PMID- 24849473
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20220129
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 28 Suppl 2
DP  - 2014 Mar
TI  - Optimization of antiretroviral therapy in HIV-infected children under 3 years of 
      age: a systematic review.
PG  - S137-46
LID - 10.1097/QAD.0000000000000240 [doi]
AB  - BACKGROUND: Treatment of young HIV-infected children is challenging because of 
      rapid disease progression, high viral loads and few drug options. This review was 
      undertaken to update evidence on the management of young HIV-infected children 
      and to inform the development of the 2013 WHO guidelines for antiretroviral 
      therapy (ART) in low and middle-income countries. DESIGN: A systematic review and 
      meta-analysis. METHODS: We identified and critically assessed randomized 
      controlled trials that evaluated treatment strategies in perinatally HIV-infected 
      infants and young children (aged <3 years). RESULTS: Eight studies were included. 
      Antiretroviral therapy (ART) initiation in asymptomatic infants led to 74% 
      reduction in mortality or disease progression [hazard ratio 0.36, 95% confidence 
      interval (CI) 0.18-0.74, P = 0.0002]. Regardless of previous exposure to 
      prevention of mother to child transmission (PMTCT), treatment failure at 24 weeks 
      was more likely in children starting nevirapine-based than in those starting 
      lopinavir/ritonavir (lopinavir/r)-based ART (hazard ratio 1.79, 95% CI 1.33-2.41, 
      P = 0.0001). Infants starting lopinavir/r-based ART and substituting lopinavir/r 
      with nevirapine once virologic suppression was achieved were less likely to 
      experience viral load more than 50 copies/ml (hazard ratio 0.62, 95% CI 
      0.41-0.92, P = 0.02) but more likely to have confirmed virologic failure (>1000 
      copies/ml) than those remaining on lopinavir/r (hazard ratio 10.19, 95% CI 
      2.36-43.94, P = 0.002). Children receiving induction-maintenance ART (four-drug 
      NNRTI-based regimen for 36 weeks followed by three-drug ART) showed better 
      short-term immunologic and virologic responses, but no long-term benefits. The 
      only trial comparing continuous ART from infancy with interrupted ART beyond 
      infancy was terminated early because the duration of treatment interruption was 
      less than 3 months in most infants. CONCLUSION: ART initiation in asymptomatic 
      infants reduces morbidity and mortality. Lopinavir/r-based first-line ART is 
      superior to nevirapine-based regimens in young children, regardless of PMTCT 
      exposure, but lopinavir/r use is challenging. Substituting lopinavir/r with 
      nevirapine following virologic suppression may be feasible where viral load 
      testing is available. Considering current evidence, induction-maintenance and 
      treatment interruption strategies are not recommended. This review contributed to 
      the evidence base for the 2013 WHO guidelines on antiretroviral therapy, which 
      recommend that all children below 3 years start lopinavir/r-based ART and that 
      lopinavir/r can be substituted with nevirapine once sustained virologic 
      suppression is achieved.
FAU - Penazzato, Martina
AU  - Penazzato M
AD  - aMRC Clinical Trials Unit at UCL, London, UK bHIV Department, World Health 
      Organization, Geneva, Switzerland cCentre for Paediatrics, Blizard Institute, 
      Queen Mary University of London, London, UK dZvitambo Institute for Maternal 
      Child Health Research, Harare, Zimbabwe eAfrican Network for the Care of Children 
      Affected by HIV/AIDS (ANECCA), Kampala, Uganda fICAP, Mailman School of Public 
      Health and College of Physicians and Surgeons, Columbia University, Columbia, New 
      York, USA. *Martina Penazzato and Andrew J. Prendergast contributed equally to 
      the development of this manuscript.
FAU - Prendergast, Andrew J
AU  - Prendergast AJ
FAU - Muhe, Lulu M
AU  - Muhe LM
FAU - Tindyebwa, Denis
AU  - Tindyebwa D
FAU - Abrams, Elaine J
AU  - Abrams EJ
LA  - eng
GR  - 001/WHO_/World Health Organization/International
GR  - 100714/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Anti-Retroviral Agents)
SB  - IM
CIN - AIDS. 2014 Mar;28 Suppl 2:S133-5. PMID: 24849472
MH  - Anti-Retroviral Agents/*administration & dosage
MH  - Child, Preschool
MH  - Disease Progression
MH  - HIV Infections/*drug therapy/immunology/mortality/transmission
MH  - Humans
MH  - Infant
MH  - Infectious Disease Transmission, Vertical/*prevention & control
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Outcome
EDAT- 2014/05/23 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/05/23 06:00
PHST- 2014/05/23 06:00 [entrez]
PHST- 2014/05/23 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - 00002030-201403002-00007 [pii]
AID - 10.1097/QAD.0000000000000240 [doi]
PST - ppublish
SO  - AIDS. 2014 Mar;28 Suppl 2:S137-46. doi: 10.1097/QAD.0000000000000240.