Background: Excess risks for death/opportunistic disease in adults randomized to CD4-driven planned treatment interruption (PTI) in the Strategies for Management of Antiretroviral Therapy (SMART) trial remained after antiretroviral therapy (ART) re-initiation. Risks for children following PTI were evaluated in long-term follow-up of children in the PENTA 11 trial.
Methods: Children with HIV RNA below 50 copies/ml and CD4 at least 30% (2–6 years) or at least 500 cells/μl (7–15 years) were randomized to continuous ART (cART) or PTI in PENTA 11 (ISRCTN 36694210). After the end of the trial, all were recommended to resume ART. Data were collected annually and analysed up to the second year of visit.
Results: One hundred and one (51 cART, 50 PTI; median baseline age 9.2 years) children had median overall follow-up 4.6 (range 3.7–5.0) years. During 2-year post-trial period, there were no deaths or new Centers for Disease Control and Prevention (CDC) stage B/C events. Rate of clinical grade of at least two events was similar between PTI and cART [relative risk (RR) 1.03; 95% confidence interval (CI) 0.43, 2.50; P = 0.94]. At 2 years, difference in absolute CD4% between PTI and cART was −1.6% (−4.5%; 1.3%; P = 0.27), and proportions with HIV RNA below 50 copies/ml were 82 versus 86% (P = 0.57), respectively; no differences in growth or fasting lipids were observed. Key predictors of greater CD4% recovery after re-initiating ART were higher CD4% at baseline (P < 0.001) and longer time since ART re-initiation (P < 0.001). During overall follow-up, 4 (8%) PTI versus 5 (10%) CT children switched ART for failure (P = 0.75) and 9 (18%) versus 1 (2%) (P = 0.008) substituted ART for simplification.
Conclusions: No adverse clinical, immunological or virological consequences of PTI were observed 2 years after the end of PENTA 11 trial. Although ART interruption is not generally recommended, it may be an acceptable option for children, particularly when there is high risk of unplanned treatment interruptions.
aHIV-NAT, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand
bMRC Clinical Trials Unit, UK
cINSERM SC10, France
dNorth Manchester General Hospital, UK
eOspedale Bambino Gesù, Rome, Italy
fNakornping Hospital, Chiang Mai, Thailand
gUniversity of Padova, Italy
hHôpital Robert Debré, Paris, France
iInstitute of Child Health, London, UK
jSEARCH, the Thai Red Cross AIDS Research Centre
kFaculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
*Torsak Bunupuradah, Trinh Duong, Jintanat Ananworanich, and Diana Gibb contributed equally to the writing of this article.
Correspondence to Torsak Bunupuradah, MD, HIV-NAT, The Thai Red Cross AIDS Research Center, 104 Ratchadamri Road, Pathumwan, Bangkok 10330, Thailand. Tel: +66 2 652 3040; fax: +66 2 252 5779; e-mail: email@example.com
Received 10 April, 2012
Revised 24 September, 2012
Accepted 30 October, 2012