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Children living with perinatally acquired HIV (CLWH) survive into adulthood on antiretroviral therapy (ART). HIV, ART, and malnutrition can all lead to low bone mineral density (BMD). Few studies have described bone health among CLWH in Sub-Saharan Africa. We determined the prevalence and factors associated with low BMD among CLWH switching to second-line ART in the CHAPAS-4 trial (ISRCTN22964075) in Uganda. BMD was determined using dual-energy X-ray Absorptiometry (DXA). BMD Z-scores were adjusted for age, sex, height and race. Demographic characteristics were summarized using median interquartile range (IQR) for continuous variables and proportions for categorical variables. Logistic regression was used to determine the associations between each variable and low BMD. A total of 159 children were enrolled (50% male) with median age (IQR) 10 (7-12) years, median duration of first -line ART 5.2(3.3-6.8) years; CD4 count 774 (528-1083) cells/mm3, weight-for-age Z-score -1.36 (-2.19, -0.65) and body mass index Z-score (BMIZ) -1.31 (-2.06, -0.6). Low (Z-score≤ -2) total body less head (TBLH) BMD was observed in 28 (18%) children, 21(13%) had low lumbar spine (LS) BMD, and15 (9%) had both. Low TBLH BMD was associated with increasing age (adjusted odds ratio [aOR] 1.37; 95% CI: 1.13-1.65, p = 0.001), female sex (aOR: 3.8; 95% CL: 1.31-10.81, p = 0.014), low BMI (aOR 0.36:95% CI: 0.21-0.61, p<0.001), and first-line zidovudine exposure (aOR: 3.68; 95% CI: 1.25-10.8, p = 0.018). CD4 count, viral load and first- line ART duration were not associated with TBLH BMD. Low LS BMD was associated with increasing age (aOR 1.42; 95% CI: 1.16-1.74, p = 0.001) and female sex: (aOR 3.41; 95% CI: 1.18-9.8, p = 0.023). Nearly 20% CLWH failing first-line ART had low BMD which was associated with female sex, older age, first-line ZDV exposure, and low BMI. Prevention, monitoring, and implications following transition to adult care should be prioritized to identify poor bone health in HIV+adolescents entering adulthood.

Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand. Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4-9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997-2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm3 in 1997-2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9-8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time. In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.

Background The aim of this study was to compare quantitative ultrasound (QUS) and dual energy X-ray absorptiometry (DXA) for determining bone mineral density (BMD) among children living with HIV (CLWH) who were switching to second-line antiretroviral therapy (ART). Methods We conducted a cross-sectional study among CLWH as a sub-study of the CHAPAS-4 trial. Total body less head (TBLH) BMD and lumbar spine (LS) BMD were determined by DXA while the sound of speed (SOS), broad band ultrasound attenuation (BUA) and bone quality index (BQI) were determined by QUS. We evaluated the correlation between the DXA and QUS measurements using spearman correlation coefficient. Results A total of 167 children were enrolled; the median age was 9.4 (interquartile range = 6.0–12.0) years. Eighty-five (50.9%) were male. The median weight- for- age Z- score (IQR) was − 1.29(-2.16, -0.49) and height for age Z-score was − 1.03(-1.56, 0.01). SOS was weakly correlated with TBLH BMD R  = 0.35, P  < 0.001), lumbar spine bone apparent density (LSBMAD) ( R  = 0.19, P  = 0.01) and LS bone mineral content (BMC) ( R  = 0.31, P  < 0.001). BUA was moderately correlated with TBLH BMD ( R  = 0.50, P  < 0.001), BMC ( R  = 0.47, P  = 0.001), and LS BMC ( R  = 0.43, P  < 0.001) but weakly correlated with LSBMAD ( R  = 0.28, P  < 0.001). BQI was moderately correlated with TBLH BMC ( R  = 0.46, P  < 0.001), TBLH BMD ( R  = 0.46, P  < 0.001) and LSBMC ( R  = 0.41, P  < 0.001). There was weak correlation between LSBMAD and BUA ( R  = 0.28, P  < 0.001) BQI ( R  = 0.29, P  < 0.001). QUS Z-score was weakly correlated with TBLH BMD and ( R  = 0.30, P  < 0.01) and no correlation with LSBMAD ( R  = 0.07, P  = 0.35). Conclusion In CLWH, there was moderate correlation observed for TBLH measurements when comparing DXA to QUS, and weak correlation was found between LSBMAD and QUS measurements. There was a moderate correlation detected between the LSBMC and QUS.QUS may not be an appropriate substitute for DXA scan.

Background. Recent evidence suggests that decreases in morbidity and mortality in cohorts of adults infected with human immunodeficiency virus (HIV) are showing signs of reversal. We describe changes over time in these characteristics and in the response to treatment among children in the United Kingdom and Ireland with perinatally acquired HIV infection, many of whom are now adolescents. Methods. We analyzed prospective cohort data reported to the National Study of HIV in Pregnancy and Childhood (NSHPC) and the Collaborative HIV Paediatric Study. Results. By mid 2006, 1441 HIV-infected children were reported to NSHPC; 40% were ⩾10 years old at their most recent follow-up visit, and 34% were receiving care outside London. The proportion of children born abroad increased from 24% during 1994–1996 to 64% during 2003–2006. The percentage of total child time during which children received highly active antiretroviral therapy (HAART) increased from 36% during 1997–1999 to 61% during 2000–2002 and 63% during 2003–2006. Of children who were naive to antiretroviral therapy at the start of HAART, the percentage with an HIV-1 RNA load of <400 copies/mL after 12 months increased from 52% during 1997–1999 to 79% during 2003–2006. In multivariate analysis, only calendar time predicted virological response, whereas both younger age and lower CD4 cell percentage at HAART initiation predicted increases of >10% in the CD4 cell percentage. A total of 31% of children aged 5–14 years and 38% aged ⩾15 years at their most recent follow-up visit had been exposed to drugs from each of the 3 main HAART classes. The rate of AIDS and mortality combined decreased from 13.3 cases per 100 person-years before 1997 to 3.1 and 2.5 cases per 100 person-years, respectively, during 2000–2002 and 2003–2006; rates of hospital admission also declined during this interval. Of 18 children known to have died since 2003, 9 died within 1 month after presentation. Conclusions. Morbidity and mortality rates among HIV-infected children continue to decrease over time. Because these children are increasingly dispersed outside London, specialist care is now provided in national clinical networks. Transition pathways to adolescent and adult services and long-term observation to monitor the effects of prolonged exposure to both HIV and HAART are required.

[This corrects the article DOI: 10.1371/journal.pone.0288877.].

In this clinical trial of second-line antiretroviral therapy in children with HIV in Africa, regimens including tenofovir alafenamide fumarate as the backbone and dolutegravir as the anchor drug were most effective.

Little evidence is available on the pharmacokinetics of antituberculous medication in premature infants. We report rifampicin (RMP) pharmacokinetics in an extremely premature, low-birthweight female infant born to a mother with known miliary tuberculosis. Intravenous RMP, isoniazid (INH), ciprofloxacin and amikacin were used, as the enteral route was not possible. Area under the curve calculations revealed low average RMP concentrations at doses of 5–10 mg/kg. We review the literature with regard to the dosing regimen and therapeutic drug levels of RMP and INH in premature infants and discuss issues of management. Evidence from this case suggests 10 mg/kg/day is the minimum dose required.