In countries where patients have access to modern antiretroviral therapy (ART), people are more likely to age with HIV if they adhere to their medication regimens, tolerate the medications, and have nonresistant strains of the virus that are controlled by medication (Antiretroviral Therapy Cohort Collaboration, 2008; Cellerai, Little, & Loes, 2008; Perez & Moore, 2003). According to the Centers for Disease Control and Prevention (CDC, 2008), in 2005 in the United States, the number of adults aged 50 years or older comprised 15% of new diagnoses, 24% of people living with HIV, 29% of people living with a diagnosis of AIDS, and 35% of AIDS-related deaths (CDC, 2008). In fact, by 2015, those who are 50 years of age and older with HIV will constitute 50% of this clinical population (Kirk & Goetz, 2009). Coupled with later-life infections and the historic aging of the population in general, the number of older adults with HIV will undoubtedly grow (Effros et al., 2008; Vance, Childs, Moneyham, & McKie-Bell, 2009). The success of ART is welcome, but it ushers in a new set of challenges, including age-associated comorbidity and long-term toxicity related to ART (Bisson et al., 2003). Therefore, nurse clinicians and researchers will be confronting emerging issues of how to facilitate successful aging in this growing population and will need information on the patterns of comorbidity prevalence as well as immunological and clinical characteristics between different age groups with HIV.
Welch and Morse (2002) examined the clinical characteristics of 2,583 HIV-infected men in New Orleans and compared those under and over 45 years of age. They found that older men had significantly higher incidence of Pneumocystis jiroveci pneumonia, wasting, neoplasms, congestive heart failure, stroke, nephropathy, dialysis, hypertension, diabetes, and weight loss. Though important, these data were based on records from the year 2000, and significant changes to therapy have emerged over the intervening years, including abandonment of less effective triple nucleoside regimens, the use of once-daily fixed-dose combination therapy, and the introduction of novel classes of medications (i.e., entry inhibitors, integrase inhibitors). Moreover, the awareness of aging with HIV has increased, owing in large part to the reduction of AIDS-related deaths with resultant prolonged survival. As HIV-infected patients have lived longer, mortality due to cardiovascular and liver disease and cancer has increased proportionately (Lewden et al., 2005, 2008). Taken together, a more modern assessment of the comorbidities and complications of HIV infection is needed.
The purpose of this study was to examine the comorbidity prevalence and immunological and clinical characteristics of adults with HIV engaged in outpatient clinical care across each decade of life (e.g., 18-29, 30-39, 40-49, 50-59, and 60+ years). Previous studies often compare older and younger adults with HIV using a dichotomous demarcation of under and over 50 years; however, the definition of “older” in HIV-infected patients is constantly changing and requires refinement (Lima et al., 2007). Furthermore, collapsing data into two categories prevents assessment of more precise age-related trends. This study reports the findings of an evaluation of comorbid conditions among deciles of patients followed up at a large HIV-specialty outpatient clinic in the Southeastern United States, which is becoming the epicenter of HIV disease in this country (Henry J. Kaiser Family Foundation, 2007). Finally, most HIV studies in the area collapse analyses of those 50 years of age and older into a single group (Vance et al., 2009), which does not provide a clear picture of the issues as people with HIV age past the fiftieth decade. Thus, given the topical emphasis on aging, post-hoc comparisons between those in their 50s and 60+ will be made when age differences across all deciles of life are detected.
The sample consisted of adults who attended an HIV clinic at the University of Alabama at Birmingham between May 2006 and August 2007. The University of Alabama at Birmingham 1917 Clinic Cohort is an institutional review board approved, prospective, observational study of patients receiving primary and subspecialty HIV care that was established in 1992, and has been described in detail previously (Chen et al., 2006). Briefly, sociodemographic, psychosocial, and clinical information are systematically collected from all patients receiving care at the 1917 Clinic through point-of-care, locally-programmed electronic medical records coupled with a 100% quality control program that was recognized for excellence in information integrity (www.uab1917cliniccohort.org). For the purpose of analysis, race/ethnicity was collapsed into two categories (nonminority/minority) because more than 95% of racial/ethnic minorities in care at the 1917 Clinic were African American. No patient identifiers were included in the database.
