HIV-infected Youth Research Articles

Understanding Care Linkage and Engagement Across 15 Adolescent Clinics: Provider Perspectives and Implications for Newly HIV-Infected Youth.

The National HIV/AIDS Strategy emphasizes rapid care linkage and engagement for HIV-infected individuals, though many adolescents are never tested, delay entering care, and frequently drop out. We conducted 183 staff interviews at 15 adolescent medicine clinics (baseline, n = 64; Year 1, n = 60; Year 2, = 59). We used a constant comparative thematic method to examine how providers approached and discussed care linkage/engagement. Qualitative analyses revealed differences in providers' conceptualizations of linkage and engagement. Providers saw linkage as mechanistic and health system driven. It was defined by number of clinic visits and involved relatively little youth agency. In contrast, providers defined engagement by youths' responsibility and participation in their own care. Linkage and engagement are related but distinct aspects of care that require different resources and levels of staff involvement. Integrating an understanding of these differences into future interventions will allow clinic staff to help youth improve long-term health outcomes.

Long-term pulmonary complications in perinatally HIV-infected youth

Increased incidence and prevalence of asthma have been documented for perinatally HIV-infected youth 10 to 21years of age compared with HIV-exposed uninfected (HEU) youth. We sought to perform objective pulmonary function tests (PFTs) in HIV-infected and HEU youth with and without diagnosed asthma. Asthma was determined in 370 participants (218 HIV-infected and 152 HEU participants) by means of chart review and self-report at 13 sites. Interpretable PFTs (188 HIV-infected and 132 HEU participants) were classified as obstructive, restrictive, or normal, and reversibility was determined after bronchodilator inhalation. Values for HIV-1 RNA, CD4 and CD8 T cells, eosinophils, total IgE, allergen-specific IgE, and urinary cotinine were measured.Adjusted prevalence ratios (PRs) of asthma and PFT outcomes weredetermined for HIV-infected participants relative toHEU participants, controlling for age, race/ethnicity, and sex. Current asthma was identified in 75 (34%) of 218 HIV-infected participants and 38 (25%) of 152 HEU participants (adjusted PR, 1.33; P=.11). The prevalence of obstructive disease did not differ by HIV status. Reversibility was less likely in HIV-infected youth than in HEU youth (17/183 [9%] vs 21/126 [17%]; adjusted PR, 0.47; P=.020) overall and among just those with obstructive PFT results (adjusted PR, 0.46; P=.016). Among HIV-infected youth with current asthma, serum IgE levels were inversely correlated with CD8 T-cell counts and positively correlated with eosinophil counts and not associated with CD4 T-cell counts. HIV-infected youth had lower association of specific IgE levels to several inhalant and food allergens compared with HEU participants and significantly lower CD4/CD8 T-cell ratios (suggesting immune imbalance). Compared with HEU youth, HIV-infected youth demonstrated decreased reversibility of obstructive lung disease, which is atypical of asthma. This might indicate an early stage of chronic obstructive pulmonary disease. Follow-up into adulthood is warranted to further define their pulmonary outcomes.

Comparing longitudinal CD4 responses to cART among non-perinatally HIV-infected youth versus adults: Results from the HIVRN Cohort.

