Caroline Foster

Mortality in perinatally HIV-infected young people in England following transition to adult care: an HIV Young Persons Network (HYPNet) audit

Mortality in young people with perinatally acquired HIV infection (PHIV) following transfer to adult care has not been characterized in the UK. We conducted a multicentre audit to establish the number of deaths and associated factors.

Tenofovir disoproxil fumarate in pregnancy and prevention of mother‐to‐child transmission of HIV‐1: is it time to move on from zidovudine?

Objectives Zidovudine (ZDV) has been the cornerstone of antiretroviral (ARV) therapy for pregnant women infected with HIV‐1 in the prevention of mother‐to‐child transmission (MTCT) and remains the only licensed ARV for use in pregnancy. We explored the current and future roles of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT of HIV‐1.

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life.

The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

Optimizing antiretroviral therapy in adolescents with perinatally acquired HIV-1 infection.

In resourced settings with access to highly active antiretroviral therapy, perinatally acquired HIV-1 infection has become a chronic disease of childhood with increasing numbers of adolescents surviving to adulthood and transitioning from pediatric to adult services. Advances in antiretroviral therapy, reductions in side effects, new classes and new drugs within existing antiretroviral classes offer enormous benefits, although issues around adherence during adolescence persist. The longer term impact of exposure to HIV and antiretroviral therapy throughout childhood are becoming apparent, with growing concern over neurocognitive, cardiovascular, renal and bone health. Careful follow-up of this early perinatal cohort as they enter adulthood will inform the future management of the growing numbers of adolescents surviving worldwide as access to therapy increases.

“Payment by Results”—Financial Incentives and Motivational Interviewing, Adherence Interventions in Young Adults with Perinatally Acquired HIV-1 Infection: A Pilot Program

Emerging evidence suggests financial incentives (FIs) improve medication adherence in select populations. A small proportion of adolescents with perinatal HIV (PaHIV) transfer to adult services with established poor adherence and advanced disease. We describe a single center adherence intervention combining FIs with motivational interviewing (MI). Eligible patients (PaHIV,16-25 years, CD4 count ≤ 200, off ART despite multiple attempts) received MI, and FI dependent on viral load (VL) reduction for 1 year. Outcome measures compared CD4 gain from baseline at 1 year and 12 months post cessation of FI/MI. Eleven young people enrolled; median age 19 years, 8 female. Baseline median CD4 count 30 cells/μL (IQR 10-160), VL 12,870 c/mL. Outcomes at 12 months: 9/11 ever achieved VL < 50, 5 sustained undetectable VL, median CD4 140, mean CD4 gain 90 cells/μL at 1 year. Twelve months post cessation of MI/FI; six VL < 50, median CD4 75, mean CD4 gain 122 cells/μL. Total FI expenditure £1,350: £68 per 50 CD4 cells at 1 year, £55 at 24 months. To prevent death, adolescents with PaHIV require novel interventions to reverse poor patterns of adherence established since childhood. FI/MI improved virological and immunological outcomes with minimal expenditure. Extension of this pilot work for vulnerable individuals is now indicated.

Pregnancy outcomes in adolescents in the UK and Ireland growing up with HIV

Adolescents with HIV infection acquired perinatally or in early childhood are becoming sexually active, but little is known about fertility and pregnancy outcomes. Multicentre data on pregnancy outcomes in this population are described here.

Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland

Objective:To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children. Design:Multicentre national cohort. Methods:Factors associated with viral load below 400 copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models. Results:Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9–11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV + 2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP + 2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI + 3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0–8.8) years. Viral load was less than 400 copies/ml by 12 months in 92% [95% confidence interval (CI) 91–94%] of the children. Time to suppression was similar across regimens (P = 0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirty-nine (34%) children experienced virological failure. Although progression to failure varied by regimen (P < 0.001) and was fastest for NVP + 2NRTIs regimens, risk after 2 years on therapy was similar for EFV + 2NRTIs and NVP + 2NRTIs, and lowest for NNRTI + 3NRTIs regimens (P-interaction = 0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9–8.9%) NVP, 8.3% (95% CI 5.6–11.6) EFV, and 9.8% (95% CI 5.7–15.3%) protease inhibitor-based regimens (P = 0.48). Conclusion:Viral load suppression by 12 months was high with all regimens. NVP + 3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children.

Early antiretroviral therapy in children perinatally infected with HIV: a unique opportunity to implement immunotherapeutic approaches to prolong viral remission

From the use of antiretroviral therapy to prevent mother-to-child transmission to the possibility of HIV cure hinted at by the Mississippi baby experience, paediatric HIV infection has been pivotal to our understanding of HIV pathogenesis and management. Daily medication and indefinite antiretroviral therapy is recommended for children infected with HIV. Maintenance of life-long adherence is difficult and the incidence of triple-class virological failure after initiation of antiretroviral therapy increases with time. This challenge shows the urgent need to define novel strategies to provide long-term viral suppression that will allow safe interruption of antiretroviral therapy without viral rebound and any associated complications. HIV-infected babies treated within a few days of birth have a unique combination of a very small pool of integrated viruses, a very high proportion of relatively HIV resistant naive T cells, and an unparalleled capacity to regenerate an immune repertoire. These features make this group the optimum model population to investigate the potential efficacy of immune-based therapies. If successful, these investigations could change the way we manage HIV infection.

Who, then what? The need for interventions to help young people with perinatally acquired HIV disclose their HIV status to others.

There has been considerable interest in paediatric HIV disclosure. This is the process leading to full disclosure (when the condition is named for the HIV-positive child, usually by a caregiver or healthcare worker). WHO guidelines state that children should be aware of the name of their condition by the age of 12, with younger children told their status incrementally to accommodate their cognitive skills and emotional maturity in preparation for full disclosure [3]. There is evidence, however, of variation in the age of full disclosure with this taking place later in resource-limited contexts than in other parts of the world [4]. Being aware of one’s status (full disclosure) is a prerequisite for onward disclosure and there is evidence of more onward disclosure if children are aware of their status earlier [5]. How one was disclosed to, for example, if there was an opportunity to ask questions about HIV and to feel listened to, may also impact on onward disclosure decision-making.

Sexual and reproductive health in a UK cohort of young adults perinatally infected with HIV

Objectives To assess sexual health and behaviour outcomes of young adults with perinatally acquired HIV-1 (PaHIV), and audit sexual health interventions against published standards of care. Methods Retrospective case note audit of 16–25-year-olds with PaHIV attending a dedicated transition clinic from January 2005 to 2011. Results Fifty-two young adults, 31 women, median age 20 years. 41 were sexually active; median age of coitarche 16 years. Median number of lifetime partners was 3.5, and five reported non-consensual sex. All had a sexually transmitted infection (STI) screen; 6 were diagnosed with an STI, genital warts (human papilloma virus) most frequently. The median interval from coitarche to first STI screen was 2 years. The pregnancy incidence was 103 per 1000 person years. 18/25 (72%) sexually active women had a cervical smear, four had colposcopy. All patients had hepatitis B virus (HBV) serology. 47 had not been vaccinated against HBV prior to transition. 23 completed HBV vaccination of which 11 had surface antibody >100 IU/ml at 1 year. Conclusions The majority of our cohort was sexually active while still under the care of paediatric health services. Cervical screening and hepatitis B vaccination rates fell short of audit standards. Vaccination for hepatitis B should be considered prior to transfer of care to adult HIV services.