J Korean Med Sci.  2013 Jan;28(1):67-73. 10.3346/jkms.2013.28.1.67.

Trends of Mortality and Cause of Death among HIV-Infected Patients in Korea, 1990-2011

• Lee SH
• Kim KH
• Lee SG
• Chen DH
• Jung DS
• Moon CS
• Park JY
• Chung JS
• Kwak IS
• Cho GJ

• KMID: 2158003
• DOI: http://doi.org/10.3346/jkms.2013.28.1.67

Abstract

Although a decrease in acquired immunodeficiency syndrome (AIDS)-related mortality has been documented in highly active antiretroviral therapy (HAART) era, there are no published data comparing specific causes of death between pre-HAART and HAART era in Korea. Mortality and cause of death were analyzed in three treatment periods; pre-HAART (1990-1997), early-HAART (1998-2001), and late-HAART period (2002-2011). The patients were retrospectively classified according to the treatment period in which they were recruited. Although mortality rate per 100 person-year declined from 8.7 in pre-HAART to 4.9 in late-HAART period, the proportion of deaths within 3 months of initial visit to study hospital significantly increased from 15.9% in pre-HAART to 55.1% in late-HAART period (P < 0.001). Overall, 59% of deaths were attributable to AIDS-related conditions, and Pneumocystis pneumonia (PCP) was the most common cause of death (20.3%). The proportion of PCP as cause of death significantly increased from 8.7% in pre-HAART to 31.8% in late-HAART period (P < 0.001). Despite of significant improvement of survival, there was still a high risk of early death in patients presenting in HAART era, mainly due to late human immunodeficiency virus (HIV) diagnosis and late presentation to care.

Keyword

HIV; Antiretroviral Therapy; Mortality; Cause of Death

MeSH Terms

Acquired Immunodeficiency Syndrome/mortality
Adult
*Antiretroviral Therapy, Highly Active
Cause of Death/*trends
Female
HIV Infections/drug therapy/*mortality
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Pneumonia, Pneumocystis/mortality
Republic of Korea
Retrospective Studies

Figure

• 

  Fig. 1 Kaplan-Meier survival plot for HIV-infected patients stratified by the treatment period in which they were recruited. Pre-HAART period (1990-1997), early-HAART period (1998-2001), and late-HAART period (2002-2011) (Generalized Wilcoxon test, χ2 test value of 28.8 on 2 degree of freedom, unadjusted P < 0.001 for comparisons among each period).

Reference

1. Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d'Arminio Monforte A, Knysz B, Dietrich M, Phillips AN, Lundgren JD. Decline in the AIDS and death rates in the EUROSIDA study: an observational study. Lancet. 2003. 362:22–29.

2. Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, d'Arminio Monforte A, Yust I, Bruun JN, Phillips AN, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. EUROSIDA study group. Lancet. 1998. 352:1725–1730.

3. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998. 338:853–860.

4. Aldaz P, Moreno-Iribas C, Egues N, Irisarri F, Floristan Y, Sola-Boneta J, Martinez-Artola V, Sagredo M, Castilla J. Mortality by causes in HIV-infected adults: comparison with the general population. BMC Public Health. 2011. 11:300.

5. Jaggy C, von Overbeck J, Ledergerber B, Schwarz C, Egger M, Rickenbach M, Furrer HJ, Telenti A, Battegay M, Flepp M, et al. Mortality in the Swiss HIV Cohort Study (SHCS) and the Swiss general population. Lancet. 2003. 362:877–878.

6. Keiser O, Taffe P, Zwahlen M, Battegay M, Bernasconi E, Weber R, Rickenbach M. All cause mortality in the Swiss HIV Cohort Study from 1990 to 2001 in comparison with the Swiss population. AIDS. 2004. 18:1835–1843.

7. Lewden C, Chene G, Morlat P, Raffi F, Dupon M, Dellamonica P, Pellegrin JL, Katlama C, Dabis F, Leport C. HIV-infected adults with a CD4 cell count greater than 500 cells/mm³ on long-term combination antiretroviral therapy reach same mortality rates as the general population. J Acquir Immune Defic Syndr. 2007. 46:72–77.

8. Lohse N, Hansen AB, Pedersen G, Kronborg G, Gerstoft J, Sorensen HT, Vaeth M, Obel N. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med. 2007. 146:87–95.

9. Obel N, Omland LH, Kronborg G, Larsen CS, Pedersen C, Pedersen G, Sorensen HT, Gerstoft J. Impact of non-HIV and HIV risk factors on survival in HIV-infected patients on haart: A population-based nationwide cohort study. PLoS One. 2011. 6:e22698.

10. Marin B, Thiebaut R, Bucher HC, Rondeau V, Costagliola D, Dorrucci M, Hamouda O, Prins M, Walker S, Porter K, et al. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy. AIDS. 2009. 23:1743–1753.

11. Sackoff JE, Hanna DB, Pfeiffer MR, Torian LV. Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New york city. Ann Intern Med. 2006. 145:397–406.

12. Smith C, Sabin CA, Lundgren JD, Thiebaut R, Weber R, Law M, Monforte A, Kirk O, Friis-Moller N, Phillips A, et al. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study. AIDS. 2010. 24:1537–1548.

13. Korea Centers for Disease Control and Prevention. KCDC Public Health Weekly Report. accessed on 1 June 2012. Available at: http://www.cdc.go.kr/phwr.

14. Kee MK, Lee JH, Kim EJ, Lee J, Nam JG, Yoo BH, Kim SS. Improvement in survival among HIV-infected individuals in the Republic of Korea: need for an early HIV diagnosis. BMC Infect Dis. 2009. 9:128.

15. Choe PG, Park WB, Song JS, Kim NH, Park JY, Song KH, Park SW, Kim HB, Kim NJ, Oh MD. Late presentation of HIV disease and its associated factors among newly diagnosed patients before and after abolition of a government policy of mass mandatory screening. J Infect. 2011. 63:60–65.

16. Department of Health and Human Services. Archived Adult and Adolescent Guidelines. accessed on 1 June 2012. http://www.aidsinfo.hih.gov/guidelines/archive/adult-and-adolescent-gudilinens.

17. International AIDS Society - USA. Guidelines archive. accessed on 1 June 2012. Available at: http: //www.iasusa.org/guidelines-archive.

18. Department of Health and Human Services. Archived Opportunistic Infection Guidelines. accessed on 1 June 2012. http://www.aidsinfo.hih.gov/guidelines/archive/Opportunistic-infection-guidelines/.

19. Centers for Disease Control and Prevention. 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.

20. Dupon M, Texier-Maugein J, Leroy V, Sentilhes A, Pellegrin JL, Morlat P, Ragnaud JM, Chene G, Dabis F. Groupe d'epidemiologie clinique du sida en aquitaine. Tuberculosis and HIV infection: a cohort study of incidence and susceptibility to antituberculous drugs, Bordeaux, 1985-1993. AIDS. 1995. 9:577–583.

21. Bisson GP, Gaolathe T, Gross R, Rollins C, Bellamy S, Mogorosi M, Avalos A, Friedman H, Dickinson D, Frank I, et al. Overestimates of survival after HAART: implications for global scale-up efforts. PLoS One. 2008. 3:e1725.

22. Crum NF, Riffenburgh RH, Wegner S, Agan BK, Tasker SA, Spooner KM, Armstrong AW, Fraser S, Wallace MR. Comparisons of causes of death and mortality rates among HIV-infected persons: analysis of the pre-, early, and late HAART (highly active antiretroviral therapy) eras. J Acquir Immune Defic Syndr. 2006. 41:194–200.

23. Jain MK, Skiest DJ, Cloud JW, Jain CL, Burns D, Berggren RE. Changes in mortality related to human immunodeficiency virus infection: Comparative analysis of inpatient deaths in 1995 and in 1999-2000. Clin Infect Dis. 2003. 36:1030–1038.

24. Krentz HB, Kliewer G, Gill MJ. Changing mortality rates and causes of death for HIV-infected individuals living in southern Alberta, Canada from 1984 to 2003. HIV Med. 2005. 6:99–106.

25. Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, Holmberg SD. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV Outpatient Study. J Acquir Immune Defic Syndr. 2006. 43:27–34.

26. Smit C, Geskus R, Walker S, Sabin C, Coutinho R, Porter K, Prins M. Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion. AIDS. 2006. 20:741–749.

27. Lundberg BE, Davidson AJ, Burman WJ. Epidemiology of Pneumocystis carinii pneumonia in an era of effective prophylaxis: the relative contribution of non-adherence and drug failure. AIDS. 2000. 14:2559–2566.

28. Moore RD, Chaisson RE. Natural history of opportunistic disease in an HIV-infected urban clinical cohort. Ann Intern Med. 1996. 124:633–642.

29. Sullivan JH, Moore RD, Keruly JC, Chaisson RE. Effect of antiretroviral therapy on the incidence of bacterial pneumonia in patients with advanced HIV infection. Am J Respir Crit Care Med. 2000. 162:64–67.

30. Wolff AJ, O'Donnell AE. Pulmonary manifestations of HIV infection in the era of highly active antiretroviral therapy. Chest. 2001. 120:1888–1893.