Instrument and Procedure
In this descriptive, cross-sectional study, data retrieved from electronic medical records included age, medical diagnoses, HIV viral load and CD4+ T lymphocyte lab values, appointment information, insurance status, and HIV risk type. Because of the large number of specific diagnoses included in patient problem lists, medical diagnoses were collapsed into broader categories to avoid overly complex tables. The 1917 Clinic electronic medical records use a customized subset of SnoMed terminologies for diagnoses (Chen et al., 2006). For the current study, two infectious disease providers at the clinic reviewed all diagnostic terms used by clinic providers and categorized specific diagnoses into broader categories that were employed analytically and presented in this article. For example, substance abuse consolidated global terms for substance use disorders along with specific diagnostic terms for individual drugs of abuse (e.g., cocaine abuse).
Data on independent variables in the study period were electronically retrieved from the 1917 Clinic Cohort Database by Cohort Data Analysts utilizing Microsoft SQL queries. Longitudinal information for the study period was obtained for variables that may have changed with time to develop an overall composite measure. For example, the number of medications prescribed and number of comorbidities listed during this period were tallied and reported. For HIV viral load and CD4+ T lymphocyte count, the laboratory values nearest the August 2007 study end date were used. In addition, if patients died during this period, their other clinical information was included.
Age, broken down by decade of life, was the independent variable of interest across all analyses. Dependent variables included sociodemographic characteristics (age, race/ethnicity, health insurance status, mode of HIV acquisition), clinical, and treatment characteristics (CD4+ T lymphocyte count, plasma HIV viral load, ART, clinic utilization, and comorbidities). Data were assessed across the entire 16-month study period for number of medical visits, consistent viral suppression, and mortality. History of CD4+ T lymphocyte nadir and years diagnosed with HIV were ascertained from existing medical records pulled beyond this 16-month window.
To examine associations between dichotomous variables, a chi-square was used and frequencies and percentages were reported. To examine associations between continuous variables, an analysis of variance was used, and means and standard deviations were reported. For all analyses, statistical significance was defined as a 2-tailed p-value < .05. All analyses were performed using SPSS version 14.0.
Demographic and clinic variables of the 1,478 study participants by decade of life are displayed in Table 1. Men comprised close to 75% of each age category. In the entire sample, 50.8% were Caucasian, 47.2% were African American, and the other 1.9% were other race/ethnicity (e.g., Asian, Hispanic, other, missing). A significant relationship was observed between minority status and age; older adults were less likely to be minorities, which may have been related to epidemiologic trends in HIV incidence and prevalence. Older adults were more likely to indicate HIV risk exposure by heterosexual contact. Older adults were also more likely to have had public or private health insurance compared with younger adults who frequently did not have any type of health insurance. No apparent difference with age was observed with the number of medical appointments scheduled. However, older adults were more likely to attend scheduled appointments and less likely to “no show” (miss an appointment without calling to cancel).
With regard to HIV clinical parameters, older adults had lower HIV viral loads than younger adults and were more likely to have an undetectable viral load and a more consistent undetectable viral load (plasma HIV RNA <50 copies/mL; Table 2). No age differences were observed for current CD4+ T lymphocyte count values. However, CD4+ T lymphocyte nadir was lower in older adults. Also, those who were older had been diagnosed with HIV longer. With increasing age, the number of prescribed medications increased significantly. Concerning antiretroviral medications, receipt was significantly less likely among younger adults, although this analysis did not consider indication for ART based on CD4+ T lymphocyte count and plasma HIV viral load parameters. The number of comorbid conditions and death increased significantly with advancing age. Patients 19 to 29 years old had an average of 2.20 (SD = 1.7) diagnosed comorbidities; 1.4% of individuals in this age group died during the study period. In contrast, an average of 4.52 (SD = 1.9) comorbidities were diagnosed in patients older than 60 years; 8.2% of this group died.
Younger patients were more likely to use tobacco, recreational drugs, and have condyloma accuminatum disease (Table 3). Older adults, in contrast, exhibited more insomnia, coronary artery disease, hypertension, hypercholesterolemia, hypogonadism, erectile dysfunction, diabetes mellitus, peripheral neuropathy, gastrointestinal reflux disease, renal disease, and shingles/herpes zoster. Concerning alcohol abuse and hepatitis C, a significant difference was observed between the age groups; however, the peak incidence occurred in the 40 to 49 and 50 to 59 years age groups.
The prevalence of five selected comorbidities and overall mortality is shown in Figure 1. Across the deciles, coronary artery disease increased by 20%, hypertension by 60%, hypercholesterolemia by 58%, diabetes by 25%, and renal disease by 21%. The prevalence of these conditions rose steadily over time.
Ad Hoc Comparisons Between 50s and 60+ Groups
When group differences were detected across deciles, ad hoc analyses were conducted between the 50 to 59 and the 60+ groups. Compared to the 50 to 59 group, these analyses revealed that the 60+ group reported significantly more heterosexual contact as a risk factor for HIV (Χ2[N = 374] = 5.00, p = .025), had more public health insurance (Χ2[N = 374] = 5.52, p = .019), were more likely to have health insurance (Χ2[N = 374] = 10.35, p = .001), and were less likely to cancel, (t = 2.07, p = .039), or not show up for appointments, (t = 2.00, p = .046).
Comorbidity differences were also found. Compared to the 50 to 59 group, the 60+ group exhibited significantly less substance use (Χ2[N = 374] = 7.79, p = .005), more coronary artery disease (Χ2[N = 374] = 15.50, p = .000), more hypertension (Χ2[N = 374] = 7.60, p = .006), more hypercholesterolemia (Χ2[N = 374] = 10.35, p = .001), more diabetes (Χ2[N = 374] = 11.52, p = .001), and more renal disease (Χ2[N = 374] = 10.86, p = .001). Meanwhile, no immunological differences on viral load and CD4+ T lymphocyte count were detected between these groups.
Our study shows that comorbidity profiles and mortality vary considerably across deciles of age in the modern era of ART. As might be expected, older patients with HIV experience more coronary artery disease, hypertension, hypercholesterolemia, diabetes, and renal disease than younger patients. This finding corresponds to other studies and reports that show similar results (e.g., Friis-Møller et al., 2003; Kirk & Goetz, 2009). The different comorbidity profiles in patients 50 to 59 years old relative to those older than 60 years suggest the commonly applied cut-off of older than 50 years to indicate advanced age with HIV infection is not a sufficient or appropriate designation. The group older than 50 years, which is one of the fastest growing groups of patients in the United States (CDC, 2008), is quite heterogeneous, suggesting future research should evaluate this group of patients with more precision and sophistication (Vance et al., 2009).
Like other geriatric patients, the number of prescribed medications increased with age for patients with HIV at this clinic, almost doubling from the 18 to 29 years age group to the 60+ years age group. This increase in medications only added to the complexity of providing care for aging patients, especially when memory problems interfered with adhering to complicated dosing schedules (Hinkin et al., 2004). As patients age, pharmacologic clearance slows and absorption may become less consistent. This leads to irregular drug levels, resulting in a higher risk for either more toxicity owing to elevated drug levels or less effective regimens owing to inadequate drug levels. The presence of concomitant comorbid conditions, such as chronic kidney disease or diabetes, can further complicate the clinical picture. Finally, taking more drugs means more opportunity for drug-drug interactions, which are more frequent and less predictable in older populations (Hanlon et al., 2006; Routledge, O'Mahony, & Woodhouse, 2004). This is of special concern; in a large study of more than 17,000 adults with HIV, the Data Collection Adverse Events of Anti-HIV Drugs (DAD) study found an association between ART and cardiovascular disease risk factors (Friis-Møller et al., 2003). Thus, the medications that sustain life in the short-term may compromise life as one grows older.
