Clinical Decisions in the Care of Elderlv Persons with AIDS J
Wayne C. McCormick, MD, MPH and Robert W. Wood, M D uring the next decade over 10% of individuals diagnosed with the acquired immunodeficiency syndrome (AIDS) will be in their sixth decade of age or older.'-3 This is more than 10% of an increasingly large number of individuals, since the total number of AIDS cases reported each year continues to i n ~ r e a s eIt. ~is likely that geriatricians currently practicing will care for persons with AIDS during their careers. Detailed information about AIDS in the elderly is still primarily in the form of case reports in the medical literat~re.~, Even in the large cohort series carried out under the auspices of the AIDS Clinical Trials Groups,7, the Multicenter AIDS Cohort Study Group,' or the cohorts of gay men being followed in San Francisco" or New York City," there have been few patients over 65 years of age in spite of the fact that, for most of these studies, there has been no upper age limit for enrollment. Even so, clinically useful corollaries emerge from analyses of very large information sources, such as the Centers for Disease Control Data Base in Atlanta, and from examining case reports of elderly persons with AIDS.' The number of cases of AIDS reported per year continues to increase; at the end of 1991,206,392 cases had been reported, of which over half (65%)had died.4 The most recent careful analysis of AIDS in older persons was carried out by Ship et al,' who analyzed cases reported to the CDC up to the end of 1989. Of the 116,000 cases reported at that time, about 3,500 (or 3.0%) were 60 years old or older.' The number of cases reported annually in older age groups (>60) increased from 1 in 1981 to over 1,000 in 1989. The proportion of cases in persons aged 60 and older has gradually increased as well, from far less than 1%of all AIDS cases in 1981 to 3% in 1989. Hence, the overall prevalence of AIDS in the elderly continues to grow in a fairly linear fashion; although the proportion of AIDS cases in persons at least 60 years of age seems to have stabilized at around 3%,' the number of reported cases of AIDS in elderly persons has increased, as exhibited in Figure 1. As reported by Ship et al,' the proportion of cases with a history of male homosexual (or bisexual) contact and/or injection drug use (IDU) fell gradually with age, although the oldest gay man among those reported in this group was 86, and the oldest person with IDU was 72. Even though elderly gay men report fewer sexual partners" and a reduced number of sexual encounters
D
From the *University of Washington; tDepartment of Gerontology and Geriatric Medicine and Greenery Speaal Care Unit, Harborview Medical Center, and the $AIDS Prevention Project, Seattle/King County Department of Public Health, Seattle, Washington. Adapted from 'Care of AIDS in the Elderly," Presented at the American Academy of Home Care Physicians and the American Geriatric Society National Meeting, Chicago, Illinois, May 1991. JAGS 40:917-921, 1992 0 1992 by the American Geriatrics Society
with those partner^,'^ this is the predominant risk behavior for HIV infection through the seventh decade. By some estimates there are at least one million gay men over the age of 65 in the United States who may continue risk behaviors into old age.'4*l5 Since the period between infection with HIV (whether such infection is symptomatic or not) and diagnosis of AIDS can be several years,I6 risk behaviors a decade or more in the past are pertinent in the evaluation of the risk of individuals for HIV infection. Changes in the distribution of cases according to sex and race were also evident in the analysis of Ship et al.' The proportion of women was lower in younger age groups than in the older age groups, and the proportion of cases who are Caucasian increased with age as well.' The proportion of cases with transfusion as the only risk behavior increased from 1% in young adults to over 60% of those aged 70 or older. Transmission of HIV by blood transfusions or cryoprecipitate for hemophilia (given prior to the implementation of widespread HIV screening in 1985) remains an important risk factor, particularly in patients aged 60 and over (and their sexual partners). Tens of thousands of patients may have received transfusions contaminated with HIV during the 1970's and early 1980's,'' and since the majority of red cell transfusions are given to older individuals, transfusion-related AIDS is more likely in older persons than in younger ones. Hence, the number of transfusion-related AIDS cases in the oldest age groups will continue to rise for the next few years in all likelihood, but at some point after the middle of this decade should recede, given the screening efforts begun in the middle of the last decade.' In summary, elderly persons with AIDS tend to be white, more are female, and receipt of blood products replaces homosexuality and IDU, to some extent, as sources of HIV infection relative to younger persons with AIDS. While the proportion of AIDS cases aged 60 or older has remained stable for the past several years at a little more than 3%, the number of persons with AIDS is substantial and growing; therefore, the number of elderly persons with AIDS is growing as well. The cases presented below illustrate parallels between the care approach typical of geriatric medicine and that which has evolved for persons with AIDS, as noted by several observers."-" Similarities in the paradigm of geriatric care and in the system of care developed for persons with AIDS include: use of multidisciplinary teams in care, incorporation of significant others into the overall picture when evaluating the health of the individual, incorporation of functional and cognitive status into patient evaluation and management, and the use of many tiers of institutional and non-hospital settings for care (eg, hospitals, nursing 0002-8614/92/$3.50
918
IAGS-SEPTEMBER 1992-VOL.40, NO.9
MCCORMICK AND WOOD CDC AIDS CASES AGE 60 OR OVER
I
'-"
1400 1200 v)
to00
Y
u)
a 0
800 600
400 200
0 1981
1982
1983
1984
1985
1996
1907
1988
1989
1990
1991
YEAR FIGURE 1. AIDS cases age 60 or over reported to the Centers for Disease Control by year reported.
homes, home care, day care, outpatient office visits). Similarities become more apparent as the treatment of opportunistic illnesses and retroviral diseases improves and as AIDS increasingly becomes a chronic illness engendering cognitive and functional impairment. When clinicians care for persons infected with (or at risk for) HIV who are also elderly, several general clinical considerations are worth remembering: (1)In elderly persons not known to be HIV seropositive, opportunistic illnesses may be misdiagnosed as common diseases of the elderly. The clinical presentation of opportunistic illness may be subtle in elderly persons with AIDS, similar to the occult presentation of many other common diseases of the elderly. Ageism can subtly and insidiously enter into the clinical judgment of even the most dedicated geriatricians (particularly regarding sexuality and drug use, the risk behaviors pertinent to HIV transmission), and we must all be on the lookout for this." (2) Conversely, in elderly persons known to be HIV seropositive, common diseases of older individuals still occur, and their presentation may be deceptive and misattributed to HIV. Elderly persons are often on multiple medications for common medical illnesses. Care must be taken when adding antiretroviral medications and other medications for AIDS-related diagnoses. Just as common medications (eg, psychotropic drugs) may have unusual side effects in the elderly, adverse effects of medications for HIV- and AIDSrelated diagnoses may be uniisual, or unusually severe, in elderly AIDS patients. (3) The progression of some opportunistic illnesses in elderly HIV-infected patients may be more rapid than in younger patients." Survival time is shorter among elderly persons with AIDS relative to younger AIDS patients.' The following cases are illustrative of these points.
The patient stated that she had been feeling weak and tired for several days and that her appetite had been poor for some time; she used canned nutritional supplements daily. It was also noted that the patient seemed "preoccupied with catching AIDS." On examination the patient was in no distress, was cooperative, and a cursory screening exam was unremarkable; vital signs were normal, without orthostasis. She was oriented to person, place, and time, and a neurological exam was non-focal. Electrocardiogram showed sinus rhythm and serum electrolytes were normal, white blood cell count was 27OO/cubic mm, and hematocrit was 29%. She was reassured regarding her AIDS fears and told that she had no risk factors for the disease. She was instructed to follow up with her primary care physician. In October of 1989 the patient was seen in the same emergency room for abdominal pain and weight loss. She had been anorexic for several months and stated she had lost weight from her usual of 125 pounds. On this visit, the ER physician contacted her primary physician who reported that he had been following the patient sporadically for several years and that, other than modest pancytopenia (for which no explanation could be found after routine bloodwork and bone marrow aspiration), the patient had been without major illnesses for all of her life. However, the primary physician went on, she was HIV seropositive as tested in his office and at the Department of Public Health in the previous year. He had diagnosed fibroids of the uterus several years ago when the patient had complained of minor, occasional abdominal pain. The ER physician found the patient to be in no acute distress, with normal vital signs and no orthostasis. She noted cachexia, slight areas of erythema of the oral mucosa, and minor, non-specific lower quadrant abdominal discomfort on palpation, with good bowel sounds and no masses. The white blood cell count was CASE 1 2200 (900 neutrophils, 1020 lymphocytes, 180 monoIn June of 1989 an 84-year-old black female was cytes, 100 eosinophils), hematocrit was 32%, and her seen in the emergency room for weakness and an electrolytes, amylase and liver function tests were again episode of light-headedness resulting in a fall at home. normal. Calcifications in the uterus consistent with
IAGS-SEPTEMBER 1992-VOL. 40, NO.9
fibroids were seen on abdominal radiographs. The low absolute granulocyte count was noted, with no signs of clinical infection. The physician instructed the patient to take ibuprofen in modest amounts and to return to see her primary care physician. The patient returned to the hospital and was admitted 2 months later in January 1990 with ongoing anorexia, weight loss, and weakness. Her weight had declined to 72% (90 pounds) of her usual or normal weight. Her physical examination again showed cachexia, oral thrush was documented, and mental status was noted to be impaired (Mini-Mental State Exam Score of 20) with deficiencies in recall, calculation, and orientation. Again, anemia and neutropenia were documented. Albumin was 2.1 gm/dL. The differential diagnosis of the weight loss included HIV infection (the wasting syndrome), malnutrition, thyroid disease, and occult malignancy. Workup revealed no reversible cause, and it was felt that the weight loss was probably due to poor oral intake and perhaps to HIV; the team noted that the CDC criteria for AIDS wasting syndrome is loss of 10% or more from usual or normal weight in the month prior to evaluation.'' The hospital physicians, like the previous doctors involved in her care, found it difficult to believe that this patient had HIV infection, despite previous testing at the County Department of Public Health. Elisa and Western blot analyses were again positive for HIV in the hospital. The CD4 count was 169/cubic mm or 11%(normal is 35%-55%). Anemia workup showed adequate iron stores as well as B12 and folate levels; the anemia was attributed to anemia of chronic disease and HIV infection. The patient was then transferred to the Geriatric Evaluation Unit for multidisciplinary assessment and treatment. Infectious disease consultants recommended modest doses of AZT, 100 mg q8h rather than the standard 200 mg TID or 100 mg q4h while awake, stating that it was difficult to predict how such a patient would react to antiretroviral therapy. Even at this low dose, the patient's neutrophil count plummeted in 2 days from an absolute granulocyte count of 1,340 cells per cubic millimeter to 360, necessitating stopping the medicine. A proper regimen for PCP (Pneumocystis carinii pneumonia) prophylaxis was the next consideration. Oral trimethoprim/sulfamethoxizole or trimethoprim and dapsone were precluded as the patient was a homozygote for glucose-6-phosphate dehydrogenase deficiency. Inhaled pentamidine was considered the best option. Oral thrush was treated with topical antifungal troches and improved oral hygiene. The Mini-Mental State Exam documented cognitive impairment consistent with dementia. The differential diagnosis included Alzheimer's disease and multi-infarct dementia, HIV encephalopathy, and other opportunistic CNS infections of AIDS such as cryptococcosis or toxoplasmosis. These were felt to be important distinctions; HIV encephalopathy often improves with antiretroviral therapy; it is among the uncommon "reversible" etiologies of dementia, albeit transiently so. Opportunistic CNS infections of AIDS (such as cryptococcosis or toxoplasmosis) affect cognition and often