BackgroundYouth have residual thymic tissue and potentially greater capacity for immune reconstitution than adults after initiation of combination antiretroviral therapy (cART). However, youth face behavioral and psychosocial challenges that may make them more likely than adults to delay ART initiation and less likely to attain similar CD4 outcomes after initiating cART. This study compared CD4 outcomes over time following cART initiation between ART-naïve non-perinatally HIV-infected (nPHIV) youth (13–24 years-old) and adults (≥25–44 years-old).MethodsRetrospective analysis of ART-naïve nPHIV individuals 13–44 years-old, who initiated their first cART between 2008 and 2011 at clinical sites in the HIV Research Network. A linear mixed model was used to assess the association between CD4 levels after cART initiation and age (13–24, 25–34, 35–44 years), accounting for random variation within participants and between sites, and adjusting for key variables including gender, race/ethnicity, viral load, gaps in care (defined as > 365 days between CD4 tests), and CD4 levels prior to cART initiation (baseline CD4).ResultsAmong 2,595 individuals (435 youth; 2,160 adults), the median follow-up after cART initiation was 179 weeks (IQR 92–249). Baseline CD4 was higher for youth (320 cells/mm3) than for ages 25–34 (293) or 35–44 (258). At 239 weeks after cART initiation, median unadjusted CD4 was higher for youth than adults (576 vs. 539 and 476 cells/mm3, respectively), but this difference was not significant when baseline CD4 was controlled. Compared to those with baseline CD4 ≤200 cells/mm3, individuals with baseline CD4 of 201–500 and >500 cells/mm3 had greater predicted CD4 levels: 390, 607, and 831, respectively. Additionally, having no gaps in care and higher viral load were associated with better CD4 outcomes.ConclusionsDespite having residual thymic tissue, youth attain similar, not superior, CD4 gains as adults. Early ART initiation with minimal delay is as essential to optimizing outcomes for youth as it is for their adult counterparts.

RUBELLA SEROPREVALENCE AMONG HIV-INFECTED AND UNINFECTED ZAMBIAN CHILDREN AND ADOLESCENTS

BackgroundCongenital rubella syndrome remains a significant cause of morbidity and mortality among children in sub-Saharan Africa. A safe and effective vaccine is available and many countries, including Zambia, plan to...

Effects of cholecalciferol supplementation on serum and urinary vitamin D metabolites and binding protein in HIV-infected youth

Vitamin D insufficiency is widespread in HIV-infected patients. HIV and/or antiretroviral therapy (ART), particularly efavirenz (EFV), may interfere with vitamin D metabolism. However, few data from randomized, controlled trials exist. Here, we investigate changes in vitamin D metabolites and binding protein (VDBP) after 6 months of supplementation in a randomized, active-control, double-blind trial investigating 2 different monthly cholecalciferol (vitamin D3) doses [60,000 (medium) or 120,000 (high) IU/month] vs. a control arm of 18,000 IU/month in 8–25year old HIV-infected youth on ART with HIV-1 RNA <1000 copies/mL and baseline 25-hydroxycholecalciferol (25(OH)D3) ≤30ng/mL. A matched healthy uninfected group was enrolled in a similar parallel study for comparison. Changes after 6 months were analyzed as intent-to-treat within/between groups [control group (low dose) vs. combined supplementation doses (medium+high)]. At 6 months, 55% vs. 82% of subjects in control and supplementation groups, respectively, reached 25(OH)D3 ≥30ng/mL (P=0.01) with no difference between medium and high doses (both 82% ≥30ng/mL). There were few differences for those on EFV vs. no-EFV, except serum VDBP decreased in EFV-treated subjects (both within- and between-groups P≤0.01). There were no significant differences between the HIV-infected vs. healthy uninfected groups. The major finding of the present study is that cholecalciferol supplementation (60,000 or 120,000 IU/month) effectively raises serum 25(OH)D3 in the majority of HIV-infected subjects, regardless of EFV use. Notably, response to supplementation was similar to that of uninfected subjects.

The interaction between equipoise and logistics in clinical trials: A case study.

Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician's sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers' willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.

Amino Acid Concentrations in HIV-Infected Youth Compared to Healthy Controls and Associations with CD4 Counts and Inflammation.

Amino acids play critical roles in metabolism, cell function, body composition and immunity, but little data on plasma amino acid concentrations in HIV are available. We evaluated plasma amino acid concentrations and associations with CD4 counts and inflammatory biomarkers in HIV-infected youth. HIV-infected subjects with a high (≥500 cells/mm3) and low (<500 cells/mm3) current CD4+ T cell counts were compared to one another and to a matched healthy control group. Plasma concentrations of 19 amino acids were determined with an amino acid analyzer. Plasma levels of interleukin-6, tumor necrosis factor receptor-I, and soluble vascular cellular adhesion molecule-I were also measured. Seventy-nine HIV-infected subjects (40 and 39 with high and low CD4+ T cell counts, respectively) and 40 controls were included. There were no differences in amino acid concentrations between HIV-infected subjects with high or low CD4+ T cell counts. When combined, the HIV-infected group exhibited significantly lower median plasma concentrations compared to controls for total, essential, branched-chain and sulfur amino acids, as well as for 12 individual amino acids. Glutamate was the only amino acid that was higher in the HIV-infected group. There were no significant correlations between amino acid endpoints and inflammatory biomarkers for either HIV-infected group or controls. Plasma amino acid concentrations were lower in HIV-infected youth compared to healthy controls, regardless of immune status, while glutamate concentrations were elevated. These findings can inform future interventional studies designed to improve metabolic and clinical parameters influenced by amino acid nutriture.

