10.8% experienced social problems due to HIV infection. The frequency of depressive symptoms was nearly two-fold higher among AYA-PHIV with compared to those without HIV-related enacted stigma (34.7% vs. 16.0%, p = 0.005). Caregiver-reported behavioral problems were detected in 14.6% of all AYA-PHIV, with no differences between those with and without HIV-related enacted stigma. Low household income and caregiver mental health problems were independent risk factors for depressive symptoms; HIV-related enacted stigma was also associated with increased risk, warranting targeted services to support AYA-PHIV.

Conducting clinical trials in sub-Saharan Africa: challenges and lessons learned from the Malawi Cryptosporidium study.

BACKGROUND: An effective drug to treat cryptosporidial diarrhea in HIV-infected individuals is a global health priority. Promising drugs need to be evaluated in endemic areas which may be challenged by both lack of resources and experience to conduct International Committee of Harmonisation-Good Clinical Practice (ICH-GCP)-compliant clinical trials. METHODS: We present the challenges and lessons learned in implementing a phase 2A, randomized, double-blind, placebo-controlled trial of clofazimine, in treatment of cryptosporidiosis among HIV-infected adults at a single site in Malawi. RESULTS: Primary challenges are grouped under study initiation, study population, study implementation, and cultural issues. The lessons learned primarily deal with regulatory system and operational barriers, and recommendations can be applied to other human experimental trials in low- and middle-income countries, specifically in sub-Saharan Africa. CONCLUSION: This study demonstrated that initiating and implementing human experimental trials in sub-Saharan Africa can be challenging. However, solutions exist and successful execution requires careful planning, ongoing evaluation, responsiveness to new developments, and oversight of all trial operations.

Brain morphometric differences in youth with and without perinatally-acquired HIV: A cross-sectional study.

Youth with perinatally-acquired HIV (PHIV) experience specific and global cognitive deficits at increased rates compared to typically-developing HIV-uninfected youth. In youth with PHIV, HIV infects the brain early in development. Neuroimaging studies have demonstrated altered grey matter morphometry in youth with PHIV compared to typically-developing youth. This study examined cortical thickness, surface area, and gyrification of grey matter in youth (age 11-20 years old) with PHIV (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) compared to typically-developing presumed HIV uninfected and unexposed youth (n = 80) from the Pediatric Imaging, Neurocognition and Genetics Study (PING) using structural magnetic resonance imaging. This study also examined the relationship between grey matter morphometry and age. Youth with PHIV had reduced cortical thickness, surface area, and gyrification compared to typically-developing youth. In addition, an inverse relationship between age and grey matter volume was found in typically-developing youth, but was not observed in youth with PHIV. Longitudinal studies are necessary to understand the neurodevelopmental trajectory of youth with PHIV.

Cervical, anal and oral human papillomavirus (HPV) infection in young women: A case control study between women with perinatally HIV infection and women with non-perinatally HIV infection.

OBJECTIVES: HPV infection may differ in women who are HIV-positive since birth (perinatally infected, P-HIV) and those who acquire HIV later in life (non-perinatally infected, NP-HIV). We assessed the HPV prevalence in relation to the HIV acquisition route and HPV vaccination status. STUDY DESIGN: Case control study comparing 22 P-HIV with 22 NP-HIV patients. Cervical, anal and oral specimen were collected for HPV PCRs. The primary outcome was the prevalence of cervical, oral and anal HPV in P-HIV and NP-HIV patients. The secondary outcome was to identify risk factors for HPV infection. Comparative statistics for two independent groups, univariate and multivariable logistic regression analyses were used. RESULTS: There were no differences between perinatally and non-perinatally infected women. Cervical dysplasia was found in 12/44 (27 %) patients and high-risk HPV (hrHPV) in 30 % of cervical (of which 89 % were hrHPV other than 16 and 18), in 3 % of oral and 65 % of anal specimens. All woman were using combined antiretroviral therapy (cART) and 64 % had HIVRNA < 20 cp/ml. A CD4 count <350/mm³ was associated with cytological abnormalities (OR: 13.52, p = 0.002) and with cervical HPV (OR: 6.11; p = 0.04); anal HPV was associated with a previous cervical dysplasia and concomitant cervical HPV infection. None of thirteen vaccinated patients had a 6/11/16/18 HPV infection. CONCLUSION: In this small series of women under cART, we did not observe a difference in HPV infection in relation to the route of HIV acquisition. The high prevalence of hrHPV other than 16 and 18 support the use of a 9-valent vaccine.

Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption.

