Lopinavir/Ritonavir Monotherapy in Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate the efficacy (clinical, immunological, virological
      outcome), pharmacokinetics and safety of lopinavir/ritonavir (LPV/r) monotherapy maintenance
      in Thai children after viral load suppression with double boosted protease inhibitors (PIs).
    

Detailed description: 
      The commonly used antiretroviral (ARV) regimen in the Thai National Access to Antiretroviral
      Program for People Living with HIV/AIDS is non-nucleoside reverse transcriptase (NNRTI) based
      HAART. However, one of the most challenging concerns of antiretroviral therapy is the
      emergence of drug resistance mutants which occurs in 30-40% of treated patients. Children
      failing nucleoside reverse transcriptase inhibitor (NRTI)/NNRTI regimens have limited options
      for second line therapy especially in a developing country such as Thailand.

      At HIV-NAT, the Thai Red Cross AIDS Research Centre, we had a trial using standard doses of
      double boosted PIs, Lopinavir/ritonavir and Saquinavir, HIV-NAT 017, in 50 HIV infected
      children who failed the first line regimen. This ongoing trial showed the good efficacy of
      the double boosted PI in children, significant increasing of CD4 and decreasing of HIV-RNA in
      children who adhered to the treatment. However, a high number of pill counts for this
      regimen, 5-8 pills every 12 hours, life long can affect adherence and treatment outcome. In
      the HIV-NAT 017 study, a 48 week intent to treat analysis, 38% and 50% of children had total
      cholesterol ≥ 200 mg/dl and triglycerides ≥ 150 mg/dl after double boosted PI. Those lipid
      levels were significantly elevated when compared to baseline (p < 0.001). Double boosted PIs
      are also very costly. Studies in adults have shown that double boosted PIs had a disadvantage
      in lipid effect compared to a single PI-based regimen.

      Lopinavir/ritonavir, the only PI co-formulated with ritonavir, is recommended as a first-line
      option for antiretroviral-naive patients initiating PI-based therapy and has shown a high
      potency, efficacy, and safety in HIV patients with high genetic barriers to resistance. LPV/r
      has also shown excellent efficacy in ARV-experienced children.

      Mono boosted PI therapy trials in HIV adults, as the maintenance therapy after suppressed
      viral load, have been shown to be effective and safe. This strategy not only decreases the
      number of pills per dose but also saves for ARV cost and might improve the patient's
      adherence. As maintenance monotherapy after HIV-1 viral suppression, lopinavir/ritonavir has
      shown efficacy in adult trials with 80-90% virological suppression. A pilot study of a switch
      to lopinavir/ritonavir (LPV/r) monotherapy from nonnucleoside reverse transcriptase
      inhibitor-based therapy was reported with 92% of the participants on treatment at week 48
      having HIV RNA < 75 copies/mL.

      Therefore, in this trial, we aim to see the efficacy and safety of lopinavir/ritonavir
      maintenance monotherapy in Thai HIV infected children after virological suppression from
      previous double boosted PIs.

      By simplifying maintenance antiretroviral treatment in children who are virally suppressed
      from previous double boosted PIs to lopinavir/ritonavir monotherapy, we hope to achieve the
      following:

        1. A decrease in total cholesterol, LDL and triglycerides

        2. An improvement in quality of life and in adherence to ARVs

        3. No change in viral load
    

Intervention name(s): LPV/r
Intervention type(s): Drug
Intervention description(s): LPV/r 230/57.5 mg/m2 orally q12h or the adjusted dose based on therapeutic drug monitoring of LPV/r prior to enrollment as maintenance monotherapy
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: efficacy; safety; pharmacokinetics; LPV/r monotherapy; Thai children; efficacy safety LPV/r monotherapy maintenance; treatment experienced