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Excess Clinical Comorbidity Among HIV-Infected Patients Accessing Primary Care in US Community Health Centers....[20% diabetes, 44% hypertension, 56% dyslipidemia, HPV, lymphoma & cancers were more prevalent in HIV+, so was stroke]
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....safety-net community health centers in the United States....community health center patients tend to be poorer and are more likely to come from racial/ethnic minority communities than those who access care in private settings.....The management of non-HIV and antiretroviral treatment regimens will increasingly complicate the primary care of HIV-infected people. To date, although guidelines on how best to clinically manage HIV-infected people with other chronic noncommunicable diseases are available,61 further research is needed to define best practices, as well as the optimal combination of treatment regimens and behavioral interventions to optimize preventive behaviors. From a health-systems perspective, appropriate health care delivery models that are diverse in medical expertise, including gerontologists, cardiologists, endocrinologists, oncologists, and nephrologists, in addition to HIV care providers, will be fundamental to the care of HIV-infected people.....the Health Resources & Services Administration funded the Community Health Applied Research Network to develop a common database of key clinical data elements from community health centers across the United States.
"The prevalence of noncommunicable diseases among HIV-infected people has implications for clinical care and health care resources. One reason that HIV-infected people develop age-related morbidities at a faster rate than HIV-uninfected people may be the cumulative effects of longstanding inflammation caused by responding to a chronic viral infection, particularly among those who initiated highly active antiretroviral therapy when symptomatic.25 Even those who initiate treatment promptly after being diagnosed with HIV do not fully recover immunologically, because the destruction of immune reserve occurs immediately after HIV infection is established. The earliest major cellular depletion is of gut-associated lymphoid tissue, making an HIV-infected person less capable than an HIV-uninfected person of limiting the circulation of gastrointestinal bacterial products that stimulate chronic immune activation.26 Subclinical immunodeficiency may be associated with decreased immune surveillance, resulting in an increased risk of neoplasia, particularly from virally associated cancers, such as HPV-related tumors (cervical, vulvar, anal, and oropharyngeal malignancies), or Epstein-Barr virus–associated lymphomas (particularly Burkitt's lymphoma and central nervous system lymphomas).27 In addition to enduring decades of chronic inflammation, HIV-infected people who have been infected for more than a decade are likely to have taken medications that can cause chronic morbidity."
"Conclusions: As HIV-infected patients live longer, the increasing burden of noncommunicable diseases may complicate their clinical management, requiring primary care providers to be trained in chronic disease management for this population. [20% diabetes, 44% hypertension, 56% dyslipidemia, HPV, lymphoma & cancers were more prevalent in HIV+, so was stroke]
Conclusions
Our study has implications for the long-term management of HIV-infected patients in primary care, given the high prevalence of common clinical morbidities detected in this large, diverse sample with tens of thousands of years of follow-up.
As HIV-infected people age, an increasing number of treatable noncommunicable diseases may give rise to issues related to polypharmacy.60 The management of non-HIV and antiretroviral treatment regimens will increasingly complicate the primary care of HIV-infected people. To date, although guidelines on how best to clinically manage HIV-infected people with other chronic noncommunicable diseases are available,61 further research is needed to define best practices, as well as the optimal combination of treatment regimens and behavioral interventions to optimize preventive behaviors. From a health-systems perspective, appropriate health care delivery models that are diverse in medical expertise, including gerontologists, cardiologists, endocrinologists, oncologists, and nephrologists, in addition to HIV care providers, will be fundamental to the care of HIV-infected people. Future studies are needed to inform the development of sensible care guidelines to identify which models best meet the needs of HIV-infected people and to bring these intersecting issues to the forefront of the research agenda for aging HIV-infected people.
"During the past 2 decades, HIV has been transformed from an untreatable immunodeficiency usually resulting in death from opportunistic infections and neoplasms to a chronic manageable infection, often requiring only 1 well-tolerated pill per day.22 As the life expectancy of HIV-infected people has increased,23 their spectrum of illnesses has evolved.24 We found higher rates of diabetes, hypertension, chronic kidney disease, stroke, and several cancers in HIV-infected patients accessing primary care at community health centers than among HIV-uninfected patients. Our study is the first to document excess morbidities among HIV-infected patients accessing care in safety-net community health centers."
⋅ RESULTS: Nearly two-thirds of HIV-infected and HIV-uninfected patients lived in poverty. Compared with HIV-uninfected patients, HIV-infected patients were significantly more likely to be diagnosed and/or treated for diabetes (odds ratio [OR] = 1.18; 95% confidence interval [CI], 1.22-1.41), hypertension (OR = 1.38; 95% CI, 1.31-1.46), dyslipidemia (OR = 2.30; 95% CI, 2.17-2.43), chronic kidney disease (OR = 4.75; 95% CI, 4.23-5.34), lymphomas (OR = 4.02; 95% CI, 2.86-5.67), cancers related to human papillomavirus (OR = 5.05; 95% CI, 3.77-6.78), or other cancers (OR = 1.25; 95% CI, 1.10-1.42). The prevalence of stroke was higher among HIV-infected patients (OR = 1.32; 95% CI, 1.06-1.63) than among HIV-uninfected patients, but the prevalence of myocardial infarction or coronary artery disease did not differ between the 2 groups......
