Clinical trial NCT00100568: Efavirenz and Lamivudine/Zidovudine for Treatment-Naive HIV Infected Adults in Senegal
Official title: A Pilot Study of Safety, Effectiveness, and Adherence of Lamivudine/Zidovudine and Efavirenz (3TC/ZDV + EFV) to Treat HIV-1 Infection in Senegal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Treatment Naive
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Initiative Senegalaise d'Acces aux Antiretroviraux (ISAARV)
First posted: 2005-01-04
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Virologic efficacy, defined as HIV-1 viral load less than 200 copies/ml
timeFrame: Through Week 24
measure: 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
timeFrame: Through Week 24
Secondary outcomes:
measure: Virologic efficacy
timeFrame: At Weeks 48 and 96
measure: Treatment related toxicity
timeFrame: At Weeks 48 and 96
measure: Virologic failure, defined as HIV-1 viral load greater than 1,000 copies/ml
timeFrame: Throughout study
measure: CD4 counts and HIV-1 RNA viral load
timeFrame: Throughout study
measure: First new or recurrent AIDS-defining event (as defined by the CDC Expanded AIDS Surveillance Case definition) or death
timeFrame: Throughout study
measure: 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
timeFrame: Throughout study
measure: 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
timeFrame: At Weeks 24 and 96
measure: Treatment adherence, defined by 95% or greater of prescribed pills taken
timeFrame: Throughout study
measure: Quality of life as measured by items and patterns of responses to the FAHI questionnaire
timeFrame: Throughout study
measure: HIV-1 DNA and RNA measurements
timeFrame: Throughout study
Other outcomes:
Locations:
city: Dakar
country: Senegal
facility: Centre National Hospitalier de Fann, Dakar CIPRA CRS
city: Dakar
country: Senegal
facility: Institut d'Hygiène Sociale, Dakar CIPRA CRS
Study officials:
affiliation: Laboratoire de Bacteriologic et de Virologie, Hospital Le Dantec Avenue Pasteur
name: Souleymane Mboup, PharmD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.