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


HIV Medicine. 2018;19(1):e1-e42. 

In This Article

Monitoring on Art

  • The aim of ART is to achieve an undetectable VL (< 50 copies/ml plasma) and CD4 reconstitution.

  • Laboratory monitoring for drug toxicity should be performed initially within 2–4 weeks of starting a new drug, then at least every 6–8 months if there are no ongoing toxicity concerns.

  • After starting ART, VL should be checked early (at around 1 month) to confirm that VL is decreasing (this can coincide with toxicity monitoring).

  • VL and CD4 count can then be monitored 3−4-monthly once the patient has been established on treatment.

  • Once CD4 cells are reconstituted and VL has been < 50 copies/ml consistently for over 1 year, CD4 parameters can be monitored less frequently (every 6–8 months, i.e. at alternate clinic visits).

  • More frequent clinical and laboratory monitoring is required:

    • in infancy;

    • if adherence is poor;

    • soon after starting or changing therapy (e.g. Liver function tests should be performed within 2 weeks);

    • in the context of ongoing drug toxicity;

    • when giving medications with significant drug interactions with ART, such as antituberculous therapy.

Clinical and laboratory monitoring requirements for children on ART are similar to those of ART-naïve children (see Section 3). In addition to the routine clinical, growth, development, urinalysis, vaccination status/immunity and laboratory monitoring, it is important to check specifically for adherence to therapy, side effects and the need for dose modification with changing age and weight. Other current medications should be regularly reviewed, as there is potential for ART to interact with medication obtained from other sources (e.g. oral contraceptive, inhaled steroids and antacids). Other medical teams who may prescribe such medication (e.g. family doctors) should be informed of the potential for drug interactions when children are started on ART. Monitoring needs to be more frequent in infancy and shortly after initiating or changing therapy, but once children are established on treatment and stable, clinic visits can be 3–4-monthly. In order to minimize disruption to schooling, appointments can be made after school or to coincide with school holidays.

Recent modifications to adult guidelines have recommended less frequent laboratory monitoring in those on long-term suppressive ART.[2] The results of the ARROW trial in children have also shown clinical monitoring to be a safe and effective alternative to laboratory monitoring, in resource-poor settings.[71] This supports a recommendation that monitoring of CD4 count and laboratory tests for drug toxicity can safely be performed less frequently than every 3 months when a child is clinically well, has had VL < 50 copies/ml for over 1 year and is not severely immunosuppressed.

TDM of NNRTIs and PIs is available in several quality-controlled laboratories in Europe. There are no studies to inform recommendations for routine use of TDM in children, but it may be particularly useful where there is: (1) suspicion of drug toxicity, poor adherence or drug interactions (e.g. TB treatment); (2) failure to suppress viraemia despite good reported adherence; (3) renal or hepatic dysfunction; (4) use of unlicensed dosing regimens.[101,102] More evidence is required regarding the utility of TDM in monitoring use of drugs with highly variable PK (e.g. EFV). TDM may also be considered in infants and neonates, or with new drugs where PK data are less well established. TDM is generally not indicated for NRTIs as intracellular levels of the active metabolite are difficult to measure/interpret and large blood volumes are required.

One effect of starting ART may be immune reconstitution inflammatory syndrome (IRIS). This occurs within a few weeks or months after starting therapy, is often associated with an exaggerated immune response to an underlying opportunistic infection and is not specific to any drug. The diagnosis is clinical and requires the exclusion of active infection and drug toxicity. Symptoms can be severe and may need treatment with anti-inflammatory drugs (e.g. steroids) and additional therapy for underlying opportunistic infection. In the majority of cases ART should be continued.