Comparing PI-Based to a nNRTI-based ART for Clearance of Plasmodium Falciparum Parasitemia in HIV-Infected

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by AIDS Clinical Trials Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01632891
First received: June 29, 2012
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

The purpose of this study is 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.


Condition Intervention Phase
HIV-1 Infection
Pf Subclinical Parasitemia
Drug: Lopinavir/ritonavir
Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Efavirenz
Drug: Nevirapine
Drug: emtricitabine/tenofovir disoproxil fumarate
Drug: trimethoprim/sulfamethoxazole
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Proof of Concept, Randomized Trial Comparing a LPV/r-Based to an nNRTI-Based Antiretroviral Therapy Regimen for Clearance of Plasmodium Falciparum Subclinical Parasitemia in HIV-infected Adults With CD4+ Counts >200 and <350 Cells/mm3

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Plasmodium falciparum (Pf) subclinical parasitemia (SCP) clearance [ Time Frame: Within 15 days of intervention initiation ] [ Designated as safety issue: No ]
    Pf SCP clearance defined by PCR < 10 parasites/µL on three consecutive occasions within a 24-hour period


Secondary Outcome Measures:
  • Microscopy defined Pf SCP clearance (by batched centralized microscopy) defined by three consecutive negative blood samples [ Time Frame: Within 15 days of randomization ] [ Designated as safety issue: No ]
  • Time to confirmed Pf SCP clearance where confirmed clearance is defined by PCR < 10 parasites/µL on three consecutive occasions [ Time Frame: Within 15 days of intervention initiation ] [ Designated as safety issue: No ]
  • Both qualitative (yes/no) and quantitative (gametocytes/µL) Pf gametocyte carriage on Day 15 by PCR [ Time Frame: 15 days ] [ Designated as safety issue: No ]
  • Pf parasite density (parasites/µL) as determined by PCR on Day 15 [ Time Frame: 15 days ] [ Designated as safety issue: No ]
  • Uncomplicated clinical malaria at any time during the study [ Time Frame: Within 30 days ] [ Designated as safety issue: Yes ]
    Uncomplicated clinical malaria defined as the presence of non-severe fever/symptoms and parasitemia without organ complication (see section 7.1 of the protocol for more information)

  • LPV/r-related changes in sequence [ Time Frame: Within 30 days ] [ Designated as safety issue: No ]
    Plesmepsin sequences within Pf DNA extracted from selected stored dried blood spots may be sequenced to determine whether LPV/r-related changes in sequence occur


Estimated Enrollment: 52
Study Start Date: July 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: lopinavir/ritonavir (LPV/r)-based ART
Participants will receive LPV/r-based antiretroviral therapy (ART) for 15 days followed by an nNRTI-based ART and TMP/SMX prophylaxis to take from day 16 through day 30.
Drug: Lopinavir/ritonavir
Participants will receive two 200 mg/50 mg tablets of lopinavir/ritonavir orally twice daily starting on study day 1 for 15 days.
Other Name: LPV/r
Drug: Emtricitabine/tenofovir disoproxil fumarate
Participants will receive one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily starting on study day 1 for 15 days.
Other Name: FTC/TDF
Drug: Efavirenz
Participants will receive one 600 mg tablet of efavirenz orally once daily starting on study day 16 for 15 days.
Other Name: EFV
Drug: Nevirapine
For those participants unable to take efavirenz and who have not taken nevirapine in Step 1, participants will receive one 200 mg tablet of nevirapine orally once daily starting on study day 16 for 15 days for participants.
Other Name: NVP
Drug: Nevirapine
Participants unable to take Efavirenz who have taken nevirapine in Step 1 will received one 200 mg tablet or nevirapine orally twice daily starting on study day 16 for 15 days (unless not clinically warranted per discretion of the site investigator (see section 7.0 of study).
Other Name: NVP
Drug: emtricitabine/tenofovir disoproxil fumarate
Participants will receive one 200 mg/300 mg tablet of emtricitabine/tenofovir disoproxil fumarate orally once daily starting on study day 16 for 15 days.
Other Name: FTC/TDF
Drug: trimethoprim/sulfamethoxazole
Participants will receive one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily starting on study day 16 for 15 days.
Other Name: TMP/SMX
Experimental: Arm B: non-nucleoside reverse transcriptase (nNRTI)-based ART
Participants will receive nNRTI-based ART for 15 days followed by an nNRTI-based ART and TMP/SMX prophylaxis to take from day 16 through day 30.
Drug: Emtricitabine/tenofovir disoproxil fumarate
Participants will receive one 200 mg/300 mg tablet of Emtricitabine/tenofovir disoproxil fumarate orally once daily starting on study day 1 for 15 days.
Other Name: FTC/TDF
Drug: Efavirenz
Participants will receive one 600 mg tablet of efavirenz orally once daily starting on study day 1 for 15 days.
Other Name: EFV
Drug: Nevirapine
If unable to take efavirenz, participants will receive on 200 mg tablet of nevirapine orally once daily starting on study day 1 for 15 days.
Other Name: NVP
Drug: Efavirenz
Participants will receive one 600 mg tablet of efavirenz orally once daily starting on study day 16 for 15 days.
Other Name: EFV
Drug: Nevirapine
For those participants unable to take efavirenz and who have not taken nevirapine in Step 1, participants will receive one 200 mg tablet of nevirapine orally once daily starting on study day 16 for 15 days for participants.
Other Name: NVP
Drug: Nevirapine
Participants unable to take Efavirenz who have taken nevirapine in Step 1 will received one 200 mg tablet or nevirapine orally twice daily starting on study day 16 for 15 days (unless not clinically warranted per discretion of the site investigator (see section 7.0 of study).
Other Name: NVP
Drug: emtricitabine/tenofovir disoproxil fumarate
Participants will receive one 200 mg/300 mg tablet of emtricitabine/tenofovir disoproxil fumarate orally once daily starting on study day 16 for 15 days.
Other Name: FTC/TDF
Drug: trimethoprim/sulfamethoxazole
Participants will receive one 160 mg/800 mg tablet of trimethoprim/sulfamethoxazole orally once daily starting on study day 16 for 15 days.
Other Name: TMP/SMX

