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

Condition(s) targeted: HIV-1 Infection; Pf Subclinical Parasitemia

Intervention: Lopinavir/ritonavir (Drug); Emtricitabine/tenofovir disoproxil fumarate (Drug); Efavirenz (Drug); Nevirapine (Drug); Efavirenz (Drug); Nevirapine (Drug); Nevirapine (Drug); emtricitabine/tenofovir disoproxil fumarate (Drug); trimethoprim/sulfamethoxazole (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: AIDS Clinical Trials Group

Official(s) and/or principal investigator(s):
Johnstone Kumwenda, FRCP, Study Chair, Affiliation: College of Medicine-Johns Hopkins Project
Douglas Shaffer, MD, MHS, Study Chair, Affiliation: Kenya Medical Research Institute/Walter Reed Project

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Plasmodium falciparum (Pf) subclinical parasitemia (SCP) clearance

Secondary outcome:

Microscopy defined Pf SCP clearance (by batched centralized microscopy) defined by three consecutive negative blood samples

Time to confirmed Pf SCP clearance where confirmed clearance is defined by PCR < 10 parasites/µL on three consecutive occasions

Both qualitative (yes/no) and quantitative (gametocytes/µL) Pf gametocyte carriage on Day 15 by PCR

Pf parasite density (parasites/µL) as determined by PCR on Day 15

Uncomplicated clinical malaria at any time during the study

LPV/r-related changes in sequence

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601), Eldoret 30100, Kenya; Recruiting
Priscilla C. Cheruiyot, Phone: 254-53-2060850, Email: pcchepkorir@yahoo.com
Abraham M. Siika, MMED, Principal Investigator

Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501), Kericho 20200, Kenya; Recruiting
Hellen Ngeno, Phone: 254-5230388, Email: hngeno@wrp-kch.org
Fredrick Sawe, MB, ChB, MMED, Principal Investigator

College of Med. JHU CRS (30301), Blantyre, Malawi; Recruiting
Leslie H. Degnan, M.P.H., Phone: 265-888-208609, Email: ldegnan@jhu.medcol.mw
Newton Kumwenda, MPH, PhD, Principal Investigator

University of North Carolina Lilongwe CRS (12001), Lilongwe, Malawi; Recruiting
Mina Hosseinipour, MD, Phone: 265-1 758 938, Email: mina_hosseinipour@med.unc.edu
Francis Martinson, MPH, PhD, MBChB, Principal Investigator

Joint Clinical Research Centre (JCRC) (12401), Kampala, Uganda; Recruiting
Sandra Rwambuya, Phone: (256) 413-42521, Email: dxr23@case.edu
Peter Mugyenyi, MB ChB, FRCP, DSc, Principal Investigator

Starting date: July 2013
Last updated: August 5, 2015