{"id":6084,"date":"2009-12-30T12:33:18","date_gmt":"2009-12-30T11:33:18","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=6084"},"modified":"2013-08-05T05:33:52","modified_gmt":"2013-08-05T05:33:52","slug":"treating-children-exposed-to-single-dose-nevirapine-for-pmtct","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/6084","title":{"rendered":"Treating children exposed to single dose nevirapine for PMTCT"},"content":{"rendered":"

Polly Clayden, HIV i-Base<\/strong><\/p>\n

Two studies looked at treatment of HIV-infected children with prior exposure to NVP to prevent MTCT.<\/strong><\/p>\n

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]<\/p>\n

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.<\/p>\n

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]<\/p>\n

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.<\/p>\n

Several guidelines already recommend using LPV\/r-based treatment for single-dose NVP-exposed infants.<\/p>\n

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]<\/p>\n

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.<\/p>\n

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.<\/p>\n

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.<\/p>\n

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).<\/p>\n

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]<\/p>\n

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).<\/p>\n

They noted that the clinical significance of these non-fasting lipid changes requires further investigation.<\/p>\n

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.<\/p>\n

Another NEVEREST trial of efavirenz (EFV) vs LPV\/r is planned in nevirapine-exposed children >3 years old.<\/p>\n

These studies all underscore the limited treatment options available for children, particularly in resource-limited settings.<\/p>\n

This article first appeared in issue 36 of the Journal of HIV Medicine, the journal of the Southern African Clinicians Society.<\/p>\n

http:\/\/www.sahivsoc.org<\/a><\/p>\n

References<\/p>\n

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.<\/p>\n

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.
\n http:\/\/www.hivpresentation.com\/index.cfm?vID=5B52BC82-423AF6F7- C31E763DE1C6FAB7<\/a><\/p>\n

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.<\/p>\n

12. http:\/i-base.info\/htb\/261<\/a><\/p>\n

13. https:\/\/i-base.info\/htb\/1449<\/a><\/p>\n

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.
\n http:\/\/www.hivpresentation.com\/index.cfm?vID=5B526AE8-423AF6F7- C3840703869307AA<\/a><\/p>\n

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

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.
\nhttp:\/\/www.ias2009.org\/pag\/Abstracts.aspx?AID=1125<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

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 …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32],"tags":[],"class_list":["post-6084","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/6084","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=6084"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/6084\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=6084"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=6084"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=6084"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}