Child death rates still high despite HIV treatment

Barely half of all children having started antiretroviral treatment (ART) at under one year of age were still in care two years later, according to the largest single programme multi-country retrospective analysis of children on ART in Kenya, Mozambique, Rwanda and Tanzania, published in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

Of the more than 17,000 children (0 to under 15 years of age) having started ART at 192 facilities in the four countries over the six-year period, overall retention rates at 12 months and 24 months were 80 and 72%, respectively; differing considerably by country ranging from 71 to 95% and 62 to 93%, respectively.

While overall 16 and 22% were lost to follow-up (LTFU) and 5 and 7% were known to have died at these respective time points, there were significant differences among patient populations.

At 24 months, 18% of those having started ART at under one year of age died. 

“While these estimates can be considered an improvement from the reports in the pre-ART era (50% mortality at 24 months), the mortality rate remains unacceptably high in the context of ART” write the authors.

The benefits for children on ART should be the same whether in a resource-poor or -rich setting, yet the death rate among the former is eight times that of the latter.

In spite of increased early diagnosis and getting larger numbers of younger children onto treatment many paediatric HIV programmes in resource-poor settings have yet to see these benefits.

“This study builds upon evidence that overall retention, LTFU and death are suboptimal, and young children and those with advanced disease are at highest risk for LTFU and death” the authors note.

Scale-up of paediatric HIV treatment and care in sub-Saharan African, home to over 90% of children living with HIV, has resulted in over 400,000 children having started ART.

Children in resource-poor settings respond to treatment as well as those in resource-rich settings. The vast difference in outcomes is the result of both biomedical and programme factors and include having advanced disease upon diagnosis, other co-infections, malnutrition, delays in starting ART, and suboptimal retention in care.

Retaining HIV-infected children in care is critical for prevention of HIV-related illness and death. It means the timely start of ART, monitoring and managing disease progression and treatment failure, and providing ongoing treatment and supportive care.

If outcomes are to be improved factors that affect retention need to be identified.

The authors chose to undertake a retrospective cohort analysis of data of children having started ART between January 2005 and June 2011 to determine the proportion of children retained in care, LTFU and died at 12 and 24 months; to look at the variations by country and identify those individual- and facility-level associated factors.

All 192 health facilities received support from the International Center for AIDS Care and Treatment Programs (ICAP), a PEPFAR implementing partner supporting HIV treatment and care in sub-Saharan Africa since 2005.

Eligibility for starting ART followed national guidelines reflecting World Health Organization (WHO) recommendations.

Retention was defined as the proportion of children known to be alive and getting care at the health facility where treatment was started; LTFU was defined as no clinic visit for more than six months.

Individual-level factors included: CD4 count or percentage, according to WHO guidelines, to determine disease severity when starting ART; malnourishment; “severe illness” (a new category because of the high proportion of missing CD4 measurements and WHO stage); WHO definition of severe immunodeficiency or WHO Stage 4 at the time of starting ART.

Facility level factors were defined as primary and secondary/tertiary; the former any health centre and the latter district, regional or national hospitals. Locations were categorised as urban, semi-urban and rural.

Of the 37,514 children enrolled in HIV services, 17,712 started ART; Mozambique had the largest number (7226) and Rwanda the smallest (2170).

Each year, the numbers starting ART increased, from 585 in 2005 to 3653 in 2010 with the number of facilities increasing from 75 to 192.

Almost half of all facilities were in rural areas.

When starting ART the median age was 4.6 years (IQR: 1.9-8.3), the median CD4 percentage for children under five years of age was 15% (IQR: 10-20%) and 265 cells/mm³ (IQR: 111-461) for those over five.

Overall over a third of all children were severely ill when starting ART.

The proportion of young children under two starting ART increased over time (from 12% in 2005 to 33% in 2011) with a corresponding decrease in the severity of illness in children under one (from 56 to 18%). Yet contrary to what would be expected – enrolling healthier children and the benefits of getting them on treatment earlier – no improvements were seen in retention or death over time.

For children under one year of age the adjusted hazard ratio for LTFU and death was aHR=2.0, 95% CI: 1.7-2.4 and aHR=3.4, 95% CI: 2.6-4.6, respectively.

Compared to children with less advanced illness those with severe illness had higher death rates HR=1.6, 95% CI: 1.1-1.9, but similar LTFU rates, HR=0.99, 95% CI: 0.86-1.13.

While highlighting the continued need to pay special attention for infants to be diagnosed promptly, started on treatment and kept in care, these findings also show the need for more research to identify those factors affecting health outcomes among this highly vulnerable group, the authors note.

Despite all facilities receiving technical support through ICAP, having the same model of care in place with an emphasis on early infant diagnosis, family-focussed care, peer educators and active follow-up, there were considerable differences in outcomes across country programmes as well as within country.

Compared to children in Rwanda, children in Mozambique were over 16 times more likely to be lost to follow-up (aHR: 16.8, 95% CI: 8.9-32.0) and children in Tanzania had more than twice the death rate (aHR: 2.6, 95% CI: 1.8-3.6).

The authors suggest these differences result from a combination of factors including national leadership, access to care, HIV prevalence, patient-provider ratios, caseload and decentralisation.

Rwanda had the highest retention rate consistent with other findings. However, they also had the smallest proportion of young children (15.6% compared to 38.7% in Mozambique) and the smallest proportion of severely ill children, (18.6% compared to 44.5% in Mozambique).

Additionally, Rwanda had a smaller programme with a lower caseload, a factor linked to lower LTFU in resource-poor settings. This may be the result of higher staff-to-patient ratios, shorter wait times, more staff and active follow-up, factors shown to reduce LTFU, the authors note.

With the exception of Rwanda, the proportion of LTFU was higher than the proportion of known death for all age groups and time periods.

“Rwanda’s results are encouraging as they illustrate what is achievable in public programmes and suggest that improvement is obtainable,” the authors comment.

This is the largest single programme multi-country analysis on outcomes among children reflecting the scale up of HIV care and treatment in sub-Saharan Africa and can probably be generalised to other PEPFAR-supported paediatric HIV programmes.

The analysis is limited by the large amount of missing data at the start of ART. Missing data – a separate category in the regression analyses – showed that children with missing data appeared at greater risk for LTFU or death.

The authors conclude “The vast differences across country programmes illustrate that improved retention is achievable…additional attention to prompt diagnosis, early ART initiation, active follow-up of children who miss appointments and improved documentation of known transfers and death are urgent priorities for paediatric HIV programmes.”

McNairy ML et al. Retention of HIV-infected children on antiretroviral treatment in HIV care and treatment programs in Kenya, Mozambique, Rwanda and Tanzania. Advance online edition J Acquir Immun Defic Syndr, doi: 10.1097/QAI.0b013e318278bcb0, 2012.