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection
  • CD4+ count > 200 and < 350 cells/mm3 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 will be 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 temperature
  • The absence of Grade 2 or greater signs or symptoms thought to be related to clinical malaria including:

    1. headache
    2. malaise or fatigue
    3. abdominal discomfort
    4. muscle or joint pain
    5. fever
    6. chills
    7. perspiration
    8. anorexia
    9. vomiting
    10. other signs or symptoms thought to be related to clinical malaria
  • Certain laboratory values obtained within 14 days prior to study entry, as detailed in section 4.1.4 of the protocol.
  • Hepatitis B surface antigen (HBsAg) negative within 30 days prior to entry.
  • Female study volunteers of reproductive potential must have a negative serum or urine pregnancy test performed within 72 hours prior to entry.

NOTE: Female study volunteers of reproductive potential are defined as women who have reached menarche or who have not been post-menopausal for at least 24 consecutive months {i.e., who have had menses within the preceding 24 months and have not undergone a sterilization procedure (eg, hysterectomy, bilateral oophorectomy, or salpingectomy)}.

  • Female study volunteers of reproductive potential must have a negative serum or urine pregnancy test performed within 72 hours prior to entry.

NOTE: Female study volunteers of reproductive potential are defined as women who have reached menarche or who have not been post-menopausal for at least 24 consecutive months {i.e., who have had menses within the preceding 24 months and have not undergone a sterilization procedure (eg, hysterectomy, bilateral oophorectomy, or salpingectomy)}.

  • All study volunteers must agree not to participate in a conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for study duration.

If participating in sexual activity that could lead to pregnancy, all study volunteers must agree to use two reliable forms of contraceptive simultaneously while receiving protocol-specified medications. One form of contraceptive must be a barrier method if a participant receives EFV. Participants must agree to continue the use of two contraceptives for 6 months after stopping EFV and 6 weeks after stopping all other protocol-specified medications.

Note: Female participants who are unable to meet the contraception requirements for EFV should be encouraged to consider NVP.

  • Study volunteers who are not of reproductive potential (girls who have not reached menarche, or women who have been post-menopausal for at least 24 consecutive months, or women who have undergone hysterectomy, bilateral oophorectomy or salpingectomy, or men who have documented azoospermia) are eligible without requiring the use of a contraceptive. Acceptable documentation of sterilization, other contraceptive methods, and menopause are written documentation or oral communication from a clinician or clinician's staff documented in source documents of one of the following:

    • Physician report/letter
    • Operative report or other source documentation in the patient record
    • Discharge summary
    • Laboratory report of azoospermia (is required to document successful vasectomy)
    • FSH measurement elevated into the menopausal range as established by the reporting laboratory for EFV and per participant's history for all other drugs.
  • Ability and willingness of participant or legal guardian/representative to provide informed consent.
  • Willing and able to return to the clinic twice to three times a day for study visits.

Exclusion Criteria:

Step 1: Exclusion Criteria

  • Previous history or current use of ART.
  • Single dose NVP or dual therapies used for 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 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.

Step 2: Exclusion Criteria

There are no exclusion criteria for Step 2

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01632891

Locations
Kenya
AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601) Recruiting
Eldoret, Kenya, 30100
Contact: Priscilla C. Cheruiyot    254-53-2060850    pcchepkorir@yahoo.com   
Principal Investigator: Abraham M. Siika, MMED         
Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501) Recruiting
Kericho, Kenya, 20200
Contact: Hellen Ngeno    254-5230388    hngeno@wrp-kch.org   
Principal Investigator: Fredrick Sawe, MB, ChB, MMED         
Malawi
College of Med. JHU CRS (30301) Recruiting
Blantyre, Malawi
Contact: Leslie H. Degnan, M.P.H.    265-888-208609    ldegnan@jhu.medcol.mw   
Principal Investigator: Newton Kumwenda, MPH, PhD         
University of North Carolina Lilongwe CRS (12001) Recruiting
Lilongwe, Malawi
Contact: Mina Hosseinipour, MD    265-1 758 938    mina_hosseinipour@med.unc.edu   
Principal Investigator: Francis Martinson, MPH, PhD, MBChB         
Uganda
Joint Clinical Research Centre (JCRC) (12401) Recruiting
Kampala, Uganda
Contact: Sandra Rwambuya    (256) 413-42521    dxr23@case.edu   
Principal Investigator: Peter Mugyenyi, MB ChB, FRCP, DSc         
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Johnstone Kumwenda, FRCP College of Medicine-Johns Hopkins Project
Study Chair: Douglas Shaffer, MD, MHS Kenya Medical Research Institute/Walter Reed Project
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01632891     History of Changes
Other Study ID Numbers: ACTG A5297, 1U01AI068636
Study First Received: June 29, 2012
Last Updated: June 5, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Parasitemia
Parasitic Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Ritonavir
Lopinavir
Tenofovir
Tenofovir disoproxil
Nevirapine
Efavirenz
Emtricitabine
Sulfamethoxazole
Trimethoprim
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials

ClinicalTrials.gov processed this record on September 29, 2014