ADEPT STUDY: (Alcohol Drinking Effects on Progression prior to Treatment)
Does heavy alcohol consumption accelerate HIV disease progression? This is a fundamental unanswered question with far-reaching public health implications worldwide. Alcohol is one of the most commonly used drugs in the world, and heavy alcohol consumption is very prevalent among those infected with HIV both in the USA and worldwide. While animal studies that address this question suggest that alcohol consumption early in infection may cause immune system damage and accelerate HIV disease progression, the results of human observational studies of this issue have been less clear, due to several limitations. Because of this uncertainty, physicians often only begin to fully address alcohol consumption at the time of antiretroviral therapy (ART) initiation, when it hinders ART adherence. However, if heavy alcohol consumption prior to ART initiation accelerates HIV disease progression, then interventions to reduce alcohol consumption should occur as early as possible.
The study will examine this central issue of HIV-alcohol research in a longitudinal cohort study of 650 ART-naive HIV-infected individuals called the Alcohol Drinking Effects on Progression prior to Treatment (ADEPT) Study. This study will be a vital component of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium. The ADEPT Study will take place in Uganda, which has one of the highest per capita levels of alcohol consumption in the world, yet little or no other substance use. Uganda also has a high prevalence of HIV infection (6.4%) with many HIV-infected persons not yet on ART; therefore this study is highly feasible in Uganda but unlikely to be possible in the USA. The ADEPT Study participants will be recruited at their initial visit to an 8,000 patient HIV clinic.
The main goal of the ADEPT Study is to determine the impact of heavy alcohol consumption on pre-ART HIV disease progression, as measured by CD4 cell count decline. We will utilize several innovative strategies to overcome previous study limitations. First, we will use a direct metabolite of heavy alcohol consumption, phosphatidylethanol (PEth), which we have previously studied in this setting, to increase our ability to detect unreported heavy alcohol consumption. Second, because illicit substance use is rare in Uganda, the study will benefit from a lack of confounding by this factor. Third, we will assess alcohol use in repeated study visits to account for changing alcohol consumption; we will also conduct exploratory analyses of several potential factors which may explain an effect of heavy alcohol use on HIV disease progression.
The specific objectives:
1. To determine the effect of heavy alcohol consumption on HIV progression prior to the start of ART in a prospective cohort study.
Hypothesis: Heavy alcohol consumption will be associated with greater CD4 cell count decline in persons not yet on ART.
2. To explore possible biological and behavioral pathways by which heavy alcohol consumption may accelerate HIV disease progression prior to the initiation of ART.
Exploratory hypotheses: The effects of heavy alcohol use will be mediated by (a) biological factors, such as greater microbial translocation, liver fibrosis, both measured in a subsample at baseline (n=250), and malnutrition; and (b) behavioral factors such as lower clinic retention and less receipt of OI prophylaxis (begun at diagnosis in Uganda), measured in the full cohort.
Overall total number enrolled into the Study 129
Drinkers per screening form 61
Non drinkers per screening form 68
Total number of males enrolled into study 36
Total number of females enrolled into study 93
Total number disenrolled 8
The progress reported here reflects progress for one year since October 1 2012 to 31 August 2012. Pilot recruitment of potential participants started late March 2012. To date, we have enrolled one hundred twenty nine (129) participants on whom we have conducted all study related procedures.
We hold study weekly meetings to discuss progress and also have regular communication with UCSF and Boston University based teams through bi-weekly conference calls.
1. Personnel and infrastructure
Seven staff members in total have been hired since the beginning of the study and these include a study Coordinator, two Research assistants, a data manager, a patient tracker and two lab phlebotomists. The study staff has undergone extensive training by teams from UCSF and Boston University collaborators who have made two trips to Uganda to complete this in the past 6 months. Space has been allocated for the study staff and other logistical issues for the study have been worked out.
2. Study instruments, databases and protocols
Interview questionnaires and study protocols have been developed and are currently being used and followed. We have selected the software Computer Assisted Survey Information Collection (CASIC) and have begun using it for data collection. We have also developed participant tracking database to help us track participants on follow up visits.
3. IRB and sub-contracts
Human subjects’ approvals have been obtained from all collaborating sites including: Mbarara University of Science and Technology, Uganda National Council of Science and Technology, University of California San Francisco. We are in the process of renewing these approvals for year 2 of the study at all institutions.
We have successfully executed a sub-contract for the study with Mbarara University of Science and Technology, Mbarara Uganda through MUST Grants Office up to August 31, 2012 and will renew thereafter. We have also finalized the laboratory agreements with the Mbarara University Clinical and Research Laboratory which is handling specimen testing and storage.
4. Data collection
We finalized and translated all study materials into the local language, procedures for data collection and data tracking have been established. We are using CASIC data system; two Research Assistants have been hired and trained to collect data using this system and other data quality assurance practices. We have also hired a data manager to supervise data entry and ensure data integrity.
We do not yet have severe challenges for which we can comment on at the moment; however we have faced a challenge of patients declining to join the study because of reasons like stigma, disclosure issues and fear of frequent blood draws.
In the coming year, we plan to continue with the official study recruitment, we plan to hire two more research assistants as the study is growing big. Our target is 650 participants and we hope to follow them up for three and a half years. The study has got five years of funding.