ELDERLY AIDS
919
respond to specific therapy. A CT scan of the head showed atropy only. Some element of the cognitive impairment could have been attributable to depression. Psychiatry was consulted and antidepressant therapy was not felt to be indicated as the patient was not felt to be significantly depressed. It became clear during psychiatric interviewing that the patient had engaged in prostitution and injected drug use and, indeed, had participated in the former rather recently. The patient gained weight on the Geriatric Evaluation Unit after nutritional assessment. Functional assessments done by physical and occupational therapists revealed that the patient could no longer live independently. Social workers arranged for formal help at home with chores, home nursing visits, as well as informal help through friends and church volunteers. The patient was able to express her wishes not to be resuscitated in the event of cardiopulmonary failure and to live at home and "die at home in my own favorite chair." She was again discharged to receive home hospice therapy and expired 1 month later. This case illustrates severaI of the points spoken of previously: (1)the potential increased toxicity of drugs for HIV and AIDS-related diseases in the elderly; (2) the subtlety of presentation of HIV illness and AIDS in the elderly, and how similar this case is to many elderly patients evaluated in emergency rooms for weight loss, inanition, and "failure to thrive"; (3) the ageism that crept into the case- providers initially failed to identify or believe her HIV serostatus and only determined her risk behavior late in her illness; (4) the natural fit of this patient's care within the scope of the Geriatric Evaluation Unit and multidisciplinary care approach6;and (5) the rather rapid progression of AIDS in the elderly.
CASE 2 A 65-year-old gay man was followed in an AIDS clinic at a public hospital. He had tested HIV seropositive 3 years earlier and had Pneumocystis carinii pneumonia on two occasions over the preceding year and a half, both treated successfully with trimethoprim/sulfamethoxizole. Recovery from these fairly mild cases, which presented with hacking cough and sternal pain, had been rapid and complete. He was on AZT 100 mg q4h while awake and trimethoprim/sulfamethoxazole prophylaxis (double-strength daily) for PCP. He was also taking ketoconazole 200 mg daily for o r d thrush, which intermittently produced symptoms of sore mouth and throat. He was a smoker and had mild COPD, for which he used an albuterol inhaler liberally. On a routine clinic visit, he complained of an increased cough without sputum production and chest pain, which he noticed on his long walk that morning to clinic. Chest X-ray showed no infiltrate, arterial blood gas was unchanged from his best usual of pH 7.39, pCO2 of 43, PO* of 80. He stated he felt better as the clinic visit progressed that morning. The clinic physician thought that this might represent early recurrent Pneumocystiscarinii pneumonia and instructed the patient to return right away if symptoms worsened.
920
MCCORMICK AND WOOD
He returned the next morning, to the Emergency Room, with recurrent chest pain on exertion. The emergency room electrocardiogram showed evidence of a new anterolateral MI which turned out to be non-Q wave with peak CPK of 200. When presented with a 65-year-old smoker with chest pain on exertion, most physicians would immediately suspect coronary heart disease. But in the setting of known HIV disease, the clinician considered only HIV-related illnesses in the differential and delayed the opportunity to intervene in the natural history of atheroscleroticcardiovascular disease. Common diseases continue to occur in persons with HIV infection and in persons with AIDS; it behooves the physician caring for elderly HIV-infected patients to continue to look for and treat these entities.
CASE 3 A 68-year-old Hispanic man was found unresponsive on the floor of his apartment and brought by ambulance to the Emergency Room. He had a dense right hemiparesis and aphasia and was confused. Routine CT scan of the brain showed what appeared to be two areas of infarction in the left frontal and parietal lobes. The patient was hospitalized with the diagnosis of stroke, and routine rehabilitative evaluation was planned. In the first several days of the hospital stay, continuous low grade fever was noted (100-100.5° F). A rash on the buttocks was present; it stained positive for Herpes simplex and acyclovir was begun. The patient's confusion worsened. Recurrent stroke was suspected, and the patient went to CT scan again, this time with contrast. Several contrast-enhancing lesions were seen in the areas noted to have hypodensity on the previous CT. The diagnosis of metastatic tumor was entertained, and dexamethasone was begun. CT of the abdomen, lungs, bone scan, and LFT's all were unremarkable. HIV serologies were sent at the time of initiation of this workup, inspired by the primary physician who had noted the patient being visited by his male roommate. Serologies were positive for HIV by ELISA and Western Blot. Now the clinical reasoning changed to consider toxoplasmosis versus CNS lymphoma as opportunistic manifestations of HIV infection. He was begun on pyrimethamine 75 mg bid and sulfadiazine 1 g qid empirically for toxoplasmosis. Fever and confusion resolved over the next 36 hours, and strength on the right side began to improve. The CD4 count was found to be 46/mm3 with a CD4:CD8 ratio of .09, and AZT was begun at 100 q6h. The patient was transferred to a rehabilitation facility in order to continue his improvement, to taper dexamethasone, and to continue acyclovir, AZT, pyrimethamine 75 mg daily, and sulfadiazine. His recovery was complicated by nephrolithiasis due to sulfadiazine crystallinenephropathy. The sulfa was stopped and pyrimethamine was continued for chronic toxoplasmosis therapy. The patient continued to recover most of his strength on the right side and went home with visiting nurse follow-up and with
JAGS-SEPTEMBER 1992-VOL.40, NO. 9
considerable help from his roommate, who was able to take a sabbatical from his job in order to help the patient recover at home. The patient's course was further complicated by AZT-induced anemia; at the time of his last follow-up, AZT was stopped and ddI was being considered for antiretroviral therapy. Like the first case, this illustrates how HIV-related opportunistic illnesses can be misdiagnosed as common diseases of the elderly. Clinicians must pay attention to HIV risk factors in all patients, including the elderly, when they present with illnesses which could be opportunistic in nature. Furthermore, lifestyle is as diagnostically relevant in the elderly as in the young. Significant others can often be relied upon to assist with care during the chronic phases of AIDS.
