IAS: Study in Côte d’Ivoire describes factors associated with survival in older children with HIV: not all respond to treatment

Being of very low weight for their age, having a history of tuberculosis and having a viral load above 100,000 copies/ml predict poor survival in older African children with HIV, according to a study conducted in the Côte d’Ivoire and presented to the Third International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro. And even though antiretroviral treatment (ART) can dramatically improve the health of many children who go onto treatment, “it is not always enough,” said Dr Philippe Msellati of the Institut de Recherche pour le Développement (IRD)/Université Montpellier, France, especially if treatment isn’t started soon enough.

Dr Msellati reported on two survival studies as well as some of the other preliminary experiences of the Programme Enfant Yopougon, which is offering treatment and care to children with HIV in Abijan, Côte d’Ivoire.

Older children (aged over five years) with HIV

Without ART, about half of the children with HIV in Africa die before the age of two. But what about the rest? Many live for years and years — in fact, according to some estimates, 30% survive beyond four or five years of age.

“In the most affected countries, there are already a lot of HIV-infected children,” said Dr Msellati. If their risk of HIV infection wasn’t detected around the time of childbirth, the infection usually stays unidentified in most of these surviving children. “Outside of PMTCT programmes,” he continues, “diagnosis of infection is rarely performed except when young children are symptomatic.”

If they come in for care of some illness after the age of three or four, health care workers do not often think to consider an HIV or AIDS-related explanation.

When HIV is diagnosed in older children, “care management is often poor,” said Dr Msellati, “without any standardization.” Furthermore, he said that health staff may have a feeling of fatality about these children. “These children cannot be cured and for what? [why bother ?]”

In Côte d’Ivoire, there are 84,000 HIV-infected children (below 15 years of age) and 15,000 children are born with HIV each year.

The “Programme Enfant Yopougon”

However, in October 2000, free access to ART began to be offered through the Programme Enfant Yopougon (funded by the French ANRS). The programme had access to a competent paediatric department at a public health facility (with a multidisciplinary team of doctors, nurses, psychologists, a physiotherapist and nutritionists) and to good laboratories. It was also well networked with the community of people living with HIV and non-governmental organisations (NGOs).

But it wasn’t clear when exactly to start ART in older children with HIV — especially in resource-limited settings. ART for children will probably have to be “for life” but treatment options are limited. As these children have survived beyond infancy (when most HIV-infected children don’t), it is possible that they might live for many years without ART. Obviously, treatment should start before these children are at risk of serious illness or death, but “the risk factors associated with mortality in HIV-infected children over two years of age in Africa has been rarely investigated", said Dr Msellati.

Predictors of survival

So the research ran a study (ANRS 1244/1278) to identify factors predictive of good or bad survival in order to help to identify the most appropriate timing to start ART in children. This observational cohort study enrolled HIV-infected children in Abidjan between October 2000 and December 2003 and followed them until the end of September 2004.

The researchers looked at the a wide variety of factors that could impact survival: whether the parents were alive or deceased; the age and sex of the child; how the child became HIV-infected; history of tuberculosis, malnutrition or ART before being recruited into the study; anthropometrics measures (weight and height); hepatitis B infection; haemoglobin, platelets; total lymphocytes count; CD4 cell counts and percentage and viral load.

A total of 282 HIV-infected children were recruited (129 girls and 153 boys) with a mean age of a little under six years. Almost all the children (98%) were infected via mother-to-child transmission. The median CD4% was 14%, and the median viral load was 160,000 copies/ml. The average length of follow-up was 2.17 years.

In total, 86% of these children were still alive after one year of observation, and 81% of those followed were still alive at three years.

In a multivariate analysis, only very low weight for age, history of tuberculosis and viral load >5 log were strong predictors of poor survival at three years, while a CD4 percentage of 15% or above was a predictor of good survival.

The Impact of the programme on mortality and morbidity in African children

A total of 175 children in the cohort received ART (61 before entry in the cohort). Dual therapy with AZT/ddI was used in children in the country before the programme began, but after 2000, they used two nucleoside analogs plus nelfinavir(Viracept) in 72%of the children, and two nucleoside analogs plus efavirenz (Sustiva) in 24% of the children.

Side-effects were experienced by 29% of children but only 4% need to switch treatment.

After two years on ART, the probability of survival was 73% for those with CD4 percentage of 5% or less, and 98% if CD4 percentage above 5% (p

Adherence, resistance and failure

Researchers conducted a cross-sectional assessment of adherence to ART and found that one-third of the children reported less than full adherence. Those with poor adherence tended to be significantly older. In general, “compliance is good,” said Dr Msellati “but school activities and treatment, and disclosure are issues for teens and pre-teens.”

Of the 39 patients who experienced treatment failures, 27 were resistant to at least one antiretroviral drug; and 13, nine and five children were resistant to one, two or three drugs respectively. The frequency of resistant virus among the children initiating treatment in the programme was 24% (27/114).

“Very severe immunodepression, a delay to diagnosis and treatment and missed follow-up were causes of deaths in low resource settings, even with free access to ART,” Dr Msellati suggested. “Providing ART is a good start and it works. But it is not enough and must be included in an global approach —children and families need much more than that (for example, food, school, and support groups).”

Dr. Mselatti’s final recommendations

• Children with HIV must be identified as early as possible.
• Access to ART, care and service must be free for poor families.
• Community support and involvement is needed.
• Children with HIV need advocacy — directed at the healthcare establishment and public health authorities.