HIV Protease Inhibitors for the Prevention of Malaria in Ugandan Children
Condition: Malaria; HIV Infections
MeSH terms: Malaria
Intervention: Lopinavir/Ritonavir (LPV/r); Nevirapine (NVP); Efavirenz (EFV); 2 nucleoside reverse transcriptase inhibitor (NRTI)
Intervention description: NVP will be used for children < 3 years of age; EFV for children ≥3 years of age; The same NRTI choice strategy will be used for both arms. Lamivudine will be used with all children. The second NRTI will be zidovudine unless the participant has a hemoglobin < 8 gm/dL, in which case it will be Abacavir. Stavudine will be used in the event that a participant is unable to take Abacavir for safety or other reasons.
Intervention MeSH terms: Ritonavir; Lopinavir; Nevirapine; Efavirenz; Reverse Transcriptase Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 176.0
Sex: All
Minimum age: 2 Months
Maximum age: 10 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pediatric HIV; Malaria; Uganda; Nevirapine; Zidovudine; Lamivudine; Lopinavir/ritonavir; Stavudine; Efavirenz; HIV

Summary:

      HIV and malaria are major causes of morbidity and mortality in Sub-Saharan Africa and
      children bear the greatest brunt of both diseases. No single existing intervention is likely
      to control malaria in Africa. Rather, improvements in malaria prevention are likely to come
      from strategies that employ multiple proven interventions targeting different populations.
      HIV-infected children represent one of the most vulnerable subpopulations in these countries.
      It is possible that the use of protease inhibitor (PI) - based antiretroviral therapy (ART)
      in HIV-infected children living in areas of high malaria transmission could prevent malaria
      in this vulnerable population. An effective remedy that offers the possibility to further
      reduce malaria risk, such as PIs, is highly desirable. This study will determine whether a PI
      based ART regimen will reduce malaria among children living in a malaria endemic area of
      Uganda and receiving insecticide-treated bed nets (ITN) and TS. This study will compare two
      different ART regimens. Children enrolled in the study will start or continue to receive
      either standard Ugandan first line treatment ART regimen (NNRTI+2 NRTIs) or an ART regimen
      containing the HIV protease inhibitor (lopinavir/ritonavir +2 NRTIs) and followed for a
      period of 24 months.
    

Eligibility criteria:

        Inclusion criteria:

          1. Age 2 months to < 11 years

          2. Confirmed HIV diagnosis. i. Children > 18 months: Documentation of HIV status must
             come from two assays. Assays include DNA PCR, HIV RNA, Western blot, or rapid HIV
             antibody test ii. Children < 18 months: Documentation will be DNA PCR confirmation
             only along with documentation of testing from the referral entity

          3. ART-naïve patients eligible for ART initiation per WHO/Uganda guidelines (see Table 1)
             or Patients receiving first line ART regimen with NNRTI +2 NRTI with at least one HIV
             RNA <400 copies/ml within the past 6 months

          4. Agreement to come to the study clinic for any febrile episode or other illness

          5. Agreement to avoid medications administered outside study protocol

          6. Provision of informed consent by parent/guardian and agreement to have child's care at
             the clinical site

          7. Lives within 50 km of study site

        Exclusion criteria:

          1. ART-naïve children: children or their mothers that have received any dose of
             Nevirapine in the past 24 months

          2. Active medical problem requiring in-patient evaluation at the time of screening or
             enrollment

          3. History of cardiac conduction disorder or known significant cardiac structural defect

          4. Children receiving any disallowed medications (see section 4.3)

          5. Moderate, Severe or Life-threatening (Grade 2, 3, or 4) AST or ALT found within 4
             weeks prior to enrollment:

               -  AST: >113U/L (>2.5xULN)

               -  ALT: >113U/L (>2.5xULN)

          6. Life-threatening (Grade 4) screening laboratory value found within 4 weeks prior to
             enrollment for the following:

               -  Absolute neutrophil count: <500 mm3

               -  Hemoglobin: <6.5 g/dL

               -  Creatinine: >3.5xULN

               -  Platelets: <25,000/mm3