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Objective: To identify factors associated with nonadherence and unsuppressed viral load across adolescence among youth with perinatally acquired HIV., Design: Longitudinal study at 15 US clinical sites., Methods: Self-reported antiretroviral medication nonadherence (any missed dose, past week) and unsuppressed viral load (HIV RNA > 400 copies/ml) were assessed annually. Individual, caregiver, social, and structural factors associated with nonadherence and unsuppressed viral load were identified by age (years): 8-11 (preadolescence), 12-14 (early adolescence), 15-17 (middle adolescence), and 18-22 (late adolescence/young adulthood), utilizing multivariable generalized linear mixed effects models., Results: During a median 3.3-year follow-up, 381 youth with perinatally acquired HIV contributed viral load measurements and 379 completed 1190 adherence evaluations. From preadolescence to late adolescence/young adulthood, prevalence of nonadherence increased from 31 to 50% (P < 0.001); prevalence of unsuppressed viral load increased from 16 to 40% (P < 0.001). In adjusted analyses, in pre, middle, and late adolescence/young adulthood, perceived antiretroviral side effects were associated with nonadherence. Additional factors associated with nonadherence included: in preadolescence, using a buddy system (as an adherence reminder); in early adolescence, identifying as black, using buddy system; in middle adolescence, CD4% less than 15%, unmarried caregiver, indirect exposure to violence, stigma/fear of inadvertent disclosure, stressful life events. Associations with unsuppressed viral load included: in early adolescence, youth unawareness of HIV status, lower income; in middle adolescence, perceived antiretroviral side effects, lower income; in late adolescence/young adulthood, distressing physical symptoms, and perceived antiretroviral side effects., Conclusion: Prevalence of nonadherence and unsuppressed viral load increased with age. Associated factors varied across adolescence. Recognition of age-specific factors is important when considering strategies to support adherence.

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia., Methods and Findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria., Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.

Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Two doses of live-attenuated varicella-zoster vaccine are recommended for human immunodeficiency virus 1 (HIV-1)-infected children with CD4% ≥ 15%. We determined the prevalence and persistence of antibody in immunized children with perinatal HIV (PHIV) and their association with number of vaccinations, combination antiretroviral therapy (cART), and HIV status., Methods: The Adolescent Master Protocol is an observational study of children with PHIV and perinatally HIV-exposed but uninfected (PHEU) children conducted at 15 US sites. In a cross-sectional analysis, we tested participants' most recent stored sera for varicella antibody using whole-cell and glycoprotein enzyme-linked immunosorbent assay. Seropositivity predictors were identified using multivariable logistic regression models and C statistics., Results: Samples were available for 432 children with PHIV and 221 PHEU children; 82% of children with PHIV and 97% of PHEU children were seropositive (P < .001). Seropositivity after 1 vaccine dose among children with PHIV and PHEU children was 100% at <3 years (both), 73% and 100% at 3-<7 years (P < .05), and 77% and 97% at ≥ 7 years (P < .01), respectively. Seropositivity among recipients of 2 vaccine doses was >94% at all intervals. Independent predictors of seropositivity among children with PHIV were receipt of 2 vaccine doses, receipt of 1 dose while on ≥ 3 months of cART, compared with none (adjusted odds ratio [aOR]: 14.0 and 2.8, respectively; P < .001 for overall dose effect), and in those vaccinated ≥ 3 years previously, duration of cART (aOR: 1.29 per year increase, P = .02)., Conclusions: Humoral immune responses to varicella vaccine are best achieved when children with PHIV receive their first dose ≥ 3 months after cART initiation and maintained by completion of the 2-dose series and long-term cART use., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Whether adolescents can participate in clinical trials of pharmacologic therapies for HIV prevention, such as preexposure prophylaxis, without parental permission hinges on state minor consent laws. Very few of these laws explicitly authorize adolescents to consent to preventive services for HIV and other sexually transmitted infections. Unclear state laws may lead to research cessation. We have summarized legal, ethical, and policy considerations related to adolescents' participation in HIV and sexually transmitted infection prevention research in the United States, and we have explored strategies for facilitating adolescents' access.

This observational study compared uptake of infant prevention of mother-to-child transmission of HIV services pre/post implementation of Option B+ in Lilongwe, Malawi. There were 845 (pre) and 998 (post) births. Post-B+, infants had longer median predelivery maternal antiretroviral therapy {62 days [interquartile range (IQR): 38-94] pre-B+ vs. 95 days [IQR: 61-131] post-B+; P < 0.0001} and improved polymerase chain reaction testing (82.0% vs. 86.5%; P = 0.01) at younger median age [7.6 weeks (IQR: 6.6-10.9) vs. 6.9 (IQR: 6.4-8.1); P < 0.0001]. Proportion testing polymerase chain reaction positive decreased (4.6% vs. 2.6%; P = 0.03). Proportion of HIV-infected infants starting antiretroviral therapy (75% vs. 77.3%) and age at initiation [19.7 weeks (IQR: 15.4-31.1) vs. 16 (IQR: 13.3-17.9)] remained unchanged. These findings suggest modest improvements in infant care with Option B+.

