Perinatally HIV-infected Youth Research Articles

Increased Risk of Executive Function and Emotional Behavioral Problems Among Virologically Well-Controlled Perinatally HIV-Infected Adolescents in Thailand and Cambodia.

Large numbers of perinatally HIV-infected (PHIV) children are aging into adolescence. We examined cognitive and behavioral outcomes in a longitudinal cohort of Asian youth. We followed up 231 PHIV, 125 perinatally HIV-exposed, uninfected (HEU), and 138 HIV-unexposed, uninfected (HUU) adolescents (aged 10 years and older), matched by age/sex, in Thailand and Cambodia for 3 years. Executive function was assessed with Children's Color Trails Tests 1 and 2 (CCTT-1 and -2), the design fluency test, and the verbal fluency test. Working memory (Freedom from Distractibility Index) and processing speed index were assessed using WISC-III. Visual memory was assessed by design memory and design recognition subtests of the Wide Range Assessment of Memory and Learning (WRAML-2) and behavioral problems using the Child Behavior Checklist (CBCL). Generalized estimating equations examined adjusted odds ratios of cognitive impairment (Z-scores ≥2 SD below age-adjusted means of the HUU group) and CBCL T-scores in the borderline-clinical range (T-Scores ≥60) in PHIV and HEU versus HUU youth, adjusting for ethnicity, household income, and caregiver characteristics. The median age at enrollment was 13.8 years, with 58% women and 63% Thai participants. PHIV youth had >86% virological suppression and significantly higher impairment rates on CCTT-1 and -2 tests, design fluency test, verbal fluency tests, design memory, and CBCL internalizing and externalizing problems. Results were mostly similar between HEU and HUU groups, apart from higher impairment rates on CCTT-1 and internalizing problems in HEU. Asian adolescents with PHIV remain at risk of cognitive and mental health problems despite HIV treatment. Selective risks are observed among HEU youth.

Internalizing Mental Disorders and Accelerated Cellular Aging Among Perinatally HIV-Infected Youth in Uganda.

Introduction: Internalizing mental disorders (IMDs) in HIV+ children and adolescents are associated with impaired quality of life and non-adherence to anti-retroviral treatment. Telomere length is a biomarker of cellular aging, and shorter telomere length has been associated with IMDs. However, the nature of this association has yet to be elucidated. Objective: We determined the longitudinal association between IMDs and relative telomere length (rTL) and the influence of chronic stress among Ugandan perinatally HIV-infected youth (PHIY). Methods: IMDs (depressive disorders, anxiety disorders, and post-traumatic stress disorder) and IMDs were assessed using the locally adapted Child and Adolescent Symptom Inventory-5. In 368 PHIY with any IMD and 368 age- and sex-matched PHIY controls without any psychiatric disorder, rTL was assessed using quantitative polymerase chain reaction. Hierarchical cluster analysis was used to generate the three chronic stress classes (mild, moderate, and severe). t-tests were used to assess the difference between baseline and 12 month rTL and the mean difference in rTL between cases and controls both at baseline and at 12 months. Linear regression analysis was used to model the effects of chronic stress on the association between IMDs and rTL, controlling for age and sex. Results: We observed longer rTL among cases of IMDs compared with controls (p < 0.001). We also observed a statistically significant reduction in rTL between baseline and 12 months in the combined sample of cases and controls (p < 0.001). The same statistical difference was observed when cases and controls were individually analyzed (p < 0.001). We found no significant difference in rTL between cases and controls at 12 months (p = 0.117). We found no significant influence of chronic stress on the association between IMDs and rTL at both baseline and 12 months. Conclusion: rTL is longer among cases of IMDs compared with age- and sex-matched controls. We observed a significant attrition in rTL over 12 months, which seems to be driven by the presence of any IMDs. There is a need for future longitudinal and experimental studies to understand the mechanisms driving our findings.

Markers of Bone Mineral Metabolism and Cardiac Structure and Function in Perinatally HIV-Infected and HIV-Exposed but Uninfected Children and Adolescents.

Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth. The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites. Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected (PHEU) youth enrolled in the Adolescent Master Protocol, we evaluated associations of vitamin D [measured as 25-hydroxy-vitamin D (25-OHD)], parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function, and concentrations of NT-proBNP, a biomarker of cardiac damage. Among 485 participants (305 PHIV and 180 PHEU) with echocardiograms and bone mineralization measures, low 25-OHD (<20 ng/mL) was common among all participants (48% PHIV and 44% PHEU), but elevated PTH (>65 pg/mL) was identified more often among PHIV participants than PHEU participants (9% vs 3%, P = 0.02). After adjusting for HIV status and demographic covariates, both low 25-OHD and elevated PTH were associated with lower mean LV mass z-scores, whereas elevated PTH was associated with higher mean fractional shortening z-scores. Participants with low 25-OHD also had slightly higher mean LV end-systolic wall stress z-scores, but differences were more pronounced in PHEU participants than in PHIV participants. FGF-23 was inversely related to end-diastolic septal thickness, both overall and among PHIV participants. In this cohort of PHIV and PHEU youth, we observed associations of 25-OHD, PTH, and FGF-23 with both structural and functional cardiac parameters, supporting links between bone mineral metabolism and cardiac status.

Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus-infected and Exposed, Uninfected Youth.

Persons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth. This is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts. Seroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P < .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively. Antibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females.

White matter microstructure among perinatally HIV-infected youth: a diffusion tensor imaging study.

We evaluated white matter microstructure integrity in perinatally HIV-infected (PHIV)youths receiving cART compared to age- and gender-matched healthy youths through DTI metrics using voxel-based morphometry (VBM). We investigated 14 perinatally HIV-infected patients (age 17.9 ± 2.5years) on cART and 17 healthy youths (HC) (age 18.0 ± 3.0years) using a 3T MRI scanner. Four DTI-derived metrics were fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Statistical analysis was done with voxel-based analysis of covariance (ANCOVA), with age and gender as covariates. Region-of-interest secondary analyses in statistically significant regions were also performed. Regional increases in FA in the PHIV youths were found in left middle frontal gyrus, right precuneus, right lingual gyrus, and left supramarginal gyrus. Increased MD was found in the right precentral gyrus while decreased MD was found in the white matter of the right superior parietal lobule and right inferior temporal gyrus/fusiform gyrus. Regions of increased/decreased RD overlapped with regions of increased/decreased MD. Both increased and decreased AD were found in three to four regions respectively. The regional FA, MD, RD, and AD values were consistent with the voxel-based analysis findings. The findings are mostly consistent with previous literature, but increased FA has not been previously reported for perinatally HIV-infected youths. Potentially early and prolonged therapy in our population may have contributed to this new finding. Both toxicity of antiretroviral therapy and indolent infection must be considered as causative factors in the DTI metric changes that we have observed.

The association between oral disease and type of antiretroviral therapy among perinatally HIV-infected youth.

This study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth. We conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination. They assessed the decayed-missing-filled-surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and the number of teeth with gingival bleeding on probing for each participant were derived from the examination. Data for analysis included lifetime measurements of CD4 cell count and viral load, sociodemographic information and current/past history of ART. Among 209 PHIV youth, 95% were on ART at the time of enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found that the mean decayed teeth score of those receiving cART containing an integrase inhibitor was 86% higher than that of those on cART without an integrase inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was associated with a significantly lower DMFT score than participants who initiated at age 6 years and older. Our study revealed that PHIV youth who received cART containing an integrase inhibitor had a significantly higher number of untreated active caries than those on cART without an integrase inhibitor. This may warrant closer dental surveillance of those receiving an integrase inhibitor.

Cardiac and inflammatory biomarkers in perinatally HIV-infected and HIV-exposed uninfected children.