DISCUSSION As opposed to the early phases of the epidemic when the diagnosis of AIDS carried a dire prognosis, it is currently common to follow young persons with AIDS for years from diagnosis to death. However, there is epidemiologic' and biologic" evidence that HIV infection and the opportunistic illnesses of AIDS progress more rapidly in older individuals, and hence the prognosis remains grim in the elderly. The proportion of AIDS patients who have AIDS diagnosed in the same month in which they die ranges from about 1 in 10 among young adults to over a third (37%) of those aged 80 or above.' The period between seroconversion and AIDS-defining opportunistic illness tends to decrease with increasing age among transfusion recipie n t ~ there , ~ ~ is more rapid progression to immunodeficiency in older than younger hemophiliac^,'^ and there is shorter survival after AIDS diagnosis in older hemophiliac^.'^ A factor may be that AIDS may be underdiagnosed among clinicians caring for elderly patients, such that it is often not diagnosed until fulminant.', Similarities exist between the defects in cell-mediated immunity produced by HIV infection and those manifested by age-related changes in cellular immunity." HIV, by infecting T cells and monocytes bearing the CD4 receptor,z6reduces the CD4 cell count over time, eventually resulting in HIV-related diseases. While the waning of cell-mediated immunity seen in aging has not been tied to any particular cell line, T cell proliferative responses appear to be dimini~hed.~' A rise in the number of CD8 suppressor-cytotoxic T cells often seen in younger HIV-infected patients is not as vigorous in older patients; there is evidence that CD8 cells are important in suppressing HIV replication and release by CD4 cells.z6The pivotal role of the CD4 T helper cells in many immune functions suffers as their numbers are depleted in HIV infection; antigen recognition wanes, virus-specific cytotoxicity is reduced, and monocyte chemotaxis gradually becomes defective. Impaired gamma interferon production and increased levels of tumor necrosis factor-alpha (TNFalpha) reduces cell-mediated immunity as well, and there is impaired triggering of natural killer cell activity and a decrease in antibody-dependent cellular cytotoxicity.'8,26All of these changes conspire to harm cell-
JAGS-SEPTEMBER 1992-VOL. 40, NO. 9
mediated immunity and result ultimately in the occurence of opportunistic disease, and several of these changes occur to a lesser or greater extent naturally in aging.'*,27 We provide the cases herein to illustrate various cautions and pitfalls in the care of elderly patients with HIV-related illness. We do not wish to discourage geriatricians from caring for HIV-infected patients; quite the contrary, we seek to emphasize that geriatricians will be caring for these patients in any event. We would suggest that caring for HIV-infected patients can be uniquely rewarding since it is a challenging, thought-provoking area in internal medicine. We also suggest that, given their talent for dealing with complicated, concurrent, multi-system illness, for coping with many tiers of the health care system with ease, for incorporating functional and cognitive assessment in patient care, and for dealing with end-of-life issues, geriatricians are uniquely prepared to take care of persons with AIDS, regardless of the age of the patient.
REFERENCES 1. Ship JA, Wolff A, Selik RM. Epidemiology of acquired immune deficiency syndrome in persons aged 50 years or older. JAIDS 1991;4:84-88. 2. Moss RJ, Miles SH. AIDS and the geriatrician. J Am Geriatr SOC 1987;35:460-464. 3. Catalania JA, Turner H, Kegeles SM et al. Older Americans and AIDS: Transmission risks and primary prevention research needs. Gerontologist
1989;29(3):373-381. 4. Centers for Disease Control Monthly AIDS Statistics, Atlanta, GA, January 29, 1992. 5. Weiler PG, Mungas D, Pomerantz S. AIDS as a cause of dementia in the elderly. J Am Geriatr SOC1988;36:139-141. 6. Fdlit H, Fruchtman S, Sell L, Rosen N. AIDS in the elderly: A case and its implications. Geriatrics 1989;44(7):65-70. 7. Fischl MA, Richman DD, Greico MH et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: A double-blind, placebo-controlled trial. N Engl J Med 1987;317185-191. 8. Fischl MA, Richman DD, Hansen N et al. The safety and efficacy of
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zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodefieency virus type 1 (HlV) infection. Ann Intern Med
1990;112:727-737. 9. Phair J, Munoz A, Detels R et al. The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1.N Engl J Med 1990;322(3):161-165. 10. Bacchetti P, Osmond D, Chaisson RE et al. Survival patterns of the first 500 patients with AIDS in San Francisco. J Infect Dis 1988;157(5):1044-
1047. 11. Rothenberg R, Woefel M, Stoneburner R et al. Survival with the acquired
immunodeficiency syndrome: experience with 5833 cases in New York City. N Engl J Med 1987;317(21):1297-1302. 12. Benn KC, Thompson NL. Social and psychological functioning of the aging male homosexual. Br J Psychiatriy 1980;137361-370, 13. Mallet EC, Badlani GH. Sexuality in the elderly. Sem Urol 1987;5:141-
145. 14 Berger RM. Gay and gray. Urbana, I L University of Illinois, 1982. 15 Kingsley LA, Kaslow R, Rinaldo CR et al. Risk factors for HIV seroconversion among male homosexuals. Lancet 1987;2:345-349. 16. Lui KJ, Dakow WD, Rutherford GW. A model-based estimate of the mean incubation period for AIDS in homosexual men. Science 1988;240:13331335. 17. Peterman TA, Lui KJ, Lawrence DN, Allen JR. Estimating the risks of transfusion-associated AIDS and human immunodeficiency virus infection. Transfusion 1987;27371-374. 18. Kendig NE, Adler WA. The implications of the acquired immunodeficiency syndrome for gerontology research and geriatric medicine. J Gerontol
1990;45(3):M77-M81, 19. Benjamin AE. Long term care and AIDS Perspectives from experience with the elderly. Milbank 1988;66(3):415-443. 20. Allers CT. AIDS and the older adult. Gerontologist 1990;30(3):405-407. 21. Greene MG, Adelman RD, Charon R, Friedmann E. Concordance between physicians and their older and younger patients in the primary care medical encounter. Gerontologist 1989;29(6):808-813. 22. Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. MMWR 1987;36(15):35-45. 23. Medley GF, Anderson RM, Cox DR, Billard L. Incubation period of AIDS in patients infected via blood transfusion. Nature 1987;328:719-721. 24. Goedert JJ, Kessler CM, Aledort LM et al. A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. N Engl J Med 1989;321:1141-1148. 25. Stehr-Green JK, Holman RC, Mahoney MA. Survival analysis of hemophilia-associated AIDS cases in the United States. Am J Public Health