Increased Risk of Virologic Failure Among Highly Adherent HIV Infected Youth Compared to Adults in a Nigerian Cohort

Increased Risk of Virologic Failure Among Highly Adherent HIV Infected Youth Compared to Adults in a Nigerian Cohort

Measles and Rubella Seroprevalence Among HIV-infected and Uninfected Zambian Youth.

Measles and congenital rubella syndrome remain significant causes of morbidity and mortality despite available vaccines. HIV-infected youth may be at increased risk of measles because of greater waning immunity after vaccination. At a population level, they constitute a potentially large pool of susceptibles to measles and rubella. More data among HIV-infected youth in sub-Saharan Africa are needed to guide vaccination policy and control strategies. This cross-sectional study was nested within 2 ongoing studies of malaria and HIV in Zambia. Dried blood spot cards from youth (5-15 years) in these studies from 2009 to 2013 were tested for IgG antibodies to measles and rubella viruses. HIV-uninfected youth, HIV-infected treatment-naive youth and HIV-infected youth receiving antiretroviral therapy (ART) were compared. A total of 617 HIV-uninfected, 144 HIV-infected treatment-naive and 128 HIV-infected youth receiving ART were included in this study. The proportion seropositive for measles virus was significantly higher among HIV-uninfected youth (92.5%) compared with HIV-infected treatment-naive youth (74.1%) and HIV-infected youth receiving ART (71.9%). No differences by age were observed. The proportion seropositive for rubella virus was significantly higher among HIV-uninfected youth (54.7%) compared with HIV-infected treatment-naive youth (41.7%) and HIV-infected youth receiving ART (49.6%), with increases observed by age for all groups. Measles seroprevalence was lower among HIV-infected than uninfected youth, consistent with waning immunity after measles vaccination. HIV-infected youth would benefit from revaccination. Half of all youth in rural Zambia were susceptible to rubella and may need targeting for catch-up rubella campaigns when measles-rubella vaccine is introduced.

Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration.

Objective:To identify relationships between insulin resistance (IR) and mitochondrial respiration in perinatally HIV-infected youth.Design:Case–control study.Methods:Mitochondrial respiration was assessed in perinatally HIV-infected youth in Tanner stages 2–5, 25 youth with IR (IR+) and 50 without IR (IR−) who were enrolled in the Pediatric HIV/AIDS Cohort Study. IR was defined as a homeostatic model of assessment for IR value at least 4.0. A novel, high-throughput oximetry method was used to evaluate cellular respiration in peripheral blood mononuclear cells. Unadjusted and adjusted differences in mitochondrial respiration markers between IR+ and IR− were evaluated, as were correlations between mitochondrial respiration markers and biochemical measurements.Results:IR+ and IR− youth were similar on age, sex, and race/ethnicity. Mean age was 16.5 and 15.6 years in IR+ and IR−, respectively. The IR+ group had significantly higher mean BMI and metabolic analytes (fasting glucose, insulin, cholesterol, triglycerides, and venous lactate and pyruvate) compared with the IR−. Mitochondrial respiration markers were, on average, lower in the IR+ compared with IR−, including basal respiration (417.5 vs. 597.5 pmol, P = 0.074), ATP production (11 513 vs. 15 202 pmol, P = 0.078), proton leak (584.6 vs. 790.0 pmol, P = 0.033), maximal respiration (1815 vs. 2399 pmol, P = 0.025), and spare respiration capacity (1162 vs. 2017 pmol, P = 0.032). Nonmitochondrial respiration did not differ by IR status. The results did not change when adjusted for age.Conclusion:HIV-infected youth with IR have lower mitochondrial respiration markers when compared to youth without IR. Disordered mitochondrial respiration may be a potential mechanism for IR in this population.

