Human immunodeficiency virus (HIV) Infections and Infestations Human immunodeficiency virus [HIV] disease
Conditions
Interventions
Participants will be randomised in a 1:1:1 ratio at trial entry to start or continue antiretroviral therapy with either stavudine (d4T), abacavir (ABC) or zidovudine (ZDV) in combination with lamivudi
Sponsors
Medical Research Council (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 1 month to 13 years, either sex: 1.1. ART naive children in Uganda being randomised to commence therapy on a d4T based regimen must be 0 - 4 years old in accordance with local guidelines 1.2. ART experienced children being randomised to continue therapy on a d4T based regimen must be 5 years or older with no clinical symptoms of lipodystrophy. If severe clinical symptoms of lipodystrophy develop whilst randomised to d4T then children will switch to another regimen. 2. Weighing greater than 3 kg and less than 25 kg (heavier children should receive adult tablets and not be enrolled in CHAPAS-3) 3. Participants must have a confirmed documented diagnosis of HIV-1 infection 4. Parents or guardians, and children where appropriate according to age and knowledge of HIV status, must be willing and able to give informed consent for randomisation to first-line ART strategy and participation in the PK substudy if eligible 5.1. ART naive (except for exposure to perinatal ART for the prevention of mother-to-child HIV transmission), meeting World Health Organisation (WHO) or national (WHO modified) criteria for initiating therapy and ready to start an initial 2NRTI+NNRTI based regimen according to local guidelines (i.e. according to WHO stage/CD4 and guidelines concerning first-line ART in children who have been exposed to NVP perinatally), or 5.2. Currently taking d4T based regimen for at least 2 years with screening HIV RNA viral load less than 50 copies/ml, no history of receiving other ARV drugs and CD4 count and/or CD4 percent stable over the previous 6 months 6. Able and willing to take each of the possible regimens
Exclusion criteria
Exclusion criteria: 1. Cannot, or unlikely to attend regularly (e.g. usual residence too far from study centre) 2. Likelihood of poor adherence 3. Presence of acute infection 4. In receipt of medication contraindicated by ART or on chemotherapy for malignancy. Children under three years of age receiving anti-tuberculosis therapy should not be enrolled (as they will have to receive nevirapine). 5. Laboratory abnormalities which are a contra-indication for the child to start ART/change to any of the 3 possible regimens 6. Being pregnant or breast-feeding an infant 7. Perinatal exposure to NVP (either through pMTCT or breastfeeding) for children aged 3 - 6 months only
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| All children: Grade 2/3/4 clinical and/or grade 3 (confirmed) or 4 (any grade) laboratory adverse events. For PK substudies: Plasma pharmacokinetic parameters (AUC, Cmin, Cmax) of ABC, ZDV and 3TC in FDCs with or without NVP and of EFV from the full PK curves determined per age group at week 6. | — |
Secondary
| Measure | Time frame |
|---|---|
| All children: 1. Change in skinfold thicknesses from week 0 to 48 and 96 weeks (converted to age and sex-adjusted z-scores) 2. Change in body circumferences from week 0 to 48 and 96 weeks 3. Clinical and/or laboratory adverse events Grade 3 or 4, possibly or probably related to ABC, ZDV or d4T 4. Anaemia, neutropenia, lipodystrophy/lipoatrophy, mitochondrial disease, peripheral neuropathy and hypersensitivity reactions of any grade 5. Any AE leading to dose reduction or permanent/temporary interruption/substitution of ART 6. Changes in endothelial injury (functional and cellular) and inflammatory markers (D-Dimer, CRP, interleukin 6) from week 0 to 48 and 96 weeks. Vascular function parameters (Intima Media Thickness (IMT) of the carotid artery) and pulse wave velocity), CECs and EMPs will be measured using portable equipment, by a single investigator in each site. 7. Adherence as measured by electronic recording devices (MEMScaps) clinic-based pill counts, carer and child questionnaire including visual analogue scale from randomisation 8. Acceptability of once versus twice daily dosing by carer questionnaire 9. Change in HIV RNA viral load and proportion of children with HIV RNA less than 50 and less than 400 copies/ml from week 0 to 48 and 96 weeks (assayed retrospectively) 10. Cost and cost effectiveness 11. Change in CD4 and CD4 percent from week 0 to 48 and 96 weeks 12. Change in growth parameters (weight-for-age, height-for-age, weight-for-height) from week 0 to 48 and 96 weeks (converted to age and sex-adjusted z-scores) 13. Mortality and disease progression For PK substudies: Variability in pharmacokinetic parameters (AUC, Cmin, Cmax) at week 6 according to degree of malnourishment, degree of immune activation, age, weigh | — |
Countries
Uganda, Zambia
Outcome results
None listed