Differences in Malaria Infection Levels in HIV-infected Infants and Children Receiving PI- and NNRTI-based HAART

Study Overview
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Brief Summary
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More than 1.5 million deaths of African children under 5 years of age have been due to Plasmodium falciparum malaria. When HIV and malaria are present as coinfections, they enhance each other's progression. The primary purpose of this study is to compare the malarial infection levels in HIV-infected infants and children receiving protease inhibitor (PI)- or non-nucleotide reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART).

Detailed Description
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The World Health Organization (WHO) reports 1 to 2 million malaria deaths annually, with most malaria-related deaths occurring in children. The malaria burden is compounded by the HIV epidemic, which is most prevalent in areas endemic for malaria, notably Sub-Saharan Africa where nine in ten children younger than 15 years of age are infected with HIV. The purpose of this study is to compare parasitemia levels in HIV-infected infants and children receiving PI- or NNRTI-based HAART regimens. This study will enroll a total of 140 participants, 35 from each of the 4 groups in IMPAACT P1060. This substudy will last until 24 weeks after the last P1060 enrollment or until P1060 study discontinuation. Participants must meet enrollment criteria for P1060 as well as additional criteria for this study. Study visits will occur as a part of P1060 study visits, all of which include a physical exam, blood collection, and assessments of HIV-related symptoms. Participants are also encouraged to return to the primary clinic site for intercurrent illness visits for assessment, thick and thin blood smear, and filter paper blood collection, however these visits are not mandatory for study participation.

Official Title
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P1060 Substudy Comparing Differences in Malaria Parasitemia by Real Time Quantitative PCR in HIV-Infected Infants and Children on PI-Based HAART Versus NNRTI-Based HAART

Conditions
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HIV Infections, Malaria

Intervention / Treatment
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* Drug: Lamivudine
* Drug: Lopinavir/Ritonavir
* Drug: Nevirapine
* Drug: Zidovudine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolling in study IMPAACT P1060 Parent/legal guardian agrees to seek medical care for intercurrent illness at the study site, whenever possible, and agree to not use at-home remedies for febrile illness in the child Exclusion Criteria: None.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Previously received single-dose nevirapine (SD NVP); assigned to receive either an NNRTI- or PI-based regimen as a part of the study IMPAACT P1060 | Drug: Lamivudine<br>* Taken orally twice daily<br>* Other names: 3TC;Drug: Lopinavir/Ritonavir<br>* Taken orally twice daily<br>* Other names: LPV/r;Drug: Nevirapine<br>* Taken orally twice daily<br>* Other names: NVP;Drug: Zidovudine<br>* Taken orally twice daily<br>* Other names: ZDV;|
| Active Comparator: 2<br>Have not previously received SD NVP; assigned to receive either an NNRTI- or PI-based regimen as a part of the study IMPAACT P1060 | Drug: Lamivudine<br>* Taken orally twice daily<br>* Other names: 3TC;Drug: Lopinavir/Ritonavir<br>* Taken orally twice daily<br>* Other names: LPV/r;Drug: Nevirapine<br>* Taken orally twice daily<br>* Other names: NVP;Drug: Zidovudine<br>* Taken orally twice daily<br>* Other names: ZDV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasitemia in blood samples |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of initiation of treatment for clinical malaria requiring conventional anti-malarial therapy |  | Throughout study | 
| Severity of malarial disease |  | Throughout study | 
| Measured anti-malaria IgG, protein in plasma, and mRNA transcripts in PBMC of chemokines |  | Throughout study | 
| IL4-589C/T genotypes |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coinfection