Impact of Vitamin D and Calcium Supplementation on Bone Mineral Density and Bone Metabolism Among Thai Adolescents With Perinatally Acquired Human Immunodeficiency Virus (HIV) Infection: A Randomized Clinical Trial.

BACKGROUND: To evaluate the impact of vitamin D and calcium supplementation (VitD/Ca) on lumbar spine bone mineral density (LSBMD) and bone metabolism among Thai adolescents with perinatally acquired HIV (PHIVA). METHODS: A multicenter, randomized, active-control, open-labeled trial was conducted. PHIVA (aged 10-20 years) who were on stable cART were enrolled. Baseline LSBMD status was defined as low (z-score ≤ -2) and normal (> -2). Eligible PHIVA were randomly assigned to receive standard-dose (400 IU/1200 mg/day) or high-dose (400 IU/1200 mg/day plus ergocalciferol 20 000 IU/week) VitD/Ca supplementation for 48 weeks (ratio 1:1, stratified by baseline LSBMD). Study outcomes were changes in LSBMD, LSBMD z-scores, and bone metabolism-related biomarkers (25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone [iPTH], C-terminal telopeptide [CTX], procollagen type I amino-terminal propeptide [PINP]) from baseline to week 48. RESULTS: Among 200 enrolled PHIVA, median age was 16 (IQR:14-18) years; 61% were on NNRTI-based cART. Median 25(OH)D level was 25.5 (IQR: 20.8-33.0) ng/mL. After 48-week VitD/Ca supplementation, LSBMD significantly increased in both treatment groups (high-dose: median: +0.07 [IQR: +0.04 to +0.11] g/cm2; P < .001; standard-dose: +0.09 [+0.03 to +0.13] g/cm2; P < .001). Notably, the change in LSBMD z-scores was significantly greater in high-dose versus standard-dose groups (median: +0.4 [IQR: -0.1 to +0.9] vs +0.1 [-0.4 to +0.7]; P = .02). Levels of 25(OH)D increased, whereas iPTH, CTX, and PINP declined significantly in both groups (P < .05), but no between-group differences were demonstrated. CONCLUSIONS: Over 48-week VitD/Ca supplementation, significant increases in LSBMD, and significant decreases in bone metabolism-related markers were observed among our Thai PHIVA in both treatment groups. The improvement in LSBMD z-score was more enhanced with high-dose VitD/Ca supplementation than standard-dose. High-dose VitD/Ca supplementation might be considered to promote bone health in this population. CLINICAL TRIALS REGISTRATION: NCT02426840.

Major Depressive Disorder Among HIV Infected Youth in Uganda: Incidence, Persistence and Their Predictors.

Incidence and persistence of major depressive disorder (MDD) in children and adolescents with HIV (CA-HIV) in Uganda is described. 1339 CA-HIV attending care were enrolled and followed up for 12 months. MDD was assessed using the DSM-5 referenced Child and Adolescent Symptom Inventory-5 (CASI-5), with a prevalence for MDD at baseline of 5% (95% CI 3.3-7.3). Kaplan-Meir method was used to estimate incidence of MDD and Cox models were fitted to investigate predictors of incident MDD. Cumulative incidence of MDD over 12 months was 7.6 per 100 person-years 95% CI (6.2-9.4) and a rate of persistent MDD of 10/105 (9.5% CI 3.9-15.1). Significant independent predictors of incident MDD were: highest educational level of CA-HIV (protective), increasing depressive scores and decreasing CD4 Nadir. These finding have implications for what should constitute components of a mental health integration model in HIV youth services and for the future development of individualised mental health care.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Biomarkers of oral inflammation in perinatally HIV-infected and perinatally HIV-exposed, uninfected youth.

AIM: To examine oral biomarkers that have been associated with periodontal disease progression in HIV-infected adults in perinatally HIV-infected and HIV-exposed but uninfected youth. MATERIAL AND METHODS: This was a cross-sectional, multicentre substudy of youth participating in the Oral Health Pediatric HIV/AIDS Cohort study. Gingival crevicular fluid repository samples from participants with and without periodontal disease (using Gingival Index [GI] and Bleeding on Probing [BOP] parameters on dental examination) were tested for concentration levels of inflammatory biomarkers. Associations were assessed using Wilcoxon test and Spearman correlation. RESULTS: For perinatal HIV youth (n = 129), the markers consistently elevated (p < .05) in sites with GI ≥2 and in sites with BOP were interleukin-1ß, 6 and 13, macrophage inflammatory protein-1α and metalloproteinase-9. Serum tumour necrosis factor-α and soluble CD14 were positively correlated with a summary count of elevated cytokines. No associations were seen among HIV-uninfected subjects (n = 71). CONCLUSIONS: The association of oral biomarkers of inflammation with clinical indicators of periodontal inflammation and systemic immune activation suggests that perinatal HIV-infected youth may be at higher risk for developing significant periodontal disease, associated with tooth loss and HIV progression. More frequent dental care of this group is needed to prevent potential periodontal progression.

