Co-receptor Tropism Determination of HIV-1 Subtype A Spread in the Russian Federation Using V3-based Genotyping Tools (CoTrAST)
|First Received Date ICMJE||March 30, 2013|
|Last Updated Date||February 4, 2014|
|Start Date ICMJE||November 2012|
|Primary Completion Date||August 2013 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Determination of the Prevalence of R5 and X4-tropic Variants of HIV in HIV-infected Population in Russia [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE
||Determination of the prevalence of R5, X4, and R5X4-tropic variants of HIV in HIV-infected population in Russia [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]|
|Change History||Complete list of historical versions of study NCT01823614 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Estimation of the R5- and X4-tropic HIV Variants Ratio Stratified by CD4 Cell Count [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]|
|Original Secondary Outcome Measures ICMJE
||Estimation of the R5- and X4-tropic HIV variants ratio from the duration of infection, HIV infection stage, and CD4 count [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]|
|Current Other Outcome Measures ICMJE
||Estimation of the R5- and X4-tropic HIV Variants Ratio Stratified by CD4 Cell Count Among Naive Patients [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]|
|Original Other Outcome Measures ICMJE
||Estimation of the prevalence of R5- and X4-tropic HIV variants in cohorts of naïve and ARVT experienced patients [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]|
|Brief Title ICMJE||Co-receptor Tropism Determination of HIV-1 Subtype A Spread in the Russian Federation Using V3-based Genotyping Tools|
|Official Title ICMJE||Epidemiological Study of the Co-receptor Tropism of HIV-1 Subtype A Spread in the Russian Federation Among naïve and ART-experienced Patients Using V3-based Genotyping Tools|
To date, all work related to the study of HIV tropism, was performed on HIV B and C subtypes. In the studied samples, HIV variants of subtype A were virtually absent. However, the existence has been shown previously of some differences in the nucleotide sequences in the V3 loop of env region of subtype A from other subtypes of virus. In the Russian Federation the subtype A of HIV-1 is predominant, and, according to some estimates, accounts for about 89% of all newly diagnosed cases of HIV infection. Thus, it seems interesting and effective to study the characteristics of HIV-1 subtype A, associated with the tropism, in the Russian Federation.
The primary objective is determination of the prevalence of R5 (chemokine receptor 5), X4 (chemokine receptor 4), and R5X4-tropic variants of HIV in HIV-infected population in Russia, and analysis of the possible features of tropism of viruses belonging to subtype A.
This study is a multicenter, single-step; with estimation of the prevalence of R5, X4, and R5X4-tropic HIV variants in a population of HIV-infected Russians naïve to CCR5-antagonists antiretroviral (ARV) therapy. Additional study objectives are to identify dependence of R5- and X4-tropic HIV variants relations from the duration of infection, stage of HIV infection, the values of CD4-lymphocytes; and to compare the prevalence of R5- and X4-tropic HIV variants in cohorts of naïve and ARVT experienced patients. The study consists of single visit of all patients, during which the following procedures will be performed: obtaining of informed consent, initial evaluation of the possibility of including of the patients in the study, stratification of the patient, and if the quota for this cohort has not yet been reached, inclusion of the patient in the study. Also the detailed information will be collected on the date of birth, place of residence (region, city), date of the 1st HIV+ immune blot test, route of infection, estimation year (month) of infection, stage of HIV infection, all the known results of CD4 cell count and viral load measurements, as well as all the known schemes of ARV therapy. Additionally, the study provides a single blood sampling (of 6.4 mL volume) into a test tube in order to study the HIV tropism by sequencing. It is expected that the inclusion in the study will be completed within approximately 3 months, but this period may be extended depending on the actual inclusion of patients in each of the study centers. The Coordination Center of the study is the Central Research Institute for Epidemiology (hereinafter — the Coordination Center). Patient selection will be performed in 13 participating centers:
The study will include approximately 900 HIV-infected patients of both sexes aged 18 years or older, citizens of Russia. Patient will be selected from the AIDS centers and the Republican Clinical Hospital for Infectious Diseases, which are participants of the study. List of the study participants includes 12 AIDS centers and one Republican Clinical Infectious Diseases Hospital, so the expected number of patients will be 70 people per participant. The minimum number of patients included in the study must be at least 40 people for each participant, but the actual amount will depend on the success of patient recruitment in each of the study centers. Starting from the 4th month of study, a competitive selection of patients will be allowed, which will end as soon as the total number of enrolled patients will reach 900 people. According to the objectives of the study, HIV tropism in patients not received ART with different immune status, and experienced in ART will be analyzed, so the inclusion of patients in the study should take place according to the following quotas:
Scheme of the study procedures. The study procedures
Determination of HIV tropism by sequencing.
Procedure of HIV tropism determination in a sample involves the consistent implementation of the following stages: extraction of nucleic acids from the blood sample, amplification of the env gene of HIV genome, determining the nucleotide sequence of the resulting specific DNA product and its analysis by means of the Internet resource geno2pheno, located at http://coreceptor.bioinf.mpi-inf.mpg.de/index.php. According to the instructions to a set of reagents for tropism study, there are two possible results:
Standard laboratory tests. The standard laboratory tests mean measuring of viral load in a plasma sample, as well as CD4 cell count. These studies are carried out only in case when they are routinely needed. When they are performed, the results are provided in the Case Report Form of the study participant.
Determination of HIV subtype. Determination of HIV subtype is carried out by Coordination Center selectively in 10% of patients after receipt by the Coordination Center of clinical samples from all study participants (study centers). Determination of subtype includes the following stages: extraction of nucleic acids from a plasma sample, amplification of fragment of pol region of the HIV genome, determining the nucleotide sequence of obtained specific DNA products, and their bioinformatics analysis by means of Internet applications REGA Subtyping tool and Comet.
General information about the methods of statistical analysis. Parameters of descriptive statistics will be calculated for the indices for the patients and human immunodeficiency virus by calculating the proportion of patients showing some signs of corresponding categorical variables and by calculating the mean values, standard deviations, medians, 25 and 75 percentiles, minimum and maximum values of the distribution of all continuous variables from all patients with the results of their evaluation.
Also proportions of patients from different regions at different stages of the disease, and infected with HIV variants with different tropism will be calculated. Evaluation of reliability of differences of categorical variables (for example, when differences in the distribution of HIV variants with different tropism in different regions) will be performed using the chi-square test. Estimation of reliability of differences of continuous variables (eg, the level of HIV viral load) will be performed using parametric (eg, t test, ANOVA) or nonparametric (eg, Wilcoxon rank-sum test) methods.
Univariate and multivariate logistic (when the dependent variable is binary) and linear regression (when the dependent variable is continuous) analyses will be used to assess associations between exploratory (eg, CXCR4-tropic variants) and dependent (eg, the level of HIV viral load) variables.
All statistical tests will be two-sided, with 5% significance level.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Cohort
Time Perspective: Cross-Sectional
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples With DNA
plasma peripheral blood mononuclear cells
|Sampling Method||Probability Sample|
primary care clinic
|Condition ICMJE||HIV Infection|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||December 2013|
|Primary Completion Date||August 2013 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Russian Federation|
|NCT Number ICMJE||NCT01823614|
|Other Study ID Numbers ICMJE||WS2041679|
|Has Data Monitoring Committee||No|
|Responsible Party||Dmitry Kireev, Central Institute of Epidemiology, Moscow, Russia|
|Study Sponsor ICMJE||Dmitry Kireev|
|Information Provided By||Central Institute of Epidemiology, Moscow, Russia|
|Verification Date||February 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP