Between 1996 and 2000, rates of hospitalization among HIV-infected patients 50 years and over increased while hospitalization rates for those 18 to 30 years old decreased dramatically (Gebo et al 2005
). However, reasons for hospitalizations among HIV-infected patients 50 years and older has also changed since the introduction of HAART, with fewer hospitalizations for OIs, but more hospitalizations related to cerebrovascular and ischemic heart diseases. Additionally, older age was associated with higher rates of hospitalizations for liver-related diseases, pneumonia, and diabetes, and higher odds of death during hospitalization compared to younger ages.
Heart disease, diabetes, and cancers are among the most prevalent chronic medical conditions affecting older adults and account for some of the leading causes of death in the US population age 65 years and older (FIARS 2006
). Other conditions such as hypertension, hyperlipidemia, cerebrovascular diseases, and declining renal function also become more prevalent as a person ages. Even among HIV-infected patients, a higher percentage of older patients have diabetes, chronic respiratory disorders, hypertension, and hyperlipidemia, as well as other cardiac conditions, such as coronary heart disease and heart failure (Skiest et al 1996
; Butt et al 2004
; Palacios et al 2006
). In one study of HIV-infected persons 55 years and older, 89% had one or more co-morbidities, with an average of 2.4 co-morbid conditions per person (Shah et al 2002
). Whether any or all of these co-morbid conditions can exacerbate the natural history of HIV infection in older patients, further compound toxicities from HIV therapy, or affect morbidity and mortality in this patient population remains to be determined.
There is limited evidence-based literature to guide therapy of metabolic complications specifically in HIV-infected patients although various groups have developed general guidelines to assist the clinician in areas of managing metabolic complications associated with HAART (Schambelan et al 2002
) and separate guidelines for addressing dyslipidemia in HIV (Dube et al 2003
). A brief review of these recommendations and of current HIV clinical practice is provided for the reader under the section titled “Primary care issues.”
As mentioned earlier, declining CD4 cell counts in HIV infection is associated with increased risk for certain types of malignancy. The CDC’s AIDS case definition includes Kaposi’s sarcoma (KS), lymphomas, such as Burkitt’s lymphoma and non-Hodgkin’s lymphoma (NHL), and invasive cervical carcinoma (CDC 1992
). Since the introduction of HAART, the incidences of KS and NHL among AIDS patients have significantly declined (Clifford et al 2005
; Engels et al 2006
). Nonetheless, regardless of HAART, there are other non-AIDS defining malignancies found in a greater proportion of HIV-infected patients compared to the general population, including lung, liver, brain, and anal cancers (Dal Maso et al 2003
; Clifford et al 2005
; Engels and Goedert 2005
; Engels et al 2006
Cancer risk also increases with age in non-HIV-infected persons, but very limited data is available evaluating the impact of HIV infection on cancer risk in older persons and vice versa. Using data from the AIDS-Cancer Registry Match study, Engels (2001)
determined risk for KS and lung cancer in AIDS patients stratified by age. In AIDS patients 60 years and older, risk for KS was significantly lower than that among patients 30 to 39 years old. The author noted that this trend was quite different from KS previously seen at a higher rate in non-HIV infected elderly European and Mediterranean men. Conversely, the incidence of lung cancer among AIDS patients increased with age from 0.1 per 1,000 persons-years in the 15 to 29 years old age group to 3.7 per 1,000 persons-years in the 60 years and older age group. Even though this mirrored the increasing incidence of lung cancer with aging in the general population, the overall incidence was still higher in AIDS patients than in the age-matched population.
The same study group also sought to determine effects of HIV infection on the cancer risk profile of AIDS patients 60 years and older. Compared to the general population, elderly AIDS patients had a relative risk of 1.3 for all non-AIDS defining cancers (Biggar et al 2004
). In this analysis, elderly AIDS patients had a higher risk for Hodgkin’s lymphoma, anal cancer, liver cancer, and multiple myeloma. Additionally, lung and stomach cancer risks were higher in this group. One interesting observation was that prostate cancer was negatively associated with AIDS. The authors speculated that this may be due to reduced screening in the elderly HIV/AIDS population. These data demonstrate that information on cancer risk in elderly HIV-infected persons is still evolving, and until more definitive information becomes available, the clinician should be aware of and continue screening for HIV-associated and age-associated malignancies.
