Lopinavir/r/ Lamivudine/ Abacavir as an Easy to Use Paediatric Formulation

A phase I/II, open label, randomized crossover pharmacokinetic, safety and acceptability study of the Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination vs. Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg tablets) in HIV infected Children.

The study is intended to support the adoption of the 4-in-1 by healthcare providers and will provide data that may support its registration in certain countries. The study will be carried out in HIV-infected children in Uganda weighing 3 to 25 kg (inclusive) and unable to swallow tablets and will provide supportive clinical data on the pharmacokinetics, safety, tolerability and acceptability of the 4-in-1.

The primary objective is to estimate the population average exposure to LPV, ABC and 3TC provided by the 4-in-1 formulation in HIV-infected children dosed per WHO weight bands.

The secondary objectives:

* To determine the proportion of children overall, and within each weight band, with a lopinavir C12 \<1.0 mg/L while receiving the 4-in-1 formulation
* To evaluate and compare the safety and tolerability of the 4-in-1 formulation versus a reference treatment regimen.
* To compare the bioavailability of LPV, ABC and 3TC in the 4-in-1 formulation versus a reference treatment regimen.
* To assess post exposure CD4 and viral load
* To assess the factors that contribute to acceptability of the new 4-in-1 formulation.

Eligibility Criteria:
Inclusion Criteria:

* Children \> 4 weeks old and weighing ≥3 and \<25 kg at the time of enrolment
* Past or current documentation of a confirmed diagnosis of HIV infection defined as two positive assays from two different samples. The two results may be in any combination of the following:
* At any age: HIV-1 DNA PCR positive
* Documented past HIV-1 RNA viral load \> 1,000 copies/mL plasma
* At any age \>18 months of age: HIV-1 antibody reactive on two different rapid tests based on national testing algorithm
* ARV treatment eligible children with LPV-based treatment indication\* as defined by country-specific guidelines or the WHO paediatric treatment guidelines and confirmed by the investigator
* HIV RNA viral load \<1000 copies/mL (suppressed) at the screening visit\*
* Inability to swallow LPV/r tablets
* Parent or guardian able and willing to provide written informed consent.
* For lowest weight band (≥3 and ≤ 5.9kgs) ONLY: under treatment for at least 3 weeks but not more than 12 weeks.

  * Does not apply to the youngest children (≥3 and ≤ 5.9kgs)

Exclusion Criteria:

* Planned or concurrent use of NNRTIs, integrase inhibitors, entry inhibitors, or Protease Inhibitors (PIs) other than LPV/r.
* Treatment failure with proven resistances to PIs.
* Contraindication to use of PIs
* Clinical condition requiring the use of a prohibited medication (see section 7.6) in association with LPV/r, ABC/3TC (Refer to section 7.2- 7.3 of the IB)
* Pulmonary Tuberculosis and any clinically significant disease or finding during screening that, in the investigator's opinion, would compromise participation in this study.
* Treatment with experimental drugs (except for LPV/r Pellets) for any indication within 30 days prior to study entry
* Anticipated transfer of care to a non-participating health facility during the study period