The cascade of care in the Eastern European country of Georgia

Authors


Abstract

Objectives

Individual and public health benefits of antiretroviral therapy (ART) rely on successful engagement of HIV-infected patients in care. We aimed to evaluate the HIV care continuum in the Eastern European country of Georgia.

Methods

The analysis included all adult (age ≥ 18 years) HIV-infected patients diagnosed in Georgia from January 1989 until June 2012. Data were extracted from the national HIV/AIDS database as of 1 October 2012. The following stages of the HIV care continuum were quantified: HIV infected, HIV diagnosed, linked to care, retained in care, eligible for ART and virologically suppressed.

Results

Of 3295 cumulative cases of adult HIV infection reported in Georgia, 2545 HIV-infected patients were known to be alive as of 1 October 2012, which is 52% of the estimated 4900 persons living with HIV in the country. Of the 2545 persons diagnosed with HIV infection, 2135 (84%) were linked to care and 1847 (73%) were retained in care. Of 1446 patients eligible for ART, 1273 (88%) were on treatment and 985 (77%) of them had a viral load < 400 HIV-1 RNA copies/mL. Overall, 39% of those diagnosed and 20% of those infected had a suppressed viral load.

Conclusions

The findings of our analysis demonstrate that the majority of patients diagnosed with HIV infection are retained in care. Loss of patients occurs at each step of the HIV care continuum, but the major gap is at the stage of HIV diagnosis. Reducing the number of persons living with undiagnosed HIV infection and simultaneously enhancing engagement in continuous care will be critical to achieve maximum individual and public health benefits of ART.

Introduction

The global scaling up of antiretroviral therapy (ART) has resulted in a significant increase in the life expectancy of people living with HIV (PLHIV) [1]. Recently it has become clear that ART not only saves lives, but also prevents HIV transmission [2, 3]. As a result, the World Health Organization (WHO) has recently modified HIV treatment guidelines and further expansion of ART coverage is viewed as an essential component of a comprehensive prevention strategy [4].

Individual and public health benefits of ART rely on successful HIV testing programmes and engagement of HIV-infected individuals in the HIV care continuum, including linkage to care, retention in care and ART prescription, to achieve the ultimate goal of sustained viral suppression. Gaps in each of these stages, as described by Gardner and colleagues for the USA [5], present a threat to the ability of ART to achieve optimal health outcomes and reduce HIV transmission. Today the care cascade is regarded as a powerful tool with which to assess programme performance in terms of monitoring patient engagement, identifying gaps in the continuum of care and targeting programmatic and intervention activities.

Georgia is an independent nation located in the Eastern European region between Russia and Turkey. Georgia's HIV epidemic is primarily driven by injecting drug users (IDUs). In 2012, the estimated adult prevalence of HIV infection was 0.3%. Georgia's National HIV Prevention and Treatment Program began in the early 1990s, but its coverage was limited because of low levels of financing. Since 2004, the national HIV response in Georgia has been strengthened by substantial resource allocation from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Currently HIV testing activities include community-based programmes for most-at-risk populations (IDUs, men who have sex with men, female sex workers and prisoners) and facility-based HIV indicator diseases guided testing, universal screening of pregnant women, and mandatory screening of donated blood.

Georgia has also made substantial progress in scaling up ART, achieving universal access in 2004. Until 2011, ART was recommended for patients with a CD4 count < 200 cells/μL. In 2012, Georgia completed a phased implementation of the 2010 WHO guidelines which recommended ART initiation for all patients with CD4 counts < 350 cells/μL. The Infectious Diseases, AIDS and Clinical Immunology Research Center (National AIDS Center) is Georgia's coordination and reference institution for HIV diagnosis, treatment and care. The National AIDS Center and three affiliated regional centres provide HIV-related medical services free of charge. We conducted an analysis of routinely available patient-level data to evaluate the HIV care continuum in Georgia.

Methods

The study included all adult (age ≥ 18 years) HIV-infected patients diagnosed in Georgia from January 1989 until June 2012. We used routinely available patient-level data extracted from the national HIV/AIDS database as of 1 October 2012. The database collects case-based information on all HIV-positive individuals diagnosed in Georgia, including demographic, epidemiological, clinical and laboratory data. Patients are registered in the database using unique national ID and passport numbers. Currently the database is a secure web-based system networking all centres providing HIV care countrywide.

Definitions

‘HIV diagnosis’ was defined as a positive HIV test result obtained by any method and confirmed by a positive western blot or nucleic acid-based test. ‘Linkage’ was defined as at least one documented clinical visit (CD4 cell count or HIV-1 viral load measurement) after HIV diagnosis. ‘Retention’ was defined as at least one documented clinical visit (CD4 cell count or HIV-1 viral load measurement) within 12 months prior to the date of censoring. ‘Eligible for ART’ was defined as a CD4 count < 350 cells/μL or the presence of an AIDS-defining illness. ‘ART’ was defined as a combination of at least three antiretroviral drugs. ‘Being on ART’ was defined as at least one documented prescription refill within 3 months prior to the date of censoring. ‘Viral suppression’ was defined as a plasma HIV RNA level < 400 HIV-1 RNA copies/mL at the most recent measurement.

