Research Open Access
Like 0



Development of additional diagnostic strategies for earlier HIV diagnosis are needed as approximately 50% of newly diagnosed HIV-infected individuals continue to present late for HIV care.


We aimed to analyse antimicrobial consumption in the 3 years preceding HIV diagnosis, assess whether there was a higher consumption in those diagnosed with HIV compared with matched controls and whether the level of consumption was associated with the risk of HIV infection.


We conducted a nested case–control study, identifying all individuals (n = 2,784 cases) diagnosed with HIV in Denmark from 1998 to 2016 and 13 age-and sex-matched population controls per case (n = 36,192 controls) from national registers. Antimicrobial drug consumption was estimated as defined daily doses per person-year. We used conditional logistic regression to compute odds ratios and 95% confidence intervals.


In the 3 years preceding an HIV diagnosis, we observed more frequent and higher consumption of antimicrobial drugs in cases compared with controls, with 72.4% vs 46.3% having had at least one prescription (p < 0.001). For all antimicrobial classes, the association between consumption and risk of subsequent HIV diagnosis was statistically significant (p < 0.01). The association was stronger with higher consumption and with shorter time to HIV diagnosis.


HIV-infected individuals have a significantly higher use of antimicrobial drugs in the 3 years preceding HIV diagnosis than controls. Prescription of antimicrobial drugs in primary healthcare could be an opportunity to consider proactive HIV testing. Further studies need to identify optimal prescription cut-offs that could endorse its inclusion in public health policies.


Article metrics loading...

Loading full text...

Full text loading...



  1. European Centre for Disease Prevention and Control (ECDC). HIV/AIDS surveillance in Europe 2018 (2017 data). Stockholm: ECDC; 2018. Available from: https://ecdc.europa.eu/en/publications-data/hivaids-surveillance-europe-2018-2017-data
  2. Late presenters working group in COHERE in EuroCoord. Late presentation for HIV care across Europe: update from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study, 2010 to 2013. Euro Surveill. 2015;20(47):30070.  https://doi.org/10.2807/1560-7917.ES.2015.20.47.30070  PMID: 26624933 
  3. Helleberg M, Engsig FN, Kronborg G, Laursen AL, Pedersen G, Larsen O, et al. Late presenters, repeated testing, and missed opportunities in a Danish nationwide HIV cohort. Scand J Infect Dis. 2012;44(4):282-8.  https://doi.org/10.3109/00365548.2011.626440  PMID: 22066814 
  4. Mocroft A, Furrer HJ, Miró J-M, Reiss P, Mussini C, Kirk O, et al. The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/μL in the post-combination antiretroviral therapy era. Clin Infect Dis. 2013;57(7):1038-47.  https://doi.org/10.1093/cid/cit423  PMID: 23921881 
  5. May M, Gompels M, Delpech V, Porter K, Post F, Johnson M, et al. Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study. BMJ. 2011;343(oct11 2):d6016.  https://doi.org/10.1136/bmj.d6016  PMID: 21990260 
  6. Marcus JL, Chao CR, Leyden WA, Xu L, Quesenberry CP Jr, Klein DB, et al. Narrowing the gap in life expectancy between HIV-infected and HIV-uninfected individuals with access to care. J Acquir Immune Defic Syndr. 2016;73(1):39-46.  https://doi.org/10.1097/QAI.0000000000001014  PMID: 27028501 
  7. INSIGHT START Study Group. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015;373(9):795-807.  https://doi.org/10.1056/NEJMoa1506816  PMID: 26192873 
  8. Robbins GK, Spritzler JG, Chan ES, Asmuth DM, Gandhi RT, Rodriguez BA, et al. Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384. Clin Infect Dis. 2009;48(3):350-61.  https://doi.org/10.1086/595888  PMID: 19123865 
  9. Fleishman JA, Yehia BR, Moore RD, Gebo KAHIV Research Network. The economic burden of late entry into medical care for patients with HIV infection. Med Care. 2010;48(12):1071-9.  https://doi.org/10.1097/MLR.0b013e3181f81c4a  PMID: 21063228 
  10. Montaner JS, Lima VD, Barrios R, Yip B, Wood E, Kerr T, et al. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet. 2010;376(9740):532-9.  https://doi.org/10.1016/S0140-6736(10)60936-1  PMID: 20638713 
  11. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med. 2000;342(13):921-9.  https://doi.org/10.1056/NEJM200003303421303  PMID: 10738050 
  12. Mocroft A, Lundgren JD, Sabin ML, Monforte A, Brockmeyer N, Casabona J, et al. 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). PLoS Med. 2013;10(9):e1001510.  https://doi.org/10.1371/journal.pmed.1001510  PMID: 24137103 
  13. Paltiel AD, Weinstein MC, Kimmel AD, Seage GR 3rd, Losina E, Zhang H, et al. Expanded screening for HIV in the United States--an analysis of cost-effectiveness. N Engl J Med. 2005;352(6):586-95.  https://doi.org/10.1056/NEJMsa042088  PMID: 15703423 
  14. Sanders GD, Bayoumi AM, Sundaram V, Bilir SP, Neukermans CP, Rydzak CE, et al. Cost-effectiveness of screening for HIV in the era of highly active antiretroviral therapy. N Engl J Med. 2005;352(6):570-85.  https://doi.org/10.1056/NEJMsa042657  PMID: 15703422 
  15. Yazdanpanah Y, Sloan CE, Charlois-Ou C, Le Vu S, Semaille C, Costagliola D, et al. Routine HIV screening in France: clinical impact and cost-effectiveness. PLoS One. 2010;5(10):e13132.  https://doi.org/10.1371/journal.pone.0013132  PMID: 20976112 
  16. EuroTest. HIV indicator conditions. Copenhagen: EuroTest; 2012. Available from: http://www.eurotest.org/HIV-Indicator-Conditions
  17. Raben D, Mocroft A, Rayment M, Mitsura VM, Hadziosmanovic V, Sthoeger ZM, et al. Auditing HIV testing rates across Europe: results from the HIDES 2 Study. PLoS One. 2015;10(11):e0140845.  https://doi.org/10.1371/journal.pone.0140845  PMID: 26560105 
  18. Omland LH, Legarth R, Ahlström MG, Sørensen HT, Obel N. Five-year risk of HIV diagnosis subsequent to 147 hospital-based indicator diseases: a Danish nationwide population-based cohort study. Clin Epidemiol. 2016;8:333-40.  https://doi.org/10.2147/CLEP.S101288  PMID: 27660491 
  19. Søgaard OS, Lohse N, Østergaard L, Kronborg G, Røge B, Gerstoft J, et al. Morbidity and risk of subsequent diagnosis of HIV: a population based case control study identifying indicator diseases for HIV infection. PLoS One. 2012;7(3):e32538.  https://doi.org/10.1371/journal.pone.0032538  PMID: 22403672 
  20. British HIV Association (BHIVA). UK National guidelines for HIV testing 2008. Letchworth: BHIVA; 2008. Available from: https://www.bhiva.org/HIV-testing-guidelines
  21. Champenois K, Cousien A, Cuzin L, Le Vu S, Deuffic-Burban S, Lanoy E, et al. Missed opportunities for HIV testing in newly-HIV-diagnosed patients, a cross sectional study. BMC Infect Dis. 2013;13(1):200.  https://doi.org/10.1186/1471-2334-13-200  PMID: 23638870 
  22. Tominski D, Katchanov J, Driesch D, Daley MB, Liedtke A, Schneider A, et al. The late-presenting HIV-infected patient 30 years after the introduction of HIV testing: spectrum of opportunistic diseases and missed opportunities for early diagnosis. HIV Med. 2017;18(2):125-32.  https://doi.org/10.1111/hiv.12403  PMID: 27478058 
  23. Joore IK, Twisk DE, Vanrolleghem AM, de Ridder M, Geerlings SE, van Bergen JEAM, et al. The need to scale up HIV indicator condition-guided testing for early case-finding: a case-control study in primary care. BMC Fam Pract. 2016;17(1):161.  https://doi.org/10.1186/s12875-016-0556-2  PMID: 27855639 
  24. European Centre for Disease Prevention and Control (ECDC). Continuum of HIV care. Stockholm: ECDC; 2019. Available from: https://ecdc.europa.eu/en/publications-data/continuum-hiv-care-monitoring-implementation-dublin-declaration-2018-progress
  25. Martin-Iguacel R, Pedersen C, Llibre JM, Søndergaard J, Jensen J, Omland LH, et al. Primary health care: An opportunity for early identification of people living with undiagnosed human immunodeficiency virus infection. HIV Med. 2019;20(6):404-17.  https://doi.org/10.1111/hiv.12735  PMID: 31016849 
  26. Statistics Denmark. Population in Denmark. Copenhagen: Statistics Denmark. [Accessed: 31 Dec 2017]. Available from: https://www.dst.dk/en/Statistik/emner/befolkning-og-valg/befolkning-og-befolkningsfremskrivning/folketal
  27. Omland LH, Ahlström MG, Obel N. Cohort profile update: the Danish HIV Cohort Study (DHCS). Int J Epidemiol. 2014;43(6):1769-9e.  https://doi.org/10.1093/ije/dyu153  PMID: 25074406 
  28. Schmidt M, Pedersen L, Sørensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014;29(8):541-9.  https://doi.org/10.1007/s10654-014-9930-3  PMID: 24965263 
  29. Pottegård A, Schmidt SAJ, Wallach-Kildemoes H, Sørensen HT, Hallas J, Schmidt M. Data Resource Profile: The Danish National Prescription Registry. Int J Epidemiol. 2017;46(3):798-798f. PMID: 27789670 
  30. Raben D, Peters L, Cowan S, Jakobsen ML, Mocroft A. Missed opportunities for HIV and viral hepatitis testing in the Danish health care system. Poster presentation. HIV Glasgow 2018. Glasgow, Scotland, 28 -31 October 2018. Available from: https://chip.dk/Portals/0/files/Conferences/Glasgow%202018/Glasgow18_missedopportunities_poster_final.pdf?ver=2018-10-30-104426-047&timestamp=1540892668629
  31. Hoover JB, Tao G, Heffelfinger JD. Monitoring HIV testing at visits to emergency departments in the United States: very-low rate of HIV testing. J Acquir Immune Defic Syndr. 2013;62(1):90-4.  https://doi.org/10.1097/QAI.0b013e3182742933  PMID: 23018376 
  32. Zucker J, Cennimo D, Sugalski G, Swaminathan S. Identifying areas for improvement in the HIV screening process of a high-prevalence emergency department. AIDS Patient Care STDS. 2016;30(6):247-53.  https://doi.org/10.1089/apc.2016.0068  PMID: 27286295 
  33. Dailey AF, Hoots BE, Hall HI, Song R, Hayes D, Fulton P Jr, et al. Vital signs: human immunodeficiency virus testing and diagnosis delays - United States. MMWR Morb Mortal Wkly Rep. 2017;66(47):1300-6.  https://doi.org/10.15585/mmwr.mm6647e1  PMID: 29190267 
  34. Joore IK, Reukers DFM, Donker GA, van Sighem AI, Op de Coul ELM, Prins JM, et al. Missed opportunities to offer HIV tests to high-risk groups during general practitioners’ STI-related consultations: an observational study. BMJ Open. 2016;6(1):e009194.  https://doi.org/10.1136/bmjopen-2015-009194  PMID: 26801464 
  35. Pottegård A, Christensen R, Houji A, Christiansen CB, Paulsen MS, Thomsen JL, et al. Primary non-adherence in general practice: a Danish register study. Eur J Clin Pharmacol. 2014;70(6):757-63.  https://doi.org/10.1007/s00228-014-1677-y  PMID: 24756147 

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error