Different paediatric responses to antiretroviral therapy in Uganda and the United Kingdom/Ireland may reflect differences in nutrition and access to cotrimoxazole

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Researchers have reported that while HIV-positive children in Uganda and the United Kingdom and Ireland responded similarly to antiretroviral therapy in most regards, the Ugandan children lagged behind in CD4 cell recovery and body growth. The study, published in the December 1st issue of Journal of Acquired Immune Deficiency Syndromes, calls attention to the potential for malnutrition and opportunistic infections to undercut the benefits of antiretroviral therapy.

The scale-up of antiretroviral therapy in resource-limited countries has included a paediatric component, but little is known about how children in those countries respond to treatment in comparison to children in well-resourced countries. Insight into the matter could translate into refinements in treatment guidelines.

The comparative study utilised prospective cohort data from the Pediatric Infectious Diseases Clinic at Mulago Hospital in Kampala, Uganda and from the Collaborative HIV Pediatric Study in the United Kingdom (UK) and Ireland.

Glossary

CD4 cell percentage

The CD4 cell percentage measures the proportion of all white blood cells that are CD4 cells.

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

paediatric

Of or relating to children.

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

Children were eligible for enrollment if they had been taking a combination antiretroviral regimen for at least six months with no previous exposure to antiretroviral therapy other than regimens used to reduce the likelihood of mother-to-child transmission of HIV. The Ugandan cohort was comprised of 876 children ranging in age from 4.4 to 11.6 years (median age 7.6 years) and the UK/Irish cohort was comprised of 582 children ranging in age from 1.6 to 8.9 years (median age 5.0 years).

Researchers examined CD4 and viral load measures at baseline and then at six and twelve months. They also examined two other markers of children’s health, weight and height, which were reported in accordance with a standard weight-for-age and height-for-age scoring system.

Wasting and stunting are characteristics of untreated HIV in children in well-resourced countries, and when those children begin antiretroviral therapy, gains in growth are often seen. Thus a key question in the comparative study was whether the Ugandan children would exhibit height and weight gains that matched the height and weight gains of their counterparts.

At both follow-up points, the two cohorts had comparable reductions in viral load and gains in CD4 cell percentages. (The CD4 cell percentage provides a more reliable marker of immune function in children than the CD4 cell count.) Weight gains were comparable, but the Ugandan children’s weight scores showed greater variation, which the researchers suggest may reflect variations in food availability in Uganda.

The most notable difference in the two cohorts’ responses related to height. The children from the UK and Ireland had significantly greater height-for-age changes at six months and twelve months (p

The researchers also looked at whether the two cohorts had the same predictors of six-month response to antiretroviral therapy. In both cohorts, older children were more likely to achieve virological suppression (adjusted odds ratio [aOR] = 1.04 per year older, p = 0.05) and younger children were more likely to experience CD4 percentage increases of ≥10% (aOR = 0.85 per year older, p 10 higher).

One predictor that differed markedly between the cohorts was baseline CD4 percentage. In Uganda, a lower baseline CD4 percentage predicted a worse six-month immune response (aOR = 1.26 per 5% increase, p = 0.01). In the UK and Ireland, it predicted a better response (aOR = 0.69, p

At the same time, a lower baseline CD4 percentage predicted a better weight response in the Ugandan cohort (aOR = 0.78, p = 0.001). There was no association between baseline CD4 percentage and weight response in the UK and Ireland. The researchers speculate that in Uganda, non-HIV factors may contribute more to malnutrition at higher CD4 percentage values.

Because about three-quarters of the UK and Irish children were black Africans, the researchers believe it to be unlikely that underlying racial differences account for their findings.

“Better immune recovery among the most immunocompromised children in the United Kingdom/Ireland may relate to their better nutritional status and/or other environmental factors such as a lower burden of coinfections,” the researchers state. Their overall conclusion is that differences in height, weight and immunological responses “point to the need for earlier HIV diagnosis, nutritional support, and cotrimoxazole prophylaxis for children in Kampala.”

Cotrimoxazole, a low-cost antibiotic that protects HIV-positive people from a number of opportunistic infections, is widely used in well-resourced countries. World Health Organization guidelines call for cotrimoxazole prophylaxis in adults and children with symptoms of HIV, and a number of studies have suggested that it can greatly reduce mortality in resource-limited settings. However, HIV treatment programmes have been slow to act on this evidence.

References

Kekitiinwa A et al. Differences in factors associated with initial growth, CD4, and viral load responses to ART in HIV-infected children in Kampala, Uganda, and the United Kingdom/Ireland. Acquir Immune Defic Syndr 49: 384-392, 2008.