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

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

Sponsors

Lead Sponsor: AIDS Clinical Trials Group

Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)

Source AIDS Clinical Trials Group
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.

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.

Overall Status Completed
Start Date 2014-01-10
Completion Date 2016-06-19
Primary Completion Date 2016-06-19
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Proportion of Participants With Plasmodium Falciparum (Pf) Subclinical Parasitemia (SCP) Clearance Day 15 (3 samples collected, separated by at least 5 hours and all three collected within 24-hours)
Secondary Outcome
Measure Time Frame
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
Change in log10(Pf Gametocyte Density) From Entry to Day 30 Entry, Day 30
Enrollment 52
Condition
Intervention

Intervention Type: Drug

Intervention Name: Lopinavir/ritonavir

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

Arm Group Label: LPV/r-based ART

Other Name: LPV/r

Intervention Type: Drug

Intervention Name: Emtricitabine/tenofovir disoproxil fumarate

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

Other Name: FTC/TDF

Intervention Type: Drug

Intervention Name: Efavirenz

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

Other Name: EFV

Intervention Type: Drug

Intervention Name: Nevirapine

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

Other Name: NVP

Intervention Type: Drug

Intervention Name: Trimethoprim/sulfamethoxazole

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

Other Name: TMP/SMX

Eligibility

Criteria:

Inclusion Criteria: - 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: 1. Microscopy confirmed parasitemia (see section 6.3.6 and the A5297 Manual of Procedures [MOPS]) 2. An oral temperature < 37.5°C. 3. 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 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. Exclusion Criteria: 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. - 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.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Location
Facility:
AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601) | Eldoret, 30100, Kenya
Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501) | Kericho, 20200, Kenya
Kisumu Crs (31460) | Kisumu, 40100, Kenya
College of Med. JHU CRS (30301) | Blantyre, Malawi
Joint Clinical Research Centre (JCRC) (12401) | Kampala, Uganda
Location Countries

Kenya

Malawi

Uganda

Verification Date

2019-07-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: LPV/r-based ART

Type: Experimental

Description: 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.

Label: nNRTI-based ART

Type: Experimental

Description: 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.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News