Increased Immune Activation and Exhaustion in HIV-infected Youth.

Immune activation and exhaustion drive several comorbidities and disease progression in HIV-infected adults; however, they are not well studied in HIV-infected youth. Thus, this study sought to examine levels of immune activation and exhaustion in this population, investigate associated HIV- and non-HIV-related variables and compare results with a matched healthy control group. HIV-infected youth 8-25 years of age on stable antiretroviral therapy with an HIV-1 RNA level <1000 copies/mL were enrolled, along with matched healthy controls. We measured T-cell and monocyte immune activation and exhaustion markers in cryopreserved peripheral blood mononuclear cell and plasma samples. A total of 136 subjects (80 HIV+: 66% male; 91% black) were enrolled. Markers of CD4+ and CD8+ T-cell activation were higher in the HIV-infected group versus controls [mean % CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ = 2.2 versus 1.5 (P=0.002) and 4.9 versus 2.2 (P<0.0001), respectively], as were exhausted CD4+ and CD8+ T-cells [mean % CD4+CD38+HLA-DR+PD-1+ and CD8+CD38+HLA-DR+PD-1+ = 1.0 versus 0.5 (P<0.0001) and 1.6 versus 0.7 (P<0.0001), respectively]. There were no differences in proportions of inflammatory or patrolling monocytes between groups (P>0.05); however, soluble CD14 was higher in HIV-infected compared with controls (1.6 versus 1.4 µg/mL; P=0.01). Current CD4 count, low-density lipoprotein cholesterol and age were the variables most associated with CD4+ and CD8+ T-cell activation. CD4+ and CD8+ T-cell immune activation and exhaustion are higher in HIV-infected youth compared with matched controls, while monocyte subpopulations are not altered despite a high soluble CD14 level. The clinical significance of the increased immune activation and exhaustion should be further explored.

Resilience and Life Expectations of Perinatally HIV-1 Infected Adolescents in France.

Background:Resilience of perinatally HIV-infected youth in European countries is poorly studied. Life satisfaction and expectations for adulthood are rarely examined.Objective:This cross-sectional, descriptive study of a French cohort of 54 perinatally HIV-infected adolescents raised in France (age 14-20 years) aimed to (1) evaluate their psychosocial adjustment, (2) identify their expectations for adulthood and (3) delineate risk and protective factors associated with mental health, life satisfaction, and HIV-1 viral load level.Method:Medical evaluation, psychological semi-structured interview, and self-report questionnaires were used.Results:All the adolescents had been receiving Highly Active Anti-Retroviral Therapy (HAART) for 9 to 11 years and 2/3 were healthy with controlled viral load (<50 copies/mL). The majority had medium to high levels of life satisfaction. They viewed HIV as having only minor impact on their current daily life and had positive expectations for adulthood. However, 46% exhibited psychiatric symptomatology. Multivariable analysis showed that having a deceased parent and current worries about HIV were substantial risk factors for psychiatric symptoms. Having two living parents and being satisfied with life were protective factors for mental health. Good quality of caregiver-adolescent relationships and high life satisfaction were significant protective factors for controlled viral load.Conclusion:These data indicate psychosocial resilience among perinatally HIV-1 infected adolescents with 10 years of HAART treatment. These findings demonstrate the influence of life satisfaction, parent’s life status and quality of caregiver-adolescent relationships on resilience and health outcomes in these patients. We conclude that healthcare providers should attend to these factors.

Neurocognitive dysfunction in HIV-infected youth: investigating the relationship with immune activation.

