A Global Village
Issue 9 » Adolescent Health

Growing Up With HIV

Dr. Caroline Foster, Imperial College Healthcare NHS Trust

30 years after AIDS was first discovered, increasing numbers of children born with HIV in regions of the world with access to highly active antiretroviral therapy (HAART) are surviving childhood, entering adolescence and transitioning towards adult care. Hence perinatally acquired HIV (PaHIV) has become a chronic condition of childhood. 

Improved survival due to HAART, high rates of uptake of antenatal HIV screening and successful interventions reducing mother-to-child transmission (MTCT) to less than 1%, has resulted in an aging European paediatric population of PaHIV patients, the average age in the UK being 14 years1. However, worldwide an estimated 2.1 million children live with HIV, the vast majority infected during pregnancy, delivery or breastfeeding. Whilst HAART has markedly reduced HIV-associated mortality, in low and middle-income countries, only 23% of children requiring HAART had access to therapy in 20102. Without treatment more than 50% of infected African infants die before their second birthday, yet adults acquiring HIV horizontally with access to HAART have a near normal life expectancy. 

This article concentrates on issues faced by adolescents growing up with HIV acquired at birth, yet young people are affected by this global epidemic disproportionately; more than 40% of the 2.7 million annual new infections occur in 16-24 year olds, the majority infected sexually2. Navigating adolescence with any chronic disease may be difficult, but to do so with a disease potentially transmissable to future partners and children is even harder and more complicated, and often compounded by the stigma and secrecy associated with HIV.

Antiretroviral Therapy
Adolescents with PaHIV have a varied antiretroviral history determined by treatment availability, the timing of their diagnosis and the rate of disease progression. Whilst around a quarter of infected children will present with symptoms within the first year of life, up to 10% will survive into adolescence with no or minimal symptoms and well maintained immune function – termed ‘long term nonprogressors’. Hence it is possible for adolescents born with HIV to become sexually active with the risk of onward transmission to partners whilst being unaware of their own status. 

In the UK more than 90% of children diagnosed with HIV are followed prospectively in the Collaborative HIV Paediatric Study (CHIPS) until transfer to adult services at an average age of 17 years1. In this UK cohort of more than 650 adolescents aged 10 years and over, at the last follow up two thirds were on antiretroviral therapy, three quarters of whom had HIV viral loads of <400 copies/ml, and 18% were treatment naïve3. Nearly a third of the adolescent cohort had commenced treatment prior to 1998, in the era of mono/dual therapy and almost half of those who had received HAART had received the 3 main antiretroviral drug classes. Of the 166 adolescents with resistance assays available, 52% and 12% had evidence of dual- and triple-class HIV-1 associated resistance mutations respectively and 12% of the cohort had evidence of severe immunosuppression with CD4 counts <200 cells/uL3

an estimated
2.1 million
children live
with HIV, the
vast majority
infected during
delivery or

Higher HIV viral loads in early childhood, a lack of palatable paediatric formulations, limited data on antiretroviral pharmacokinetics in adolescence and the complexities of dosing dependent on changing weight during growth, all play a role in poorer virological response rates in paediatric populations when compared to adults. However response rates to first line therapy in paediatric populations have improved markedly over the last decade. 

The management of adolescents with extensive antiretroviral experience and limited treatment options differs from those initiating therapy for the first time. Whilst  naïve adolescents have once daily or even combined single pill options available, those who have developed resistance mutations have more limited options, typically twice daily regimens with higher pill burdens. Since virological failure and acquisition of resistance is most commonly due to poor adherence, the issue is further compounded by the need for more complex regimens.

Sticking With It
Issues of poor adherence and responsiveness to therapy, often worse during adolescence, play a prominent role in the complexities of disease management for young people. Conflicting data exists about the factors associated with adherence in adolescents, but mental health issues including depression, substance abuse including alcohol, and lack of wider disclosure of HIV status to family and friends have been associated with poorer adherence4

A lack of randomised controlled trials of adherence interventions and small study numbers limit interpretation, but patient education and support with a treatment ‘buddy’, directly observed therapy and motivational interviewing have shown a positive impact, although sustainability after cessation of the intervention is less clear. Adherence patterns appear to be set early in treatment and predict long term virological and immunological control, and hence the time spent by the child’s family or carer and the multidisciplinary team prior to the initiation of first line therapy is of great importance. In addition, medication fatigue occurs, so adherence messages need to be frequently repeated to prevent virological failure over time. 

More recently, a pilot study using motivational interviewing with financial incentives linked to HIV virological response has shown some benefit in adherence in a small UK adolescent cohort with advanced disease and longstanding poor adherence5

Toxic Therapy?
As this first population of young adults born with HIV transitions into adulthood, the long term effects of living with HIV and prolonged exposure to antiretroviral therapy throughout postnatal growth and development are becoming apparent. Data is accumulating regarding neurocognitive development and mental health, cardiovascular and bone toxicity, yet the long term outcomes remain uncertain6

The impact of HIV on the developing brain results in a wide spectrum of disease from infantile HIV encephalopathy and hypertonic diplegia, through expressive speech delay in preschool children and increased requirements for educational support in school-aged children. Early data suggests higher rates of asymptomatic neurocognitive impairment with poorer executive functioning in college students living with PaHIV. Increased rates of behavioural disorders and psychiatric diagnoses, most frequently anxiety and depression, impact on quality of life and adherence. 