To compare distributions of serum cardiac and inflammatory biomarkers between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) children, to evaluate their associations with echocardiographic measures, and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity measures. Cross-sectional analysis of temporally paired serum samples for biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV and PHEU youth. Serum samples were analyzed among 402 youth in the PHACS Adolescent Master Protocol (AMP) for high-sensitivity cardiac troponin-T (hs-cTnT, a cardiomyocyte injury marker), N-terminal-pro-brain natriuretic peptide (NT-proBNP, a myocardial stress marker), and inflammatory markers [high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α (TNF-α), and soluble TNF receptor II (sTNF-RII)]. Echocardiograms were centrally measured and parameters converted to z cores to account for differences in age and body size. Compared with PHEU (N = 156), PHIV youth (N = 246) more often had detectable hs-cTnT and higher levels of sTNF-RII and IL-18. Higher inflammatory biomarkers were generally associated with higher left ventricular (LV) wall stress and lower LV function and LV mass in the two groups. Among PHIV youth, the biomarkers were more strongly associated with current rather than historical immunologic and virologic status. PHEU and PHIV have modest, significant differences in serum levels of specific inflammatory and active myocardial injury biomarkers. Higher biomarker levels were associated with lower LV mass and shifts in LV structure. Further study is warranted on the longitudinal role of cardiac and inflammatory biomarkers for targeting interventions among PHIV and PHEU youth.

Oral microbiota in youth with perinatally acquired HIV infection

BackgroundMicrobially mediated oral diseases can signal underlying HIV/AIDS progression in HIV-infected adults. The role of the oral microbiota in HIV-infected youth is not known. The Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study is a longitudinal study of perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) youth. We compared oral microbiome levels and associations with caries or periodontitis in 154 PHIV and 100 PHEU youth.ResultsSpecies richness and alpha diversity differed little between PHIV and PHEU youth. Group differences in average counts met the significance threshold for six taxa; two Corynebacterium species were lower in PHIV and met thresholds for noteworthiness. Several known periodontitis-associated organisms (Prevotella nigrescens, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Filifactor alocis) exhibited expected associations with periodontitis in PHEU youth, associations not observed in PHIV youth. In both groups, odds of caries increased with counts of taxa in four genera, Streptococcus, Scardovia, Bifidobacterium, and Lactobacillus.ConclusionsThe microbiomes of PHIV and PHEU youth were similar, although PHIV youth seemed to have fewer “health”-associated taxa such as Corynebacterium species. These results are consistent with the hypothesis that HIV infection, or its treatment, may contribute to oral dysbiosis.

CARDIAC AND INFLAMMATORY BIOMARKERS IN PERINATALLY HIV-INFECTED AND HIV-EXPOSED UNINFECTED CHILDREN

OBJECTIVES To compare distributions of serum cardiac and inflammatory biomarkers between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) children, to evaluate their associations with echocardiographic measures, and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity measures. DESIGN Cross-sectional analysis of temporally paired serum samples for biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV and PHEU youth. METHODS Serum samples were analyzed among 402 youth in the PHACS Adolescent Master Protocol (AMP) for high-sensitivity cardiac troponin-T (hs-cTnT, a cardiomyocyte injury marker), N-terminal-pro-brain natriuretic peptide (NT-proBNP, a myocardial stress marker), and inflammatory markers [high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α (TNF-α), and soluble TNF receptor II (sTNF-RII)]. Echocardiograms were centrally measured and parameters converted to z cores to account for differences in age and body size. RESULTS Compared with PHEU (N = 156), PHIV youth (N = 246) more often had detectable hs-cTnT and higher levels of sTNF-RII and IL-18. Higher inflammatory biomarkers were generally associated with higher left ventricular (LV) wall stress and lower LV function and LV mass in the two groups. Among PHIV youth, the biomarkers were more strongly associated with current rather than historical immunologic and virologic status. CONCLUSION PHEU and PHIV have modest, significant differences in serum levels of specific inflammatory and active myocardial injury biomarkers. Higher biomarker levels were associated with lower LV mass and shifts in LV structure. Further study is warranted on the longitudinal role of cardiac and inflammatory biomarkers for targeting interventions among PHIV and PHEU youth.

Prevalence of periodontal diseases in a multicenter cohort of perinatally HIV-infected and HIV-exposed and uninfected youth.

To compare the prevalence and severity of periodontal diseases between 180 perinatally HIV-infected (PHIV) and 118 perinatally HIV-exposed and uninfected (PHEU) youth in a cross-sectional study conducted at 11 clinical sites in the United States and Puerto Rico from the Adolescent Master Protocol study of the Pediatric HIV/AIDS cohort study (PHACS) network. Several analyses were conducted, employing the current CDC/AAP classification for periodontitis and incorporating a definition of gingivitis based on a bleeding on probing (BOP) threshold, and analyses based on more detailed whole-mouth, intra-oral regionally, site-based and tooth-based criteria of BOP, plaque levels, pockets depths and clinical attachment levels. After adjusting for plaque control habits and behavioural and sociodemographic factors, there were no significant differences in periodontal diseases between the PHIV and PHEU youth using any of these criteria. For PHIV youth, there was no significant association between parameters of periodontal disease and current HIV status. Although no significant differences in periodontal parameters were noted between the PHIV and PHEU youth, the influence of antiretroviral therapy merits further exploration in this cohort in a longitudinal study.

