Understanding dynamics of HIV epidemic in Georgia through implementing molecular HIV surveillance
Project Status: 3 Approved without Funding
Duration in months: 24 months
Objective
HIV/AIDS remains one of most serious health challenges worldwide, especially in the region of Eastern Europe and Central Asia (EECA) represented by countries of former Soviet Union. Data from the United Nation’s Joint Programme on AIDS (UNAIDS) indicate that between 2010 and 2016 the number of new infections in EECA increased by 60%. At early stages, the HIV epidemic in EECA region was primarily driven by injection drug use (IDU) and was closely linked to socio-political upheavals in 1990s following the collapse of Soviet Union. However, recent reports show increase in the number of sexually acquired infections, including among men who have sex with men (MSM).
This transition requires changes in response activities to identify and target sub-populations that drive the epidemic. However, monitoring active transmission networks using standard surveillance systems is challenging. Recent advances in sequencing techniques and computational/statistical methodologies provided researchers with new tools to better characterize the dynamics and structure of HIV transmission networks using phylogenetic analysis.
In addition to phylogenetics, HIV sequence provides very important data on HIV drug resistance to antiretroviral therapy (ART). Along with the obvious benefits of ART in terms of reducing mortality and preventing new infections, expanded use of ART raised concerns of the emergence of HIV drug resistance.
Similar to the rest of the region, the HIV epidemic continues to grow in Georgia. At the end of 2017, a cumulative 6,763 cases of HIV infection were registered in the country, of whom 1368 died. Georgia’s HIV epidemic shows signs of transitioning from IDU-driven to sexually driven epidemic. There was 5-fild increase in number of new diagnosis among MSM between 2010 and 2017. The HIV prevalence in this population increased from 4% in 2007 to 21% in 2015.
Dynamics of HIV epidemic in Georgia (shift to sexual transmission and surge of the epidemic in MSM) along with increasing number of patients receiving ART, justify the need of conducting the proposed study. The goal of this study is to better understand driving forces of continuing transmission of HIV in the country and to expand knowledge on HIV drug resistance. The long-term objective is to move obtained knowledge into effective treatment and prevention strategies. Specific aims of the study include: Specific aim 1: Evaluate dynamics of HIV transmission using phylogenetics
a. Identify active HIV transmission clusters
b. Evaluate time trends in subtype distribution
Specific aim 2: Evaluate patterns of HIV drug resistance
a. Estimate the prevalence of transmitted HIV drug resistance (TDR) among newly diagnosed HIV patients
b. Characterize HIV drug resistance profile among ART-experienced patients
Study will use hybrid design combining prospective and retrospective data to accomplish proposed aims. For the prospective component the study will analyze sequences from 200 newly diagnosed persons, with evidence of recent infection. Persons aged 18 to 25 with CD4 cell count >500 cells/mm3 will be defined as recently infected, in all other newly diagnosed persons test for recent infection will be performed using Sedia™ HIV-1 LAg-Avidity EIA (Portland, OR, USA).
Retrospective component will use secondary data, including HIV sequences and patient-related information, from 300 ART-naive HIV patients diagnosed during the period of 1998-2015 and from 580 ART-experienced patients failing on therapy.
HIV sequences will be obtained using ViroSeq™ HIV-1 Genotyping System (Abbott diagnostics, Wiesbaden, Germany) on 24 capillary automated 3500xl Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). The consensus nucleotide sequences consisting of entire HIV-1 protease gene from codons 1 to 99 and two-thirds of the reverse transcriptase (RT) gene from codons 1 to 335 will be used for reconstructing phylogenetic trees and identification of transmission clusters. The analysis will integrate molecular, demographic and epidemiological data to describe structure of transmission clusters.
Trends in molecular epidemiology will be evaluated in phylogenetic analysis. Viral sequences from 200 newly enrolled patients and 300 ART-naive patients from previous studies will be used for this purpose.
Prevalence of transmitted drug resistance will be estimated using the WHO surveillance drug-resistance mutations list and this will include 200 newly diagnosed persons, prospectively enrolled in this study. Drug resistance test is performed routinely among patients failing on therapy as part of standard of care. Characterization of drug resistance profiles among ART-experienced patients will include sequences from patients who already underwent drug resistance testing by the time of study inceptions and all patients who will undergo testing during study implementation. We expect to have at least 750 sequences available for final analysis.
Participating Institutions
LEADING
Georgian AIDS and Clinical Immunology Research Center