1989;79:832-835. 26. NIH Conference: Immunopathogenic mechanisms of human immunodeficiency virus (HIV) infection. AIM 1991;114(8):678-693. 27. Saltzman RL, Peterson PK. Immunodeficiency of the elderly. Rev Infect Dis 1987;9(6):1127-1139.
Wayne C. McCormick, MD, MPH and Robert W. Wood, M D uring the next decade over 10% of individuals diagnosed with the acquired immunodeficiency syndrome (AIDS) will be in their sixth decade of age or older.'-3 This is more than 10% of an increasingly large number of individuals, since the total number of AIDS cases reported each year continues to i n ~ r e a s eIt. ~is likely that geriatricians currently practicing will care for persons with AIDS during their careers. Detailed information about AIDS in the elderly is still primarily in the form of case reports in the medical literat~re.~, Even in the large cohort series carried out under the auspices of the AIDS Clinical Trials Groups,7, the Multicenter AIDS Cohort Study Group,' or the cohorts of gay men being followed in San Francisco" or New York City," there have been few patients over 65 years of age in spite of the fact that, for most of these studies, there has been no upper age limit for enrollment. Even so, clinically useful corollaries emerge from analyses of very large information sources, such as the Centers for Disease Control Data Base in Atlanta, and from examining case reports of elderly persons with AIDS.' The number of cases of AIDS reported per year continues to increase; at the end of 1991,206,392 cases had been reported, of which over half (65%)had died.4 The most recent careful analysis of AIDS in older persons was carried out by Ship et al,' who analyzed cases reported to the CDC up to the end of 1989. Of the 116,000 cases reported at that time, about 3,500 (or 3.0%) were 60 years old or older.' The number of cases reported annually in older age groups (>60) increased from 1 in 1981 to over 1,000 in 1989. The proportion of cases in persons aged 60 and older has gradually increased as well, from far less than 1%of all AIDS cases in 1981 to 3% in 1989. Hence, the overall prevalence of AIDS in the elderly continues to grow in a fairly linear fashion; although the proportion of AIDS cases in persons at least 60 years of age seems to have stabilized at around 3%,' the number of reported cases of AIDS in elderly persons has increased, as exhibited in Figure 1. As reported by Ship et al,' the proportion of cases with a history of male homosexual (or bisexual) contact and/or injection drug use (IDU) fell gradually with age, although the oldest gay man among those reported in this group was 86, and the oldest person with IDU was 72. Even though elderly gay men report fewer sexual partners" and a reduced number of sexual encounters
D
From the *University of Washington; tDepartment of Gerontology and Geriatric Medicine and Greenery Speaal Care Unit, Harborview Medical Center, and the $AIDS Prevention Project, Seattle/King County Department of Public Health, Seattle, Washington. Adapted from 'Care of AIDS in the Elderly," Presented at the American Academy of Home Care Physicians and the American Geriatric Society National Meeting, Chicago, Illinois, May 1991. JAGS 40:917-921, 1992 0 1992 by the American Geriatrics Society
with those partner^,'^ this is the predominant risk behavior for HIV infection through the seventh decade. By some estimates there are at least one million gay men over the age of 65 in the United States who may continue risk behaviors into old age.'4*l5 Since the period between infection with HIV (whether such infection is symptomatic or not) and diagnosis of AIDS can be several years,I6 risk behaviors a decade or more in the past are pertinent in the evaluation of the risk of individuals for HIV infection. Changes in the distribution of cases according to sex and race were also evident in the analysis of Ship et al.' The proportion of women was lower in younger age groups than in the older age groups, and the proportion of cases who are Caucasian increased with age as well.' The proportion of cases with transfusion as the only risk behavior increased from 1% in young adults to over 60% of those aged 70 or older. Transmission of HIV by blood transfusions or cryoprecipitate for hemophilia (given prior to the implementation of widespread HIV screening in 1985) remains an important risk factor, particularly in patients aged 60 and over (and their sexual partners). Tens of thousands of patients may have received transfusions contaminated with HIV during the 1970's and early 1980's,'' and since the majority of red cell transfusions are given to older individuals, transfusion-related AIDS is more likely in older persons than in younger ones. Hence, the number of transfusion-related AIDS cases in the oldest age groups will continue to rise for the next few years in all likelihood, but at some point after the middle of this decade should recede, given the screening efforts begun in the middle of the last decade.' In summary, elderly persons with AIDS tend to be white, more are female, and receipt of blood products replaces homosexuality and IDU, to some extent, as sources of HIV infection relative to younger persons with AIDS. While the proportion of AIDS cases aged 60 or older has remained stable for the past several years at a little more than 3%, the number of persons with AIDS is substantial and growing; therefore, the number of elderly persons with AIDS is growing as well. The cases presented below illustrate parallels between the care approach typical of geriatric medicine and that which has evolved for persons with AIDS, as noted by several observers."-" Similarities in the paradigm of geriatric care and in the system of care developed for persons with AIDS include: use of multidisciplinary teams in care, incorporation of significant others into the overall picture when evaluating the health of the individual, incorporation of functional and cognitive status into patient evaluation and management, and the use of many tiers of institutional and non-hospital settings for care (eg, hospitals, nursing 0002-8614/92/$3.50
918
IAGS-SEPTEMBER 1992-VOL.40, NO.9
MCCORMICK AND WOOD CDC AIDS CASES AGE 60 OR OVER
I
'-"
1400 1200 v)
to00
Y
u)
a 0
800 600
400 200
0 1981
1982
1983
1984
1985
1996
1907
1988
1989
1990
1991
YEAR FIGURE 1. AIDS cases age 60 or over reported to the Centers for Disease Control by year reported.
