Impact of Malnutrition on Pharmacokinetic of Rifampicin, Isoniazid, Pyrazinamide and Ethambutol in TB-HIV Co-infected Children (TB-Speed TB-PK)

Institut National de la Santé Et de la Recherche Médicale, France

Status: Completed

Conditions: Tuberculosis; Pulmonary

Study type: Observational

Funder types: Other

Identifiers

NCT04972903

C20-17

Details and patient eligibility

About

TB-Speed TB-PK is a cross-sectional PK study of anti-TB treatment nested in the TB-Speed HIV and TB-Speed SAM studies aiming at assessing the impact of malnutrition on PK of rifampicin, isoniazid, pyrazinamide, and ethambutol in TB-HIV co-infected children in Uganda and Zambia.

Full description

Tuberculosis can worsen malnutrition and in turn malnutrition increases the risk of TB. HIV infection is prevalent in children with TB and SAM and is often associated with poor outcomes when present. TB alone is the leading cause of death of among HIV-infected children worldwide accounting for a third of all the death in this group.

In 2010, the WHO recommended increased dose for rifampicin (+50%), isoniazid (+100%), and pyrazinamide (+33%) based on PK data showing that plasma drug concentrations in children using standard adult dosages did not reach target levels. In children that are TB/HIV co-infected, drug-drug interactions between anti-TB drugs and antiretroviral drugs are of concern.

The investigators hypothesize that HIV-infection and SAM, each one on its own, may have an impact on TB drugs concentrations. Furthermore, SAM is frequent in children with HIV, and may affect the metabolism of anti-TB drugs and consequently result in low serum concentration.

TB-Speed TB-PK is a cross-sectional PK study of anti-TB treatment nested in the TB-Speed HIV and TB-Speed SAM studies aiming at assessing the impact of malnutrition on PK of rifampicin, isoniazid, pyrazinamide, and ethambutol in TB-HIV co-infected children. It will be implemented in Uganda and Zambia. Children will also be enrolled from routine care for TB outside of the TB- Speed HIV and TB-Speed SAM studies.

Enrollment: 85 patients

Sex: All

Ages: 6 months to 5 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA:

• Gr1. HIV-infected children with SAM

  • Age 6 months to 5 years
  • Diagnosed with TB and first line TB treatment to be initiated or started less than 4 weeks prior to inclusion
  • HIV-infection
  • SAM as defined by WHO at the time of starting TB treatment
  • Weight-for-height z-score (WHZ) < -3 SD,
  • OR MUAC <11.5 cm or
  • OR presence of bilateral pitting oedema of nutritional origin
  • Ability to take drugs orally during the planned PK day
  • Signed informed consent from parents or guardian

• Gr2. HIV-infected children without SAM

  • Age 6 months to 5 years
  • Diagnosed with TB and first line TB treatment to be initiated or started less than 4 weeks prior to inclusion
  • HIV-infection
  • Absence of SAM as defined by WHO at the time of starting TB treatment
  • Weight-for-height z-score (WHZ) > -3 SD,
  • AND MUAC >11.5 cm or
  • AND absence of bilateral pitting oedema of nutritional origin
  • Ability to take drugs orally during the planned PK day
  • Signed informed consent from parents or guardian

• Gr3. HIV-negative children with SAM

  • Age 6 months to 5 years
  • Diagnosed with TB and first line TB treatment to be initiated or started less than 4 weeks prior to inclusion
  • HIV-negative
  • SAM as defined by WHO at the time of starting TB treatment
  • Weight-for-height z-score (WHZ) < -3 SD,
  • OR MUAC <11.5 cm or
  • OR presence of bilateral pitting oedema of nutritional origin
  • Ability to take drugs orally during the planned PK day
  • Signed informed consent from parents or guardian

• Gr4. HIV-negative children without SAM

  • Age 6 months to 5 years
  • Diagnosed with TB and first line TB treatment to be initiated or started less than 4 weeks prior to inclusion
  • HIV-negative
  • Absence of SAM as defined by WHO at the time of starting TB treatment
  • Weight-for-height z-score (WHZ) > -3 SD,
  • AND MUAC >11.5 cm or
  • AND absence of bilateral pitting oedema of nutritional origin
  • Ability to take drugs orally during the planned PK day
  • Signed informed consent from parents or guardian

NON INCLUSION CRITERIA:

• Very ill or moribund children unable to take drugs orally or requiring nasogastric drug intake
• Severe anaemia (Hb < 6 g/dl),
• Severe renal impairment (DAIDS grade 3 and above)
• Severe hepatic impairment (DAIDS grade 3 and above)
• Children on second line TB drugs

Trial design

85 participants in 4 patient groups

Group 1.HIV+/SAM+

Description:

Group 1. HIV-infected with SAM (WHZ\<-3SD or edematous malnutrition or MUAC \<115) (HIV+/SAM+)

Group 2. HIV+/SAM-

Description:

Group 2. HIV-infected without SAM (none of the 3 criteria above) (HIV+/SAM-)

Group 3. HIV-/SAM+

Description:

Group 3. HIV-negative with SAM (WHZ\<-3SD or edematous malnutrition or MUAC \<115) (HIV-/SAM+)

Group 4. HIV-/SAM-

Description:

Group 4. HIV-negative without SAM (none of the 3 criteria above) (HIV-/SAM-)