BACKGROUND: HIV-associated cognitive deficiency in perinatally HIV-infected (PHIV) children has been studied in Western countries in a population of which an increasing proportion has been internationally adopted. Studies often lack an appropriate internationally adopted HIV-uninfected control group, potentially confounding the relationship between HIV and cognitive functioning. This study aims to further elucidate the association between treated HIV infection and cognitive development by addressing the background of international adoption. METHODS: We cross-sectionally studied the impact of HIV on cognition by comparing PHIV children and HIV- uninfected controls, matched for age-, sex-, ethnicity-, socioeconomic status (SES)- and adoption status. We used a standardized neuropsychological test battery to measure intelligence (IQ), and the cognitive domains of processing speed, working memory, executive function, learning ability and visual-motor function and compared outcomes using lineair regression models, adjusted for IQ. We determined cognitive profiles and cognitive impairment by using multivariate normative comparison (MNC) and explored associations with HIV disease- and treatment-related factors. RESULTS: We enrolled fourteen PHIV children (mean age 10.45 years [1.73 SD], 93% adopted from sub-Saharan Africa at a median age of 3.3 years [IQR 2.1-4.2]) and fifteen HIV- uninfected controls. Groups did not clinically nor statistically differ in age, sex, ethnicity, SES, region of birth, adoption status and age at adoption. PHIV scored consistently lower on all cognitive domains and MNC outcomes. Compared to controls, PHIV children had a significant lower IQ (mean 81 [SD 11] versus mean 97 [SD 15], p = 0.005), and a poorer cognitive profile by MNC (Hotelling's T2 mean -4.36 [SD 5.6] versus mean 0.16 [SD 4.5], p = 0.021), not associated with HIV disease- and treatment-related factors. Two PHIV (14%) and one control (7%) were classified as cognitively impaired (p = 0.598). CONCLUSIONS: Findings indicate treated HIV-infection to be independently associated with lower IQ and poorer cognitive profiles in PHIV children, irrespective of a background of international adoption.

Left Ventricular Function, Epicardial Adipose Tissue, and Carotid Intima-Media Thickness in Children and Adolescents With Vertical HIV Infection.

BACKGROUND: Life expectancy of HIV patients has increased considerably as a result of antiretroviral therapy (ART), and cardiovascular (CV) disease has emerged as an important late concern. People with HIV infection could have an impaired systolic function; however data on diastolic function and markers of CV risk, such as epicardial adipose tissue (EAT) and intima-media thickness (IMT), are lacking. Aim of this study is to evaluate left ventricular function, EAT, and IMT in children and adolescents with vertically acquired HIV infection. METHODS: We enrolled 29 subjects on ART (13, 45% men; median age of 13.0, and interquartile range 9-18), and 29 age-matched controls. All patients and controls underwent echocardiographic evaluation, with study of the systolic and diastolic function and measurement of the EAT, and a carotid ultrasound study for IMT measurement. RESULTS: Comparing HIV-infected patients to healthy controls, we found a statistically significant increase of EAT and IMT (mean ± SD) (EAT: 3.16 ± 1.05 vs 1.24 ± 0.61 mm; P < 0.0001. IMT: 0.77 ± 0.15 vs 0.51 ± 0.11 mm; P < 0.0001), and a significant reduction of ejection fraction, evaluated with the biplane Simpson method (mean ± SD) (58.5% ± 6.66% vs 66% ± 4.24%; P = 0.029). These results are not related with age, gender, degree of lipodystrophy, dyslipidemia, hyperinsulinism, and ART duration or the use of single antiretroviral classes. CONCLUSIONS: Vertically infected HIV children and adolescents show an increased thickness of EAT and IMT, expression of potentially increased CV risk. They also show an impaired systolic function.

Reduced Time to Suppression Among Neonates With HIV Initiating Antiretroviral Therapy Within 7 Days After Birth.

There are limited data on infants with HIV starting antiretroviral therapy (ART) in the neonatal period. We investigated the association between the timing of ART initiation and time-to-suppression among infants who tested HIV-positive and initiated ART within the first 28 days of life. The effect was estimated using cumulative probability flexible parametric spline models and a multivariable generalized additive mixed model was performed to test nonlinear associations. Forty-four neonates were included. Nineteen (43.2%) initiated ART within 7 days of life and 25 (56.8%) from 8 to 28 days. Infants treated within 7 days were 4-fold more likely to suppress earlier than those treated after 7 days [Hazard ratio (HR) 4.01 (1.7-9.5)]. For each week the ART initiation was delayed, the probability of suppression decreased by 35% (HR 0.65 [0.46-0.92]). Age at ART start was linearly associated with time-to-suppression. However, a linear association with normally distributed residuals was not found between baseline viral load and time-to-suppression, with no association found when baseline viral loads were ≤5 log(10) copies/mL, but with exponential increase in time-to-suppression with > log5 copies/mL at baseline. Starting ART within 7 days of life led to 4-fold faster time to viral suppression, in comparison to initiation from 8 to 28 days.

