Updated paediatric HIV treatment guidelines (PENTA, 2009)
7 February 2010. Related: Guidelines.
Polly Clayden, HIV i-Base
The updated PENTA guidelines were published in the November 2009 edition of HIV Medicine. These guidelines offer practical recommendations for treating children with HIV in Europe.
The main changes since the 2004 guidelines are:
When to start?
Universal treatment is recommended as soon as possible after diagnosis for all
infants less than 12 months of age. The guidelines stress particular urgency for infants infected despite prevention of mother to child transmission (PMTCT).
For children 12 months or older, HAART should be started in all symptomatic cases (CDC stage B or C, WHO stage 3 or 4). Children 12 months or older with no or minor symptoms (CDC stage A or N or WHO stage 1 or 2) treatment should be started when CD4 count or percentage falls below the following thresholds:
1 to <3 years CD4<25% or 1000 cells/mm3
3 to <5years CD4<20% or <500 cells/mm3
Above 5 years CD4 count <350 cells/mm3
These treatment thresholds differ significantly from the 2004 guidelines, see Table 1 for comparison of PENTA guidelines 2004 and 2009. Some recommendations also differ from the WHO and US treatment thresholds, see Table 2 comparison of PENTA, WHO and US treatment thresholds.
In children aged more than 12 months with no or minor symptoms and CD4 counts or percentages above these thresholds, HAART should be considered if the viral load exceeds 100,000 copies/mL.
What to start with?
The guidelines recommend a regimen of two NRTIs and either an NNRTI or a boosted PI for ARV-naive children with no evidence of resistance. They note that a PI may be preferred in children with anticipated poor adherence.
Abacavir and 3TC are recommended for children who are HLA-B*5701 negative and AZT and 3TC for those who are HLA-B*5701 positive.
Nevirapine is recommended for children <3 years and efavirenz for older children.
Lopinavir/ritonavir is recommended for young children. For older children alternative boosted PIs may be used, including fosamprenavir/r and duranavir/r which are licensed for children from 6 years, atazanavir/r (which is licensed in the US for children from 6 years but not in Europe) and saquinavir/r (which is not licensed for children but may be suitable for adolescents.
Table 1: Comparison of PENTA guidelines 2004 and 2009
| PENTA 2009 | PENTA 2009 | |
| 0-11 months | 0-11 months | |
| Clinical | Treat all | Treat CDC stage B or C |
| Immunological (CD4%/count) | – | Treat <35% |
| Virological | – | Consider >1,000,000 copies/mL |
| 12-35 months | 12-47 months | |
| Clinical | Treat CDC stage B or C/WHO stage 3or4 | Treat CDC stage C |
| Immunological (CD4%/count) | Treat <25% or <1000 cells/mm3 |
Treat <20% |
| Virological | Consider >100,000 copies/mL | Consider >250,000 copies/mL |
| 36-59 months | 4-12 years | |
| Clinical | Treat CDC stage B or C/WHO stage 3or4 | Treat CDC stage C |
| Immunological (CD4%/count) | Treat <20% or <500 cells/mm3 | Treat <15% |
| Virological | Consider >100,000 copies/mL | Consider >250,000 copies/mL |
| 5 years + | 13-17 years |
|
| Clinical | Treat CDC stage B or C/WHO stage 3or 4 | Treat CDC stage C |
| Immunological (CD4%/count) |
Treat <350cells/mm3 | Treat <200 cells/mm3 |
Table 2: Comparison of current PENTA, WHO and US treatment thresholds
| PENTA 2009 | US 2008 | WHO 2008 | |
| 0-11 months | |||
| Clinical | Treat all | Treat all | Treat all |
| Immunological (CD4%/count) | – | – | – |
| Virological | – | – | – |
| 12-35 months | |||
| Clinical | Treat CDC stage B or C/WHO stage 3 or 4 | Treat CDC stage B | Treat WHO stage 4 and severe 3 |
| Immunological (CD4%/count) | Treat <25% or <1000 cells/mm3 | Treat <25% | Treat <20% or <750 cells/mm3 |
| Virological | Consider >100,000 copies/mL | Consider >100,000 copies/mL | – |
| 36-59 months | |||
| Clinical | Treat CDC stage B or C/WHO stage 3 or 4 | Treat CDC stage B | Treat WHO stage 4 and severe 3 |
| Immunological (CD4%/count) | Treat <20% or <500 cells/mm3 | Treat <25% | Treat <20% or <350 cells/mm3 |
| Virological | Consider >100,000 copies/mL | Consider >100,000 copies/mL | – |
| 5 years + | |||
| Clinical | Treat CDC stage B or C/WHO stage 3 or 4 | Treat CDC stage B or C |
WHO stage 4 or severe 3 |
| Immunological (CD4%/count) | Treat <350 cells/mm3 | Treat <25% or <500 cells/mm3 |
Treat <15% or <200 cells/mm3 |
| Virological | Consider >100,000 copies/mL | Consider >100,000 copies/mL |
– |
Other recommendations
Recommendations on the use of resistance testing, TDM and HLA testing are informed by adult data and paediatric cohorts in Europe. The guidelines highlight the paucity of data from RCTs on which to base recommendations for children and note that available trials tend to be small, therefore
we continue to rely on cohort studies, extrapolation from adult
data and expert opinion. They recommend that wherever possible children should be enrolled in clinical trials.
Drug information will be available alongside the guideline, and will be kept updated, on the PENTA website:
http://www.pentatrials.org
COMMENT
WHO paediatric guidance is due for update imminently, and is likely to recommend earlier treatment in line with updated WHO adult guidance.
WHO and PENTA will provide different recommendations based on the same data. This reflects both the paucity of high quality evidence from randomised clinical trials, on which the guidelines are based, and that PENTA guidelines are intended for use in Europe while WHO guidelines will predominantly inform national guidelines in less well resourced countries, where the ability of treatment programmes to deliver care may also be an issue.
We intend to summarise and review new WHO paediatric guidance later in 2010 when it is published. PENTA guidelines are not likely to change when new WHO paediatric guidance is published, and remain the current recommendations for treating children with HIV in Europe.
Ref: PENTA Steering Committee. PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric infection. HIV Medicine 2009, 10, 591-613.