homes, home care, day care, outpatient office visits). Similarities become more apparent as the treatment of opportunistic illnesses and retroviral diseases improves and as AIDS increasingly becomes a chronic illness engendering cognitive and functional impairment. When clinicians care for persons infected with (or at risk for) HIV who are also elderly, several general clinical considerations are worth remembering: (1)In elderly persons not known to be HIV seropositive, opportunistic illnesses may be misdiagnosed as common diseases of the elderly. The clinical presentation of opportunistic illness may be subtle in elderly persons with AIDS, similar to the occult presentation of many other common diseases of the elderly. Ageism can subtly and insidiously enter into the clinical judgment of even the most dedicated geriatricians (particularly regarding sexuality and drug use, the risk behaviors pertinent to HIV transmission), and we must all be on the lookout for this." (2) Conversely, in elderly persons known to be HIV seropositive, common diseases of older individuals still occur, and their presentation may be deceptive and misattributed to HIV. Elderly persons are often on multiple medications for common medical illnesses. Care must be taken when adding antiretroviral medications and other medications for AIDS-related diagnoses. Just as common medications (eg, psychotropic drugs) may have unusual side effects in the elderly, adverse effects of medications for HIV- and AIDSrelated diagnoses may be uniisual, or unusually severe, in elderly AIDS patients. (3) The progression of some opportunistic illnesses in elderly HIV-infected patients may be more rapid than in younger patients." Survival time is shorter among elderly persons with AIDS relative to younger AIDS patients.' The following cases are illustrative of these points.
The patient stated that she had been feeling weak and tired for several days and that her appetite had been poor for some time; she used canned nutritional supplements daily. It was also noted that the patient seemed "preoccupied with catching AIDS." On examination the patient was in no distress, was cooperative, and a cursory screening exam was unremarkable; vital signs were normal, without orthostasis. She was oriented to person, place, and time, and a neurological exam was non-focal. Electrocardiogram showed sinus rhythm and serum electrolytes were normal, white blood cell count was 27OO/cubic mm, and hematocrit was 29%. She was reassured regarding her AIDS fears and told that she had no risk factors for the disease. She was instructed to follow up with her primary care physician. In October of 1989 the patient was seen in the same emergency room for abdominal pain and weight loss. She had been anorexic for several months and stated she had lost weight from her usual of 125 pounds. On this visit, the ER physician contacted her primary physician who reported that he had been following the patient sporadically for several years and that, other than modest pancytopenia (for which no explanation could be found after routine bloodwork and bone marrow aspiration), the patient had been without major illnesses for all of her life. However, the primary physician went on, she was HIV seropositive as tested in his office and at the Department of Public Health in the previous year. He had diagnosed fibroids of the uterus several years ago when the patient had complained of minor, occasional abdominal pain. The ER physician found the patient to be in no acute distress, with normal vital signs and no orthostasis. She noted cachexia, slight areas of erythema of the oral mucosa, and minor, non-specific lower quadrant abdominal discomfort on palpation, with good bowel sounds and no masses. The white blood cell count was CASE 1 2200 (900 neutrophils, 1020 lymphocytes, 180 monoIn June of 1989 an 84-year-old black female was cytes, 100 eosinophils), hematocrit was 32%, and her seen in the emergency room for weakness and an electrolytes, amylase and liver function tests were again episode of light-headedness resulting in a fall at home. normal. Calcifications in the uterus consistent with
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fibroids were seen on abdominal radiographs. The low absolute granulocyte count was noted, with no signs of clinical infection. The physician instructed the patient to take ibuprofen in modest amounts and to return to see her primary care physician. The patient returned to the hospital and was admitted 2 months later in January 1990 with ongoing anorexia, weight loss, and weakness. Her weight had declined to 72% (90 pounds) of her usual or normal weight. Her physical examination again showed cachexia, oral thrush was documented, and mental status was noted to be impaired (Mini-Mental State Exam Score of 20) with deficiencies in recall, calculation, and orientation. Again, anemia and neutropenia were documented. Albumin was 2.1 gm/dL. The differential diagnosis of the weight loss included HIV infection (the wasting syndrome), malnutrition, thyroid disease, and occult malignancy. Workup revealed no reversible cause, and it was felt that the weight loss was probably due to poor oral intake and perhaps to HIV; the team noted that the CDC criteria for AIDS wasting syndrome is loss of 10% or more from usual or normal weight in the month prior to evaluation.'' The hospital physicians, like the previous doctors involved in her care, found it difficult to believe that this patient had HIV infection, despite previous testing at the County Department of Public Health. Elisa and Western blot analyses were again positive for HIV in the hospital. The CD4 