Paediatric European Network for Treatment of AIDS (PENTA) Guidelines for Treatment of Paediatric HIV-1 Infection 2015

Optimizing Health in Preparation for Adult Life

A Bamford; A Turkova; H Lyall; C Foster; N Klein; D Bastiaans; D Burger; S Bernadi; K Butler; E Chiappini; P Clayden; M Della Negra; V Giacomet; C Giaquinto; D Gibb; L Galli; M Hainaut; M Koros; L Marques; E Nastouli; T Niehues; A Noguera-Julian; P Rojo; C Rudin; HJ Scherpbier; G Tudor-Williams; SB Welch

Disclosures

HIV Medicine. 2018;19(1):e1-e42. 

In This Article

Prophylaxis Against Opportunistic Infections

  • Prophylaxis against Pneumocystis jirovecii should be given to all HIV-infected infants from age 1 month and to older children with low CD4 counts (see criteria below). Co-trimoxazole is the drug of first choice (see drug table in Supplementary Table S1 for dosing).

  • No routine primary prophylaxis against other infections is recommended.

Prophylaxis with co-trimoxazole is highly effective at preventing potentially life-threatening infection with P. jirovecii, and also at reducing bacterial infections.[24,25] In view of their susceptibility to severe P. jirovecii infection, all HIV-infected infants should receive prophylaxis from 4 weeks of age until their first birthday, regardless of CD4 and VL.[26] HIV-exposed babies at high risk for transmission should also commence P. jirovecii prophylaxis at 4 weeks of age and continue until HIV infection has been excluded. Co-trimoxazole is the first-choice drug unless contraindicated. Co-trimoxazole has not previously been recommended before the age of 4 weeks because of the theoretical risk of kernicterus with sulphonamide administration in neonates. Hard evidence for this is lacking[27] and it is unclear what the relative risks of this are compared with the risks of P. jirovecii infection in young infants in whom the diagnosis of HIV infection is made before 4 weeks of age.

Children aged 1 to 4 years should receive prophylaxis against P. jirovecii if they have a CD4 count below 500 cells/μL or 15% of total lymphocyte count. Children aged 5 years and above should receive prophylaxis against P. jirovecii if they have a CD4 count below 200 cells/μl or 15%, and it should be considered when they are approaching these thresholds.[28,29] While intermittent dosing (3 days a week) is sufficient for P. jirovecii prophylaxis, daily co-trimoxazole prophylaxis according to weight bands, as in the current WHO guidelines,[6] simplifies recommendations with the additional benefit of protecting against bacterial infections. This option is also therefore endorsed by these guidelines. Daily co-trimoxazole prophylaxis may also be considered for children travelling to countries with a high prevalence of bacterial infections and/or malaria, irrespective of their CD4 count/percentage and current treatment status.[6,24,30,31] The use of co-trimoxazole in this context may also have additional benefit as antimalarial prophylaxis,[32] although specific malaria prophylaxis appropriate to the regions being visited should always be prescribed.

Once ART has been started and the CD4 count has risen, the risk of P. jirovecii infection decreases.[33,34] Most paediatricians stop co-trimoxazole in children over 1 year of age living in well-resourced settings 6 months after CD4 count recovery. The AntiRetroviral Research for Watoto (ARROW) trial has reported additional benefits of continuing co-trimoxazole prophylaxis after immune reconstitution in children in resource-poor settings. It is likely that these additional benefits are related to antibacterial, antimalarial and anti-inflammatory effects. The findings of this trial are therefore less likely to be of relevance in most European settings.[30]

Prophylaxis against other infections has been suggested for those with very low CD4 counts. There is insufficient evidence to make any recommendations for routine primary prophylaxis, but specific guidance is available.[35] Prophylaxis against TB can be considered for children visiting countries highly endemic for TB (see Section 10 below). The most important means to reduce susceptibility to all opportunistic infections is prompt initiation of ART when indicated.

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