Infección congénita por el VIH con cribado serológico gestacional negativo. Importancia de la implementación de la segunda prueba en el tercer trimestre de gestación / Congenital HIV infection after failure of serological screening. Importance of implementing a second screening for HIV infection during the third trimester of pregnancy

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Sounding the Alarm: Perinatally HIV-Infected Youth More Likely to Attempt Suicide Than Their Uninfected Cohort Peers.

PURPOSE: Suicide is the second leading cause of death among youth in the U.S., yet there are few studies on suicide among youth with perinatally acquired HIV infection (YPHIV). Our aim was to determine if suicide attempts differed for YPHIV compared with perinatally HIV-exposed but uninfected peers (YPHEU). METHODS: Data come from a longitudinal behavioral health cohort (N = 340) of YPHIV (n = 206) and YPHEU (n = 134) recruited between ages 9 and 16 years and interviewed with psychosocial batteries every 12-18 months. Logistic regression analyses were conducted to assess the association between reported suicide attempt and participants' HIV status. We assessed whether baseline demographic characteristics and sexual orientation were potential confounding factors. Fisher's exact tests were used to evaluate the association between first attempted suicide and HIV status within age groups. RESULTS: YPHIV were more likely to make a suicide attempt than YPHEU (odds ratio = 2.35, 95% confidence interval = 1.28-4.34). Youth most often reported their first attempt between the ages of 14-18 years. Demographic characteristics and sexual orientation were not associated with attempted suicide. CONCLUSIONS: YPHIV compared with YPHEU were more likely to report a suicide attempt, and this difference emerged during late adolescence and persisted through young adulthood.

Follow up of HIV perinatal exposure and accomplishment of strategies to reduce the risk of viral transmission, experience in a reference hospital in Medellín / Calidad del seguimiento a la exposición perinatal al HIV y observancia de las estrategias reconocidas para disminuir su transmisión en un centro de referencia de Medellín

Introduction: Prevention of mother-to-child transmission of the human immunodeficiency virus (HIV) is essential to limit the spread of the disease. Colombian data about HIV infection in pregnancy are scarce, as well as on the results of the strategies used worldwide to reduce perinatal transmission. Objective: To describe the characteristics and outcomes of pregnant women infected with HIV and their children in a reference center in Medellín. Materials and methods: We conducted a retrospective observational study for the 2012-2015 period by studying the clinical records of newborns exposed to HIV and their mothers. We evaluated the characteristics of prenatal care, deliveries, and infant postnatal care, as well as the follow-up data to confirm or exclude HIV transmission. Results: We included 106 infants and their mothers. We found that 39,6% of mothers knew about the HIV diagnosis before pregnancy and 58,5% were diagnosed during pregnancy; 95.3% of them attended prenatal controls, but only 46.5% as of the first trimester; 95% of them received antiretrovirals, but 23.9% started therapy just during the third trimester. Only 63% of women had a viral load for HIV after 34 weeks of gestation. None of the 103 children with follow up had confirmed presence for HIV and in 88% of them, it was discarded. Conclusions: No cases of perinatal HIV transmission were found in the study. However, difficulties and delays persist in prenatal care, in timely maternal follow-up to confirm or discard HIV, and for early detection of maternal co-infections and their effects on newborns.

Introducción. La prevención de la transmisión materno-infantil del virus de la inmunodeficiencia humana (Human Immunodeficiency Virus, HIV) es una estrategia fundamental para evitar la infección en niños. A nivel local, se desconoce la situación de las mujeres gestantes infectadas por HIV y el grado de observancia de las estrategias reconocidas mundialmente para disminuir la transmisión perinatal. Objetivo. Describir las características sociodemográficas y clínicas de las mujeres gestantes con HIV y de sus hijos en un centro de referencia de Medellín. Materiales y métodos. Se hizo un estudio descriptivo retrospectivo entre 2012 y 2015 mediante la revisión de las historias clínicas de las mujeres gestantes con HIV y de sus neonatos habidos en partos atendidos en el Hospital San Vicente Fundación. Se describieron las variables de atención prenatal, parto, recién nacido y seguimiento de los neonatos. Resultados. Se analizaron 106 madres y sus hijos expuestos al HIV. El 39,6 % de las mujeres gestantes conocía el diagnóstico antes del embarazo y al 58,5 % se le diagnosticó durante este. El 95,3 % de las mujeres gestantes asistió a control prenatal, 46,5 % de ellas a partir del primer trimestre. Si bien el 95 % recibió antirretrovirales, el 23,9 % comenzó a tomarlos tardíamente en el tercer trimestre. Solo el 63 % de las mujeres registró carga viral para el HIV después de la semana 34 de gestación. El 90,6 % de los partos fueron por cesárea, y el virus del papiloma humano y la sífilis fueron las principales infecciones concomitantes. Se hizo seguimiento de 103 niños (no fue posible localizar a tres de ellos para el seguimiento), a ninguno se le confirmó la presencia del HIV y, en el 88 %, se descartó. Conclusiones. En este estudio, no se registraron casos de transmisión perinatal. Sin embargo, siguen presentándose fallas y retrasos en la atención prenatal y en la oportunidad del seguimiento materno para confirmar oportunamente el HIV y para detectar tempranamente infecciones maternas concomitantes que eviten la morbilidad y las secuelas en los neonatos.