Current techniques for creating clouds in games and other real time applications produce static, homogenous clouds. These clouds, while viable for real time applications, do not exhibit an organic feel that clouds in nature exhibit. These clouds, when viewed over a time period, were able to deform their initial shape and move in a more organic and dynamic way. With cloud shape technology we should be able in the future to extend to create even more cloud shapes in real time with more forces. Clouds are an essential part of any computer model of a landscape or an animation of an outdoor scene. A realistic animation of clouds is also important for creating scenes for flight simulators, movies, games, and other. Our goal was to create a realistic animation of clouds.

Background: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown., Methods: During December 2009 to February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at 6 HIV clinics using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation., Results: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared with 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 to 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age and had been used to feed children aged 1-36 months., Conclusions: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and health care providers should educate the public about the potential risk of disease transmission via premastication.

Objective: To assess the characteristics and outcomes of antiretroviral treatment (ART) interruption (TI) in perinatally HIV-infected children., Design: The Adolescent Master Protocol (AMP) of the Pediatric HIV/AIDS Cohort Study is a prospective cohort study that enrolled 7- to 16-year-old perinatally HIV-infected children between 2007 and 2009 from 15 sites in the United States and Puerto Rico., Methods: TI was defined as ART discontinuation for ≥ 3 months after ≥ 6 months of continuous ART. Subjects with and without TI were compared. Rates of change (slopes) in CD4 T-lymphocyte (CD4) count and percentage (%) per month during TI were calculated. Factors related to CD4 slope in univariable analyses were included in multivariable linear regression., Results: Of 444 eligible AMP subjects, 101 (23%) had at least one TI. Subjects with TI were born in earlier years but were otherwise similar to those without TI. For 81 TI subjects with complete data, the median (range) CD4% and CD4 count slopes were -0.66% per month (-3.54% to +1.34% per month) and -12.7 cells per cubic millimeter per month (-148 cells/mm to +31 cells/mm per month), respectively. On multivariable linear regression, there was a trend for lower CD4% slope to be associated (P < 0.1) with female sex, higher CD4% at TI, and higher peak viral load before TI. Advanced HIV disease stage and numerous ART regimens were more common in TI subjects in the lowest (fastest declining) CD4% slope quartile., Conclusions: TIs in perinatally HIV-infected youth are common. During TIs, CD4 values decline on average but with high intersubject variability. Factors predicting CD4 slope during TI need further study.

Background: Limited data are available from India regarding the distribution and profile of childhood obesity and hypertension. We examined the time trends in childhood obesity in a representative sample of schoolchildren from Ernakulam District, Kerala and determined the relationship of obesity with blood pressure., Methods: We used a stratified random cluster sampling method to select the children. Anthropometric data were collected from 24 842 students, 5-16 years of age, during 2003-04. Blood pressure and anthropometric data were collected from 20 263 students during 2005-06. Overweight and obesity were defined by body mass index for gender and age. Gender, age and height were considered for determining hypertension., Results: The proportion of overweight children increased from 4.94% of the total students in 2003 to 6.57% in 2005 (OR: 1.36; 95% CI: 1.25-1.47; p < 0.0001). The increase was significant in both boys and girls. The proportion of overweight children was significantly higher in urban regions and in private schools, and the rising trend was limited to private schools. Systolic or diastolic incident hypertension was found in 17.34% of overweight children versus 10.1% of the remaining students (OR: 1.87; 95% CI: 1.60-2.17; p < 0.0001)., Conclusion: Childhood obesity showed an increasing trend in a short period of 2 years. Hypertension was common in overweight children. The results suggest the need for greater public awareness and prevention programmes on childhood obesity and hypertension.

Background: To evaluate rate and types of birth defects according to timing of antiretroviral exposure among babies born to HIV-infected women., Methods: Anomalies identified during the prenatal, neonatal, or follow-up period were classified using criteria of the Antiretroviral Pregnancy Registry. Antiretroviral use was classified as none, second or third trimester only, or first trimester., Results: From January 1, 1990 through June 30, 2004, 2527 live births (LBs) occurred to 2353 women. Defects were identified in 90 babies for a rate of 3.56 defects per 100 LBs. The rate of defects was 3.19 per 100 LBs (24 of 752 LBs) with first-trimester antiretroviral exposure, 3.54 per 100 LBs (41 of 1158 LBs) with exposure later in pregnancy, and 4.05 of 100 LBs (25 of 617 LBs) with no antiretroviral use. Only genital abnormalities, specifically hypospadias, were significantly increased among babies born to women with first-trimester exposure to antiretrovirals (7 of 382 male LBs) compared with the 2 other groups (2 of 892 male LBs; P = 0.007). On logistic regression, use of zidovudine in the first trimester was associated with hypospadias (adjusted odds ratio = 10.68, 95% confidence interval: 2.11 to 54.13; P = 0.004)., Conclusions: In general, data were reassuring, although the frequency of exposure to newer agents was limited. The increased risk of hypospadias after first-trimester exposure must be explored, because this association has not been detected previously.

