NNRTI vs PI HAART regimens for children in resource-limited settings

Treatment for paediatric HIV can be NNRTI or PI based but it is not clear whether either type of regimen offers advantage over the other.

Heather Jaspen and coworkers from the University of Cape Town presented findings from a study comparing outcomes of children (n=389) receiving PI vs NNRTI containing regimens. [1]

In this study, data were collected prospectively on all children receiving HAART through the infectious diseases clinic in a public hospital. Children were started on HAART that included two RTIs, and either a NNRTI (nevirapine [NVP] or efavirenz [EFV]) or a PI (lopinavir/r [LPV/r] or ritonavir [RTV]). Approximately 50% of the children received a PI (n=199) vs NNRTI (n=188).

The median age at baseline was 26.3 (IQR 12.4 to 53.8) months, the median baseline CD4 percentage 13 (IQR 8.0 to17.0) % and median viral load 5.5 (IQR 4.8 to 6.0) log10.

Few children in this group were exposed to NVP for PMTCT. The median baseline weight-for-age z-score (WAZ) was 2.5. There were obvious improvements in the infants in all parameters after the initiation of HAART.

There was no significant difference in the baseline characteristics of patients on the different regimens with viral load, CD4 percentage or WAZ, however the age of the infants initiating treatment with an NNRTI was higher (34.3 vs 21.8 months, p<0.01).

The investigators reported a significantly better virological response among those infants receiving a PI at all times through 48 months, although there were no differences in CD4 percentage, WAZ or in survival.

In a multivariate analysis predicting virological suppression, PI-based regimens were strongly associated with virological suppression as was WAZ and age (see Table 1).

The investigators wrote: Despite profound improvements in outcomes for all children on HAART, an unexpected finding in this study was the inferiority of NNRTI-based regimens in achieving and maintaining virological suppression.

They noted that the implications of detectable vireamia in children are that resistance may develop and switches to second line regimens may, therefore, be needed sooner. In resource-limited settings where regimens are limited, the goal of HAART should be to reach and maintain undetectable viral loads.

They suggest that the effectiveness of regimens containing NNRTIs may be decreased in this setting, due to less than optimal dosing, drug-drug interactions (such as TB therapy), or to exposure to NVP within PMTCT programmes.

They concluded: There is an urgent need to further explore optimal regimens, dosing, and pharmacokinetic interaction studies for children on HAART in these settings.

Variable	Adjusted OR	95% CI	p value
CD4 %	1.04	1.02-1.06	0.001
WAZ	1.23	1.07-1.42	0.004
NNRTI	0.26	0.13-0.53	<0.001
Age (years)	1.34	1.2-1.5	<0.001
Years on HAART	1/02	0.69-1.53	0.90
HAART >6 months	0.5	0.37-0.70	<0.001

Unfortunately, children are probably frequently being under dosed with EFV (also see Ren et al above) – even the original PK studies from PACTG had low serum levels using manufacturer-recommended doses.

CHIPS data has previously reported under dosing of both NVP and EFV as did Verweel et al AIDS 2003 with NVP.

There were not enough kids in this group who were known to have had PMTCT or TB treatment to see an effect (only 19 had a documented change in meds due to TB).