HIV-infected individuals are at increased risk of neurocognitive impairment compared to the general population. Studies suggest that, despite combination antiretroviral therapy (cART), HIV infection causes immune activation which results in neural damage; however, few data exist in HIV-infected youth. HIV-infected youth 8-26-years-old on cART with virological suppression were prospectively enrolled along with healthy controls. Neurocognitive performance was assessed by age-appropriate Wechsler Intelligence Scales. Soluble and cellular markers of T-lymphocyte and monocyte activation were measured by ELISA and flow cytometry, respectively. 45 HIV-infected subjects and 21 controls were enrolled. Markers of T-cell and monocyte activation were higher in the HIV-infected subjects compared to controls, but proportions of inflammatory and patrolling monocytes were similar. Although there were no significant differences in neurocognitive scores between the HIV-infected and control groups, scores were low-average for four of five testing domains for the HIV-infected subjects and average for all five in the controls, and % of HIV-infected subjects with scores classified as 'low average' or below was higher than in the controls. Variables most associated with neurocognitive performance among HIV-infected subjects included activated CD4+ T-cells (% CD4+CD38+HLA-DR), monocyte activation (soluble CD14), HIV duration, age and sex. HIV-infected youth on cART with virological suppression show subtle evidence of neurocognitive impairment compared to healthy controls, and increased immune activation appears to play a role. Additional studies are needed to develop strategic interventions beyond cART to potentially improve neurocognitive performance and/or minimize further impairment in this vulnerable population. ClinicalTrials.gov Identifier: NCT01523496.

Uptake and Virologic Outcomes of 1-Pill versus Multipill Antiretroviral Therapy Among Treatment-Naive Nonperinatally HIV-Infected Youth (2006–2014)

Uptake and Virologic Outcomes of 1-Pill versus Multipill Antiretroviral Therapy Among Treatment-Naive Nonperinatally HIV-Infected Youth (2006–2014)

Living Conditions as a Driving Factor in Persistent Methicillin-resistant Staphylococcus aureus Colonization Among HIV-infected Youth

Methicillin-resistant Staphylococcus aureus (MRSA) colonization has been linked to HIV-related sexual and social behaviors. MRSA risk factors may be different for HIV-infected children, adolescents and young adults. We investigated the association of MRSA colonization, persistent colonization and genotypes with potential risk factors among HIV-infected youth. For this case-control study, patients 24 years of age or younger attending 2 HIV reference centers were recruited from February to August 2012 and followed for 1 year. Nasal swabs were collected at enrollment and every 3 months. MRSA clones were characterized by staphylococcal chromosomal cassette mec typing, spa typing and multilocus sequence typing. We compared MRSA colonization and persistent colonization with patient demographic and clinical characteristics. Among 117 participants, MRSA colonization frequency (calculated for each collection based on the number of positive cultures per patient) was 12.8% at the first collection. The average MRSA colonization frequency was 10.4%. Our results showed 11.1% were persistent carriers (subjects with more than 1 positive culture in at least 3). Crowding was the only factor associated with MRSA colonization (P = 0.018). Persistent carriers had significantly higher (4.2 times) odds of living in a crowded household (95% confidence interval-1.1-16.2). We observed high genetic diversity among MRSA isolates, with t002/ST5 and t318/ST30 being the most frequent. MRSA colonization among HIV-infected youth is more closely related to living in a low-income or slum community than to HIV-related clinical factors. High genetic MRSA isolate diversity in our population suggests frequent transmission.

Systematic review and meta-analysis of the adolescent HIV continuum of care in South Africa: the Cresting Wave

ContextSouth Africa has the most HIV infections of any country in the world, yet little is known about the adolescent continuum of care from HIV diagnosis through viral suppression.ObjectiveTo determine...

HIV Stigma: Perspectives from Kenyan Child Caregivers and Adolescents Living with HIV.

Stigma shapes all aspects of HIV prevention and treatment, yet there are limited data on how HIV-infected youth and their families are affected by stigma in sub-Saharan Africa. The authors conducted a qualitative study using focus group discussions among 39 HIV-infected adolescents receiving care at HIV clinics in western Kenya and 53 caregivers of HIV-infected children. Participants felt that while knowledge and access to treatment were increasing, many community members still held negative and inaccurate views about HIV, including associating it with immorality and believing in transmission by casual interactions. Stigma was closely related to a loss of social and economic support but also included internalized negative feelings about oneself. Participants identified treatment-related impacts of stigma, including nonadherence, nondisclosure of status to child or others, and increased mental health problems. Qualitative inquiry also provided insights into how to measure and reduce stigma among affected individuals and families.

