Child development affected by late treatment start in resource-limited settings

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Children infected with HIV in resource-poor settings are at a significant risk for developmental impairment – affecting neurocognitive functions as well as growth – in spite of increased access to antiretroviral treatment, researchers reported at the Eighteenth International Conference on AIDS in Vienna on July 19.

Earlier initiation of treatment for optimum growth is strongly indicated in the light of these findings, said researchers from the Perinatal HIV Research Unit, Soweto, and colleagues in Vancouver. They found that children who had started treatment with a CD4 count over 200 had better improvements in weight-for-age and height-for-age scores after starting treatment.

Another study in Jamaica showed that healthcare workers having appropriate screening tools to detect the signs and symptoms of neurological damage (and referring to appropriate treatment and services) as children move into adolescence will be key to mitigating the impact of HIV in children.

Glossary

inter-quartile range

The spread of values, from the smallest to the largest. The inter-quartile range (IQR) only includes the middle 50% of values and measures the degree of spread of the most common values.

encephalopathy

A disease or infection affecting the brain. HIV-encephalopathy (also called AIDS dementia complex) is the result of damage to the brain by advanced HIV disease.

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

neurological

Relating to the brain or central nervous system.

perinatal

Relating to the period around the time of birth. Perinatal transmission is when HIV is passed on during pregnancy, childbirth or breastfeeding. People with perinatally-acquired HIV have been living with HIV since birth or infancy.

In additional, Luminita Ene and colleagues in Romania reported that the presence of viral subtype F may worsen neurological problems.

They found a high prevalence of neurocognitive impairment and of AIDS-defining opportunistic infections among a cohort of HIV-infected Romanian children,  a homogenous group that included those exposed to HIV clade F and who had been on combination antiretroviral treatment for at least ten years.

Among 528 children treated between 1996 and 2008, 43.7% (231) had central nervous system complications. While the number of cases of HIV encephalopathy and opportunistic central nervous system infections decreased with the introduction of combination antiretroviral treatment, the proportion within all AIDS-defining illnesses remained unchanged.

In Jamaica, researchers conducted a two-part analysis (consisting of a database review and a prospective nested case-control study ) of the neurological outcomes of infected children at four paediatric clinics in the Greater Kingston Metropolitan Area of Jamaica from September 2002 to August 2008. Samantha Walker and colleagues found that 23.3% (67) of the children had been diagnosed with HIV encephalopathy, at a median age of 1.57 years (IQR: 1.08 to 3.43).

The primary neuro-developmental abnormalities at diagnosis included: delayed growth (88%); hyperreflexia (being overactive, causing twitching, muscle tension) (88%); spasticity (muscle tension and stiffness) (65%); microcephaly (small skull circumference for age) (63%); and quadriparesis (muscle weakness in all four limbs) (31%).

No significant changes in neurodevelopmental abnormalities were seen after one year on antiretroviral therapy.

Children who had previously been diagnosed  with HIV encephalopathy had difficulty with concept-forming tests, poor short-term memory and inconsistent attention spans, and small skull circumference (for age), as well as needing more time to complete tests that required motor-skill co-ordination, compared to the case controls.

Dr Walker said it was possible that antiretroviral treatment may have started after irreversible central nervous system damage had already happened. She stressed the importance of having feasible, cost-effective screening tools for early detection of neurocognitive impairment to allow for appropriate intervention strategies – for example, rehabilitation services – particularly as children grow into adolescence.

Erica Maxine Lazarus and colleagues reported on a retrospective cross-sectional analysis at the Perinatal HIV Research Unit in Soweto, South Africa, of adolescents (aged 11 to 19 years) on antiretroviral therapy, to look at the effects of baseline CD4 cell count (categorised as above and below 200 cells/mm3), viral response (categorised as above and below 400 copies/ml), and length of time on treatment, on growth.

Of the 107 adolescents, median age at the start of antiretroviral treatment was 8.4 years (IQR: 6.07 to 11.4), and 14.75 years (IQR: 13.49 to 16.47) at the time of the review. Median time on antiretroviral therapy was 6.1 years (IQR: 2.4 to 9.1).

Fifty-nine per cent of the adolescents had a CD4 cell count greater than 200 cells/mm3 at the start of treatment. Eighty-four per cent had viral loads under 400 copies/ml at their most recent visit. Of the four measures (CD4 cell count; baseline age; length of time on treatment; and most recent viral load), baseline CD4 cell count alone was associated with significant increases in height.

Children with CD4 cell counts greater than 200 cells/mm3 at the start of treatment had almost three times the odds of improved height compared to those with baseline CD4 cell count under 200 cells/mm3.

For best growth outcomes into adolescence, Dr Lazarus and her colleagues recommended starting antiretroviral treatment in children over five years of age with CD4 cell counts over 200 cells/mm3.

Further information

Presentations and abstracts from this session are available on the official conference website.

References

Walker S et al. Neurocognitive function in HIV positive children in a developing country. Abstract MOAB0401. Eighteenth International AIDS Conference, Vienna, July 2010.

Duiculescu D et al. High prevalence and particular aspects of HIV-related neurological complications in a Romanian cohort of HIV-infected children and young adults. Abstract MOAB0402. Eighteenth International AIDS Conference, Vienna, July 2010.

Lazarus EM et al. Effect of baseline immunological condition, virological response and duration of HAART on growth in HIV-infected adolescents. MOAB0403.Eighteenth International AIDS Conference, Vienna, July 2010.