Contributions of Disease Severity, Psychosocial Factors, and Cognition to Behavioral Functioning in US Youth Perinatally Exposed to HIV

Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth, we evaluated the contributions of home environment, psychosocial, and demographic factors and, among PHIV only, HIV disease severity and antiretroviral treatment (ART), to cognitive functioning (CF) and behavioral functioning (BF). A structural equation modeling (SEM) approach was utilized. Exploratory factor analysis was used to reduce predictor variables to major latent factors. SEMs were developed to measure associations between the latent factors and CF and BF outcomes. Participants included 231 PHIV and 151 PHEU youth (mean age=10.9years) enrolled in the PHACS adolescent master protocol. Youth and caregivers completed assessments of CF, BF, psychosocial factors and HIV health. Medical data were also collected. Clusters of predictors were identified, establishing four parsimonious SEMs: child-assessed and caregiver-assessed BF in PHIV and PHEU youth. Among both groups, higher caregiver-child stress predicted worse BF. Caregiver resources and two disease severity variables, late presenter and better past HIV health, were significant predictors of CF in PHIV youth. Higher youth CF was associated with better caregiver-reported BF in both groups. Caregiver resources predicted caregiver-reported BF in PHEU youth, which was mediated via youth CF. Among PHIV youth, better past HIV health and caregiver resources mediated the effects of CF on caregiver-assessed BF. Using SEMs, we found a deleterious impact of caregiver and child stress on BF in both groups and of HIV disease factors on the CF of PHIV youth, reinforcing the importance of early comprehensive intervention to reduce risks for impairment.

The Burden of Oral Disease among Perinatally HIV-Infected and HIV-Exposed Uninfected Youth.

ObjectiveTo compare oral health parameters in perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected youth (PHEU).MethodsIn a cross-sectional substudy within the Pediatric HIV/AIDS Cohort Study, participants were examined for number of decayed teeth (DT), Decayed, Missing, and Filled Teeth (DMFT), oral mucosal disease, and periodontal disease (PD). Covariates for oral health parameters were examined using zero-inflated negative binomial regression and ordinal logistic regression models.ResultsEleven sites enrolled 209 PHIV and 126 PHEU. Higher DT scores were observed in participants who were PHIV [Adjusted Mean Ratio (aMR) = 1.7 (95% CI 1.2–2.5)], female [aMR = 1.4 (1.0–1.9)], had no source of regular dental care [aMR = 2.3 (1.5–3.4)], and had a high frequency of meals/snacks [≥5 /day vs 0–3, aMR = 1.9 (1.1–3.1)] and juice/soda [≥5 /day vs 0–3, aMR = 1.6 (1.1–2.4)]. Higher DMFT scores were observed in participants who were older [≥19, aMR = 1.9 (1.2–2.9)], had biological parent as caregiver [aMR = 1.2 (1.0–1.3)], had a high frequency of juice/soda [≥5 /day vs 0–3, aMR = 1.4 (1.1–1.7)] and a low saliva flow rate [mL/min, aMR = 0.8 per unit higher (0.6–1.0)]. Eighty percent had PD; no differences were seen by HIV status using the patient-based classifications of health, gingivitis or mild, moderate, or severe periodontitis. No associations were observed of CD4 count and viral load with oral health outcomes after adjustment.ConclusionsOral health was poor in PHIV and PHEU youth. This was dismaying since most HIV infected children in the U.S. are carefully followed at medical health care clinics. This data underscore the need for regular dental care. As PHIV youth were at higher risk for cavities, it will be important to better understand this relationship in order to develop targeted interventions.

Phenotypic Coreceptor Tropism in Perinatally HIV-infected Youth Failing Antiretroviral Therapy.

