There is a low risk of death for children starting HIV treatment in sub-Saharan Africa, an international team of investigators report in the December 15th edition of the Journal of Acquired Immune Deficiency Syndromes. The risk of death after starting HIV treatment was 7% and three-quarters of deaths occurred in the six months after antiretroviral therapy was started.
But the researchers found that there was a “worryingly” high risk of children being lost to follow-up, particularly as severe ill health was a major risk factor for loss to follow-up.
It is estimated that at the end of 2006 there were over 2 million HIV-positive children in the world. Most (90%) are located in sub-Saharan Africa. Approximately 780,000 children are thought to be in need of antiretroviral therapy, but fewer than 5% are actually receiving therapy with anti-HIV drugs, despite the fact that children who receive antiretroviral therapy in resource-limited settings can achieve good outcomes.
Investigators from the Kids’ Antiretroviral Treatment in Lower-Income Countries (KIDS-ART-LINC) Collaboration, a network of paediatric HIV treatment programmes in sub-Saharan Africa, wished to determine the two-year risk of death or loss to follow-up for children aged under 15 who started HIV treatment.
A total of 2405 children attending 16 clinics were included in the investigators’ analysis. The majority of these children (52%) were male and the median age was five years.
Severe immunodeficiency was present in 70% of children at baseline, with 6% having severe anaemia and 53% assessed as being in very poor health.
Two-thirds of children started antiretroviral therapy with a combination that included an NNRTI, with the remaining third taking a protease inhibitor-containing regimen.
The median duration of follow-up was 20 months and during this time 153 deaths were recorded. Given the severe immunodeficiency and poor health of many of the children at baseline, it is not surprising that over half (57%) of these deaths occurred during the first three months after the initiation of treatment. A further 17% of deaths occurred in the next three months, with 16% being recorded in the next six months. Only 9% of deaths were recorded in the second year of antiretroviral treatment.
A total of 187 children were lost to follow-up with 42% being lost during the second year of treatment.
Overall, the probability of death was estimated to be 5% at six months, 6% at twelve months and 7% at 24 months. The probabilities of being lost to follow-up were 3% at six months, 5% at twelve months and 10% at 24 months.
Next, the investigators tried to determine the factors associated with these outcomes. They restricted their analysis to the 1058 children for whom complete data was available on clinical status, immunodeficiency and anaemia.
In this group of patients, 72 deaths occurred and 66 children were lost to follow-up. Most of the deaths (68) and losses to follow-up (44) occurred in the first year. The probability of death was 5% at six months and 8% after two years. The probability of loss to follow-up was 3% after six months and 8% after two years.
Severe immunodeficiency, severe anaemia and very poor health were all associated with an increased risk of death. Only poor health was associated with an increased risk of being lost to follow-up.
There was no association between the risk of death and age when HIV treatment was started, or type of HIV regimen used.
“This pooled analysis of routinely collected individual data on about 2400 children on antiretroviral therapy followed in health care facilities in sub-Saharan Africa up to mid-2007 indicates a relatively low probability of death within the first two years of treatment (7%), with 75% of the deaths occurring in the first six months”, comment the investigators.
They add, “our data confirm the relatively low mortality of children enrolled in antiretroviral treatment programmes in other low-income countries”.
However, they emphasise the risk of loss to follow-up was higher and that 60% of losses occurred in the first year.
Limitations of the study are noted by the investigators. A high proportion of children were taking a protease inhibitor-based regimen. This is not recommended by World Health Organization paediatric HIV treatment guidelines. Furthermore, important data were missing for many of the children.
The major limitation of this study, however, is the lack of data on viral load and CD4 cell responses to treatment. Data also published this month from the Central African Republic show a very high rate of non-adherence to treatment and consequent detectable viral load and drug resistance, which will compromise the future treatment options for these children.
The KIDS-ART-LINC Collaboration. Low risk of death, but substantial program attrition, in paediatric HIV treatment cohorts in sub-Saharan Africa. J Acquir Immune Defic Syndr 49: 523-31, 2008.