⋅The increasing age of HIV-infected patients also contributes to renal morbidity; rates of chronic kidney disease are <1% in patients aged <40 and increase to >6% among patients aged >60.44 propensity toward diabetes for HIV-infected patients was robust
⋅ The excess risk for chronic kidney disease in HIV-infected patients was particularly high among younger patients: a relative risk of 4.6 in those aged <40, but a nonsignificant difference among those aged >60 (ie, aging HIV-uninfected patients acquire chronic kidney disease from many other causes).45 The North American AIDS Cohort Collaboration on Research and Design found that race was also independently associated with chronic kidney disease among HIV-infected people; black HIV-infected patients had a 46% increased risk of progressive chronic kidney
disease than white HIV-infected patients.46
⋅ The least prevalent condition was HPV-associated malignancy (cervix, vulvar, rectal, oropharyngeal), which was diagnosed in 0.8% of HIV-infected versus 0.3% of HIV-uninfected patients (P < .001). The prevalence of cancers not associated with HIV or HPV was also greater among HIV-infected patients than among HIV-uninfected patients. Although the absolute numbers of lymphomas and HPV-associated cancers were lower than numbers of other cancers, their relative prevalence was greater among HIV-infected patients than among HIV-uninfected patients (P < .001 for all comparisons). Although strokes were uncommon (1.1% of the entire sample), they were more common among HIV-infected patients than among HIV-uninfected patients (P = .002), but the relative prevalence of myocardial infarction and coronary artery disease did not differ between the 2 groups.
⋅ HIV-infected patients were more likely than HIV-uninfected patients to be diagnosed with lymphomas
(OR = 4.02; 95% CI, 2.86-5.67), HPV-related cancers (OR = 5.05; 95% CI, 3.77-6.78), and other cancers (OR = 1.25; 95% CI, 1.10-1.42) (P < .001 for all comparisons). Although HIV-infected patients did not differ from HIV-uninfected patients in their prevalence of myocardial infarction or coronary artery disease, they were more likely to have a stroke (OR = 1.32; 95% CI, 1.06-1.63).
⋅ the absolute rates of all of these conditions were high among HIV-infected patients accessing care in community health centers; for example, more than 40% had hypertension and dyslipidemia, and almost 20% had diabetes. Thus, primary care community health center providers will need to be attentive to the need for routine management ofcomorbid conditions in medically complex HIV-infected patients
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Excess Clinical Comorbidity Among HIV-Infected Patients Accessing Primary Care in US Community Health Centers
Kenneth H. Mayer, MD1,2,3 , Stephanie Loo, MSc1, Phillip M. Crawford, MS4, Heidi M. Crane, MD, MPH5, Michael Leo, PhD4, Paul DenOuden, MD6, Magda Houlberg, MD7, Mark Schmidt, PhD4, Thu Quach, PhD, MPH8, Sebastian Ruhs, MD9, Meredith Vandermeer, MPH4, Chris Grasso, MPH1, and Mary Ann McBurnie, PhD4
1 The Fenway Institute, Fenway Health, Boston, MA, USA
2 Harvard Medical School, Boston, MA, USA
3 HIV Prevention Research, Beth Israel Deaconess Hospital, Boston, MA,
USA
4 Kaiser Permanente Center for Health Research, Portland, OR, USA
5 University of Washington, Seattle, WA, USA
6 Multnomah County Community Health Center, Portland, OR, USA
7 Howard Brown Community Health Center, Chicago, IL, USA
8 Asian Health Services, Oakland, CA, USA
9 Chase Brexton Health Care, Baltimore, MD, USA
Abstract
Objectives: As the life expectancy of people infected with human immunodeficiency virus (HIV) infection has increased, the spectrum of illness has evolved. We evaluated whether people living with HIV accessing primary care in US community health centers had higher morbidity compared with HIV-uninfected patients receiving care at the same sites.
Methods: We compared data from electronic health records for 12 837 HIV-infected and 227 012 HIV-uninfected patients to evaluate the relative prevalence of diabetes mellitus, hypertension, chronic kidney disease, dyslipidemia, and malignancies by HIV serostatus. We used multivariable logistic regression to evaluate differences. Participants were patients aged 18 who were followed for 3 years (from January 2006 to December 2016) in 1 of 17 community health centers belonging to the
Community Health Applied Research Network.