Perinatally HIV-infected (PHIV) children and youth are often heavily treatment-experienced, with resultant antiretroviral resistance and limited treatment options. For those with virologic failure (VF), new agents such as CCR5 (R5) antagonists may be useful; however, reports of R5 antagonist susceptibility in children have mostly relied on genotypic testing, which may not accurately reflect the phenotypic tropism of the viral populations. We characterized phenotypic coreceptor usage among PHIV children and youth with VF on antiretroviral treatment to identify predictors of CXCR4 (X4) tropism which preclude R5 antagonist use. Plasma samples with >1000 HIV RNA copies/mL were obtained from 73 PHIV antiretroviral treatment-treated children and youth (age 9-21 years) enrolled in the multicenter Pediatric HIV/AIDS Cohort Study. Samples were analyzed using the Trofile phenotypic assay. Multiple logistic regression was performed to identify factors associated with detectable X4 tropism. Tropism results were obtained for 59 (81%) of the 73 children and youth; 32 (54%) had X4-tropism. Persistent viremia (≥80% of HIV RNA measurements >400 copies/mL) was associated with detectable X4 tropism (adjusted odds ratio: 6.6, 95% confidence interval: 1.4, 31.4), while longer cumulative nucleoside reverse transcriptase inhibitor use was associated with lower risk of X4 tropism (adjusted odds ratio: 0.6, 95% confidence interval: 0.5, 0.9). Using a phenotypic assay, >50% of PHIV children and youth with VF had X4 tropism, similar to that in experienced adults, and higher than the 30% reported for children using genotypic assays. Persistent viremia and shorter nucleoside reverse transcriptase inhibitor exposure are associated with X4-tropism in children and youth and may help target phenotypic testing to those most likely to benefit from R5 antagonist.

"That's True Love:" Lived Experiences of Puerto Rican Perinatally HIV-Infected Youth within Their Families' Context.

The burden of HIV affects not only HIV-infected patients but also their families and caregivers. It is also known that family support is crucial for people living with HIV. A qualitative study was conducted to explore the life experiences, within the family context, of perinatally HIV-infected (pHIV-I) youth in Puerto Rico. Twenty in-depth interviews were performed and audio-recorded. Within the family context, study participants experienced acceptance, love and support but also stigma and discrimination. They reported that family is an essential component in their lives and treatment. Losing one or both parents at a young age was considered more difficult than having HIV. Most participants who lost their parents lived with other family members. This was a challenging situation for both pHIV-I youth and their caregivers. Participants described their healthcare providers as part of their families and would like to keep in touch as they transition to adult care. Despite the challenges, participants expressed a desire to have children. Services targeted to this population should stress social support, incorporate family members into the medical process, provide special guidance and support while transitioning to adult care, and provide them with the latest information regarding HIV and reproductive options.

Rates and Correlates of Antiretroviral Therapy Use and Virologic Suppression Among Perinatally and Behaviorally HIV-Infected Youth Linked to Care in the United States

To measure rates of antiretroviral therapy (ART) use and virologic suppression among perinatally HIV-infected youth (PIY) and behaviorally HIV-infected youth (BIY) linked to care in the United States and examine the effects of demographic, biomedical, and psychosocial factors on those rates. Between 2009 and 2012, 649 PIY and 1547 BIY in 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions sites completed cross-sectional surveys through audio computer-assisted self-interviews. Viral load data were collected from chart abstraction or blood draw. Overall 82.4% of PIY and 49.1% of BIY reported current ART use. Only 37.0% of PIY and 27.1% of BIY were virologically suppressed. Virologic suppression rates did not vary as a function of time since HIV diagnosis in either group. Consistent HIV care and no current substance abuse were significant correlates of ART use among PIY. These variables and non-African American race were some factors associated with virologic suppression for PIY [odds ratios (ORs) P < 0.05]. Among BIY, older age, heterosexuals, employment, and education were significantly related to ART use (ORs: P < 0.05); suppression was related to ART use ≥6 months, ≥90% ART adherence, and consistent HIV care (ORs: P < 0.05). Nearly 75% (n = 498) of nonsuppressed youth reported unprotected sex in the past 3 months. There are continued challenges with successfully treating youth even once diagnosed and linked to HIV care. Strategies targeting barriers to ART access, use, and virologic suppression are needed to optimize the impact of the "Treatment as Prevention" paradigm among PIY and BIY.