Despite the hazards of increased numbers of medications and complexity of clinical conditions, older patients in this clinic population had better HIV-related outcomes than their younger counterparts. Older adults exhibited better viral control as expressed with a lower HIV viral load, and a higher proportion of patients achieving an undetectable viral load (<50 copies/mL). This finding may reflect the fact that older adults with HIV, if not suffering from cognitive impairments, have been shown to be more adherent to medication regimens (Hinkin et al., 2004). It was also observed that the older patients were more likely to show up for medical appointments––a factor associated with improved virologic outcomes in other studies (Collazos, Asensi, Carton, & Ibarra, 2009; Giordano et al., 2003). Older adults also had comparable CD4+ T lymphocyte count values. On the surface, this may be an unexpected outcome, based on biologic observations that CD4+ T lymphocyte production and function declines over time as the thymus involutes (Effros et al., 2008). However, this finding may have been related, in part, to survivor bias in patients with higher CD4+ T lymphocyte counts who may be more likely to survive into the 6th and 7th decades, or it may simply have been a reflection of better control of viral replication in this group.
The younger generations in our study reported more tobacco abuse, substance abuse, and alcohol abuse in this clinic. Researchers reported that patients tended to decrease the amount of substance use as they aged; however, in a large cohort of veterans with and without HIV, this trend was not observed for older adults with HIV (Justice et al., 2004). However, those who survive and age with HIV could just be physically and psychologically more hardy (Vance, Burrage, Couch, & Raper, 2008); in that sense, survivor bias is inherent in most studies of aging with HIV.
Concerning psychological health, there were no differences between the age groups on depression or anxiety, both of which displayed a high prevalence across age groups. However, studies have indicated that older adults with HIV may be more susceptible to psychological distress, such as stigma, loneliness, and suicidal ideation, especially when experiencing health problems (Casau, 2005; Goulet et al., 2007; Shippy & Karpiak, 2005). Further assessment of the frequency of affective disorders in this population is warranted.
Limitations and Strengths
The findings of this study should be interpreted with respect to study limitations. As an observational study, the identified associations cannot determine causality. As a single center study, our findings may not be generalizable to other practice settings or geographic regions. Implicit in the cross-sectional design of this study is the possibility of survival bias influencing findings regarding aging with HIV. However, the purpose of this approach generates a snapshot into the current comorbidities of older adults with HIV at a large HIV clinic and accordingly provides evidence on real-world issues faced by these individuals.
The use of current clinical data to examine differences across the lifespan of a large sample of HIV-infected patients was a strength of this study. However, as is endemic to HIV research, the length of time infected with HIV cannot be accurately quantified; the best approximation is length of time diagnosed, which was used in this study. Such information may be relevant in examining how well someone can age successfully with HIV. Likewise, no data on treatment tolerance was available for analysis; this is a limitation that will need to be addressed in future research (Casau, 2005). Our study also lacked an uninfected control group; fortunately, Goulet et al. (2007) examined a large population-based sample of HIV-infected and uninfected veterans and found that older adults with HIV were more likely to have comorbidities than their uninfected counterparts; this finding paralleled our results. Also, Goulet et al. found that HIV-infected adults were at lower risk for diabetes, hypertension, vascular disease, and psychiatric disorders, but were at a higher risk for substance use disorders, renal disease, liver disease, and comorbidity. This study by Goulet et al. placed our study findings within a context of an uninfected sample. Yet, from the current study, an overview of the clinical characteristics of patients treated for HIV provided tools to forecast the medical needs of this growing population.
