Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Background: Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings: LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). Conclusions: LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP

Characteristics at HIV diagnosis of late presenters and late presenters with advanced disease: COHERE 2000–2011.

<p>Late presentation: diagnosed with HIV with a CD4 count below 350/mm³ or an AIDS defining event regardless of the CD4 count, in the 6 mo following HIV diagnosis. Late presentation with advanced disease: diagnosed with HIV with a CD4 count below 200/mm³or an AIDS defining event, regardless of CD4 cell count, in the 6 mo following HIV diagnosis.</p>a<p>Delayed entry into care: ≥3 mo between HIV diagnosis and first clinic visit, in those patients where both dates were recorded (<i>n</i> = 34,561). Baseline was defined as the earliest of HIV test, first study visit, or cohort enrolment. “Other” regions included Central/Southern America (<i>n</i> = 4,277) and Asia (<i>n</i> = 1,005). “Other” HIV male and female transmission groups included 5,350 (84.8%) and 2,046 (70.8%) patients with unknown HIV-exposure group, respectively, likely to include a number of IDUs, MSMs, and heterosexuals.</p><p>IQR, interquartile range.</p

(A–D) Progression to new AIDS/death: role of late presentation or late presentation with advanced disease: COHERE 2000–2011.

<p>(A) Southern Europe. (B) Central Europe. (C) Northern Europe. (D) Eastern Europe. LP, diagnosed with HIV with a CD4 count below 350/mm³ or an AIDS defining event regardless of the CD4 count, in the 6 mo following HIV diagnosis. Presentation with advanced disease (AD): diagnosed with HIV with a CD4 count below 200/mm³ or an AIDS defining event regardless of the CD4 count, in the 6 mo following HIV diagnosis.</p

Changes over time in late presentation and CD4 count at HIV diagnosis: COHERE 2000–2011.

<p>Late presentation: diagnosed with HIV with a CD4 count below 350/mm³ or an AIDS defining event regardless of the CD4 count, in the 6 mo following HIV diagnosis. Late presentation with advanced disease: diagnosed with HIV with a CD4 count below 200/mm³or an AIDS defining event, regardless of CD4 cell count, in the 6 mo following HIV diagnosis.</p

(A–D) Changes in late presentation over calendar time; stratified by HIV exposure group: COHERE 2000–2011.

<p>(A) Southern Europe. (B) Central Europe. (C) Northern Europe. (D) Eastern Europe. All models adjusted for age, delayed entry into care (≥3 mo) after HIV diagnosis, region of origin, European region of care, and HIV mode of infection. F, female; Het, heterosexual; M, male.</p

Number and percentage of AIDS/deaths and adjusted incidence rate ratios of AIDS/death after HIV diagnosis in COHERE 2000–2011; late presenters versus non late presenters stratified by European region of care and time since presentation.

<p>Adjusted additionally for age, region of origin, delayed entry into care (≥3 mo between HIV diagnosis and first clinic visit), and HIV-exposure group. Late presentation: presenting for care with a CD4 count below 350/mm³ or presenting with an AIDS defining event regardless of the CD4 count, in the 6 mo following presentation. Advanced disease: presenting for care with a CD4 count below 200/mm³or presenting with an AIDS defining event, regardless of CD4 cell count, in the 6 mo following presentation.</p>a<p>Figures are <i>n</i> (%) of clinical events (AIDS/deaths) in late presenters or late presenters with advanced disease.</p

Sensitivity analyses showing the proportion of late presenters or late presenters with advanced disease using different inclusion criteria for CD4 count at HIV diagnosis: COHERE 2000–2011.

<p>Late presentation: diagnosed with HIV with a CD4 count below 350/mm³ or an AIDS defining event regardless of the CD4 count, in the 6 mo following HIV diagnosis. Late presentation with advanced disease: diagnosed with HIV with a CD4 count below 200/mm³or an AIDS defining event, regardless of CD4 cell count, in the 6 mo following HIV diagnosis.</p>a<p>Corresponds to main analyses presented in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001510#s4" target="_blank">Results</a>.</p><p>AD, advanced disease; LP, late presenter.</p

Risk factors and outcomes for late presentation for HIV-positive persons in europe:results from the collaboration of observational HIV epidemiological research europe study (COHERE)

Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95–0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43). Conclusions LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP