IntroductionThe 50% increase in HIV-related deaths in youth and adolescents (aged 10–24) from 2005 to 2012 highlights the need to improve HIV treatment and care in this population, including treatment adherence and retention. Youth and adolescents from key populations or young key populations (YKP) in particular are highly stigmatized and may face additional barrier(s) in adhering to HIV treatment and services. We reviewed the current knowledge on treatment adherence and retention in HIV care among YKP to identify gaps in the literature and suggest future directions to improve HIV care for YKP.MethodsWe conducted a comprehensive literature search for YKP and their adherence to antiretroviral therapy (ART) and retention in HIV care on PsycInfo (Ovid), PubMed and Google Scholar using combinations of the keywords HIV/AIDS, ART, adolescents, young adults, adherence (or compliance), retention, men who have sex with men, transgender, injection drug users, people who inject drugs and prisoners. We included empirical studies on key populations defined by WHO; included the terms youth and adolescents and/or aged between 10 and 24; examined adherence to or retention in HIV care; and published in English-language journals. All articles were coded using NVivo.Results and discussionThe systematic search yielded 10 articles on YKP and 16 articles on behaviourally infected youth and adolescents from 1999 to 2014. We found no studies reporting on youth and adolescents identified as sex workers, transgender people and prisoners. From existing literature, adherence to ART was reported to be influenced by age, access to healthcare, the burden of multiple vulnerabilities, policy involving risk behaviours and mental health. A combination of two or more of these factors negatively impacted adherence to ART among YKP. Collectively, these studies demonstrated that future programmes need to be tailored specifically to YKP to ensure adherence.ConclusionsThere is an urgent need for more systematic research in YKP. Current limited evidence suggests that healthcare delivery should be tailored to the unique needs of YKP. Thus, research on YKP could be used to inform future interventions to improve access to treatment and management of co-morbidities related to HIV, to ease the transition from paediatric to adult care and to increase uptake of secondary prevention methods.

Oncogene-specific downregulation mediated by RNA interference (RNAi) is a promising avenue for cancer therapy. In addition to specific gene silencing, in vivo RNAi treatment with short interfering RNAs (siRNAs) can initiate immune activation through innate immune receptors including Toll-like receptors, (TLRs) 7 and 8. Two recent studies have shown that activation of innate immunity by addition of tri-phosphate motifs to oncogene-specific siRNAs, or by co-treatment with CpG oligos, can potentiate siRNA antitumor effects. To date, there are no reports on applying such approach against human papillomavirus (HPV)-driven cancers. Here, we characterized the antitumor effects of non-modified siRNAs that can target a specific oncogene and/or recruit the innate immune system against HPV-driven tumors. Following the characterization of silencing efficacy and TLR7 immunostimulatory potential of 15 siRNAs targeting the HPV type 16 E6/E7 oncogenes, we identified a bifunctional siRNA sequence that displayed both potent gene silencing and active immunostimulation effect. In vivo systemic administration of this siRNA resulted in reduced growth of established TC-1 tumors in C57BL/6 mice. Ablation of TLR7 recruitment via 2¢O-methyl modification of the oligo backbone reduced these antitumor effects. Further, a highly immunostimulatory, but non-HPV targeting siRNA was also able to exert antitumoral effects although for less prolonged time compared with the bifunctional siRNA. Collectively, our work demonstrates for the first time that siRNA-induced immunostimulation can have antitumoral effects against HPV-driven tumors in vivo, even independent of gene silencing efficacy.

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Human Papillomavirus (HPV)-induced diseases are a significant burden on our healthcare system and current therapies are not curative. Vaccination provides significant prophylactic protection but effective therapeutic treatments will still be required. RNA interference (RNAi) has great promise in providing highly specific therapies for all HPV diseases yet this promise has not been realised. Here we review the research into RNAi therapy for HPV in vitro and in vivo and examine the various targets and outcomes. We discuss the idea of using RNAi with current treatments and address delivery of RNAi, the major issue holding back clinical adoption. Finally, we present our view of a potential path to the clinic.