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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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown., Methods: We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings., Results: Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P < .020 and P < .001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P < .01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during 3 years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARVs before starting ART and those who delayed ART initiation without receiving prior prophylaxis., Conclusions: Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure., Methods: HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure., Results: A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001)., Conclusions: Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: There are scarce data on the long-term survival of human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) in lower-middle income countries beyond 2 years of follow-up., Methods: Previously untreated children who initiated ART on meeting immunological and/or clinical criteria were followed in a prospective cohort in Thailand. The probability of survival up to 5 years from initiation was estimated using Kaplan-Meier methods, and factors associated with mortality were assessed using Cox regression analyses., Results: Five hundred seventy-eight children received ART; of these, 111 (19.2%) were followed since birth. At start of ART (baseline), the median age was 6.7 years, 128 children (22%) were aged <2 years, and the median CD4 cell percentage was 7%. Median duration of follow-up was 53 months; 42 children (7%) died, and 38 (7%) were lost to follow-up. Age <12 months, low CD4 cell percentage, and low weight-for-height z score at ART initiation were independently associated with mortality (P < .001). The probability of survival among infants aged <12 months at baseline was 84.3% at 1 year and 76.7% at 5 years of ART, compared with 95.7% and 94.8%, respectively, among children aged ≥1 year. Low CD4 cell percentage and wasting at baseline had a strong association with mortality among older children but weak or no association among infants., Conclusions: Children who initiated ART as infants after meeting immunological and/or clinical criteria had a high risk of mortality which persisted beyond the first year of therapy. Among older children, those with severe wasting or low CD4 cell percentage at treatment initiation were at high risk of mortality during the first 6 months of therapy. These findings support the scale-up of early HIV diagnosis and immediate treatment in infants, before advanced disease progression in older children.

Background: Programs for access to antiretroviral treatment were only recently implemented in developing countries. This study aimed to describe the effect of highly active antiretroviral therapy (HAART) in treating human immunodeficiency virus (HIV)-infected children in Thailand's National Access to Antiretroviral Program for People Living with HIV/AIDS., Methods: From August 2002 to July 2003, a total of 107 children were enrolled in the study. They received HAART consisting of either nevirapine or efavirenz, together with lamivudine and stavudine. Generic drugs and/or adult formulations were used. CD4 lymphocyte count, plasma HIV RNA level, and weight-for-age and height-for-age z scores were measured before, 2 months after, and every 6 months after initiation of HAART. A genotypic resistance assay was performed for patients with poor virological response., Results: The mean age of the patients was 7.7 years (range, 2.1-13.8 years). At baseline, the median CD4 cell percentage was 3%, and the plasma HIV RNA level was 5.4 log10 copies/mL. Four patients died from HIV-related illness. After 72 weeks of HAART, the median CD4 cell percentage was 21%, and 76% of patients had HIV RNA levels of < 50 copies/mL. The mean weight-for-age and height-for-age z scores increased from -1.9 to -1.3 (P < .0001) and from -2.3 to -2.0 (P < .0001), respectively. The percentage of patients who took > or = 95% of prescribed medications during the interval between every follow-up visit was 86% For patients with suboptimal virological response, the most common resistance mutations among HIV isolates were associated with lamivudine and with nonnucleoside reverse-transcriptase inhibitors., Conclusion: In this resource-limited setting, HAART is safe and effective for HIV-infected children despite initiation of treatment during the advanced stage of disease. The use of generic and nonpediatric drug formulations is feasible.