Background: In the Women and Infants Transmission Study (WITS), a prospective cohort study of HIV-infected pregnant women at six US mainland and Puerto Rican sites, changes in the HIV-1 epidemic have included higher income, better education, and better-controlled HIV disease among more recently enrolled women. Because these changes may alter the reproductive patterns of these women an awareness of these women's current reproductive behaviors is essential. We examined predictors of repeat pregnancy among HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS)., Methods: Women enrolled in WITS without a history of sterilization were included. Using bivariate and multivariate analyses, predictors of a repeat pregnancy were modeled. Changes in risk factors for repeat pregnancy over time were examined and important predictors of repeat pregnancy were determined., Results: Of 2246 eligible women, 22% had more than one WITS-enrolled pregnancy. In bivariate analyses, risk of repeat pregnancy was associated with younger age, lower educational status, higher CD4%, and lower viral loads. There was little change in risk factors for repeat pregnancy over time., Conclusions: HIV-1-infected women who are younger and healthier are more likely to have more than one pregnancy. Factors associated with repeat pregnancy among HIV-1-infected women have remained stable over time. Awareness of these factors will better equip healthcare providers to address the reproductive needs of HIV-1-infected women.

Objective: To identify predictors of in utero and intrapartum HIV-1 transmission in infants born in the Women and Infants Transmission Study between 1990 and 2000., Methods: In utero HIV-1 infection was defined as an infant with the first positive HIV-1 peripheral blood mononuclear cell culture and/or DNA polymerase chain reaction assay at 7 days of age or younger; intrapartum infection was defined as having a negative HIV-1 culture and/or DNA polymerase chain reaction assay at 7 days of age or younger and the first positive assay after 7 days of age., Results: Of 1709 first-born singleton children with defined HIV-1 infection status, 166 (9.7%) were found to be HIV-1 infected; transmission decreased from 18.1% in 1990-1992 to 1.6% in 1999-2000. Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection, in 66%. Among infected children, the proportion with in utero infection increased over time from 27% in 1990-1992 to 80% (4 of 5) in 1999-2000 (P = 0.072). Maternal antenatal viral load and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Controlling for maternal antenatal viral load and antiretroviral therapy, low birth weight was significantly associated with in utero transmission, while age, antenatal CD4 cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission., Conclusion: Although there have been significant declines in perinatal HIV-1 infection over time, there has been an increase in the proportion of infections transmitted in utero.

Objective: To compare the safety of nelfinavir and nevirapine-based antiretroviral treatment in HIV-1-infected pregnant women., Methods: In Pediatric AIDS Clinical Trials Group Protocol 1022, 38 antiretroviral-naive pregnant women at 10-30 weeks' gestation were randomized to nelfinavir or nevirapine with zidovudine plus lamivudine. The study was suspended because of greater than expected toxicity and changes in nevirapine prescribing information. The incidence of treatment-limiting hepatic or cutaneous toxicity was compared between groups for all subjects and for the subset with CD4 cell counts greater than 250 cells/microL at study entry., Results: Toxicity was seen in 1 (5%) of 21 subjects randomized to nelfinavir and 5 (29%) of 17 subjects randomized to nevirapine (P = 0.07). Within the nevirapine group, 1 subject developed fulminant hepatic failure and died, and another developed Stevens-Johnson syndrome. The one adverse event associated with nelfinavir occurred in a subject with a CD4 cell count less than 250 cells/microL. All 5 events among subjects with a CD4 cell count greater than 250 cells/microL were associated with nevirapine (P = 0.04)., Conclusions: Continuous nevirapine may be associated with increased toxicity among HIV-1-infected pregnant women with CD4 cell counts greater than 250 cells/microL, as has been observed in non-pregnant women.

Background: Little is known about the cytokine production by peripheral blood cells of pediatric patients who have suppressed HIV-1 replication after highly active antiretroviral therapy (HAART)., Objective: We sought to determine the effect of HAART on the production of T(H)1 and T(H)2 cytokines by HIV-infected children who have suppressed HIV replication., Methods: At 3- to 6-month intervals over a 5-year period, CD4(+) T cells were enumerated, plasma HIV-1 RNA was measured, and levels of cytokine production by whole blood cultures were determined in 21 HIV-1-infected children., Results: Ten patients achieved an HIV-1 RNA level of less than 3000 copies/mL of plasma and maintained that level for at least 15 months (virus-suppressed [VS] group). Eleven patients had a mean HIV-1 RNA level of greater than 10(4) copies/mL of plasma and a mean CD4(+) T-cell count of less than 500/microL of blood (active infection group). The median levels of anti-CD3-induced IL-2, IFN-gamma, and IL-10 in the active infection group were significantly lower than those in the VS group after suppression of the virus. The median slope of IFN-gamma production by means of PHA-stimulated culture after achieving VS status (4.04) was significantly higher than the level before VS status (-1.31, P =.004). The difference in the median slopes for IL-10 production by anti-CD3-stimulated cultures before (0.21) and after (-0.16) achieving VS status was statistically different (P =.027)., Conclusion: The immune restoration of HIV-1-infected children receiving HAART might be related to an increase in IFN-gamma production and a decrease in the rate of IL-10 production after virus suppression.