count was 169/cubic mm or 11%(normal is 35%-55%). Anemia workup showed adequate iron stores as well as B12 and folate levels; the anemia was attributed to anemia of chronic disease and HIV infection. The patient was then transferred to the Geriatric Evaluation Unit for multidisciplinary assessment and treatment. Infectious disease consultants recommended modest doses of AZT, 100 mg q8h rather than the standard 200 mg TID or 100 mg q4h while awake, stating that it was difficult to predict how such a patient would react to antiretroviral therapy. Even at this low dose, the patient's neutrophil count plummeted in 2 days from an absolute granulocyte count of 1,340 cells per cubic millimeter to 360, necessitating stopping the medicine. A proper regimen for PCP (Pneumocystis carinii pneumonia) prophylaxis was the next consideration. Oral trimethoprim/sulfamethoxizole or trimethoprim and dapsone were precluded as the patient was a homozygote for glucose-6-phosphate dehydrogenase deficiency. Inhaled pentamidine was considered the best option. Oral thrush was treated with topical antifungal troches and improved oral hygiene. The Mini-Mental State Exam documented cognitive impairment consistent with dementia. The differential diagnosis included Alzheimer's disease and multi-infarct dementia, HIV encephalopathy, and other opportunistic CNS infections of AIDS such as cryptococcosis or toxoplasmosis. These were felt to be important distinctions; HIV encephalopathy often improves with antiretroviral therapy; it is among the uncommon "reversible" etiologies of dementia, albeit transiently so. Opportunistic CNS infections of AIDS (such as cryptococcosis or toxoplasmosis) affect cognition and often
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respond to specific therapy. A CT scan of the head showed atropy only. Some element of the cognitive impairment could have been attributable to depression. Psychiatry was consulted and antidepressant therapy was not felt to be indicated as the patient was not felt to be significantly depressed. It became clear during psychiatric interviewing that the patient had engaged in prostitution and injected drug use and, indeed, had participated in the former rather recently. The patient gained weight on the Geriatric Evaluation Unit after nutritional assessment. Functional assessments done by physical and occupational therapists revealed that the patient could no longer live independently. Social workers arranged for formal help at home with chores, home nursing visits, as well as informal help through friends and church volunteers. The patient was able to express her wishes not to be resuscitated in the event of cardiopulmonary failure and to live at home and "die at home in my own favorite chair." She was again discharged to receive home hospice therapy and expired 1 month later. This case illustrates severaI of the points spoken of previously: (1)the potential increased toxicity of drugs for HIV and AIDS-related diseases in the elderly; (2) the subtlety of presentation of HIV illness and AIDS in the elderly, and how similar this case is to many elderly patients evaluated in emergency rooms for weight loss, inanition, and "failure to thrive"; (3) the ageism that crept into the case- providers initially failed to identify or believe her HIV serostatus and only determined her risk behavior late in her illness; (4) the natural fit of this patient's care within the scope of the Geriatric Evaluation Unit and multidisciplinary care approach6;and (5) the rather rapid progression of AIDS in the elderly.
CASE 2 A 65-year-old gay man was followed in an AIDS clinic at a public hospital. He had tested HIV seropositive 3 years earlier and had Pneumocystis carinii pneumonia on two occasions over the preceding year and a half, both treated successfully with trimethoprim/sulfamethoxizole. Recovery from these fairly mild cases, which presented with hacking cough and sternal pain, had been rapid and complete. He was on AZT 100 mg q4h while awake and trimethoprim/sulfamethoxazole prophylaxis (double-strength daily) for PCP. He was also taking ketoconazole 200 mg daily for o r d thrush, which intermittently produced symptoms of sore mouth and throat. He was a smoker and had mild COPD, for which he used an albuterol inhaler liberally. On a routine clinic visit, he complained of an increased cough without sputum production and chest pain, which he noticed on his long walk that morning to clinic. Chest X-ray showed no infiltrate, arterial blood gas was unchanged from his best usual of pH 7.39, pCO2 of 43, PO* of 80. He stated he felt better as the clinic visit progressed that morning. The clinic physician thought that this might represent early recurrent Pneumocystiscarinii pneumonia and instructed the patient to return right away if symptoms worsened.
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He returned the next morning, to the Emergency Room, with recurrent chest pain on exertion. The emergency room electrocardiogram showed evidence of a new anterolateral MI which turned out to be non-Q wave with peak CPK of 200. When presented with a 65-year-old smoker with chest pain on exertion, most physicians would immediately suspect coronary heart disease. But in the setting of known HIV disease, the clinician considered only HIV-related illnesses in the differential and delayed the opportunity to intervene in the natural history of atheroscleroticcardiovascular disease. Common diseases continue to occur in persons with HIV infection and in persons with AIDS; it behooves the physician caring for elderly HIV-infected patients to continue to look for and treat these entities.