A unique strength of this study was the set of ad hoc comparisons between those in their 50s and 60+. From this analysis, it was clear that patients aged 50 to 59 years with HIV exhibited different clinical and comorbidity characteristics from those aged more than 60 years, suggesting that studies that collapse these age groups together should be done with more pause and consideration. However, it is interesting to note that no immunological characteristic differences were found between these groups.
Several implications for nursing practice can be derived from this study. First, nurses treating patients with HIV need to be aware of the common comorbidities patients will face as they age with this disease, especially coronary artery disease, renal disease, diabetes, hypertension, and hypercholesterolemia. Such comorbidities may be aggravated by antiretroviral medications and the number of other medications that older adults with HIV are more likely to take.
Second, as mentioned, patients aging with HIV are more likely to be prescribed more medications. Although older adults with HIV are more likely to adhere to their medication regimens if they are not experiencing cognitive impairments (Hinkin et al., 2004), for many older adults with HIV who do have age- and/or HIV-related cognitive impairments, keeping track of and taking medications as prescribed (e.g., missing doses, doubling doses because they forgot they already took the medication, taking medications with food when instructed not to do so, etc.) presents a unique medical concern. This difficulty with proper medication adherence may be especially problematic for those with alcohol and substance use issues as were observed in approximately 25% of those 50 to 59 years and approximately 10% in those 60 years and older. Therefore, nurses need to discuss medication compliance issues with patients to avoid poor health maintenance habits as well as dangerous drug interactions and side effects. Nurses must also be mindful of the effects these medications can exert on metabolic, renal, hepatic, and cardiovascular systems (Vance et al., 2009).
Third, given the concern over coronary artery disease, hypercholesterolemia, diabetes, hypertension, and renal disease, nurses and nurse researchers need to examine ways to promote successful aging in this growing clinical population. Given the problems related to polypharmacy, more nonmedication approaches should be encouraged and evaluated, (e.g., diet, exercise, stress reduction, sleep hygiene, reduction in substance use, and health education).
Finally, nurses can rest assured that as a group, older adults with HIV are more likely to have some form of health insurance, either public or private. Perhaps it is for this reason that older adults are less likely to cancel or not show up for their medical appointments. Compliance with clinic visits provides nurses with unique opportunities to have on-going contact with patients during which support and education can be provided to promote wellness.
In summary, adults older than 50 years with HIV infection represent a heterogeneous group as it relates to comorbidity profiles and clinical characteristics. Perhaps most striking is the dramatic rise in several comorbid conditions with advancing age, particularly coronary artery disease, hypertension, diabetes, renal disease, and hypercholesterolemia. In the short-term, these data inform research on aging and HIV, strongly suggesting that future studies should not casually combine those older than 50 years into a single group, as has often been done in the past. Clearly, as observed in this study, the clinical characteristics of those in their 50s are indeed different from those older than 60 years and should be treated as such and reflected in the literature. In the longer-term, our study provides empirical data to support recent calls for greater attention to the aging HIV population, highlighting the critical importance of cardiovascular comorbidity management with advancing age. Finally, this study provides insight into future policy related to funding required to pay for the growing costs of treating non–HIV-related comorbidities, which certainly will increase over time as the number of older individuals with HIV infection continues to grow owing to the durable effectiveness of ART.
- Thanks largely to the effectiveness of ART, by 2015 approximately half of the adults with HIV living in the United States will be 50 years or older.
- However, conventional comparisons of HIV-positive adults under and over 50 years may not be as useful now that we are treating much older adults with HIV.
- Nurses treating patients with HIV need to be aware of the common comorbidities patients will face as they age with this disease, especially coronary artery disease, renal disease, diabetes, hypertension, and hypercholesterolemia.
- Fortunately, older adults with HIV are more likely to have some form of health insurance and seem to be more adherent to medical appointments.
The author(s) report(s) no real or perceived vested interests that relate to this article (including relationships with pharmaceutical companies, biomedical device manufacturers, grantors, or other entities whose products or services are related to topics covered in this manuscript) that could be construed as a conflict of interest. The authors report no financial interests or potential conflicts of interest.
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