Comparable to HIV infected adults, adolescents with PaHIV show higher rates of various conditions including dyslipidaemia, insulin resistance, thrombophilic abnormalities, inflammation and endothelial activation with growing concern regarding the potential for increased rates of cardiovascular disease in middle age6. In order to perform a careful long-term follow up of this unique cohort, recruitment of 400 infected adolescents and 300 household age matched controls is currently underway in ‘The UK and Ireland Adolescents and Adults Living with Perinatal HIV Cohort (AALPHI)’ Study, with comparable observational cohort studies in the US and France.

Sexual and Reproductive Health
Teens with PaHIV are developing their sexual identity, negotiating relationships, becoming sexually active and in some cases even giving birth to the next generation. Hence, issues such as disclosure to sexual partners or other family members, and the risk of onward transmission to partners and future children are inevitably raised during the adolescent years. Discussions, started early, can prepare a young person for such situations and should cover negotiating relationships, disclosure and safe sex, routes and risk factors for HIV transmission, condom use, additional contraceptive choices and interactions with HAART, post exposure prophylaxis (PEP) and emergency contraception in the event of condom failure, and potential criminalisation of transmission. 

As adolescents with PaHIV become sexually active they require on-going education, contraceptive options in addition to condoms ‘doubling up’, optimisation of Hepatitis B vaccination and an annual STI screen. This screen is particularly important as a concomitant STI can increase the risk of HIV transmission to partners. 

Whilst an increased risk of cervical neoplasia is well recognised for women with horizontally acquired HIV infection, a lack of data for those with PaHIV makes recommendations for the onset and frequency of cervical screening difficult. Further, the impact of HPV vaccination, the optimal vaccine, and booster interval in this population is unknown. Recent cohort data from the UK and US suggest adolescents with PaHIV may have increased rates of cervical premalignant change, and therefore currently annual screening within a year of coitarche is recommended. 

At 17, Rafael is among the first generation of young people who have always lived with HIV. [DFID UK]

HAART treatment markedly reduces the risk of HIV transmission to partners and children7 and so teenagers should also be aware that they can have healthy uninfected children if they so choose. Reassuringly, so far rates of mother-to-child transmission of HIV (where the mother has PaHIV) are low, despite the extensive maternal antiretroviral history and complex perinatal case management6. Whilst no congenital abnormalities were reported for infants in the small PaHIV cohorts described, no long-term data exists for this unique population, where the mothers have been exposed to HAART throughout pubertal development, and ongoing surveillance of these infants is required. 

Teens Grow Into Adults
Over 400 UK adolescents with PaHIV already attend adult services1. In chronic childhood diseases, planned transition programmes improve attendance, disease control, self management and patient and carer satisfaction. Data is emerging on the transition preferences of adolescents with PaHIV, with lack of confidence in negotiating adult services, stigma associated with HIV and fear of ending life-long patient/carer relationships identified as barriers to transition8

Integrated paediatric and adult care in an age specific environment, increasing autonomy, patient-centred timing of transition and comprehensive management explanations are known to facilitate transition to adult care. There is little point in providing high level tertiary paediatric care if transition itself is not well managed, allowing children to become independent young adults, who are retained in medical services appropriate to their needs and are able to fulfil their potential within society.

In only two decades, HIV has become a chronic manageable condition. An ‘AIDS Free Generation’ is a theoretical possibility: HAART dramatically reduces transmission to sexual partners and infants. However, globally this requires enormous resources and increased access to treatment. Prevention of transmission would require greater than 90% adherence to HAART irrespective of the disease status, a goal yet to be achieved. 

However the success of HAART means HIV infected children in the UK are growing into young adults and, whilst the future may be uncertain, this is a remarkable achievement to build upon. Lessons learnt in these small but evolving cohorts will hopefully improve the outcomes for the much larger numbers of children globally as access to treatment improves.

Dr. Caroline Foster is a Consultant in Adolescent Infectious Diseases/HIV Transitional Care at Imperial College Healthcare NHS Trust. She is the current chair of HYPNET (HIV Young Persons Network www.hypnet.org.uk) and research interests include the longterm neurocognitive, cardiovascular and reproductive impact of perinatally acquired HIV infection and of antiretroviral therapy.

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[1] Collaborative HIV Paediatric Study [online] Available at: <http://www.chipscohort.ac.uk/summary_data.asp> [Accessed 30 December 2012].
[2] Key facts on global HIV epidemic and progress in 2010. WHO. [online] Available at: <http://www.who.int/hiv/pub/progress_report2011/global_facts/en/index1.html> [Accessed 30 December 2012].
[3] Foster, C. Judd, A., Tookey, P. et al. (2009) Young People in the UK and Ireland with Perinatally Acquired HIV: the Paediatric Legacy for Adult Services. On behalf of CHIPS. AIDS Patient Care STDs. 23(3):159-66.
[4] Reisner, S.L., Mimiaga, M.J., Skeer, M., et al. (2009) A Review of HIV Antiretroviral Adherence and Intervention Studies Among HIV-Infected Youth. Top HIV Med. 17(1):14-25.
[5] Foster, C. McDonald, S., Frize, G. et al. (2012) Financial Incentives and Motivational Interviewing for Adolescents with Advanced HIV Disease; A Pilot Service. BHIVA. April [P85].
[6] Foster, C. & Fidler, S. (2011) Adolescents with Perinatally Acquired HIV-1 Infection. European Infectious Diseases. B(1):10–6.
[7] Cohen, M.S., Chen, Y.Q., McCauley, M. et al. (2011) HPTN 052 Study Team. Prevention of HIV-1 infection with Early Antiretroviral Therapy. N Engl J Med. 365(6):493-505.
[8] Bundock, H., Tudor-Williams, G., McDonald, S. et al. (2011) Crossing the Divide: Transitional Care for Young Adults with HIV- Their Views. AIDS Pt care & STDs. 25(8):465-73.