HTB

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. [16]

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.

http://www.sahivsoc.org

References

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.
http://www.hivpresentation.com/index.cfm?vID=5B52BC82-423AF6F7- C31E763DE1C6FAB7

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.

12. http:/i-base.info/htb/261

13. http://i-base.info/htb/1449

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.
http://www.hivpresentation.com/index.cfm?vID=5B526AE8-423AF6F7- C3840703869307AA

15. Coovadia A et al. Randomized clinical trial of switching to nevirapine-based therapy for infected children exposed to nevirapine prophylaxis. Abstract MOAB103.
http://www.ias2009.org/pag/Abstracts.aspx?AID=3746

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.
http://www.ias2009.org/pag/Abstracts.aspx?AID=1125

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