ART improves impact of therapeutic feeding in malnourished infants with HIV

HIV-infected malnourished children in urban Malawi who got ART within three weeks of therapeutic feeding were more likely to recover nutritionally (86% compared to 60%, p<0.01) and gained over twice as much weight (3.6 compared to 1.6 g/k/day; p=0.02) than those who started ART later, researchers report in a retrospective observational study in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

HIV among children in sub-Saharan Africa is often combined with malnutrition. This can lead to longer and lower rates of nutritional recovery as well as an increased risk of death in cases of severe and acute malnutrition.

In those areas where HIV is prevalent and food insecurity is the main cause of childhood malnutrition, malnutrition is usually treated first. Only when the child has failed to improve in a feeding programme will HIV be taken into account and ART started. This often results in a very high death rate.

Treating HIV-infected children early with ART has been shown to improve survival as well as their nutritional status. Yet severe wasting is also seen in children after having started ART.

The authors note little data exists on the best time to start ART in HIV-infected and malnourished children. So they chose to look at a cohort of HIV-infected malnourished children, of which some had started ART together with nutritional therapy (prompt ART), to compare the effect of prompt ART on nutritional recovery and rates of weight gain and death.

Prompt ART was defined as having started ART within 21 days of starting ready-to-use therapeutic food (RUTF). This time frame was chosen by taking into account the time it takes to diagnose the need for ART in a clinic setting, identification of caregivers and training them on correct ART administration.

All HIV-infected children aged six to 60 months with uncomplicated acute malnutrition and a good appetite who were outpatients between February 2007 and February 2008 at the Baylor College of Medicine-Abbott Fund-Children’s Clinical Center of Excellence (COE) in Lilongwe, Malawi, were included in the analysis. COE, offering free care in the largest urban area of Malawi, is the main referral centre for complicated paediatric HIV cases in the country. HIV care is integrated with malnutrition treatment.

Good appetite was defined as being able to consume 30 grammes of RUTF when offered at admission. Children who got ART for more than 21 days before entering the feeding programme were excluded.

Data collected included electronic medical records and the children’s written medical records. Children with severe malnutrition were seen weekly and those with moderate malnutrition every two weeks. Weight, height, mid-upper arm circumference (MUAC), appetite, symptoms, ART status, CD4 count and CD4 percentage were recorded. Use of RUTF was reviewed. 200 kcal/kg each day of RUTF was given. Nutritional recovery was defined as children having reached 85% weight for height, MUAC greater than 12 centimetres with a resolution of any swelling (edema).

Children got cotrimoxazole prophylaxis. ART was available for children during the time of the study.

Among the 140 children included in the analysis 79% (111) were eligible for ART, only 39% (55) started ART within 21 days of the start of RUTF. A higher proportion of children on prompt ART recovered nutritionally and none developed edema.

16 children died: four children among those who got prompt ART in which three had multiple underlying problems; of the remaining 12 who did not receive prompt ART all had underlying problems.

Prompt ART was the most significant factor associated with nutritional recovery.

The authors note that because they represent a retrospective comparison, the findings are preliminary. The relatively small sample size representing a referral population to an urban speciality HIV clinic does not account for socio-economic factors or the severity of HIV. This population, then, is not representative of either all HIV-infected or all malnourished children in Malawi.

Anecdotal observations have prompted some to suggest that some development of edema in severely malnourished HIV-infected children upon starting ART is an example of Immune Reconstitution Inflammatory Syndrome (IRIS).

The authors note in their study no child developed edema and very few needed hospitalisation. They suggest this may be because of their young age and an absence of any serious clinical illness.

While this cohort of children had uncomplicated acute malnutrition, 14% nonetheless died while getting RUTF and even among those not eligible for ART nutritional recovery was poor.

The authors stress this highlights ‘the critically ill nature of the malnourished, HIV-infected child and the need for comprehensive, coordinated care for malnutrition, HIV, TB and opportunistic infections. This is best provided during a single clinic visit at the same location.” Investing resources, they add, for better coordination is key if child survival and growth is to be improved.

Delaying the start of ART to see if wasting was related to causes other than HIV was common in this study. This practice, they caution, results in a significant increased risk of death among HIV-infected children “and needs urgent re-evaluation.”

The authors conclude “this preliminary evidence suggests that prompt ART is associated with improved outcomes in HIV-infected Malawian children with uncomplicated malnutrition.”

Kim MH et al. Prompt initiation of ART with therapeutic food is associated with improved outcomes in HIV infected Malawian children with malnutrition. Advance online edition JAIDS, doi:10.1097/QAI.0b013e3182405f8f, 2011.