CASE 3 A 68-year-old Hispanic man was found unresponsive on the floor of his apartment and brought by ambulance to the Emergency Room. He had a dense right hemiparesis and aphasia and was confused. Routine CT scan of the brain showed what appeared to be two areas of infarction in the left frontal and parietal lobes. The patient was hospitalized with the diagnosis of stroke, and routine rehabilitative evaluation was planned. In the first several days of the hospital stay, continuous low grade fever was noted (100-100.5° F). A rash on the buttocks was present; it stained positive for Herpes simplex and acyclovir was begun. The patient's confusion worsened. Recurrent stroke was suspected, and the patient went to CT scan again, this time with contrast. Several contrast-enhancing lesions were seen in the areas noted to have hypodensity on the previous CT. The diagnosis of metastatic tumor was entertained, and dexamethasone was begun. CT of the abdomen, lungs, bone scan, and LFT's all were unremarkable. HIV serologies were sent at the time of initiation of this workup, inspired by the primary physician who had noted the patient being visited by his male roommate. Serologies were positive for HIV by ELISA and Western Blot. Now the clinical reasoning changed to consider toxoplasmosis versus CNS lymphoma as opportunistic manifestations of HIV infection. He was begun on pyrimethamine 75 mg bid and sulfadiazine 1 g qid empirically for toxoplasmosis. Fever and confusion resolved over the next 36 hours, and strength on the right side began to improve. The CD4 count was found to be 46/mm3 with a CD4:CD8 ratio of .09, and AZT was begun at 100 q6h. The patient was transferred to a rehabilitation facility in order to continue his improvement, to taper dexamethasone, and to continue acyclovir, AZT, pyrimethamine 75 mg daily, and sulfadiazine. His recovery was complicated by nephrolithiasis due to sulfadiazine crystallinenephropathy. The sulfa was stopped and pyrimethamine was continued for chronic toxoplasmosis therapy. The patient continued to recover most of his strength on the right side and went home with visiting nurse follow-up and with
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considerable help from his roommate, who was able to take a sabbatical from his job in order to help the patient recover at home. The patient's course was further complicated by AZT-induced anemia; at the time of his last follow-up, AZT was stopped and ddI was being considered for antiretroviral therapy. Like the first case, this illustrates how HIV-related opportunistic illnesses can be misdiagnosed as common diseases of the elderly. Clinicians must pay attention to HIV risk factors in all patients, including the elderly, when they present with illnesses which could be opportunistic in nature. Furthermore, lifestyle is as diagnostically relevant in the elderly as in the young. Significant others can often be relied upon to assist with care during the chronic phases of AIDS.
DISCUSSION As opposed to the early phases of the epidemic when the diagnosis of AIDS carried a dire prognosis, it is currently common to follow young persons with AIDS for years from diagnosis to death. However, there is epidemiologic' and biologic" evidence that HIV infection and the opportunistic illnesses of AIDS progress more rapidly in older individuals, and hence the prognosis remains grim in the elderly. The proportion of AIDS patients who have AIDS diagnosed in the same month in which they die ranges from about 1 in 10 among young adults to over a third (37%) of those aged 80 or above.' The period between seroconversion and AIDS-defining opportunistic illness tends to decrease with increasing age among transfusion recipie n t ~ there , ~ ~ is more rapid progression to immunodeficiency in older than younger hemophiliac^,'^ and there is shorter survival after AIDS diagnosis in older hemophiliac^.'^ A factor may be that AIDS may be underdiagnosed among clinicians caring for elderly patients, such that it is often not diagnosed until fulminant.', Similarities exist between the defects in cell-mediated immunity produced by HIV infection and those manifested by age-related changes in cellular immunity." HIV, by infecting T cells and monocytes bearing the CD4 receptor,z6reduces the CD4 cell count over time, eventually resulting in HIV-related diseases. While the waning of cell-mediated immunity seen in aging has not been tied to any particular cell line, T cell proliferative responses appear to be dimini~hed.~' A rise in the number of CD8 suppressor-cytotoxic T cells often seen in younger HIV-infected patients is not as vigorous in older patients; there is evidence that CD8 cells are important in suppressing HIV replication and release by CD4 cells.z6The pivotal role of the CD4 T helper cells in many immune functions suffers as their numbers are depleted in HIV infection; antigen recognition wanes, virus-specific cytotoxicity is reduced, and monocyte chemotaxis gradually becomes defective. Impaired gamma interferon production and increased levels of tumor necrosis factor-alpha (TNFalpha) reduces cell-mediated immunity as well, and there is impaired triggering of natural killer cell activity and a decrease in antibody-dependent cellular cytotoxicity.'8,26All of these changes conspire to harm cell-
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mediated immunity and result ultimately in the occurence of opportunistic disease, and several of these changes occur to a lesser or greater extent naturally in aging.'*,27 We provide the cases herein to illustrate various cautions and pitfalls in the care of elderly patients with HIV-related illness. We do not wish to discourage geriatricians from caring for HIV-infected patients; quite the contrary, we seek to emphasize that geriatricians will be caring for these patients in any event. We would suggest that caring for HIV-infected patients can be uniquely rewarding since it is a challenging, thought-provoking area in internal medicine. We also suggest that, given their talent for dealing with complicated, concurrent, multi-system illness, for coping with many tiers of the health care system with ease, for incorporating functional and cognitive assessment in patient care, and for dealing with end-of-life issues, geriatricians are uniquely prepared to take care of persons with AIDS, regardless of the age of the patient.
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1989;29(3):373-381. 4. Centers for Disease Control Monthly AIDS Statistics, Atlanta, GA, January 29, 1992. 5. Weiler PG, Mungas D, Pomerantz S. AIDS as a cause of dementia in the elderly. J Am Geriatr SOC1988;36:139-141. 6. Fdlit H, Fruchtman S, Sell L, Rosen N. AIDS in the elderly: A case and its implications. Geriatrics 1989;44(7):65-70. 7. Fischl MA, Richman DD, Greico MH et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex: A double-blind, placebo-controlled trial. N Engl J Med 1987;317185-191. 8. Fischl MA, Richman DD, Hansen N et al. The safety and efficacy of
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