Efavirenz and Lamivudine/Zidovudine for Treatment-Naive HIV Infected Adults in Senegal

A Pilot Study of Safety, Effectiveness, and Adherence of Lamivudine/Zidovudine and Efavirenz (3TC/ZDV + EFV) to Treat HIV-1 Infection in Senegal

The purpose of this study is to determine the safety and effectiveness of the anti-HIV drugs efavirenz and lamivudine/zidovudine given to treatment-naive HIV-infected people in Dakar, Senegal.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Efavirenz; Drug: Lamivudine/zidovudine

Detailed Description

Despite a relatively low prevalence of HIV infection, all HIV subtypes have been documented in Senegal. Data on mutations that confer resistance to antiretroviral (ARV) drugs are limited to HIV subtype B; adherence data are also limited. The study will evaluate the safety and efficacy of an ARV regimen given to treatment-naive HIV infected adults and adolescents. The study will also examine the characteristics of virologic failure and adherence in this treatment group. Participants will be recruited at two sites in Dakar, Senegal.

This study will last 96 weeks. At study entry, all participants will be given an ARV regimen of lamivudine/zidovudine twice daily and efavirenz once daily. If toxicity or treatment failure occurs, some participants may require changes in their ARV regimens. There will be 14 study visits during the study; a physical exam, blood collection, and sociodemographic and medication history assessments will occur at each visit. Participants will also be asked to complete quality-of-life and adherence questionnaires. An off-study visit will occur at approximately one month after Week 96, with assessments and procedures similar to visits during the study.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Senegal
  • Dakar, Senegal
    • Centre National Hospitalier de Fann, Dakar CIPRA CRS
  • Dakar, Senegal
    • Institut d'Hygiène Sociale, Dakar CIPRA CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-infected
• Have never taken ARV drugs
• CD4 count of 200 cells/mm3 or less within 30 days of study entry if asymptomatic OR CD4 count of 350 cells/mm3 or less within 60 days of study entry if CDC Category A or B clinical condition present OR clinical diagnosis of AIDS, regardless of CD4 count
• Willing to stay in the study area for the duration of the study
• Willing to use acceptable forms of contraception

Exclusion Criteria:

• HIV-2 infected
• Systemic chemotherapy (except interferon) within 6 months prior to study entry
• Current drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study
• Serious illness, including any active AIDS-defining infection, active tuberculosis, malaria, or any illness requiring systemic treatment or hospitalization. People who have completed therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded.
• Serious psychiatric problems within 60 days of study entry, including depression, suicidal thoughts or attempts, aggressive behavior, or psychosis-like symptoms
• Have taken certain medications within 30 days of study entry
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; All participants will be given an ARV regimen of lamivudine/zidovudine and efavirenz at study entry. If toxicity or treatment failure occurs, some participants may require changes in their ARV regimens.	Drug: Efavirenz; 600 mg tablet taken orally daily; Other Names: EFV; Drug: Lamivudine/zidovudine; 150mg lamivudine/300mg zidovudine tablet taken orally twice daily; Other Names: 3TC/ZDV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Virologic efficacy, defined as HIV-1 viral load less than 200 copies/ml	Through Week 24
Treatment-related toxicity of Grade 3 or higher as measured by development of drug-related toxicities severe enough to warrant dose modification, interruption, or permanent discontinuation	Through Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Virologic efficacy	At Weeks 48 and 96
Treatment related toxicity	At Weeks 48 and 96
Virologic failure, defined as HIV-1 viral load greater than 1,000 copies/ml	Throughout study
CD4 counts and HIV-1 RNA viral load	Throughout study
First new or recurrent AIDS-defining event (as defined by the CDC Expanded AIDS Surveillance Case definition) or death	Throughout study
Treatment discontinuation, defined as premature discontinuation of participation in the study, failure to take ARV therapy for 8 or more consecutive weeks, or to switch to another ARV regimen for any reason during the full course of the study	Throughout study
Genotypic resistance measured by at least 1 genotypic mutation associated with resistance among subjects with a confirmed virologic failure (as described previously) and evaluation of genotypic drug resistance patterns	At Weeks 24 and 96
Treatment adherence, defined by 95% or greater of prescribed pills taken	Throughout study
Quality of life as measured by items and patterns of responses to the FAHI questionnaire	Throughout study
HIV-1 DNA and RNA measurements	Throughout study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Initiative Senegalaise d'Acces aux Antiretroviraux (ISAARV)
• Investigators: Study Chair: Souleymane Mboup, PharmD, Laboratoire de Bacteriologic et de Virologie, Hospital Le Dantec Avenue Pasteur

Publications and helpful links

General Publications

• Meda N, Ndoye I, M'Boup S, Wade A, Ndiaye S, Niang C, Sarr F, Diop I, Carael M. Low and stable HIV infection rates in Senegal: natural course of the epidemic or evidence for success of prevention? AIDS. 1999 Jul 30;13(11):1397-405. doi: 10.1097/00002030-199907300-00018.
• DeJesus E, Herrera G, Teofilo E, Gerstoft J, Buendia CB, Brand JD, Brothers CH, Hernandez J, Castillo SA, Bonny T, Lanier ER, Scott TR; CNA30024 Study Team. Abacavir versus zidovudine combined with lamivudine and efavirenz, for the treatment of antiretroviral-naive HIV-infected adults. Clin Infect Dis. 2004 Oct 1;39(7):1038-46. doi: 10.1086/424009. Epub 2004 Sep 10.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: January 3, 2005
• First Submitted That Met QC Criteria: January 3, 2005
• First Posted (Estimate): January 4, 2005

Study Record Updates

• Last Update Posted (Estimate): September 6, 2013
• Last Update Submitted That Met QC Criteria: September 4, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Treatment Naive
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Lamivudine; Zidovudine; Efavirenz; Lamivudine, zidovudine drug combination
• Other Study ID Numbers: CIPRA-SN-001; SN-CIPRA-001; 10412 (Registry Identifier: DAIDS-ES)