Interaction Effects of Neighborhood Disadvantage and Individual Social Support on Frequency of Alcohol Use in Youth Living with HIV.

Youth living with HIV (YLH) experience multiple disease-related stresses along with the same structural and developmental challenges faced by their uninfected peers; alcohol use among YLH represents a risk behavior by virtue of potential effects on youth health and increased likelihood of engaging in unprotected sex while drinking alcohol. Research aimed at better understanding the interplay of individual- and neighborhood-level influences on alcohol use for YLH is needed to inform interventions. This study examined whether socioeconomic disadvantage (SED) and social support influence, independently and through interaction, alcohol use in YLH. Data from the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) consisted of YLH across 538 neighborhoods in the United States who acquired HIV behaviorally. Neighborhood-specific data were compiled from the 2010 U.S. Census Bureau and matched with individual-level data from the ATN (N = 1,357) to examine effects that contribute to variation in frequency of alcohol use. Other drug use, being male, being non-Black, and older age were associated with greater alcohol use. Higher social support was negatively associated with alcohol use frequency. A cross-level interaction indicated that the association found between decreasing social support and increasing alcohol use frequency was weakened in areas with lower SED. Implications are discussed.

Psychosocial needs of perinatally HIV-infected youths in Thailand: lessons learnt from instructive counseling.

Identifying psychosocial needs of perinatally HIV-infected (pHIV) youth is a key step in ensuring good mental health care. We report psychosocial needs of pHIV youth identified using the "Youth Counseling Needs Survey" (YCS) and during individual counseling (IC) sessions. pHIV youth receiving care at two tertiary-care hospitals in Bangkok or at an orphanage in Lopburi province were invited to participate IC sessions. The youths' psychosocial needs were assessed using instructive IC sessions in four main areas: general health, reproductive health, mood, and psychosocial concerns. Prior to the IC session youth were asked to complete the YCS in which their concerns in the four areas were investigated. Issues identified from the YCS and the IC sessions were compared. During October 2010-July 2011, 150 (68.2%) of 220 eligible youths participated in the IC sessions and completed the YCS. Median age was 14 (range 11-18) years and 92 (61.3%) were female. Mean duration of the IC sessions was 36.5 minutes. One-hundred and thirty (86.7%) youths reported having at least one psychosocial problem discovered by either the IC session or the YCS. The most common problems identified during the IC session were poor health attitude and self-care (48.0%), lack of life skills (44.0%), lack of communication skills (40.0%), poor antiretroviral (ARV) adherence (38.7%), and low self-value (34.7%). The most common problems identified by the YCS were lack of communication skills (21.3%), poor health attitude and self-care (14.0%), and poor ARV adherence (12.7%). Youth were less likely to report psychosocial problems in the YCS than in the IC session. Common psychosocial needs among HIV-infected youth were issues about life skills, communication skills, knowledge on self-care, ARV adherence, and self-value. YCS can identify pHIV youths' psychosocial needs but might underestimate issues. Regular IC sessions are useful to detect problems and provide opportunities for counseling.

Knowledge, attitudes, and practices regarding antiretroviral management, reproductive health, sexually transmitted infections, and sexual risk behavior among perinatally HIV-infected youth in Thailand.

More than 30% of perinatally HIV-infected children in Thailand are 12 years and older. As these youth become sexually active, there is a risk that they will transmit HIV to their partners. Data on the knowledge, attitudes, and practices (KAP) of HIV-infected youth in Thailand are limited. Therefore, we assessed the KAP of perinatally HIV-infected youth and youth reporting sexual risk behaviors receiving care at two tertiary care hospitals in Bangkok, Thailand and living in an orphanage in Lopburi, Thailand. From October 2010 to July 2011, 197 HIV-infected youth completed an audio computer-assisted self-interview to assess their KAP regarding antiretroviral (ARV) management, reproductive health, sexual risk behaviors, and sexually transmitted infections (STIs). A majority of youth in this study correctly answered questions about HIV transmission and prevention and the importance of taking ARVs regularly. More than half of the youth in this study demonstrated a lack of family planning, reproductive health, and STI knowledge. Girls had more appropriate attitudes toward safe sex and risk behaviors than boys. Although only 5% of the youth reported that they had engaged in sexual intercourse, about a third reported sexual risk behaviors (e.g., having or kissing boy/girlfriend or consuming an alcoholic beverage). We found low condom use and other family planning practices, increasing the risk of HIV and/or STI transmission to sexual partners. Additional resources are needed to improve reproductive health knowledge and reduce risk behavior among HIV-infected youth in Thailand.

