Treating children exposed to single dose nevirapine for PMTCT
Polly Clayden, HIV i-Base
Two studies looked at treatment of HIV-infected children with prior exposure to NVP to prevent MTCT.
Preliminary findings from IMPAACT 1060 confirmed concerns that NVP-exposed children could do less well receiving NVP containing HAART than protease inhibitor (PI)-containing HAART. [10, 11]
This was a randomised trial of treatment-eligible children aged 6 months – 3 years conducted in seven African countries. NVPexposed (cohort 1, n=288) and unexposed (cohort 2, n=288) children received either LPV/r or NVP, plus 3TC and AZT. Children were stratified by age <12months v. =12 months with an equal number to be enrolled in each age group.
A similar study of exposed and unexposed mothers had also been conducted (A5208). In this trial, the arm in which exposed mothers received NVP-containing HAART, was stopped early by the Data Safety Monitoring Board (DSMB). This was due to superior performance of the LPV/r-containing HAART arm. [12, 13]
Following a scheduled DSMB review of IMPAACT 1060 on 20 April 2009, enrolment to cohort 1 also closed prematurely owing to a trend towards consistency with the A5208 results. At 24 weeks, virological failure (<400 copies/mL) was observed in 40% of the 60 infants <12 months v. 23% =12 months receiving NVP and LPV/r, respectively. Among the older children, 29% out of 22 and 17% of 19 receiving NVP and LPV/r experienced failure.
Several guidelines already recommend using LPV/r-based treatment for single-dose NVP-exposed infants.
The NEVEREST study investigated whether NVP-exposed children, initially suppressed on LPV/r-based HAART, can safely switch to a NVP-based regimen. [14, 15]
In this study children aged 6 weeks – 2 years and eligible for treatment (n=323) were initiated on LPV/r plus 3TC and d4T. Children achieving a viral load <400 copies/mL and stable for =3 months were randomised (N=195) to either remain on LPV/r (control, n=99) or switch to NVP (switch, n=96), and then followed up to 52 weeks.
When the investigators looked at viral load <50 copies/ml to 52 weeks they found that 42.4% of children in the control group and 56.2% in the switch group sustained viral suppression (p=0.01). However, allowing for one elevated result (blip) the two groups were similar, 72.8% vs 73.4% in the control and switch groups, respectively.
They suggested that poorer adherence in the control group, due to the unpleasantness in taste of LPV/r syrup, may have led to more blipping and, in turn, unsustained viral suppression to 50 copies/mL during follow-up.
In contrast, when they looked at sustained suppression to <1 000 copies/mL, 98% v. 80% of children in the control and switch groups achieved this (p=0.001).
The investigators suggest that this study provides proof of concept that re-use of NVP is possible under some circumstances for HIV-infected children exposed to NVP prophylaxis and should be further investigated. They note that the clinical significance of low-level viraemia in the control group needs further study. This group also showed data from an evaluation of lipid profiles in children in the control and switch groups. 
They found no difference between the two groups at randomisation. But at 9 months after the change in regimen non-fasting total cholesterol (TC) and high-density lipoprotein (HDL) were significantly higher among the switch group (mean TC 4.13, HDL 1.36 mmol/l) compared with the control group (mean TC 3.73, HDL 1.07 mmol/l). Significantly lower triglyceride (TG) levels were found in the switch group (mean TG 1.36 mmol/l) compared with the control group (mean TG 1.53 mmol/l).
They noted that the clinical significance of these non-fasting lipid changes requires further investigation.
Switching may provide a promising option for children originally initiated on PI-based HAART to preserve second-line options. At this stage, switching requires close virological monitoring after the switch in order to be done safely.
Another NEVEREST trial of efavirenz (EFV) vs LPV/r is planned in nevirapine-exposed children >3 years old.
These studies all underscore the limited treatment options available for children, particularly in resource-limited settings.
This article first appeared in issue 36 of the Journal of HIV Medicine, the journal of the Southern African Clinicians Society.
Unless otherwise stated, all references are to the programme and abstracts of the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 19 – 22 July 2009, Cape Town.
10. Violari A et al. Nevirapine vs. lopinavir-ritonavir-based antiretroviral therapy (ART) in single dose nevirapine (sdNVP)-exposed HIV infected infants: preliminary results from the IMPAACT P1060 trial. HIV Pediatrics, 17 – 18 July 2009, Cape Town. Abstract O_08.
11. Palumbo P et al. Nevirapine (NVP) vs. lopinavir-ritonavir (LPV/r)- based antiretroviral therapy (ART) in single dose nevirapine (sdNVP)-exposed HIV-infected infants: preliminary results from the IMPAACT P1060 trial. Abstract LBPEB12.
14. Coovadia A et al . Randomized clinical trial of switching to NVP-based therapy for infected children exposed to nevirapine prophylaxis. HIV Pediatrics, 17 – 18 July 2009, Cape Town. Abstract O_09.
15. Coovadia A et al. Randomized clinical trial of switching to nevirapine-based therapy for infected children exposed to nevirapine prophylaxis. Abstract MOAB103.
16. Strehlau R et al. Changes in lipid profiles after switching young children from a suppressive lopinavir/ritonavir-based regimen to a nevirapine-based regimen. Abstract TUPEB166.