Statistical analysis

Statistical analyses were performed using sas v9.2 (SAS Institute, Cary, NC). The significance of differences was determined using Pearson's χ2 test. Factors associated with a failure to link to care and attrition from care were assessed in modified Poisson regression analysis. All tests were two-sided at a significance level of 0.05. The number of PLHIV was estimated using The Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended Spectrum/EPP software (http://www.unaids.org/en/dataanalysis/datatools/spectrumepp2013).

Results

Figure 1 summarizes the HIV care cascade in Georgia. As of 30 June 2012, a cumulative 3295 cases of HIV infection had been reported among adults > 18 years old. Of these, 2545 HIV-infected individuals were known to be alive as of 1 October 2012, representing 52% of the estimated 4900 adult PLHIV in Georgia. For the 2545 patients diagnosed with HIV infection, the median age at diagnosis was 35 [interquartile range (IQR) 30–41] years and 70% were men. The majority of patients were infected through either IDU (51%) or heterosexual contact (44%). A total of 2135 (84%) patients were linked to care and 1847 (73%) were retained in care. The median time to linkage was 1 month (IQR 0.5–3 months) and 76% were linked within 3 months of HIV diagnosis. The median CD4 count at entry into care was 228 cells/μL (IQR 106–391 cells/μL). Overall, 1847 patients were retained in care, representing 73% of those diagnosed and 38% of the total HIV-infected population. Of 1446 patients eligible for ART, 1273 (88%) were on treatment and 985 (77%) of them had an HIV-1 viral load < 400 copies/mL at the last assessment. Overall, 39% of those diagnosed and 20% of the estimated number of PLHIV had a suppressed HIV-1 viral load.

Figure 1.

The cascade of care in the Eastern European Country of Georgia. ART, antiretroviral therapy.

Comparison of engagement in HIV care among diagnosed patients showed that, compared with non-IDUs, persons with a history of IDU were less likely to initiate care (88% vs. 80%, respectively; P < 0.0001), to remain in care (79% vs. 67%, respectively; P < 0.0001) and to achieve viral suppression (42% vs. 36%, respectively; P < 0.003). Compared with men, women showed higher levels of engagement at various stages of care: 89% of women vs. 82% of men were linked to care (P < 0.0001), 80% vs. 69%, respectively, were retained in care (P < 0.0001), and 42% vs. 37%, respectively, were virally suppressed (P = 0.02). The observed gender difference can be explained by the fact that, of 1297 IDUs, 99% were men. Similar proportions of men and women, as well as IDUs and non-IDUs, were prescribed ART.

In multivariate analysis, failure to link to care was associated with a history of IDU [relative risk (RR) 1.39; 95% confidence interval (CI) 1.09–1.77] and having an HIV diagnosis made before universal access to ART (RR 2.52; 95% CI 2.10–3.02) (Table 1). Factors associated with attrition from care included a history of IDU (RR 1.35; 95% CI 1.01–1.82), having an HIV diagnosis made before universal access to ART (RR 2.08; 95% CI 1.63–2.66), and having a first CD4 count > 350 cells/μL (RR 2.17; 95% CI 1.72–2.73) (Table 1).

Table 1. Multivariate analysis of risk factors for failure to link to care and for attrition from care
 Risk factors for not linking to care*Risk factors for attrition from care
RR (95% CI)P-valueRR (95% CI)P-value
  1. ART, antiretroviral therapy; CI, confidence interval; IDU, injecting drug use; RR, relative risk.
  2. *Included all diagnosed patients (n = 2545).
  3. †Included patients linked to care (n = 2135).
Age    
< 30 years0.95 (0.77–1.16)0.590.88 (0.69–1.13)0.32
≥ 30 years1 1 
Sex    
Male1.20 (0.89–1.61)0.231.12 (0.79–1.57)0.52
Female1 1 
Mode of HIV transmission    
IDU1.39 (1.09–1.77)0.0091.35 (1.01–1.82)0.04
Non-IDU1 1 
Period of HIV diagnosis    
Before universal ART2.52 (2.10–3.02)<0.00012.08 (1.63–2.66)<0.0001
After universal ART1 1 
First CD4 cell count    
≥ 350 cells/μL  2.17 (1.72–2.73)<0.0001
< 350 cells/μL  1 

Discussion

This national-level description of the HIV care cascade in Georgia demonstrates that patients diagnosed with HIV infection are successfully engaged in clinical care. However, nearly half of the estimated 4900 HIV-infected individuals thought to live in Georgia remain unaware of their infection. Our analysis indicates that, of 3053 persons not engaged in continuous care, 2355 (77%) were people with undiagnosed HIV infection. They also made up 60% of the approximately 3900 persons with detectable viral load. This has serious implications for the success of ART at both the individual and the population levels. Delays in HIV diagnosis lead to late presentation to care and subsequently unfavourable health outcomes [6], as well as significantly contributing to onwards transmission of HIV [7].

