Late Presenters in New HIV Diagnoses from An Italian Cohort of HIV-Infected Patients: Prevalence and Clinical Outcome

Abstract

Background

To study the prevalence, predictors and outcome of late HIV diagnosis in the Icona cohort, according to the new European consensus definition of late diagnosis.

Methods

In this observational cohort study we investigated patients diagnosed with HIV over 3 months preceding enrolment who were defined as diagnosed late if they presented with AIDS or a CD4⁺ T-cell count ≤350/mm³ (European consensus definition). We estimated the prevalence of late diagnosis, identified factors associated with being diagnosed late and looked at the prognostic value of the European consensus definition of late presentation to predict subsequent clinical progression (new AIDS events or death).

Results

In total, 1,438/2,276 patients (63%) were defined as diagnosed late using the new European Consensus definition. Of these, 387 (16%) were AIDS-presenters. Predictors of being diagnosed late were older age, non-Italian origin, high HIV RNA and unemployment (versus retirement). A total of 293 patients showed clinical progression (3 events/100 person-years of follow-up, 95% CI: 2.7–3.4). Presenting late was strongly associated with a >5-fold increased risk of disease progression.

Conclusions

In our observational setting with free access to care, more than 60% of new HIV diagnoses occurred below the recommended threshold for initiating anti-retroviral treatment. Presenting late for care was associated with a high risk of clinical progression.

References

Núñez

, Asencio

, Valencia

, Leal

, González-Lahoz

, Soriano

Rate, causes, and clinical implications of presenting with low CD4⁺ cell counts in the era of highly active antiretroviral therapy. AIDS Res Hum Retroviruses 2003; 19: 363–368.

Easterbrook

P.J.

, Yu

, Goetghebeur

, Boag

, McLean

, Gazzard

Ten-year trends in CD4 cell counts at HIV and AIDS diagnosis in a London HIV clinic. AIDS 2000; 14: 561–571.

Girardi

, Aloisi

, Arici

Delayed presentation and late testing for HIV: demographic and behavioral risk factors in a multicenter study in Italy. J Acquir Immune Defic Syndr 2004; 36: 951–959.

Mocroft

, Phillips

, Gatell

Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study. Lancet 2007; 370: 407–413.

Kelley

C.F.

, Kitchen

, Hunt

Incomplete peripheral CD4⁺ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 2009; 48: 787–794.

Egger

, May

, Chêne

Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 2002; 360: 119–129.

Kaufmann

G.R.

, Perrin

, Pantaleo

CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med 2003; 163: 2187–2195.

Smith

C.J.

, Olsen

, Mocroft

The role of antiretroviral therapy in the incidence of pancreatitis in HIV-positive individuals in the EuroSIDA study. AIDS 2008; 22: 47–56.

Curkendall

S.M.

, Richardson

, Emons

, Fisher

, Everhard

Incidence of anaemia among HIV-infected patients treated with highly active antiretroviral therapy. HIV Med 2007; 8: 483–490.

10.

Jericó

, Knobel

, Montero

Metabolic syndrome among HIV-infected patients: prevalence, characteristics, and related factors. Diabetes Care 2005; 28: 132–137.

11.

Elzi

, Marzolini

, Furrer

Treatment modification in human immunodeficiency virus-infected individuals starting combination antiretroviral therapy between 2005 and 2008. Arch Intern Med 2010; 170: 57–65.

12.

Marks

, Crepaz

, Janssen

Estimating sexual transmission of HIV from persons aware and unaware that they are infected with the virus in the USA. AIDS 2006; 20: 1447–1450.

13.

Crepaz

, Marks

, Liau

Prevalence of unprotected anal intercourse among HIV-diagnosed MSM in the United States: a meta-analysis. AIDS 2009; 23: 1617–1629.

14.

Metsch

L.R.

, Pereyra

, Messinger

HIV transmission risk behaviors among HIV-infected persons who are successfully linked to care. Clin Infect Dis 2008; 47: 577–584.

15.

Krentz

H.B.

, Auld

, Gill

The high cost of medical care for patients who present late (CD4 <200 cells/microL) with HIV infection. HIV Med 2004; 5: 93–98.

16.

Manavi

, McMillan

, Ogilvie

, Scott

Heterosexual men and women with HIV test positive at a later stage of infection than homo- or bisexual men. Int J STD AIDS 2004; 15: 811–814.

17.

Gay

C.L.

, Napravnik

, Eron

J.J.

Advanced immunosuppression at entry to HIV care in the southeastern United States and associated risk factors. AIDS 2006; 20: 775–778.

18.

Sabin

C.A.

, Smith

, Gumley

Late presenters in the era of highly active antiretroviral therapy: uptake of and responses to antiretroviral therapy. AIDS 2004; 18: 2145–2151.

19.

Castilla

, Sobrino

, De La Fuente

, Noguer

, Guerra

, Parras

Late diagnosis of HIV infection in the era of highly active antiretroviral therapy: consequences for AIDS incidence. AIDS 2002; 16: 1945–1951.

20.