A Three-Year Follow-Up of Bone Density Among Thai Adolescents With Perinatally Acquired HIV After Completion of Vitamin D and Calcium Supplementation.

PURPOSE: To determine changes in bone mineral density (BMD) and bone metabolism-related biomarkers among Thai adolescents with perinatally acquired HIV infection (PHIVA) at 3 years following completion of vitamin D and calcium (VitD/Cal) supplementation. METHODS: An observational follow-up study was conducted among PHIVA who received 48-week VitD/Cal supplementation (either high-dose [3,200 IU/1,200 mg daily] or standard-dose [400 IU/1,200 mg daily]). Lumbar spine BMD (LSBMD) was assessed by dual-energy x-ray absorptiometry. Serum 25-hydroxyvitamin D, intact parathyroid hormone, and bone turnover markers were measured. Changes in LSBMD z-scores and other bone parameters at 3 years after stopping VitD/Cal supplementation compared with baseline or week 48 of supplementation were assessed among participants previously receiving high-dose and standard-dose VitD/Cal supplementation. RESULTS: Of 114 enrolled PHIVA, 46% and 54% had previously received high-dose and standard-dose VitD/Cal supplementation, respectively. The median age was 20 years; 53% were male. At 3 years after completion of VitD/Cal supplementation, we observed a significant decline in 25-hydroxyvitamin D and increase in intact parathyroid hormone but no significant rebounds of C-terminal telopeptides of collagen type I and procollagen type I amino-terminal propeptides and no significant changes in LSBMD z-scores among PHIVA in both treatment groups, compared with the measurements at week 48 of supplementation. Notably, LSBMD z-scores at 3 years after stopping VitD/Cal supplements were not significantly altered from baseline evaluations in both PHIVA groups. DISCUSSION: Three years after completion of high-dose or standard-dose VitD/Cal supplementation, LSBMD z-scores of our Thai PHIVA were not significantly changed from baseline and week 48 of supplementation. VitD/Cal supplementation of PHIVA during periods of peak bone mass accrual may have sustained and long-term skeletal benefits.

Depression and Anxiety in Youth and Young Adults Living with HIV: Frequency and Associated Factors in Thai Setting.

Integrative mental health care in HIV patients is an important contributor to successful therapy. This is a cross-sectional study in youth and young adults who attend routine HIV clinic at a tertiary care centre in Bangkok. We recruited 100 youth and 130 young adults living with HIV to evaluate the frequency of depression and anxiety and associated sociodemographic including sexual orientation and health-related behaviours. Overall, about a fifth of the participants had significant depression or anxiety. Interestingly, we found different factors associated with depression in youth and young adults living with HIV. Loss of their father, loss of close relatives or friends, and being unemployed or school exclusion were the factors associate with depression in youth; while dangerous alcohol use, feeling discriminated against and having lipodystrophy were factors in young adults. The understanding of the frequency and different associated factors can inform more effective prevention and treatment strategies.

Disclosure of HIV status to sexual partners among perinatally HIV-infected youth in Thailand.

Data regarding disclosure of HIV status to sexual partners among perinatally acquired HIV-infected (PHIV) youth are limited, particularly from Asian countries. This cross-sectional study assessed the patterns of, attitudes about, and factors associated with HIV disclosure to sexual partners among PHIV youth aged 15-24 years who attended a pediatric HIV clinic in Thailand. Participants were interviewed using a semi-structured questionnaire designed to elicit demographic and sexual behavior information. Those who had sexual partners were queried about their relationship and HIV status disclosure. Reasons to disclose or not to disclose were assessed accordingly. Among the 51 (44.4%) youth who had sexual partners, 55.8% had steady partners, 45.1% did not always use condoms, and 41.2% disclosed their HIV status. Reasons to disclose included trust and concern about the risk of infection to their partners. Reasons not to disclose included fear of rejection and stigmatization, and not knowing how to disclose. Most youth reported a need for disclosure-related guidance. Knowing their sexual partner's HIV status was the only independent factor associated with disclosure (aOR 14.6; 95% CI 2.8-75.4). This study demonstrates a high rate of unsafe sex and a low rate of partner disclosure in PHIV youth, and highlights the need for a comprehensive guideline for HIV disclosure to sexual partners.

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.