Children with human immunodeficiency virus (HIV) in Africa - Pharmacokinetics and Adherence of Simple Antiretroviral Regimens

Completed

• Conditions: Human immunodeficiency virus (HIV); Infections and Infestations

• Registration Number: ISRCTN31084535
• Lead Sponsor: Medical Research Council (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-02-23
• Last Update Posted: 13 January 2015

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 200

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
5. Previously untreated with antiretrovirals, including any ART given to prevent mother to child transmission
6. Fulfilling one of the World Health Organisation (WHO) criteria for initiating treatment:
a. WHO paediatric stage 4 or severe stage 3 disease regardless of CD4 %
b. CD4 percent <15% if >18 months of age, or <20% if <18 months of age
c. WHO paediatric stage 2 disease with consideration of CD4 percentage (<15% for children >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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
For Dose Escalation Trial (all children): Adverse events (AEs) of grade 3 or 4, possibly or probably related to NVP <br><br>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 Outcome Measures

Name	Time	Method
For Dose Escalation Trial (all children):<br>1. All AEs (Grade 2, 3 or 4) possibly or probably related to NVP<br>2. Viral load change between weeks 0 and 4 and between weeks 0 and 24<br>3. Adherence and acceptability measurements (from questionnaires, visual analogue scale, pill counts and MEMs caps) <br>4. Mortality, disease progression, growth parameters (weight for age, height for age, weight for height), change in CD4 count and percent from baseline<br>5. Population pharmacokinetic parameters of 3TC, d4T and NVP, determined per age group (and according to concomitant medication)<br><br>For PK Sub-study (64 children): Variability in pharmacokinetic parameters (AUC, Cmin, Cmax) according to degree of malnourishment<br><br>For Adherence Sub-study (96 children): Validity of visual analogue scale as a simple measure of adherence compared to scheduled and unannounced pill counts