Antinori

, Johnson

, Moreno

, Yazdanpanah

, Rockstroh

J.K.

Report of a European Working Group on late presentation with HIV infection: recommendations and regional variation. Antivir Ther 2010; 15 Suppl 1: 31–35.

21.

Antinori

, Coenen

, Dedes

Late presentation of HIV infection: a consensus definition. HIV Medicine 2011; 12: 61–64.

22.

When To Start Consortium. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 2009; 373: 1352–1363.

23.

Kitahata

M.M.

, Gange

, Abraham

Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009; 360: 1815–1826.

24.

Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. (Updated 10 January 2011. Accessed 3 November 2010.) Available from http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.

25.

EACS. Guidelines for clinical management and treatment of HIV infected adults in Europe. (Accessed 3 November 2010.) Available from http://europeanaidsclinicalsociety.org/images/stories/EACS-Pdf/1_treatment_of_hiv_infected_adults.pdf.

26.

d'Arminio Monforte

, Lepri

, Rezza

Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naïve Patients. AIDS 2000; 14: 499–507.

27.

Centers for Disease Control. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992; 41: 1–19.

28.

Wolbers

, Bucher

, Furrer

Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study. HIV Med 2008; 9: 397–405.

29.

Delpierre

, Lauwers-Cances

, Pugliese

Characteristics trends, mortality and morbidity in persons newly diagnosed HIV positive during the last decade: the profile of new HIV diagnosed people. Eur J Public Health 2008; 18: 345–347.

30.

Begovac

, Gedike

, Lukas

, Lepej

Late presentation to care for HIV infection in Croatia and the effect of interventions during the Croatian Global Fund Project. AIDS Behav 2008; 12: S48–S53.

31.

Sullivan

A.K.

, Curtis

, Sabin

, Johnson

Newly diagnosed HIV infections: review in UK and Ireland. BMJ 2005; 330: 1301–1302.

32.

Borghi

, Girardi

, Bellelli

Late presenters in an HIV surveillance system in Italy during the period 1992-2006. J Acquir Immune Defic Syndr 2008; 49: 282–286.

33.

The UK Collaborative HIV Cohort (UK CHIC) Steering Committee. Late diagnosis in the HAART era: proposed common definitions and associations with mortality. AIDS 2010; 24: 723–727.

34.

Lanoy

, Mary-Krause

, Tattevin

Frequency, determinants and consequences of delayed access to care for HIV infection in France. Antivir Ther 2007; 12: 89–96.

35.

Quinn

T.C.

, Wawer

, Sewankambo

Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000; 342: 921–929.

36.

Zolopa

, Andersen

, Powderly

Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS ONE 2009; 4: e5575.

37.

Chadborn

T.R.

, Delpech

, Sabin

, Sinka

, Evans

The late diagnosis and consequent short-term mortality of HIV-infected heterosexuals (England and Wales, 2000–2004). AIDS 2006; 20: 2371–2379.

38.

Chadborn

T.R.

, Baster

, Delpech

No time to wait: how many HIV-infected homosexual men are diagnosed late and consequently die? (England and Wales, 1993-2002). AIDS 2005; 19: 513–520.

39.

Smit

, Hallett

, Lange

, Garnett

, de Wolf

Late entry to HIV care limits the impact of anti-retroviral therapy in the Netherlands. PLoS One 2008; 3: e1949.

40.

The antiretroviral therapy cohort collaboration (ART-CC). Prognosis of patients treated with cART from 36 months after initiation, according to current and previous CD4 cell count and plasma HIV-1 RNA measurements. AIDS 2009; 23: 2199–2208.

41.

Guiguet

, Kendjo

, Carcelain

CD4⁺ T-cell percentage is an independent predictor of clinical progression in AIDS-free antiretroviral-naive patients with CD4⁺ T-cell counts >200 cells/mm³. Antivir Ther 2009; 14: 451–457.

42.

Ray

, Gupta

, Bala

, Muralidhar

, Kumar

CD4/CD8 lymphocyte counts in healthy, HIV-positive individuals & AIDS patients. Indian J Med Res 2006; 124: 319–330.

43.

Anderson

R.E.

, Shiboski

, Royce

, Jewell

, Lang

, Winkelstein

W.J.

CD8⁺ T lymphocytes and progression to AIDS in HIV-infected men: some observations. AIDS 1991; 5: 213–215.

44.

Chevret

, Roquin

, Ganne

, Lefrère

Prognostic value of an elevated CD8 lymphocyte count in HIV infection. Results of a prospective study of 152 asymptomatic HIV-positive individuals. AIDS 1992; 6: 1349–1352.

45.

Reus

, Portilla

, Gimeno

Predictors of progression and death in patients with advanced HIV infection in the era of highly active antiretroviral therapy. Enferm Infecc Microbiol Clin 2004; 22: 142–149.

46.

Prosperi

M.C.F.

, Cozzi-Lepri

, Castagna

The incidence of malignancies in HIV-infected patients and postic role of current CD4 cell count: evidence from a Italian study. Clin Infect Dis 2010; 50: 1316–1321.