Introduction    The prognosis of adults in the developed world with human immunodeficiency virus (HIV) or acquired immune deficiency Syndrome (AIDS)  who are adherent with combination antiretroviral therapy (cART) is now approaching that of the general population (1,2).  This is attributable to the decreased incidence of AIDS opportunistic infections (OI) from cART use and improved care for those with HIV related complications (3-5).  Worldwide, the availability of cART is estimated to have saved nearly 8 million people between 2000-2014 (6). Consequently, an increased proportion of deaths in HIV patients are due to organ failure; non-AIDS malignancies; substance abuse; and limitations in health care access.  This Fast Fact will provide prognostic information on the non-malignant complications of the syndrome.  Fast Fact #214 will cover prognosis on AIDS related malignancies. 

Prognostic Principles  

• Certain factors are correlated with a worse prognosis from AIDS related conditions: African American or mixed races, the number of OIs, poor functional and nutritional status, anemia, active substance abuse, a low CD4+ count, and a high HIV viral load (7-10).
• For patients who do not receive cART with a CD4 count < 50 cells/mm3, survival ranges between 12-27 months; those with CD4+ counts <20 cells/mm3 have a median survival of 11 months (2).
• Many patients die with HIV or AIDS, not from it.  In one large hospital based study, 78% of the deaths were non-AIDS related (11). Surprisingly, these deaths were more closely associated with cART use, a higher CD4+ count and a suppressed HIV viral load (1).
• Hospice eligibility criteria include: absence of cART therapy, decreased performance status (Palliative Perfomance Scale <50%), a CD4+ count <25 cells/mcL, and a viral load >100,000 copies/mL plus either CNS lymphoma, AIDS wasting syndrome (>10% weight loss not attributable to another condition); Mycobacterium avium complex (MAC); progressive multifocal leukoencephalopathy (PML); systemic lymphoma; visceral Kaposi’s sarcoma, renal failure in the absence of dialysis, cryptosporidium infection, or toxoplasmosis. 
• Some experts have described a “Lazarus effect” wherein AIDS patients appear to be imminently dying, only to experience a dramatic medical recovery with (re)institution of cART therapy. 
• Because the field of HIV medicine is rapidly evolving, close collaboration with the treating HIV specialist is recommended regarding prognosis and treatment options.

OIs and Non-malignant HIV Related Conditions   Not only has the incidence of OIs declined dramatically since the early 1990s, but the 5 year survival following an AIDS defining OI is now 65% (12).  Below are prognostic data for the most common OIs and HIV related conditions in descending incidence during 2000-2015:

• Pneumocystis jiroveci pneumonia (PCP): incident mortality 9.7-11.6%. Poor prognostic indicators include: age >50, respiratory failure, ICU admission, anemia, low albumin, new HIV diagnosis (13). Following successfully treatment of PCP, one year survival is 94% and 5 year survival is 73% (14).
• AIDS Wasting Syndrome: 5 year mortality is 23% (15).
• Cryptococcal meningitis: 90 day mortality is 10-19%. 1 year mortality is 16-26%. Increased age, intracranial pressure >25 cm, positive CSF cultures after 2 weeks therapy, cryptococcemia, and absence of cART are risk factors for mortality (16-19).
• HIV-associated dementia: 1 year survival is about 65% (19-20).
• Disseminated MAC infection: median survival 10 months; mortality is four fold that of MAC negative matched HIV+ patients (15).
• Cryptosporidial enteritis: 5 year survival is 81% (3,21).
• Cytomegalovirus disease including retinitis: median survival is 13-35 months (22-23).
• Toxoplasma encephalitis: 77-90% survival at 12months if on cART with most deaths occurring within 6 months (19,24).
• PML: median survival without cART is 4 months; overall 1 year survival is 50-63%.  Predictors of survival beyond one year include cART adherence and CD4+ > 100 cells/mm3 at diagnosis (25-27).

