Antiretroviral adherence for adolescents growing up with HIV: understanding real life, drug delivery and forgiveness.

Poorer adherence to medication is normal in adolescence and is one of a range of risk-taking behaviours common during a developmental stage that encompasses enormous cognitive, physical, sexual, social and emotional change. For adolescents living with human immunodeficiency virus (HIV) infection, poor adherence to antiretroviral therapy (ART) confers two significant challenges: poor health, but also the specific additional burden of onward transmission to partners. Late adolescence (15-19 years) is the only age group where HIV-associated mortality is rising, driven by poor adherence to ART and lack of access to second-line therapy, particularly amongst surviving perinatally infected young people. A previous lack of well-powered randomised multimodal behavioural ART adherence interventions specifically targeting adolescents is now being addressed and ongoing studies registered to ClinicalTrials.gov are described in the context of previous data. Accepting that despite enhanced support, some adolescents will continue to struggle with adherence, we must address how best to use existing ART agents to reduce mortality and allow adolescents the time to mature into adult life. Single-tablet regimens with a high genetic barrier to resistance based on integrase inhibitors and boosted protease inhibitors exist, but global access, in resource limited settings of young people living with HIV reside, is limited. Pragmatically, such regimens tolerate the intermittent adherence so characteristic of adolescence, preserving immune function, without the rapid evolution of resistance. The potential role of long-acting injectable ART, specifically cabotegravir and rilpivirine, is discussed and future strategies including ultra-long-acting drug-delivery systems and broadly neutralising monoclonal antibodies explored.

Malignancy and all-cause mortality; incidence in adolescents and young adults living with perinatally acquired HIV.

BACKGROUND: Adults living with HIV have an increased risk of malignancy yet there is a paucity of data for adolescents and young adults (AYA) with perinatally acquired HIV (PaHIV). METHODS: Retrospective cohort analysis of all-cause mortality and malignancies in AYA with PaHIV aged 10-24 years attending a tertiary unit from 01 January 2004 to 31 December 2017, assessing cancer presentation, immunology and comparing mortality and malignancy incidence to age-matched UK general population rates. RESULTS: A total of 290 AYA with PaHIV contributed 2644 person-years of follow up. Six (2.0%) died within the study period at a median age of 17 years (interquartile range [IQR]15-19), 3 of malignancy, 2 with end-stage HIV and 1 with cryptococcal meningitis. Overall mortality rate was 2.3/1000 person-years, with an age-matched general population rate of 0.2/1000 person-years. Eight (2.8%) were diagnosed with a malignancy; 6 with lymphoma (n=3 Hodgkin's, n=1 Burkitt's, n=2 B-cell) and one each with hepatocellular carcinoma and gastrointestinal adenocarcinoma. At cancer diagnosis the median age was 19 years (IQR 14-23), median CD4 T cell count was 453 cells/mm3 (IQR 231-645) and median length of HIV viremia was 15 years (IQR 12-17). The incidence rate of a malignancy was 3.0/1000 person-years in AYA with PaHIV, whilst that in the age-matched general population is 0.2/1000 person-years. CONCLUSION: AYA living with PaHIV had an increased risk of all-cause mortality and of malignancy compared to their uninfected peers, with the excess in malignancy driven by lymphomas. It is hoped that earlier access to antiretroviral therapy will mitigate some of the AIDS-defining and non-AIDS defining risks for future generations.

Clinical outcomes post transition to adult services in young adults with perinatally acquired HIV infection: mortality, retention in care and viral suppression.

OBJECTIVE: Adolescence is the only age group globally where HIV-associated mortality is rising, with poorer outcomes at all stages of the care cascade compared with adults. We examined post transition outcomes for young adults living with perinatal HIV. DESIGN: Retrospective cohort analysis. SETTING: A tertiary Youth Friendly Service London, UK. PARTICIPANTS: A total of 180 young adults living with perinatal HIV registered between 1 January 2006 and 31 December 2017 contributed 921 person-years of follow-up post transition to adult services. INTERVENTION: Youth Friendly Service with multidisciplinary care and walk-in access. MAIN OUTCOME MEASURES: Mortality, morbidity, retention in care, antiretroviral therapy (ART) uptake and HIV-viral load suppression. Crude incidence rates are reported per 1000 person-years. RESULTS: Of 180 youth registered, four (2.2%) died, 14 (7.8%) transferred care and four (2.2%) were lost to follow-up. For the 158 retained in care, the median age was 22.9 years [interquartile ranges (IQR) 20.3-25.4], 56% were female, 85% Black African, with a median length of follow-up in adult care of 5.5 years (IQR 2.9-7.3). 157 (99.4%) ever received an ART prescription, 127/157 (81%) with a latest HIV-viral load less than 200 copies RNA/ml, median CD4 cell count of 626 cells/µl (IQR 441-820). The all-cause mortality was 4.3/1000 person-years [95% confidence interval (CI) 1.2-11.1], 10 fold the aged-matched UK HIV-negative population [0.43/1000 person-years (95% CI 0.41-0.44)]. Post transition, 17/180 (9.4%) developed a new AIDS diagnosis; crude incidence rates 18.5/1000 person-years (95% CI 10.8-29.6). CONCLUSION: While this youth-friendly multidisciplinary service achieved high engagement and coverage of suppressive ART, mortality remains markedly increased compared with the general UK population.