Late-Presenting HIV Infection Remains Elevated in Spain Despite Improvements

This new study from Spain represents the first extensive look at late presentation of persons living with HIV, following the 2014 introduction of guidelines on early HIV diagnosis.

Late presentation of HIV infection is an ongoing and significant health problem in Spain, representing close to 45% of cases of persons who presented with the disease and were recruited for the study between January 1, 2004, and November 30, 2018, according to study results published in PLoS One.

This new study represents the first extensive look at late presentation of persons living with HIV in 3 time periods (2004-2008, 2009-2012, and 2013-2018) following the 2014 introduction of guidelines from the Spanish Ministry on Health on early HIV diagnosis, particularly prevalence, risk factors, and the risk factors’ impact on clinical outcomes. The primary composite end point was first AIDS-defining event (ADE), first serious non-AIDS event (SNAE; eg, cardiovascular disease, renal disease, liver disease, and non–AIDS defining cancer or death from 1 of those 4), or overall all-cause mortality.

Prior to the guidelines’ introduction, there was a 46.9% rate of late presentation of HIV infection, according to Cohort of the Spanish HIV/AIDS Research Network (CoRIS). Late presentation of HIV infection was classified as HIV diagnosis with CD4 count < 350 cells/mcL or having an AIDS-defining event (ADE) between 4 and 24 weeks after trial enrollment.

The overall prevalence of late presentation of HIV infection was 44.6% (95% CI, 43.8%-45.4%), and the primary risk factors independently associated with late presentation were the following:

  • Older age: 77% for persons 50 years and older vs 36% among those aged 30 to 49 years
  • Infection through injection drug use: 49%
  • Heterosexual intercourse (men): 41%
  • Heterosexual intercourse (women): 27%
  • Low education level: 31% for primary education vs 9% for secondary education
  • From a non-European country:
    • sub-Saharan Africa: 17%
    • Latin America: 23%

Late presentation was associated with an increased risk of mortality, with a risk increase of 71% (incident rate ratio [IRR], 1.71; 95% CI, 1.41-2.08), followed by 39% for ADE (IRR, 1.39; 95% CI, 1.18-1.64), 34% for the composite end point (IRR, 1.34; 95% CI, 1.20-1.50), and 22% for SNAE (IRR, 1.22; 95% CI, 1.01-1.47).

In addition, among those who experienced any of the events of the composite end point (n = 435 non–late presenters; n = 726 late presenters), the incidence rates per 100 person-years were consistently elevated in the late presenters:

  • Any of the events: 2.34 (95% CI, 2.17-2.52) vs 1.21 (95% CI, 1.10-1.33)
  • First ADE: 0.99 (95% CI, 0.88-1.12) vs 0.51 (95% CI, 0.44-0.59)
  • First SNAE: 1.32 (95% CI, 1.19-1.45) vs 0.73 (95% CI, 0.65-0.83)
  • Mortality: 1.00 (95% CI, 0.89-1.11) vs 0.36 (95% CI, 0.30-0.42)

Those presenting late with advanced disease also had an 89% higher mortality rate vs 40% seen in non–late presenters.

For the study, CoRIS provided data on 14,876 persons—all antiretroviral treatment–naïve adults 18 years and older. Most of the participants were men (85.0%), men who have sex with men (61.7%), and from Europe (72.6%). Their median age was 35.2 years and median CD4 count, 397 cells/mcL. Among those with an AIDS diagnosis, their viral load was at least 100,000 copies/mL.

The authors’ analysis also shows that the prevalence of late-presenting HIV infection improved overall before levelling off: from 51.8% (95% CI, 50.4%-53.3%) in 2004 to 2008 to 40.9% (95% CI, 39.4%-42.4%) in 2009 to 2012, before stabilizing at 42.0% (95% CI, 40.8%-43.2%) in 2013 to 2018 (P for trend < .001). Late presentation with advanced disease followed a similar course, decreasing from 33.9% (95% CI, 32.5%-35.3%) in 2004 to 2008 to 22.7% (95% CI, 21.5%-24.0%) in 2009 to 2012, before stabilizing at 23.6% (95% CI, 22.6%-24.7%) in 2013 to 2018 (P for trend < .001).

“The reasons why the prevalence of [late presentation] has stopped decreasing may be linked to the persistent low HIV testing frequency in Spain,” the authors wrote. “This low rate may be due to lack of awareness about HIV infection, stigma, lack of knowledge about health care services, and lack of offered testing.”

They also attribute the still-high rate of late-presenting disease from the influence of the factors associated with it, namely low education level, migrant status, and low self-perceived risk.

“Public policies should be implemented to expand screening and early diagnosis of HIV infection for a focus on those at greatest risk of late presentation,” the authors concluded. “As an example, targeted diagnostic programs could be run in emergency department, primary care and other medical centers; HIV testing could be considered as a priority in primary care protocols and information campaigns aimed at medical professionals could be carried out to publicize and improve the application of clinical guidelines.”


Rava M, Domínguez-Domíguez L, Bisbal O, et al; Cohort of the Spanish HIV/AIDS Research Network (CoRIS). Late presentation for HIV remains a major health issue in Spain: results from a multicenter cohort study, 2004–2018. PLoS One. Published online April 21, 2021. doi:10.1371/journal.pone.0249864

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