References

1. Cowell A, Shenoi SV, Kyriakides TC, Friedland G, Bakarat. Trends in Hospital Deaths Among Human Immunodeficiency Virus-Infected Patients During the Antiretroviral Therapy Era, 1995 to 2011. Journal of Hospital Medicine.2015; 10(9):608-614.
2. Bhaskaran K, Hamouda O, Sannes M, Boufassa F, Johnson AM, Lambert PC, Porter K. Changes in the Risk of Death After HIV Seroconversion Compared With Mortality in the General Population. JAMA 2008; 300(1):51-59.
3. Djawe K, Buchacz K, Hsu L, Chen MJ, Selik RM, Rose C, Williams T, Brooks JT, Schwarcz. Mortality Risk After AIDS-Defining Opportunistic Illness Among HIV-Infected Persons – San Francisco, 1981-2012. Journal of Infectious Diseases, 2015:212:1366-1375.
4. Schwarcz L, Chen MJ, Vittinghoff E, Hsu L, Schwarcz. Declining incidence of AIDS-defining opportunistic illnesses: results from 16 years of population-based AIDS surveillance. AIDS. 2013; 27:597-605.
5. Lima VD, Lourenco L, Yip B, Hogg RS, Phillips P, Montaner JSG. AIDS incidence and AIDS- related mortality in British Columbia, Canada, between 1981 and 2013: a retrospective study. Lancet. 2015; 2:e92-97.
6. Fauci AS, Marston HD. Ending the HIV-AIDS Pandemic- Follow the Science. NEJM. 2015; 373(23):2197-2199.
7. An Q, Song R, Hernandez A, Hall HI. Trends and Differences Among Three New Indicators of HIV Infection Progression. Public Health Reports. 2015; 130: 468-474.
8. Lemly DC, Shepherd BE, Hulgan T, Rebeiro P, Stinnette S, Blackwell RB, Bebawy S, Kheshti A, Sterling TR, Raffanti SP. Race and Sex Differences in Antiretroviral Therapy Use and Mortality among HIV-Infected Persons in Care. Journal of Infectious Diseases. 2009. 199: 991-998.
9. Adih WK, Selik RM, Hu X. Trends in Diseases Reported on US Death Certificates That Mentioned HIV Infection, 1996-2006. Journal of the International Association of Physicians in AIDS Care. 2011; 10(1):5-11.
10. Grant PM, Komarow L, Sanchez A, Sattler FR, Asmuth DM, Pollard RB, Zolopa AR. Clinical and Immunologic predictors of Death After an Acute Opportunistic Infection: Results from ACTG A5164. HIV Clinical Trials. 2014; 15(4): 133-139.
11. Kim JH, Psevdos G, Gonzalez E, Singh S, Kilayko MC, Sharp V. All- Cause mortality in hospitalized HIV-infected patients at an acute tertiary care hospital with a comprehensive outpatient HIV care program in New York City in the era of highly active antiretroviral therapy (HAART). Infection. 2013; 41: 545-551.
12. Masur H, Read SW. Opportunistic Infections and Mortality: Still Room for Improvement. Journal of Infectious Diseases. 2015; 212: 1348-1350.
13. Miller RF, Huang L, Walzer PD. Pneumocystis Pneumonia Associated with Human Immunodeficiency Virus. Clinics in Chest Medicine. 2013; 34: 229-241.
14. Lopez-Sanchez, C, Falco V, Burgos J, Navarro J, Martin T, Curran A, Miguel L, Ocana I, Ribera E, Crespo M, Almirante B. Epidemiology and Long-Term Survival in HIV-Infected Patients with Pneumocystis jirovecii Pneumonia in the HAART Era. Medicine. 2015; 94(12): 1-8.
15. Scherzer R, Heymsfield SB, Lee D, Powderly WG, Tien PC, Bacchetti P, Shlipak MG, Grunfeld C. Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection. AIDS 2011; 25(11): 1405-1414.
16. Brizendine KD, Baddley JW, Pappas PG. Predictors of Mortality and Differences in Clinical Features among Patients with Cryptococcosis According to Immune Status. PLoS ONE. 2013; 8(3): e60431.
17. Bratton EW, Husseini NE, Chastain CA, Lee MS, Poole C, Sturmer T, Juliano JJ, Weber DJ, Perfect JR> Comparison and Temporal Trends of Three Groups with Cryptococcosis: HIV- Infected, Solid Organ Transplant, and HIV-Negative/Non-Transplant. PLoS ONE 2012; 7(8): e43582.
18. Shun S, Mody CH. Cryptococcus. Proceedings of the American Thoracic Society. 2010; 7: 186-196.
19. Lanoy E, Guiguet M, Benata M, Rouveix E, Dhiver C, Poizot-Martin, I, Costaglioa D, Gasnault J. Survival after neuro AIDS. Neurology 2011; 76: 644-651.
20. Wright E. Neurocognitive Impairment and neuroCART. Current Opinions in HIV AIDS. 2011; 6:303-308.
21. O’Connor RM, Shaffie R, Kang G, Ward HD. Cryptosporidiosis in patients with HIV/AIDS. AIDS 2011; 25:549-560.
22. Jabs DA, Martin BK, Forman MS. Mortality associated with resistany cytomegalovirus among patients with cytomegalovirus retinitis and AODS. Opthalmology. 2010; 117(1): 128.
23. Kemper JH, Jabs DA, Wilson LA, Dunn JP, West SK, Tonascia J. Mortality risk for patients with cytomegalovirus retinitis and acquired immunodeficiency syndrome. Clinics in Infectious Diseases. 2003; 37: 1365-1373.
24. Hoffman C, Ernst M, Wolf E, Wolf E, Rosenkranz T, Plettenberg A, Stoehr A, Horst HA, Marienfeld K, Lange C. Evolving characteristics of toxoplasmosis in patients infected with human immunodeficiency virus-1: Clinical course and Toxoplasma gondii-specific immune responses. 2007; 13: 510-515.
25. Lima MA, Bernal-Cano F, Clifford DB, Gandhi RT, Koralnik IJ. Clinical outcome of long-term survivors of progressive multifocal leukoencephalopathy. Journal of Neurology Neurosurgery Psychiatry. 2010; 81: 1288-1291.
26. Delbue S, Elia F, Carloni C, Tavazzi E, Marchioni E, Carluccio S, Signorini L, Novati S, Maserati R, Ferrante P. JC Virus Load in Cerebrospinal Fluid and Transcriptional Control Region Rearrangements May Predict the Clinical Course of Progressive Multifocal Leukoencephalopathy. Journal of Cellular Physiology. 2012; 227: 3511-3517.
27. Casado JL, Corral I, Garcia J, Martinez-San Millian J, Navas E, Moreno A, Moreno S. Continued declining incidence and improved survival of progressive multifocal leukoencephalopathy in HIV/AIDS patients in the current era. European Journal of Clinial Microbiology and Infectious Diseases. 2014; 33: 179-187.

Author Affiliation:  The University of Arizona College of Medicine and Banner Medical Group Division of Palliative Medicine

Version History:   Originally published March 2009.  Significant revision occurred in February 2016 by Steven Oppenheim MD to reflect updates in the literature.