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Introduction : Limited data describe outcomes on second-line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second-line ART in the context of routine care within a large global cohort collaboration. Methods : Patient-level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow-up were summarized for children who switched to second-line ART after starting a standard first-line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub-Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow-up (LTFU) were estimated using a competing risks framework. Results : Of the 85,389 children on first-line ART, 3,555 (4%) switched to second-line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second-line regimens were protease inhibitor-based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow-up after switch to second-line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second-line ranged from 235 cells/mm(3) in SSA to 828 cells/mm(3) in North America. Improvements in CD4 counts were observed over two years of follow-up, particularly in regions with lower CD4 counts at second-line switch. Improvements in weight-for-age z-scores were not observed during follow-up. Cumulative incidence of LTFU at two years was

Background : Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. Methods : In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. Findings : At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90.0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3.9 years (IQR 1.6-6.9) and 82 885 (88.8%) patients initiated NNRTI-based and 10 466 (11.2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4.2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3.1% (95% CI 3.0-3.2), but this estimate varied widely depending on the cohort monitoring strategy, from 6.8% (6.5-7.2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0.8% (0.6-1.0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

Background. Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodefciency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). Methods. We included HIV-infected individuals aged =16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-e?ect models were used to smooth trends in median CD4 cell counts. Results. A total of 951 855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/μL (95% confdence interval, 58-104/μL) to 287/μL (250-328/μL) in LICs, from 99/μL (71-140/μL) to 234/μL (192-285/μL) in LMICs, from 71/μL (49-104/μL) to 311/μL (255-379/μL) in UMICs, and from 161/μL (143-181/μL) to 327/μL (286-372/μL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Conclusions. Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional e?orts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART. © 2017 The Author(s).

Background : The pediatric antiretroviral (ARV) market is poorly described in the literature, resulting in gaps in understanding treatment access. We analyzed the pediatric ARV market from 2004 to 2012 and assessed pricing trends and associated factors. Methods : Data on donor funded procurements of pediatric ARV formulations reported to the Global Price Reporting Mechanism database from 2004 to 2012 were analyzed. Outcomes of interest were the volume and mean price per patient-year ARV formulation based on WHO ARV dosing recommendations for a 10 kg child. Factors associated with the price of formulations were assessed using linear regression; potential predictors included: country income classification, geographical region, market segment (originator versus generic ARVs), and number of manufacturers per formulation. All analyses were adjusted for type of formulations (single, dual or triple fixed-dose combinations (FDCs)) Results: Data from 111 countries from 2004 to 2012 were included, with procurement of 33 formulations at a total value of USD 204 million. Use of dual and triple FDC formulations increased substantially over time, but with limited changes in price. Upon multivariate analysis, prices of originator formulations were found to be on average 72 % higher than generics (p