Although many factors are associated with the development of osteopenia and osteoporosis, recent studies have suggested that women with HIV infection are at greater risk for this condition, which can be further accentuated when taking certain ARV regimens (Dolan et al 2004
; Pan et al 2006
; Anastos et al 2007
). HIV-infected older men also manifest decreased bone mineral density compared to uninfected men (Arnsten et al 2007
). Whereas some studies have determined that HIV infection and lower CD4 counts result in earlier onset of menopause (Schoenbaum et al 2005
), the effect of HIV infection on women’s hormonal levels, menstrual cycles and the relationship with resultant osteoporosis is not clear. HIV infection and increasing age in men are also associated with hypogonadism (Crum-Cianflone et al 2007
). A multitude of clinical conditions including sexual dysfunction, fatigue, poor appetite and osteopenia are associated with hypogonadism (Klein et al 2005
). Androgen replacement and treatment of erectile dysfunction even in elderly men can result in significant improvements in some of these conditions and in quality of life (Crum et al 2005
). Practitioners should keep in mind that in HIV-infected patients treated with protease inhibitors, caution should be used with the concurrent administration of phosphodiesterase enzyme inhibitor medications for erectile dysfunction (eg, sildenafil) due to clinically important drug interactions. Protease inhibitors can inhibit the metabolism of the erectile dysfunction agent, thereby leading to high blood levels and increased risk for side effects such as severe hypotension.
Psychiatric disorders may predispose persons to HIV risk behaviors and ultimately HIV infection. HIV infection itself can also increase the likelihood of active psychiatric disorders, including depression, bipolar disorder and mania, psychosis, and anxiety disorders as well as cognitive decline, dementia, and substance abuse disorders. In their review of the literature on psychiatric co-morbidity in HIV-infected older patients, Skapik and Treisman (2007)
revealed that HIV-positive older adults had higher rates of depression and poorer cognitive function compared to HIV-negative older adults. Furthermore, it is postulated that various psychiatric disorders may contribute to the progression of HIV disease through a number of interactions leading to further immunosuppression. When managing psychiatric disorders in HIV-infected patients, the clinician should keep in mind that a number of psychotropics (including, but not limited to selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and tricyclic antidepressants) can have significant interactions with antiretroviral therapy and thus dosing titration is key. In addition, Efavirenz can cause psychiatric and neurologic disturbances and should be used with caution; patients should be counseled regarding its potential effects. A number of review articles summarizing the data and treatment considerations on this topic are currently available and the reader is referred to these references for further information as needed (Hinkin et al 2001
; Dolder et al 2004
; Skapik and Treisman 2007
In advanced immunosuppression, symptoms of opportunistic infections that preferentially infect the central nervous system (eg, cryptococcal meningitis and toxoplasma encephalitis) may be difficult to distinguish from age-related neurologic changes. HIV neurologic syndromes, such as AIDS dementia and progressive multifocal leukoencephalopathy (PML), can also manifest as or aggravate underlying dementia symptoms in the elderly. HIV-associated dementia has been found to have higher prevalence and tends to be more severe in HIV-infected patients age 50 years and older than in younger patients (age 20 to 39 years old) (Valcour et al 2004
). In contrast, the Veterans Aging Cohort Five-Site Study did not find depression and alcohol/drug abuse to increase with age – in fact, just the opposite, when comparing HIV-infected patients by age group (Justice et al 2004
). What the investigators did find was that HIV-infected patients had higher prevalence of depression and alcohol/drug abuse than age-matched non-HIV-infected patients. Regardless of HIV infection status, memory problems were positively correlated with increased age in this study population. Thus, the presence of both psychiatric disorders and cognitive decline can be a significant morbidity in the aging HIV-infected patient.