{"id":24872,"date":"2014-03-24T11:52:37","date_gmt":"2014-03-24T11:52:37","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=24872"},"modified":"2014-03-28T16:26:30","modified_gmt":"2014-03-28T16:26:30","slug":"efavirenz-maintenance-therapy-effective-in-children-exposed-to-nevirapine-prophylaxis-2","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/24872","title":{"rendered":"Efavirenz maintenance therapy effective in children exposed to nevirapine prophylaxis"},"content":{"rendered":"

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

\"CROIChildren exposed to nevirapine prophylaxis who are initially suppressed on lopinavir\/ritonavir-based therapy can safely switch to efavirenz-based maintenance therapy, according to data presented at CROI 2014. <\/strong><\/p>\n

Lopinavir\/ritonavir is recommended as first-line therapy for infants and young children in resource-limited settings. This is partly to overcome NNRTI resistance following nevirapine prophylaxis, which is still widely used in PMTCT programmes globally. However, treatment with lopinavir\/ritonavir has a number of shortcomings including: cost, palatability, managing concomitant TB treatment and potential metabolic complications.<\/p>\n

The NEVEREST 3 trial was designed to find out whether switching nevirapine-exposed children who start on lopinavir\/ritonavir-based ART (and are stable) to efavirenz-based maintenance therapy is equivalent virologically to staying on lopinavir\/ritonavir.<\/p>\n

Ashraf Coovadia from Rahima Moosa Mother and Child Hospital in Johannesburg, presented data from NEVEREST 3 on behalf of colleagues from University of the Witwatersrand, Johannesburg; Columbia University, New York; and Institute of Communicable Diseases, Johannesburg.<\/p>\n

This was a 48-week, non-inferiority, open label, randomised trial, enrolling 300 children; two were lost before starting the trial and 294 completed follow up.<\/p>\n

Children who had been exposed to nevirapine prophylaxis, initiated lopinavir-based therapy <24 months of age and suppressed <50 copies\/mL at enrollment. They were randomised to switch to efavirenz or stay on lopinavir\/ritonavir. Children had regular viral load, CD4 and other laboratory tests, growth measurements and clinical assessments throughout 48 weeks follow up.<\/p>\n

Primary endpoints were: viral load >50 copies\/mL at any time during follow up; and confirmed viral failure >1000 copies\/mL. The non-inferiority margin was 10% ie the study was powered to exclude this difference between arms in virologic efficacy.<\/p>\n

At baseline, children were an average of 4.1 years of age, just over half were girls, they had initiated ART at about 9 months and had been on treatment for about 3.5 years. About 60% received abacavir, 35% d4T, and the remainder AZT; all children received 3TC.<\/p>\n

Both primary endpoints were non-inferior in the efavirenz arm vs lopinavir-ritonavir. A higher proportion of children in the lopinavir\/ritonavir than the efavirenz arm had viral rebound >50 copies\/mL: 28% vs 17%, difference +11% (95% CI 1.6 to 20.5), p=0.03. Similar proportions had viral failure >1000 copies\/mL: 2% vs 2.6%, difference 0.6% (95% CI -4.1 to 2.8) p=0.68. Professor Coovadia noted that this rate of viral failure was exceptionally low.<\/p>\n

At 48-weeks there was a greater increase in CD4 percentage in the efavirenz arm vs lopinavir\/ritonavir: to 37% vs 34%, p<0.001. Professor Coovadia remarked that this might mean very little clinically.<\/p>\n

There were no deaths in either arm, hospital admissions were rare but two children had efavirenz related seizures that stopped after discontinuing the drug. There was a spike in reported sleep difficulties and nightmares in the efavirenz arm, with 28% of children reporting this at 4 weeks, but there was no difference between the arms at 8 weeks. There were no differences by arm in behavioral problems assessed by the Strengths & Difficulties Questionnaire (SDQ). Weight- and height-for-age were in the normal range and similar across arms. Laboratory abnormalities and other complications were rare.<\/p>\n

In conclusion, the investigators wrote: \u201cWe advise consideration of such a switch strategy in treatment programmes particularly in resource constrained settings.\u201d<\/p>\n

comment<\/h3>\n

These results are welcome, not least as Professor Coovadia pointed out where \u201cpractice is preceding what the science shows\u201d \u2013 programmes are already switching children from lopinavir\/ritonavir to efavirenz in this situation. \u00a0<\/strong><\/p>\n

WHO and national guidelines are clear in recommending that young infants and children start on lopinavir\/ritonavir-based treatment. They are also clear that older treatment na\u00efve children should start on efavirenz. What is less clear is whether children initiated on lopinavir\/ritonavir should switch to the preferred regimen for older children once they become older. Professor Coovadia suggested that there would need to be a lot of discussion about what these results mean for guidelines and programmes. <\/strong><\/p>\n

Hopefully, with more widespread uptake of maternal ART in pregnancy, nevirapine prophylaxis exposure for children will soon be a thing of the past, and treatment recommendations will not need to take this into consideration. <\/strong><\/p>\n

Authors note \u2013 about halfway through the presentation Professor Coovadia gives one of the best explanations of non-inferiority I have heard and deserves a plain English award! It is worth checking out the webcast for that too. <\/strong><\/p>\n

Reference<\/p>\n

Coovadia A et al. Virologic efficacy of efavirenz maintenance therapy in nevirapine prophylaxis-exposed children. 21st CROI, 3-6 March 2014, Boston. Oral abstract 73.
\nhttp:\/\/www.croiwebcasts.org\/console\/player\/22147<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base Children exposed to nevirapine prophylaxis who are initially suppressed on lopinavir\/ritonavir-based therapy can safely switch to efavirenz-based maintenance therapy, according to data presented at CROI 2014. Lopinavir\/ritonavir is recommended as first-line therapy for infants and young …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32],"tags":[187],"class_list":["post-24872","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","tag-croi-2014"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/24872","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=24872"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/24872\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=24872"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=24872"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=24872"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}