HTB

Children on HAART do extremely well at South African clinic

Nathan Geffen, TAC

Dr Tammy Meyers presented data from a large cohort of children on HAART at Harriet Shezi ChildrenÂ’s Clinic in Chris Hani Baragwanath Hospital, Soweto, South Africa. [1]

Of the 2,102 children who started treatment between April 2004 and March 2008), 1,734 (82%) are still alive and in the programme. Most of these children started with severely compromised immune systems. Based on earlier studies of untreated children at this stage of HIV disease [2, 3], nearly all would have died had they not been placed on HAART. By the end of the study, half the children had been on HAART for at least 17 months.

Kaplan Meier analysis showed that more than 90% of the cohort suppressed viral load to <400 copies/mL after 18 months on the programme. On average, CD4 percentage rose from 11% to over 25%. The children showed remarkable improvements in both weight and height improvement.

Most of the 132 deaths (6% of the cohort) occurred within the first 90 days of treatment, relating to late treatment. Meyers stressed that infants should now be treated on diagnosis, based on the findings of the CHER study, published last year, which showed that treating infants treated immediately upon diagnosis (as opposed to deferring treatment until their CD4 percentage met the current SA guidelines for initiating treatment) had much lower mortality. [4]

The factors at baseline that predicted death included being severely underweight, having a high viral load, being on TB treatment and younger age. But even among some of these categories, children did well. For example, 28% of children were on TB treatment, a much greater percentage than the number of deaths.

Both clinical trials and cohorts of children have previously been published showing excellent results on HAART. For example, a widely publicised successful cohort on 94 Haitian children was reported in 2005. [5]

The contribution of the Harriet Shezi study is that this is a large African cohort in a resource-limited setting.

From over 3,550 children in the clinic database, 369 were excluded because they were in the clinic before the start of the cohort period. Another 389 were excluded because they had no follow-up. This left 2,795, of whom 2,216 were initiated on HAART. 91 were excluded from the study because they had no further visits after initiation. 23 were excluded because they were over 15. Of the remaining 2,102 included in the analysis, 1,734 were alive and active at study end. 132 died. 104 transferred and 132 were lost to follow up.

Interestingly, of the 579 children who did not start HAART (presumably because they were ineligible according to SA guidelines), 264 are alive and active in the programme. 78 died (double the proportion in the treatment cohort). 189 were lost to follow up (more absolutely than the treatment cohort) and 67 transferred.

The cohort was roughly half boys and half girls. Median viral load was over 100,000 [IQR log viral load: 4.6-5.8 copies/mL]. Median CD4% was 11.5% [IQR: 6.9-16.2%]. Weight and height for age z-score median was 2.12 [IQR: -3.3 to 1.14] and -2.6 [IQR: -3.6 to -1.7]. Median age was 4.3 years.

The median follow-up time on HAART was 17 months [IQR 6-29]. The mortality rate was nearly 15 per 100 child years follow-up (CY) within the first 90 days and then about 2/100 CY. The mortality rate was markedly higher in children under 18 months old: over 30/100C within the first 90 days and 5/100CY after that. Based on a graph reading, the median CD4 rose to between 25 and 30%.

An important conclusion by the authors is that a high percentage of children starting HAART are co-treated for TB, warranting investigation of drug interactions.

References:

  1. Moultrie H et al. Mortality and virological outcomes of 2105 HIV-infected children receiving ART in Soweto, South Africa. 16th CROI, Montreal, 2009.
  2. Little K et al. Disease progression in children with vertically-acquired HIV infection in sub-Saharan Africa: reviewing the need for HIV treatment. Curr HIV Res 2007, Mar;5(2):139-53.
    http://www.ncbi.nlm.nih.gov/pubmed/17346131
  3. Cross Continents Collaboration for Kids Analysis and Writing Committee. Markers for predicting mortality in untreated HIV-infected children in resource-limited settings: a meta-analysis. AIDS. 2008 Jan 2;22(1):97-105.
    http://www.ncbi.nlm.nih.gov/pubmed/18090397
  4. Violari A et al. Early antiretroviral therapy and mortality among HIV-infected infants [Internet]. N Engl J Med. 2008 Nov 20;359(21):2233-44.
    http://www.ncbi.nlm.nih.gov/pubmed/19020325
  5. Severe P et al. Antiretroviral therapy in 1000 patients with AIDS in Haiti. N Engl J Med. 2005 Dec 1;353(22):2325-2334.
    http://content.nejm.org/cgi/content/abstract/353/22/2325

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