PMID- 23013459
OWN - NLM
STAT- MEDLINE
DCOM- 20130516
LR  - 20220801
IS  - 1179-2019 (Electronic)
IS  - 1174-5878 (Linking)
VI  - 14
IP  - 6
DP  - 2012 Dec 1
TI  - When to start, what to start and other treatment controversies in pediatric HIV 
      infection.
PG  - 361-76
LID - 10.2165/11599640-000000000-00000 [doi]
AB  - Over the last decade there have been dramatic changes in the management of 
      pediatric HIV infection. Whilst observational studies and several randomized 
      control trials (RCTs) have addressed some questions about when to start 
      antiretroviral therapy (ART) in children and what antiretrovirals to start, many 
      others remain unanswered. In infants, early initiation of ART greatly reduces 
      mortality and disease progression. Treatment guidelines now recommend ART in all 
      infants younger than 1 or 2 years of age depending on geographical setting. In 
      children >1 year of age, US, European (Paediatric European Network for Treatment 
      of AIDS; PENTA) and WHO guidelines differ and debate is ongoing. Recent data from 
      an RCT in Thailand in children with moderate immune suppression indicate that it 
      is safe to monitor asymptomatic children closely without initiating ART, although 
      earlier treatment was associated with improved growth. Untreated HIV progression 
      in children aged over 5 years is similar to that in adults, and traditionally 
      adult treatment thresholds are applied. Recent adult observational and modeling 
      studies showed a survival advantage and reduction of age-associated complications 
      with early treatment. The current US guidelines have lowered CD4+ cell count 
      thresholds for ART initiation for children aged >5 years to 500 cells/mm3. 
      Co-infections influence the choice of drugs and the timing of starting ART. Drug 
      interactions, overlapping toxicities and adherence problems secondary to 
      increased pill burden are important issues. Rapid changes in the pharmacokinetics 
      of antiretrovirals in the first years of life, limited pharmacokinetic data in 
      children and genetic variation in metabolism of many antiretrovirals make correct 
      dosing difficult. Adherence should always be addressed prior to starting ART or 
      switching regimens. The initial ART regimen depends on previous exposure, 
      including perinatal administration for prevention of mother to child transmission 
      (PMTCT), adherence, co-infections, drug availability and licensing. A European 
      cohort study in infants indicated that treatment with four drugs produced 
      superior virologic suppression and immune recovery. Protease inhibitor (PI)-based 
      ART has the advantage of a high barrier to viral resistance. A recent RCT 
      conducted in several African countries showed PI-based ART to be advantageous in 
      children aged <3 years compared with nevirapine-based ART irrespective of 
      previous nevirapine exposure. Another trial in older children from resource rich 
      settings showed both regimens were equally effective. Treatment interruption 
      remains a controversial issue in children, but one study in Europe demonstrated 
      no short-term detrimental effects. ART in children is a rapidly evolving area 
      with many new antiretrovirals being developed and undergoing trials. The aim of 
      ART has shifted from avoiding mortality and morbidity to achieving a normal life 
      expectancy and quality of life, minimizing toxicities and preventing early 
      cancers and age-related illnesses.
FAU - Turkova, Anna
AU  - Turkova A
AD  - Department of Paediatric Infectious Diseases, St Mary's Hospital, Imperial 
      College NHS Trust, London, UK.
FAU - Webb, Rachel H
AU  - Webb RH
FAU - Lyall, Hermione
AU  - Lyall H
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Paediatr Drugs
JT  - Paediatric drugs
JID - 100883685
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Antitubercular Agents)
RN  - 0 (Antiviral Agents)
SB  - IM
MH  - AIDS-Related Opportunistic Infections/drug therapy
MH  - Acquired Immunodeficiency Syndrome/drug therapy/immunology
MH  - Age Factors
MH  - Anti-HIV Agents/therapeutic use
MH  - Antitubercular Agents/therapeutic use
MH  - Antiviral Agents/therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Coinfection
MH  - Drug Interactions
MH  - HIV Infections/*drug therapy/immunology/transmission
MH  - Hepatitis B/drug therapy
MH  - Hepatitis C/drug therapy
MH  - Humans
MH  - Infant
MH  - Tuberculosis, Pulmonary/drug therapy
EDAT- 2012/09/28 06:00
MHDA- 2013/05/17 06:00
CRDT- 2012/09/28 06:00
PHST- 2012/09/28 06:00 [entrez]
PHST- 2012/09/28 06:00 [pubmed]
PHST- 2013/05/17 06:00 [medline]
AID - 10.2165/11599640-000000000-00000 [doi]
PST - ppublish
SO  - Paediatr Drugs. 2012 Dec 1;14(6):361-76. doi: 10.2165/11599640-000000000-00000.