HIV Protease Inhibitors for the Prevention of Malaria in Ugandan Children

• Status: Completed
• Trial end date: 2013-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Efavirenz; HIV Protease Inhibitors; Lamivudine; Lopinavir; Nevirapine; Protease Inhibitors; Reverse Transcriptase Inhibitors; Ritonavir; Stavudine; Zidovudine

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