Human immunodeficiency virus (HIV) Infections and Infestations Human immunodeficiency virus (HIV)
Conditions
Interventions
Children will be randomised in a 1:1 ratio to start with Pedimune either at full dose in a twice daily schedule or in a dose escalation schedule of once-daily administration for 14 days, which is then
an additional 3TC/d4T tablet (Lamivir-S) will be provided during this period to allow full dosing of 3TC and D4T.
Sponsors
Medical Research Council (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 3 months to 14 years inclusive 2. Less than 30 kg in weight (heavier children should receive Triomune 30 and not be enrolled in the CHAPAS 1 trial) 3. Carers and children where appropriate, willing and able to give informed consent 4. HIV-infected, as determined by: a. Two separate HIV-antibody enzyme-linked immunosorbent assay (ELISA) or rapid tests on the same sample in children >18 months b. Two positive proviral DNA tests taken on separate samples in children 18 months of age, or 18 months; <20% for children <18 months) (Note current WHO guidelines are under review and the above criteria may be changed, particularly by raising the CD4 percentage cut-off to 25% in children <18 months; inclusion criteria would be changed accordingly for children to start ART in CHAPAS 1 trial.)
Exclusion criteria
Exclusion criteria: 1. Cannot or unwilling to regularly attend the CHAPAS clinic 2. Severe laboratory abnormalities (contra-indicating NVP based regimen) i.e. serum creatinine >5 times upper limit of normal (ULN) or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >10 times ULN 3. Active opportunistic infection and/or serious bacterial infection at the time of study entry including tuberculosis (TB) (children may be enrolled after the acute phase) 4. Current treatment with any medication known to be contra-indicated with any of the drugs prescribed for the patient's ART-therapy in this trial, including rifampicin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For Dose Escalation Trial (all children): Adverse events (AEs) of grade 3 or 4, possibly or probably related to NVP For PK Substudy (64 children): Pharmacokinetic parameters (area under curve [AUC], Cmin, Cmax) of 3TC, d4T and NVP from the full PK curves determined per age group | — |
Secondary
| Measure | Time frame |
|---|---|
| For Dose Escalation Trial (all children): 1. All AEs (Grade 2, 3 or 4) possibly or probably related to NVP 2. Viral load change between weeks 0 and 4 and between weeks 0 and 24 3. Adherence and acceptability measurements (from questionnaires, visual analogue scale, pill counts and MEMs caps) 4. Mortality, disease progression, growth parameters (weight for age, height for age, weight for height), change in CD4 count and percent from baseline 5. Population pharmacokinetic parameters of 3TC, d4T and NVP, determined per age group (and according to concomitant medication) For PK Sub-study (64 children): Variability in pharmacokinetic parameters (AUC, Cmin, Cmax) according to degree of malnourishment For Adherence Sub-study (96 children): Validity of visual analogue scale as a simple measure of adherence compared to scheduled and unannounced pill counts | — |
Countries
Zambia
Outcome results
None listed