Suchergebnisse

The global paediatric HIV epidemic is shifting into a new phase as children on antiretroviral therapy (ART) move into adolescence and adulthood, and face new challenges of living with HIV. UNAIDS reports that 3.4 million children aged below 15 years and 2 million adolescents aged between 10 and 19 years have HIV. Although the vast majority of children were perinatally infected, older children are combined with behaviourally infected adolescents and youth in global reporting, making it difficult to keep track of their outcomes. Perinatally HIV‐infected adolescents (PHIVA) are a highly unique patient sub‐population, having been infected before development of their immune systems, been subject to suboptimal ART options and formulations, and now face transition from complete dependence on adult caregivers to becoming their own caregivers. As we are unable to track long‐term complications and survival of PHIVA through national and global reporting systems, local and regional cohorts are the main sources for surveillance and research among PHIVA. This global review will utilize those data to highlight the epidemiology of PHIVA infection, treatment challenges and chronic disease risks. Unless mechanisms are created to count and separate out PHIVA outcomes, we will have few opportunities to characterize the negative consequences of life‐long HIV infection in order to find ways to prevent them.

BackgroundThe TREAT Asia Quality Assessment Scheme (TAQAS) was developed as a quality assessment programme through expert education and training, for laboratories in the Asia‐Pacific and Africa that perform HIV drug‐resistance (HIVDR) genotyping. We evaluated the programme performance and factors associated with high‐quality HIVDR genotyping.MethodsLaboratories used their standard protocols to test panels of human immunodeficiency virus (HIV)‐positive plasma samples or electropherograms. Protocols were documented and performance was evaluated according to a newly developed scoring system,agreement withpanel‐specificconsensus sequence, anddetection of drug‐resistance mutations (DRMs) and mixtures of wild‐type and resistant virus (mixtures). High‐quality performance was defined as detection of ≥95% DRMs.ResultsOver 4.5 years, 23 participating laboratories in 13 countries tested 45 samples (30 HIV‐1 subtype B; 15 non‐B subtypes) in nine panels. Median detection of DRMs was 88–98% in plasma panels and 90–97% in electropherogram panels. Laboratories were supported to amend and improve their test outcomes as appropriate. Three laboratories that detected <80% DRMs in early panels demonstrated subsequent improvement. Sample complexity factors – number of DRMs (p<0.001) and number of DRMs as mixtures (p<0.001); and laboratory performance factors – detection of mixtures (p<0.001) and agreement with consensus sequence (p<0.001), were associated with high performance; sample format (plasma or electropherogram), subtype and genotyping protocol were not.ConclusionHigh‐quality HIVDR genotyping was achieved in the TAQAS collaborative laboratory network. Sample complexity and detection of mixtures were associated with performance quality. Laboratories conducting HIVDR genotyping are encouraged to participate in quality assessment programmes.

AbstractIntroductionQuestions about the implementation of evidence‐based intervention to treat and prevent HIV have risen to the top of the field's scientific priorities. Despite the availability of highly efficacious treatment and prevention interventions, impact has fallen short of targets because these interventions are used with insufficient reach, consistency, sustainability and equity in diverse real‐world settings. At present, substantial excitement for implementation science — defined as research methods and strategies to improve use of evidence‐based interventions — has focused on developing and disseminating methods to conduct rigorous research. Yet, impactful answers depend on a sometimes less visible, but even more important, step: asking good questions about implementation.DiscussionIn this commentary, we offer several considerations for researchers formulating implementation research questions based on several distinctive features of the field. First, as findings are used not only by other researchers but by implementers, scientific questions must incorporate a range of stakeholder and community perspectives to be most relevant. Second, real‐world settings are contextually diverse, and the most relevant scientific questions must position answers to make sense within these contexts (whether geographical, organizational and sociological), rather than apart from them. Third, implementation is complex and dynamic; consequently, research questions must make use of emerging standards in describing implementation strategies and their effects whenever possible. Finally, the field of implementation science continues to evolve, so framing problems with a diverse disciplinary lens will enable researchers to pose insightful and impactful questions.ConclusionsWe are now at a juncture marked by both rich evidence‐based interventions and a persistent global pandemic. To achieve continued scientific progress against the HIV epidemic, asking the right questions might be part of the answer itself.

AbstractIntroductionAs integrase inhibitors become available in low‐ and middle‐income countries (LMICs), they offer the potential to expand extremely limited treatment options available to children and adolescents. In LMICs, only small numbers have used raltegravir, primarily as part of third‐line regimens. Using data from the IeDEA global consortium, we aimed to describe the characteristics of children on raltegravir‐containing regimens and their outcomes.MethodsWe included data from 1994 to 2017 from children (age <18 years), from East and Southern Africa, Asia and South America, who received cART regimens containing raltegravir for ≥90 days. We describe their characteristics at raltegravir start, and their immunological and virological outcomes.Results and discussionIn total, 62 children were included, with median age at raltegravir initiation of 14.3 years (IQR 11.2 to 15.8) and median CD4 count of 276 cells/µL (IQR 68 to 494). Among 40 (65%) with drug resistance testing prior to raltegravir, 71% were resistant to at least one protease inhibitor (PI), and 32% had high‐level resistance to at least one drug class. Most (n = 50; 81%) received raltegravir as part of third‐line cART following PI‐based regimens, and were on regimens containing four or more drugs (n = 47, 76%).By database closure, median duration on raltegravir was 2.0 years (IQR 0.8 to 3.0), 1 (1.6%) patient had died, 6 (9.7%) were lost to follow‐up and 21 (34%) had discontinued raltegravir. Among 15 patients reporting reasons for stopping raltegravir, six discontinued because it was no longer available. Within one year of starting raltegravir, among 53 patients with VL measures, 40 (75%) had VL < 1000 copies/mL, and among 54 with a reported CD4 count, 45 (83%) and 36 (67%) were ≥350 and ≥500 cells/µL, respectively, with median CD4 count increasing to 517.5 cells/µL (IQR 288 to 810).ConclusionsAmong children in LMICs, the initial use of raltegravir has been primarily for post PI‐based cART. We found good virological and immunological outcomes despite frequent prior triple‐class failure and high levels of drug resistance. Both access to raltegravir and long‐term adherence to regimens with large pill‐burdens remain challenging. Policies which promote earlier access to new drugs and simplify daily regimens for children and adolescents in LMICs are needed.