Design: A 2x2x2 open-label factorial multi-centre trial, conducted in 9 centres in 4 countries (Kenya, Malawi, Uganda, Zimbawe)

Participants: 1800 HIV-infected patients including adults, adolescents and children aged 5 years or older with low CD4 counts about to initiate combination antiretroviral therapy (ART). At the Eldoret site, 250 participants will be enrolled.

Intervention: Three methods to reduce early mortality following ART initiation

(i) increasing the potency of ART with a 12 week induction period using 4 antiretroviral drugs from 3 classes
(ii) augmented prophylaxis against opportunistic/bacterial infections and helminths for 12 weeks
(iii) macronutrient intervention using ready-to-use supplementary food for 12 weeks.

Each intervention will be compared with standard of care, which in previously untreated patients presenting late with very low CD4 counts is to initiate ART with 3 drugs from 2 classes, together with cotrimoxazole prophylaxis and macronutrient intervention only for those with low BMI (or low weight-for-height/mid-upper arm
circumference in children).

Duration:

• Participants will be randomised over 1.5-2 years.
• 
  Each intervention will be administered in addition to standard of care for 12 weeks.
• 
  Each participant will be followed for 48 weeks in the trial.
• 
  The overall trial duration is 3 years.