Undiagnosed HIV infection is a world-wide problem, with estimates of the percentage of HIV-infected individuals who are undiagnosed ranging from 20% in the USA to 60% in sub-Saharan Africa [5, 8-10]. The significant gap in the stage of HIV testing/diagnosis in Georgia is the result of low testing coverage of key populations at risk and missed opportunities to diagnose HIV infection in health care settings [11, 12]. HIV testing efforts, including community-based and health care-based strategies [4, 13], need to be substantially expanded in Georgia in order to reduce the number of people unaware of their infection.

The findings of our analysis indicate that the Georgian HIV programme has been effective in engaging patients in care. Of all diagnosed HIV-infected patients, 84% were linked to and 73% retained in care. Data from industrialized countries indicate that 50 to 75% of diagnosed patients are consistently retained in care [5, 8, 14], while in resource-limited settings less than half of diagnosed HIV-infected individuals remain engaged in pre-ART care [10, 15, 16]. Our analysis also indicates that a higher proportion of eligible patients initiated ART compared with data from developing countries (88% vs. 66%, respectively) [10, 15]. There are limited data on viral suppression in developing countries. The proportion of virally suppressed patients among those on ART found in our study is comparable to results reported from North America, with estimates reaching 80% [5, 8]. However, caution should be exercised when making direct comparisons between various reports, as definitions of each step of the continuum of care may vary by study.

Along with successes, challenges should be addressed. Although the majority of diagnosed patients are successfully engaged in care, loss of patients occurs at each step of the care continuum. Overall, 27% of patients were not fully engaged and 30% of those eligible for ART were not virologically suppressed. Even if all HIV-infected persons in the country were diagnosed, less than half of them would be virologically suppressed at the current levels of engagement in care. It is clear that simultaneous improvements in each stage of the continuum are required to considerably increase the proportion of HIV-infected persons with undetectable viral load from the current estimate of 20%. Gardner and colleagues suggested that at least 90% achievement of each stage of care is required to considerably increase the proportion of virally suppressed patients [5].

Similar to the recent report from the USA [17], the findings of our study indicate that persons with a history of IDU are at higher risk of suboptimal engagement in care. However, two-thirds of IDUs in our cohort were retained in care and 72% of those on ART achieved viral suppression. Factors potentially associated with these outcomes in IDUs include the provision of free HIV-related medical care, and the availability of adherence support services and methadone substitution therapy. These findings indicate that IDUs can be successfully treated, challenging prevalent misconceptions that IDUs may not fully benefit from ART [18].

Multivariate analysis showed that persons diagnosed with HIV infection before universal ART became available in Georgia were more likely to drop out from care. This is not entirely surprising. Since 2004, free access to HIV clinical services has been substantially expanded, including free antiretrovirals and comprehensive out- and in-patient services provided free of charge to all HIV-infected patients. Also, the duration of HIV-positive status may have influenced this relationship, with patients diagnosed earlier in the course of the epidemic dropping out from care more frequently than those recently diagnosed.

Our analysis showed that a CD4 count > 350 cells/μL was associated with attrition from care. Although it is not conclusive evidence, it is valid to assume that earlier treatment initiation may improve retention in care. For example, a recent programme analysis from South Africa indicated that treatment initiation at a higher CD4 cell count reduced loss to follow-up [19]. The high treatment uptake in Georgia provides solid ground for the successful roll-out of new WHO guidelines recommending ART initiation at a CD4 count < 500 cells/μL [4].

Our analysis has strengths and limitations. A mature electronic system that collects data on every person with confirmed HIV infection is the major strength of this study. The system, which captures demographic, epidemiological, clinical and laboratory data, has been a reliable resource for quantifying engagement in all stages of the continuum of care. The major limitation is that the analysis provides only a cross-sectional snapshot of the situation and does not capture longitudinal dynamics. For instance, an undetectable viral load at a single time-point does not necessarily imply consistent viral suppression. Also, comparability of our findings with other similar reports is limited because of different definitions used. WHO has been exploring the possibility of developing a framework of metrics with unified set of indicators that will be applicable at both national and global levels [20].

In summary, our analysis indicates that, despite the successful retention of diagnosed patients, the majority of PLHIV remain not engaged in care because of a significant gap in HIV testing/diagnosis. Reducing the number of persons living with undiagnosed HIV infection and simultaneously enhancing engagement in continuous care will be critical to achieve maximum individual and public health benefits of ART.

Acknowledgements

This work was supported by the NIH/FIC through the Emory AIDS International Training and Research Program (D43 TW01042) and the New York State International Training and Research Program (D43 TW000233), and the Global Fund to Fight AIDS, Tuberculosis and Malaria (GEO-H-GPIC).

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