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Increased cardiovascular risks in HIV positive children in Uganda and Zambia partially reversed by ART

Polly Clayden, HIV i-Base

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ART naive children had functional and structural cardiovascular changes compared with HIV negative controls but ART can reverse some of these changes caused by HIV, according to data shown at CROI 2015.

Julia Kenny from University College London presented findings from the CHAPAS 3 trial on behalf of the cardiovascular sub study investigators. She explained that HIV positive adults are at increased risk of cardiovascular disease. Although this has not been described in HIV positive children, there is accumulating evidence of accelerated atherosclerosis in this population.

Two ways of looking at cardiovascular structure/function are used: carotid intimal medial thickness (cIMT) and pulse wave velocity (PWV). Both are impaired in HIV positive children from high-income countries. Few data are available: only one study from Africa (with no controls) and mostly small studies in older children without longitudinal follow up.

CHAPAS 3, conducted in 2010 – 2013, looked at d4T vs AZT vs abacavir-based first-line ART in treatment naive and experienced children in Uganda and Zambia.

In the substudy – conducted at two sites, one in each country – children had cIMT and PWV measured at baseline, 48 and 96 weeks. Age matched HIV negative controls had a single assessment.

The investigators evaluated baseline differences between ART-naive and -experienced children vs controls, and compared longitudinal changes in children (using two-sample and paired t-tests respectively).

In 208 ART-naive children with median age 2 .9 years (range 0.3 – 13.6), mean CD4 percent 17% (SD: 8), and 209 HIV negative controls with median age 3.0 years (range: 0.1 – 12.8), mean cIMT was 0 .46 (SD: 0.04) vs 0.44 (SD: 0.04) mm respectively, p=0.0001; PWV was 5.85 (SD: 0.8) vs 5.67 (SD: 0 .74) m/sec respectively, p=0.04.

In 74 ART-experienced children (receiving treatment for mean 3.7 years) with median age 6.9 years (range: 5.1 – 12.3), median CD4 percent 34% (SD: 10) and 75 HIV negative controls with median age 6.7 years (range: 3.9 – 11.8), mean cIMT was 0.46 (SD: 0.05) vs 0.45 (SD: 0.04) mm respectively, p=0.09; PWV was 5.63 (SD: 0.61) vs 5.69 (SD: 0.69) m/s respectively, p=0.57.

In ART-naive children at week 96 of ART significant improvement was seen in both parameters: mean cIMT -0.02 (SD: 0.04)mm, PWV -0.38 (SD: 0.83)m/s, both comparisons p<0 .0001.

In ART-experienced children, although cIMT had significantly reduced by mean -0.2 (SD: 0.06) mm, p=0.01, at week 96 PWV increased by 0.35 (SD: 0.63) m/s, p<0.0001. Dr Kenny noted that an increase in PWV is expected, as children get older and was also seen in the HIV negative controls.

Despite concerns about abacavir and cardiovascular risk, there was no significant difference between the three randomised treatment arms at 96 weeks in either cIMT or PWV.

Comment

This is the largest study worldwide of preclinical cardiovascular changes in HIV positive children and the only longitudinal African data. It is also the first time that these techniques have been used in children less than five years old.

The study suggests that ART-naive children have poorer cIMT and PWV compared with controls but that ART can reverse some of the functional and structural changes caused by HIV. One question after the presentation was whether or not all the increase in PWV was fully accounted for by age – Dr Kenny remarked that when they looked at this the confidence intervals overlapped and there was nothing unexpected.

These data add weight to the argument that ART in early life might reduce the cardiovascular risk of HIV positive children when they become adults. Longer-term follow up of children who start ART at an early age is important.

Reference:

Kenny J et al. Structural cardiovascular changes are reversible in HIV-infected children in Zambia and Uganda. CROI 2015. Seattle, Washington. 23-26 February 2015. Oral abstract 37.
Abstract:
http://www.croiconference.org/sessions/structural-cardiovascular-changes-are-reversible-hiv-infected-children-zambia-and-uganda
Webcast:
http://www.croiwebcasts.org/console/player/25557