The Mochudi Prevention Project ART Protocol

An Evaluation of the Uptake and Safety of, and Adherence to Antiretroviral Treatment Among Individuals With CD4 ≥ 250 Cells/mm3 and HIV Virus Load ≥ 50,000 cp/mL

The goal of the "Mochudi Prevention Project" is to reduce the number of new HIV infections in the village of Mochudi, Botswana by promoting a comprehensive package of interventions that have proven to be effective in preventing the spread of HIV. This antiretroviral treatment (ART) clinical study is nested within the Mochudi Prevention Project, and is being conducted in the north-east segment (NES) of the village of Mochudi. The ART intervention component of the Mochudi Project is designed to determine the uptake of, adherence to, and feasibility of 3-drug combination ART as a component of a package of transmission prevention strategies. The hypotheses are 1) that ART (with 3 antiretrovirals from two classes of drugs) among participants with CD4 ≥ 250 cells/mm3 and VL ≥ 50,000 cp/mL will be acceptable and safe and 2) Eighty percent of eligible participants will agree to start 3-drug ART.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: highly active antiretroviral therapy: Lopinavir/Ritonavir, Lamivudine, Zidovudine, Efavirenz, Tenofovir Disoproxil Fumarate, Emtricitabine

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Botswana
  • Mochudi, Botswana
    • Deborah Retief Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 64 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-1 infection
• CD4 cell count ≥ 250 cells/mm3
• HIV-1 RNA ≥ 50,000 cp/mL
• No AIDS-defining illness or other illness that would cause volunteer to be eligible for ART through the Botswana National Program (these volunteers should be referred to the National Program for treatment)
• Age 16 to 64 years
• Botswana citizen
• Resident of the north-east segment of Mochudi

• The following laboratory values obtained within 60 days prior to study enrollment:

  • Absolute neutrophil count (ANC) ≥ 500 cells/mm3.
  • Hemoglobin ≥ 7.0 g/dL.
  • AST (SGOT), ALT (SGPT), and bilirubin ≤ 5 X ULN. Note: if the estimated creatinine clearance (by Cockgroft-Gault equation) is <60 mL/min, then TDF/FTC will be substituted with ZDV/3TC
• Ability to swallow oral medications.
• Ability and willingness of participant to give informed consent (or in case of participants < 18 years of age, ability and willingness to provide assent; and for parent/guardian to provide consent).
• Not currently involuntarily incarcerated.
• Karnofsky performance score ≥ 70 at time of study enrollment.
• If participating in sexual activity that could lead to pregnancy and of reproductive potential, female participants must use two reliable methods of contraception simultaneously, one of which must be a barrier method, while receiving protocol-specified medications, and for 12 weeks after stopping the medications.
• For participants < 18 years of age: Weight of 40kg or more

Exclusion Criteria:

• Receipt at any time prior to study enrollment of > 7 days cumulative treatment with any ARV or combination of ARVs (except ARVs taken for any length of time during pregnancy for the prevention of mother-to-child transmission (pMTCT) or ARVs taken for occupational exposure).
• Current receipt of 3-drug ART for pMTCT
• Allergy/sensitivity to any study drug or its formulations.
• Acute therapy for serious medical illnesses, in the opinion of the site investigator, within 14 days prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The proportion of individuals with CD4≥250 cells/mm3 and VL≥50,000 cp/mL who start 3-drug ART
The proportion of patients experiencing Grade 3 or 4 clinical or laboratory adverse events by the end of follow-up
The proportion of participants with excellent adherence (defined as participant self-report of taking at least 95% of doses of antiretrovirals during the previous 4 days, on all assessments) by the end of follow-up

Secondary Outcome Measures

Outcome Measure
Presence of ARV drug resistance at time of virologic failure on first- and second-line treatment, among participants experiencing virologic failure
Time to first opportunistic infections
Time to death
Time to first episode of non-adherence: the first episode of non-adherence will be the report of the failure of a patient to take 95% of prescribed pills, or participant self-discontinuation of antiretrovirals.
Motivation for / barriers to acceptance of ART will be analyzed descriptively

Collaborators and Investigators

• Sponsor: Harvard School of Public Health (HSPH)
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Max Essex, DVM, PhD, Harvard School of Public Health (HSPH); Principal Investigator: Victor DeGruttola, S.M., Sc.D., Harvard School of Public Health (HSPH)

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: April 11, 2012
• First Submitted That Met QC Criteria: April 23, 2012
• First Posted (Estimate): April 24, 2012

Study Record Updates

• Last Update Posted (Estimate): March 19, 2015
• Last Update Submitted That Met QC Criteria: March 18, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Immune System Diseases; Anti-HIV Agents; Acquired Immunodeficiency Syndrome; Antiviral Agents; Anti-Retroviral Agents; HIV Infections; Sexually Transmitted Diseases, Viral; Immunologic Deficiency Syndromes
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lopinavir; Lamivudine; Zidovudine; Efavirenz; Anti-Retroviral Agents
• Other Study ID Numbers: BHP041; R01AI083036 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No