Pubertal onset in children with perinatal HIV infection in the era of combination antiretroviral treatment.

To evaluate associations of perinatal HIV infection, HIV disease severity, and combination antiretroviral treatment with age at pubertal onset. Analysis of data from two US longitudinal cohort studies (IMPAACT 219C and PHACS AMP), conducted during 2000-2012, including perinatally HIV-infected (PHIV) and HIV-exposed but uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually. We compared the timing of pubertal onset (Tanner stage ≥2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort. The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to the 453 HEU children (10.3 vs. 9.6, 10.5 vs. 10.0, 11.3 vs. 10.4, and 11.5 vs. 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all P < 0.001). PHIV youth with HIV-1 RNA viral load above 10, 000 copies/ml (vs. ≤10, 000 copies/ml) or CD4% below 15% (vs. ≥15%) had significantly later pubertal onset (by 4-13 months). Each additional year of combination antiretroviral treatment was associated with a 0.6-1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort. Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset.

Perinatally HIV-infected youth presenting with acute stroke: Progression/evolution of ischemic disease on neuroimaging

Although HIV infection is decreasing in infants and children, there is a steady cohort of perinatally HIV-infected (PHIV) children that are growing older. Increased risk of acute stroke has been reported in PHIV children. Our goal was to evaluate evolution/progression of neuroimaging findings in PHIV youth initially presenting with acute stroke. The medical records of PHIV pediatric patients (n = 179) from 1996 to 2010 were reviewed and patients with clinical documentation of acute stroke referred to the neuroradiology service were eligible for the study. Neuroimaging (brain CT, MRI, and MRA) and charts were evaluated; clinical and neuroimaging findings at the initial acute stroke and at the last presentation to the neuroradiology service were documented and analyzed. Eight PHIV patients with clinical findings of acute stroke referred to the neuroimaging were identified. CT and MRI findings of infarction were found in all (8/8) patients in their first and/or last neuroimaging study; including basal ganglia-thalami (BGT) infarction (7/8), focal cortical infarction (4/8), and internal capsule infarction (4/8). Imaging depicted cortical atrophy (5/8), BGT calcification (3/8), and posterior reversible encephalopathy syndrome, wallerian degeneration, and periventricular white matter hyperintense T2 signal each in one patient. No tumors or infectious masses, cysts or abscesses were identified. Subsequent available neuroimaging revealed progression of the cerebrovascular disease in seven patients, 5/7 in the absence of new clinical signs or symptoms. Segmental occlusion, narrowing or narrowing/dilatation in the circle of Willis was found in 6/6 patients who underwent MR angiography and fusiform aneurysms were detected in three of them, a saccular aneurysm in one patient. Asymptomatic progression of cerebrovascular disease was found in PHIV adolescents with prior stroke. These findings may have implications for long-term risk and outcomes for this patient population. There should be a low threshold to evaluate for CNS pathology even with minor symptoms in this population. More studies are necessary to determine if there is a benefit from screening of asymptomatic patients.

Sexual Behavior and Perceived Peer Norms: Comparing Perinatally Hiv-infected and Hiv-affected Youth

A large proportion of perinatally HIV-infected (PHIV) children are becoming adolescents and exploring their sexuality. This study explored the prevalence of sexual behaviors (kissing, touching, engaging in oral sex, or having vaginal/anal intercourse) in a sample of predominantly ethnic minority youths (N = 339; 54.1% Black and 30.4% Latino; 51% female; ages 9-16) perinatally exposed to HIV (61% HIV+). Using logistic regression, we tested the association between sexual behavior and HIV status, demographic characteristics, and peer influences regarding sexual behavior. PHIV youth were less likely to be sexually active. Among sexually active youth, PHIV youth were more likely to engage in touching behavior than HIV-negative youth and were less likely to engage in penetrative sex. Youths reporting that a greater number of their peers believed that sexually active boys were "cool" or "popular" were more likely to report sexual behavior. The association between sexual behavior and peers believing sexually active girls were "cool" or "popular" varied by age, gender, and HIV status. Furthermore, friends' sexual activity was associated with sexual intercourse. Prevention programs should strengthen messages addressing peer norms regarding sexuality, as well as address specific issues related to adolescent HIV.