NCT01632891

Brief Summary

The purpose of this study was to see if antiretroviral therapy (ART) is safe and works at getting rid of malaria in blood and to see whether one type of ART is better than another. This study may offer information for further research in looking at whether ART plays a role in the prevention and treatment of malaria.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
52

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2014

Typical duration for phase_1

Geographic Reach
3 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 29, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 3, 2012

Completed
1.5 years until next milestone

Study Start

First participant enrolled

January 10, 2014

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 19, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 19, 2016

Completed
2.6 years until next milestone

Results Posted

Study results publicly available

February 4, 2019

Completed
Last Updated

August 6, 2019

Status Verified

July 1, 2019

Enrollment Period

2.4 years

First QC Date

June 29, 2012

Results QC Date

December 12, 2018

Last Update Submit

July 23, 2019

Conditions

HIV-1 InfectionPf Subclinical Parasitemia

Outcome Measures

Primary Outcomes (1)

  • Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance

    Pf SCP clearance defined by polymerase chain reaction (PCR) \< 10 parasites/µL on three consecutive occasions within a 24-hour period. If a participant had missing data on day 15, they were considered as not having clearance.

    Day 15 (3 samples collected, separated by at least 5 hours and all three collected within 24-hours)

Secondary Outcomes (6)

  • Time to First Pf SCP Clearance

    From study entry up to day 30

  • Log10(Pf Parasite Density)

    Entry, days 3, 6, 9, 12, 15, 20, 25, 30

  • Change in log10(Pf Parasite Density) From Entry to Day 30

    Entry, Day 30

  • Number of Participants With Uncomplicated Clinical Malaria

    From study entry to day 30

  • Number of Participants With Detectable Pf Gametocyte Density

    Entry, days 3, 6, 9, 12, 15, 20, 25, 30

  • +1 more secondary outcomes

Study Arms (2)

LPV/r-based ART

EXPERIMENTAL

Participants were prescribed to LPV/r-based antiretroviral therapy (ART) for 15 days, which includes lopinavir/ritonavir plus emtricitabine/tenofovir disoproxil fumarate; followed by an nNRTI-based ART, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30.

Drug: Lopinavir/ritonavirDrug: Emtricitabine/tenofovir disoproxil fumarateDrug: EfavirenzDrug: NevirapineDrug: Trimethoprim/sulfamethoxazole

nNRTI-based ART

EXPERIMENTAL

Participants were prescribed to nNRTI-based ART for 15 days, which includes efavirenz, nevirapine, plus emtricitabine/tenofovir disoproxil fumarate, followed by an nNRTI-based ART and Trimethoprim/sulfamethoxazole prophylaxis to take from day 16 through day 30.

Drug: Emtricitabine/tenofovir disoproxil fumarateDrug: EfavirenzDrug: NevirapineDrug: Trimethoprim/sulfamethoxazole

Interventions

Lopinavir/ritonavirDRUG

Participants received two 200 mg/50 mg tablets of lopinavir/ritonavir orally twice daily.

Also known as: LPV/r
LPV/r-based ART
Emtricitabine/tenofovir disoproxil fumarateDRUG

Participants received one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily.

Also known as: FTC/TDF
LPV/r-based ARTnNRTI-based ART
EfavirenzDRUG

Participants received one 600 mg tablet of efavirenz orally once daily.

Also known as: EFV
LPV/r-based ARTnNRTI-based ART
NevirapineDRUG

If unable to take efavirenz, participants received on 200 mg tablet of nevirapine orally once daily.

Also known as: NVP
LPV/r-based ARTnNRTI-based ART
Trimethoprim/sulfamethoxazoleDRUG

Participants received one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily.

Also known as: TMP/SMX
LPV/r-based ARTnNRTI-based ART

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • HIV-1 infection
  • CD4+ count \> 200 and \< 500 cells/mm\^3 obtained within 30 days prior to study entry at a DAIDS-approved laboratory.
  • Pf SCP confirmed in a laboratory approved to conduct parasitemia microscopy. Note: Pf SCP defined as meeting all three of the following criteria within 72 hours prior to study entry:
  • Microscopy confirmed parasitemia (see section 6.3.6 and the A5297 Manual of Procedures \[MOPS\])
  • An oral temperature \< 37.5°C.
  • The absence of Grade 2 or greater signs or symptoms thought to be related to clinical malaria including:
  • headache
  • malaise or fatigue
  • abdominal discomfort
  • muscle or joint pain
  • fever
  • chills
  • perspiration
  • anorexia
  • vomiting
  • +8 more criteria

You may not qualify if:

  • Previous history or current use of ART.
  • Single dose NVP or dual therapies used for Prevention of mother-to-child transmission (PMTCT) within 2 years prior to entry.
  • Use of any medication with antimalarial activity, including TMP/SMX (see list of prohibited medications in the A5297 Manual of Procedures (MOPS)), within 14 days prior to study entry.
  • Confirmed or clinically suspected OIs (including but not limited to tuberculosis, clinical malaria, PCP), or other pulmonary or gastrointestinal infections for which potential participants did not complete treatment more than 30 days prior to enrollment or have signs and symptoms during screening.
  • Breastfeeding.
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.
  • Results suggestive of active pulmonary disease from a chest x-ray performed within 30 days prior to study entry.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)

Eldoret, 30100, Kenya

Location

Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)

Kericho, 20200, Kenya

Location

Kisumu Crs (31460)

Kisumu, 40100, Kenya

Location

College of Med. JHU CRS (30301)

Blantyre, Malawi

Location

Joint Clinical Research Centre (JCRC) (12401)

Kampala, Uganda

Location

Related Publications (1)

  • Shaffer D, Kumwenda J, Chen H, Akelo V, Angira F, Kosgei J, Tonui R, Ssali F, McKhann A, Hogg E, Stewart VA, Murphy SC, Coombs R, Schooley R; A5297 Team. Brief Report: No Differences Between Lopinavir/Ritonavir and Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy on Clearance of Plasmodium falciparum Subclinical Parasitemia in Adults Living With HIV Starting Treatment (A5297). J Acquir Immune Defic Syndr. 2022 Feb 1;89(2):178-182. doi: 10.1097/QAI.0000000000002839.

    PMID: 34693933DERIVED

Related Links

MeSH Terms

Interventions

LopinavirEmtricitabine, Tenofovir Disoproxil Fumarate Drug CombinationefavirenzNevirapineTrimethoprim, Sulfamethoxazole Drug Combination

Intervention Hierarchy (Ancestors)

PyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsTenofovirOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsEmtricitabineDeoxycytidineCytidinePyrimidine NucleosidesAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesDrug CombinationsPharmaceutical PreparationsPyridinesSulfamethoxazoleBenzenesulfonamidesSulfonamidesAmidesSulfanilamidesAniline CompoundsAminesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsTrimethoprim

Results Point of Contact

Title
ACTG Clinicaltrials.gov Coordinator
Organization
ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
ACTGCT.Gov@s-3.com
(301) 628-3313

Study Officials

  • Johnstone Kumwenda, FRCP

    College of Medicine-Johns Hopkins Project

    STUDY CHAIR

  • Douglas Shaffer, MD, MHS

    Kenya Medical Research Institute/Walter Reed Project

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 29, 2012

First Posted

July 3, 2012

Study Start

January 10, 2014

Primary Completion

June 19, 2016

Study Completion

June 19, 2016

Last Updated

August 6, 2019

Results First Posted

February 4, 2019

Record last verified: 2019-07

Locations

UG(1)KE(3)MA(1)