US Provider Perceptions of Differences in the Sexual and Reproductive Health Needs of Adolescents with Perinatally Acquired and Behaviorally Acquired HIV: A Mixed Methods Study.

This study explores health care providers' perceptions of similarities and differences in the sexual and reproductive needs of adolescents with perinatally acquired HIV (PHIV) and behaviorally acquired HIV (BHIV). Interviews (n = 13) and online surveys (n = 46) were completed by medical and social service providers (n = 30, n = 29, respectively) who care for adolescents with HIV. Eligible providers were recruited using snowball sampling. Responses to open-ended questions were coded for emergent themes. Sixty-eight percent of participants perceived differences in the sexual and reproductive health needs of adolescents with PHIV and BHIV. Differences included factors related to psychosocial, sexual, and medical needs. Providers believed adolescents with PHIV had integrated their diagnosis into their identity, were more adept at communicating with providers, and were more sexually cautious than youth with BHIV. Providers perceived adolescents with BHIV as more comfortable discussing sex-related issues, and suggested youth with PHIV were more comfortable accessing health care. Adolescents with PHIV were thought to have complex medical histories/treatment and greater knowledge of illness/medications. Existing research on adolescent-reported sexual and reproductive health knowledge and experiences in care suggests that provider and adolescent perspectives do not always align. Mode of transmission may provide some information about psychosocial functioning and sexual behavior. However, assumptions about sexual and reproductive health needs based solely on mode of transmission may contribute to gaps in sexual and reproductive health care. Future research is needed to examine whether these differing perspectives indeed lead to discrepancies in the care provided to adolescents with HIV.

Use and Outcomes of Antiretroviral Monotherapy and Treatment Interruption in Adolescents With Perinatal HIV Infection in Asia.

PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. METHODS: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/µL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes. CONCLUSIONS: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.

Multisystem impairment in South African adolescents with Perinatally acquired HIV on antiretroviral therapy (ART).

INTRODUCTION: Adolescents with perinatally acquired HIV (PHIV) are at risk of chronic disease due to long-standing immune suppression, HIV disease and antiretroviral therapy (ART) exposure. However, there are few data on multisystem disease in this population. We investigated the overlapping burden of neurocognitive, cardiovascular, respiratory and/or renal impairment among PHIV positive (PHIV+) adolescents. METHODS: In this cross-sectional analysis, participants aged 9 to 14 years on ART for >6 months were recruited from seven sites across Cape Town from July 2013 through March 2015, together with age-matched HIV-negative (HIV-) adolescents. Impairment at enrolment was assessed across neurocognitive functioning (using the youth-International HIV Dementia Scale); cardiac function (echocardiogram abnormality); respiratory function (abnormal spirometry) and renal function (abnormal glomerular filtration rate). RESULTS AND DISCUSSION: Overall, 384 PHIV+ and 95 HIV- adolescents were included (mean age, 11.9 years; 49% female). Median age of ART initiation was 4.2 years (IQR: 1.7 to 7.6) and median CD4 count was 709 (IQR: 556 to 944) with 302 (79%) of PHIV+ adolescents virologically suppressed. Abacavir and Zidovudine were the most commonly used nucleoside reverse transcriptase inhibitors (NRTIs) with 60% of adolescents on non-nucleoside reverse transcriptase inhibitors (NNRTI) and 38% on a protease inhibitor (PI). Among PHIV+ adolescents, 167 (43.5%) had single system impairment only, 110 (28.6%) had two systems involved, and 39 (10.2%) had three or four systems involved. PHIV+ participants had more 2-system and 3-system impairment than HIV-, 110 (28.6%) versus 17 (17.9%), p = 0.03 and 39 (10.2%) versus 3 (4.3%), p = 0.03. PHIV+ participants who had failed a year of school (73.8% vs. 46.4%, p = 0.00) and with a viral load >1000 copies/mL at enrolment (16.8% vs. 8.1%, p = 0.03) were more likely to have dual or multisystem impairment. Of those with cardiac impairment, 86.7% had an additional system impaired. Similarly, in those with neurocognitive impairment, almost 60% had additional systems impaired and of those with respiratory impairment, 74% had additional systems impaired. CONCLUSIONS: Despite relatively early ART initiation, there is a substantial burden of multisystem chronic impairment among PHIV+ adolescents. This phenomenon needs to be further explored as this population ages and begins to engage in adult lifestyle factors that may compound these impairments.