Our results suggest that the life expectancy of HIV-positive people after starting cART has improved over time. Monitoring life expectancy into the future is important to assess how changes to cART guidelines will affect patient long-term outcomes.

We conducted a prospective monitoring study to determine whether antiretroviral (ARV) levels in hair of Asian children on second-line protease inhibitor-based ARV therapy (ART) are associated with virologic failure (VF), compared to plasma drug levels and self-reported adherence. HIV-infected Asian children on second-line ART regimens were enrolled into a longitudinal cohort. Traditional adherence measures, plasma, and hair samples were collected 24 weeks after study enrollment. Hair ARV levels were determined via liquid chromatography/ tandem mass spectrometry. Among 149 children on lopinavir/ritonavir-based regimens, 47% were female; the median [interquartile range (IQR)] age was 10.3 (7.9-13.3) years. The median CD4% was 26% (IQR 21.7-32.1%) and the median CD4 cell count 754 (IQR 596-1,013) cells/mm 3 . The median duration of lopinavirbased ART prior to week 24 of the study was 2.9 (IQR 1.6-4.2) years. Adherence was >95% in 91% (135/148) by visual analogue scale and 89% (129/145) by pill count. The median lopinavir hair concentrations were 5.43 (IQR 3.21-9.01) ng/mg in children with HIV RNA >1,000 copies/ml and 9.96 (IQR 6.51-12.31) ng/mg in children with HIV RNA <1,000 copies/ml ( p = 0.003). Plasma trough and lopinavir hair concentrations were not statistically significantly correlated (Pearson's correlation coefficient 0.20; p = 0.13). Increasing lopinavir hair concentrations in quartiles were strongly associated with virologic success (odds ratios ‡4.0, overall p = 0.02), while self-reported adherence, pill count, and plasma lopinavir levels were not. Based on this first report of hair ARV concentrations and virologic outcomes in children, ARV hair concentrations, representing longer-term adherence, may be useful to identify children at risk for VF.

Background Data on pediatric treatment outcomes and drug resistance while on second-line antiretroviral therapy (ART) are needed to guide HIV care in resource-limited countries. Methods HIV-infected children <18 years old who were switched or switching to second-line ART after first-line failure were enrolled from eight sites in Indonesia, Thailand, and Vietnam. Genotyping was performed at virologic failure (VF; HIV-RNA >1000copies/mL). Cox proportional hazards regression was used to evaluate factors predicting VF. Results Of 277 children, 41% were female. At second-line switch, age was 7.5 (5.3–10.3) years, CD4 count was 300 (146–562) cells/mm3 and percentage was 13 (7–20)%; HIV-RNA was 5.0 (4.4–5.5) log10 copies/mL. Second-line regimens contained lamivudine (90%), tenofovir (43%), zidovudine or abacavir (30%), lopinavir (LPV/r; 91%), and atazanavir (ATV; 7%). After 3.3 (1.8–5.3) years on second-line ART, CD4 was 763 (556–1060) cells/mm3 and 26 (20–31)%. VF occurred in 73 (27%), with an incidence of 7.25 per 100 person-years (95% confidence interval [CI] 5.77–9.12). Resistance mutations in 50 of 73 children with available genotyping at first VF included M184V (56%), ≥1 thymidine analogue mutation (TAM; 40%), >4 TAMs (10%), Q151M (4%), any major LPV mutation (8%), >6 LPV mutations (2%), and any major ATV mutation (4%). Associations with VF included age >11 years (hazard ratio [HR] 4.06; 95%CI 2.15–7.66) and HIV-RNA >5.0 log10 copies/mL (HR 2.42; 95%CI 1.27–4.59) at switch, and was seen more commonly in children from Vietnam (HR 2.79; 95%CI 1.55 – 5.02). Conclusions One-fourth of children developed VF while on second-line ART. However, few developed major mutations to protease inhibitors.

Background Children/adolescents display suboptimal antiretroviral therapy (ART) adherence and outcomes versus adults. Hair ART concentrations are objective adherence measures that predict viremia in adults but longitudinal data on hair levels in pediatric populations is limited. We assessed the predictive utility of hair lopinavir levels on viremia among youth on second-line ART. Methods We examined predictors of viremia (HIV-1 RNA >400 and >1000 copies/ml) at least 24 weeks after switch to lopinavir-based second-line ART in a cohort of HIV-infected Asian children followed between 2011 and 2014. Small hair samples, HIV-1 RNA, and self-reported adherence were collected biannually. Hair concentrations of lopinavir were measured via liquid-chromatography/tandem-mass-spectrometry using validated methods. Time-to-first viremia was examined using discrete-time Cox models. Results Overall, 244 children met inclusion criteria for the present analysis. Approximately half (55%) were males and the median age 10 years (interquartile range [IQR] 7–13); 40% were >11 years. At switch to second-line ART, median CD4 count was 300 (IQR 146–547) cells/mm3 and median HIV-RNA level was 5.0 (IQR 4.3–5.6) log10/mL. Median time of study follow-up was 48 weeks and a median of 3 (range 1–5) hair samples collected from each participant. Adjusting for age, sex, country, self-reported adherence, CD4, and HIV-RNA, higher lopinavir hair concentrations were the strongest predictor of lower odds of viremia (HIV-RNA >400 copies/ml adjusted odds ratio [aOR]=0.41 per doubling in hair concentration, 95% 0.29–0.58, p<0.001; HIV-RNA >1000 copies/ml aOR=0.54, 95% CI 0.45–0.65, p<0.001). Conclusions Hair concentrations predict viremia among children with HIV on 2nd-line ART and could guide clinical decisions for this population.

We studied behavioral risks among HIV-infected and uninfected adolescents using an audio computer-assisted self-interview. A prospective cohort study was initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected adolescents were matched to uninfected adolescents (4:1) by sex and age group (12-14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5 years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1 years) adolescents. At enrollment, HIV-infected adolescents were on antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14% had HIV-RNA >1000 copies/mL; 19% reported adherence <80%. Eighty-four (34%) HIV-infected and 26 (44%) uninfected adolescents reported having ever smoked cigarettes or drunk alcohol (p = 0.13); 10% of HIV-infected and 17% of uninfected adolescents reported having initiated sexual activity; 6 of the HIV-infected adolescents had HIV-RNA >1000 copies/mL. Risk behaviors were common among adolescents, with few differences between those with and without HIV.

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VF rates were observed in one-third of long-term treated Thai children on first-line HAART. Age 3-9 years at HAART initiation was associated with less VF compared with those younger or older, whereas children who used nevirapine had higher VF.

Although most children initiated ART at low CD4 levels, the majority achieved immune reconstitution and long-term virological control. Earlier treatment may improve these outcomes.