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HIV-1 InfectionPhase 1/2NCT01632891

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

A Phase 1/2 study testing Lopinavir/ritonavir, Emtricitabine/tenofovir disoproxil fumarate and Efavirenz in people with HIV-1 Infection and Pf Subclinical Parasitemia, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 5 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1 Infection, Pf Subclinical Parasitemia
What is being tested?
Lopinavir/ritonavir, Emtricitabine/tenofovir disoproxil fumarate and Efavirenz
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
5 sitesin 3 countries
Study dates
10 Jan 2014to 19 Jun 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • headache
  • malaise or fatigue
  • abdominal discomfort
  • muscle or joint pain
  • fever
  • chills
  • perspiration
  • anorexia
  • vomiting
  • 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 have a negative serum or urine pregnancy test performed within 72 hours prior to entry.
  • All study volunteers 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, 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.
  • Study volunteers who are not of reproductive potential are eligible without requiring the use of a contraceptive.
  • 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.

Who cannot join

  • Step 1: Exclusion Criteria
  • 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.
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  • 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.

Trial locations and contacts

5 sites in 3 countries.

5 sites in 3 countries

Kenya3 sites

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

    Eldoret, 30100

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

    Kericho, 20200

  • Kisumu Crs (31460)

    Kisumu, 40100

Other trials in Kenya

Malawi1 site

  • College of Med. JHU CRS (30301)

    Blantyre

Other trials in Malawi

Uganda1 site

  • Joint Clinical Research Centre (JCRC) (12401)

    Kampala

Other trials in Uganda

About this study

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 <500 Cells/mm^3

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.

Read the detailed description

A5297 was a Phase I/II, open-label, proof of concept, two-step, two-arm, randomized controlled clinical trial (RCT) to test the superiority of lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) to non-nucleoside reverse transcriptase (nNRTI)-based ART for clearance of Plasmodium falciparum (Pf) subclinical parasitemia (SCP).

The study consisted of two steps. At study Step 1 entry, participants were randomized 1:1 to either LPV/r-based ART or nNRTI-based ART for 15 days. In study Step 2, all participants received nNRTI-based ART and TMP/SMX prophylaxis for 15 days. The total study duration was 30 days.

Study visits occurred every 3 days in Step 1, and every 5 days in Step 2. At each study visit, 2 samples were taken for measurement of parasite density, except day 15 and day 30 at which 3 samples were taken.

Adverse events which occurred after randomization were also recorded. Signs/symptoms and diagnoses were evaluated at each visit, while safety labs (including Hemoglobin, hematocrit, white blood cell count (WBC), differential WBC, platelet count, and absolute neutrophil count (ANC), glucose, electrolytes (sodium, potassium, chloride, bicarbonate), total bilirubin, AST (SGOT), ALT (SGPT), albumin, alkaline phosphatase, and creatinine) were taken at day 15 and day 30, or if indicated at other study visits.

Being tested
Lopinavir/ritonavir, Emtricitabine/tenofovir disoproxil fumarate, Efavirenz, Nevirapine, Trimethoprim/sulfamethoxazole

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lopinavir/ritonavirDrug

    Also called LPV/r

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

  • Emtricitabine/tenofovir disoproxil fumarateDrug

    Also called FTC/TDF

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

  • EfavirenzDrug

    Also called EFV

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

  • NevirapineDrug

    Also called NVP

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

  • Trimethoprim/sulfamethoxazoleDrug

    Also called TMP/SMX

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

Study groups in NCT01632891
Study groupRoleWhat they receive
LPV/r-based ARTExperimentalParticipants 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.
Receives: Drug: Lopinavir/ritonavir; Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Efavirenz; Drug: Nevirapine; Drug: Trimethoprim/sulfamethoxazole
nNRTI-based ARTExperimentalParticipants 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.
Receives: Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Efavirenz; Drug: Nevirapine; Drug: Trimethoprim/sulfamethoxazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (6)

  1. Time to First Pf SCP Clearance

    Time to clearance is defined by time to first measurement with PCR < 10 parasites/µL, and is evaluated as the point estimate and 95% CI for the day when 50% of participants cleared parasite.

    Measured: From study entry up to day 30

  2. Log10(Pf Parasite Density)

    Pf parasite density was determined by PCR. If parasite density equals 0, the value is set to 0.01 before log10 transformation. The value 0.01 was chosen based on the smallest observed parasite density value of 0.017.

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

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

    Change is evaluated as log10(Pf parasite density) at day 30 minus log10(Pf parasite density) at entry.

    Change is evaluated in four groups:

    • Randomized to nNRTI-based ART with continued Pf SCP at day 15
    • Randomized to nNRTI-based ART with clearance of Pf SCP at day 15
    • Randomized to LPV/r-based ART with continued Pf SCP at day 15
    • Randomized to LPV/r-based ART with clearance of Pf SCP at day 15

    Measured: Entry, Day 30

  4. Number of Participants With Uncomplicated Clinical Malaria

    Uncomplicated clinical malaria is defined as the presence of non-severe fever/symptoms and parasitemia without organ complication.

    Measured: From study entry to day 30

  5. Number of Participants With Detectable Pf Gametocyte Density

    Number of participants with detectable Pf gametocyte density as determined by PCR. Due to the large number of undetectable results, this outcome was measured as dichotomous.

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

  6. Change in log10(Pf Gametocyte Density) From Entry to Day 30

    Change in log10(Pf gametocyte density) as evaluated using a Hodges-Lehmann estimate from entry to day 30 is evaluated in two groups:

    • Randomized to nNRTI-based ART with continued Pf SCP at day 15
    • Randomized to LPV/r-based ART with continued Pf SCP at day 15

    Analysis was not conducted in either group with clearance at day 15 due to the small sample size and high number of undetectable samples in both clearance groups at entry and day 30.

    Measured: Entry, Day 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2012 (estimated)
  2. Study start10 Jan 2014
  3. Primary completion19 Jun 2016
  4. Study completion19 Jun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01632891
Sponsor's protocol ID
ACTG A5297
Other IDs
1U01AI068636
Status last verified
Jul 2019
First submitted
29 Jun 2012
Last updated
6 Aug 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 34693933

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lopinavir/ritonavir, Emtricitabine/tenofovir disoproxil fumarate and Efavirenz in people with HIV-1 Infection and Pf Subclinical Parasitemia, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Kenya, Malawi, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance (time frame: Day 15 (3 samples collected, separated by at least 5 hours and all three collected within 24-hours)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01632891, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2019; AzTrials last refreshed its copy on 26 Oct 2026.

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