Enhancing self‐care, adjustment and engagement through mobile phones in youth with HIV.

To evaluate the effectiveness of mobile phones in enhancing self-care, adjustment and engagement in non-disclosed youth living with HIV. Youth aged 15-24years represent 42% of new HIV infections globally. Youth who are aware of their HIV status generally do not disclose it or utilize HIV-related facilities because of fear of stigma. They rely on the Internet for health maintenance information and access formal care only when immune-compromised and in crisis. This study shows how non-disclosed youth living with HIV can be reached and engaged for self-management and adjustment through mobile phone. One-group pre-test/post-test experimental design was used. Mobile phones were used to give information, motivation and counselling to 19 purposively recruited non-disclosed youth with HIV in Calabar, South-South Nigeria. Psychological adjustment scale, modified self-care capacity scale and patient activation measure were used to collect data. Data were analysed using PASW 18.0. Scores on self-care capacity, psychological adjustment and engagement increased significantly at post-test. HIV-related visits to health facilities did not improve significantly even at 6months. Participants still preferred to consult healthcare providers for counselling through mobile phone. Mobile phone-based interventions are low cost, convenient, ensure privacy and are suitable for youth. Such remote health counselling enhances self-management and positive living. Mobile phones enhance self-care, psychological adjustment and engagement in non-disclosed youth living with HIV, and can be used to increase care coverage. Findings underline the importance of policies to increase access by locating, counselling and engaging HIV-infected youth in care.

Pilot Assessment of Brain Metabolism in Perinatally HIV-Infected Youths Using Accelerated 5D Echo Planar J-Resolved Spectroscopic Imaging.

PurposeTo measure cerebral metabolite levels in perinatally HIV-infected youths and healthy controls using the accelerated five dimensional (5D) echo planar J-resolved spectroscopic imaging (EP-JRESI) sequence, which is capable of obtaining two dimensional (2D) J-resolved spectra from three spatial dimensions (3D).Materials and MethodsAfter acquisition and reconstruction of the 5D EP-JRESI data, T1-weighted MRIs were used to classify brain regions of interest for HIV patients and healthy controls: right frontal white (FW), medial frontal gray (FG), right basal ganglia (BG), right occipital white (OW), and medial occipital gray (OG). From these locations, respective J-resolved and TE-averaged spectra were extracted and fit using two different quantitation methods. The J-resolved spectra were fit using prior knowledge fitting (ProFit) while the TE-averaged spectra were fit using the advanced method for accurate robust and efficient spectral fitting (AMARES).ResultsQuantitation of the 5D EP-JRESI data using the ProFit algorithm yielded significant metabolic differences in two spatial locations of the perinatally HIV-infected youths compared to controls: elevated NAA/(Cr+Ch) in the FW and elevated Asp/(Cr+Ch) in the BG. Using the TE-averaged data quantified by AMARES, an increase of Glu/(Cr+Ch) was shown in the FW region. A strong negative correlation (r < -0.6) was shown between tCh/(Cr+Ch) quantified using ProFit in the FW and CD4 counts. Also, strong positive correlations (r > 0.6) were shown between Asp/(Cr+Ch) and CD4 counts in the FG and BG.ConclusionThe complimentary results using ProFit fitting of J-resolved spectra and AMARES fitting of TE-averaged spectra, which are a subset of the 5D EP-JRESI acquisition, demonstrate an abnormal energy metabolism in the brains of perinatally HIV-infected youths. This may be a result of the HIV pathology and long-term combinational anti-retroviral therapy (cART). Further studies of larger perinatally HIV-infected cohorts are necessary to confirm these findings.

Oral Human Papillomavirus in Youth From the Pediatric HIV/AIDS Cohort Study.

In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.