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

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

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).

Study Overview

• Status: Completed
• Conditions: HIV Infections; Malaria
• Intervention / Treatment: Drug: Lamivudine; Drug: Lopinavir/Ritonavir; Drug: Nevirapine; Drug: Zidovudine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Malawi
  • Lilongwe, Malawi
    • University of North Carolina Lilongwe (12001)
• Uganda
  • Kampala, Uganda
    • Makerere University - JHU Research Collaboration (30293)
• Zambia
  • Lusaka, Zambia
    • George Clinic CRS (30273)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; 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; Taken orally twice daily; Other Names: 3TC; Drug: Lopinavir/Ritonavir; Taken orally twice daily; Other Names: LPV/r; Drug: Nevirapine; Taken orally twice daily; Other Names: NVP; Drug: Zidovudine; Taken orally twice daily; Other Names: ZDV
Active Comparator: 2; 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; Taken orally twice daily; Other Names: 3TC; Drug: Lopinavir/Ritonavir; Taken orally twice daily; Other Names: LPV/r; Drug: Nevirapine; Taken orally twice daily; Other Names: NVP; Drug: Zidovudine; Taken orally twice daily; Other Names: ZDV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Parasitemia in blood samples	Throughout study

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Chair: William Borkowsky, MD, NYU Langone Health; Study Chair: Charlotte Hobbs, MD, NYU Langone Health

Publications and helpful links

General Publications

• Adetifa IM, Akinsulie AO, Temiye EO, Iroha EO, Ezeaka VC, Mafe AG, Grange AO. Effect of antiretroviral therapy on asymptomatic malaria parasitaemia in HIV-1 infected children. Niger Postgrad Med J. 2008 Jun;15(2):120-5.
• Brahmbhatt H, Sullivan D, Kigozi G, Askin F, Wabwire-Mangenm F, Serwadda D, Sewankambo N, Wawer M, Gray R. Association of HIV and malaria with mother-to-child transmission, birth outcomes, and child mortality. J Acquir Immune Defic Syndr. 2008 Apr 1;47(4):472-6. doi: 10.1097/QAI.0b013e318162afe0.
• Hobbs CV, Gabriel EE, Kamthunzi P, Tegha G, Tauzie J, Petzold E, Barlow-Mosha L, Chi BH, Li Y, Ilmet T, Kirmse B, Neal J, Parikh S, Deygoo N, Jean Philippe P, Mofenson L, Prescott W, Chen J, Musoke P, Palumbo P, Duffy PE, Borkowsky W; P1068s Study Team. Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060. PLoS One. 2016 Dec 9;11(12):e0165140. doi: 10.1371/journal.pone.0165140. eCollection 2016.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: July 17, 2008
• First Submitted That Met QC Criteria: July 17, 2008
• First Posted (Estimate): July 21, 2008

Study Record Updates

• Last Update Posted (Estimate): September 19, 2016
• Last Update Submitted That Met QC Criteria: September 16, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Coinfection
• Additional Relevant MeSH Terms: Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Infections; Malaria; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Nevirapine; Ritonavir; Lopinavir; Lamivudine; Zidovudine
• Other Study ID Numbers: IMPAACT P1068s; U01AI068632 (U.S. NIH Grant/Contract)