Results: Nearly two-thirds of HIV-infected and HIV-uninfected patients lived in poverty. Compared with HIV-uninfected patients, HIV-infected patients were significantly more likely to be diagnosed and/or treated for diabetes (odds ratio [OR] = 1.18; 95% confidence interval [CI], 1.22-1.41), hypertension (OR = 1.38; 95% CI, 1.31-1.46), dyslipidemia (OR = 2.30; 95% CI, 2.17-2.43), chronic kidney disease (OR = 4.75; 95% CI, 4.23-5.34), lymphomas (OR = 4.02; 95% CI, 2.86-5.67), cancers related to human papillomavirus (OR = 5.05; 95% CI, 3.77-6.78), or other cancers (OR = 1.25; 95% CI, 1.10-1.42). The prevalence of stroke was higher among HIV-infected patients (OR = 1.32; 95% CI, 1.06-1.63) than among HIV-uninfected patients, but the prevalence of myocardial infarction or coronary artery disease did not differ between the 2 groups.
Conclusions: As HIV-infected patients live longer, the increasing burden of noncommunicable diseases may complicate their clinical management, requiring primary care providers to be trained in chronic disease management for this population.
With the advent of highly active antiretroviral therapy, people who are infected with human immunodeficiency virus (HIV) are living longer, particularly now that the newer medications are better tolerated than the original medications. 1,2 Life expectancy has also increased dramatically. An HIV-infected adult aged 20 who became infected in 2016 can expect to live 53 additional years compared with a 20-year-old diagnosed 30 years ago, who was likely to die within a decade.3 Projections from a Dutch national database suggest that the median age of HIV-infected patients will increase to 57 years by 2030, with 39% of HIV-infected patients being aged >/=60.4 Despite the increased longevity, concerns have been raised that HIV disease and its treatment might accentuate and accelerate the onset of noncommunicable morbidities.5 HIV-infected people have high rates of atherosclerosis, diabetes, chronic kidney disease, and several malignancies in studies conducted at academic research centers. 6-9 Multiple factors might explain the excess morbidity, including the long-term effects of HIV-induced immune dysregulation and inflammation, behavioral risks (eg, tobacco and other substance use), and the potential long-term effects of antiretroviral medication.10
Because recent data suggest that earlier initiation of treatment is associated with decreased morbidity and mortality, the use of highly active antiretroviral therapy is increasingly common.11 Almost all studies assessing HIV morbidity have used samples of patients from specialty clinics at teaching hospitals, rather than community-based samples, raising questions about generalizability of the findings.12
To date, no studies of chronic HIV infection have been conducted in safety-net community health centers in the
United States, where disenfranchised patients may have multiple risk factors for other common conditions. Studies of HIV infected patients in the Veterans Administration system have provided important insights about the changing spectrum of HIV disease in a racially and ethnically diverse sample but may not be generalizable to community-based samples.13 The more than 9000 Federally Qualified Health Centers play an increasingly pivotal role in ensuring health care access to 25 million primary care patients. Our study is particularly important because community health center patients tend to be poorer and are more likely to come from racial/ethnic minority communities than those who access care in private settings.14 We evaluated whether the prevalence of selected conditions (diabetes mellitus, hypertension, chronic kidney disease, dyslipidemia, atherosclerotic disease, and cancer) was higher among HIV-infected patients than among HIV-uninfected patients receiving primary care at community health centers in a geographically diverse sample.
Discussion
During the past 2 decades, HIV has been transformed from an untreatable immunodeficiency usually resulting in death from opportunistic infections and neoplasms to a chronic manageable infection, often requiring only 1 well-tolerated pill per day.22 As the life expectancy of HIV-infected people has increased,23 their spectrum of illnesses has evolved.24 We found higher rates of diabetes, hypertension, chronic kidney disease, stroke, and several cancers in HIV-infected patients accessing primary care at community health centers than among HIV-uninfected patients. Our study is the first to document excess morbidities among HIV-infected patients accessing care in safety-net community health centers.
The prevalence of noncommunicable diseases among HIV-infected people has implications for clinical care and health care resources. One reason that HIV-infected people develop age-related morbidities at a faster rate than HIV-uninfected people may be the cumulative effects of longstanding inflammation caused by responding to a chronic viral infection, particularly among those who initiated highly active antiretroviral therapy when symptomatic.25 Even those who initiate treatment promptly after being diagnosed with HIV do not fully recover immunologically, because the destruction of immune reserve occurs immediately after HIV infection is established. The earliest major cellular depletion is of gut-associated lymphoid tissue, making an HIV-infected person less capable than an HIV-uninfected person of limiting the circulation of gastrointestinal bacterial products that stimulate chronic immune activation.26 Subclinical immunodeficiency may be associated with decreased immune surveillance, resulting in an increased risk of neoplasia, particularly from virally associated cancers, such as HPV-related tumors (cervical, vulvar, anal, and oropharyngeal malignancies), or Epstein-Barr virus–associated lymphomas (particularly Burkitt's lymphoma and central nervous system lymphomas).27 In addition to enduring decades of chronic inflammation, HIV-infected people who have been infected for more than a decade are likely to have taken medications that can cause chronic morbidity.
Some of the earlier drugs that aging HIV-infected patients with longstanding infection took included stavudine, which could
result in hyperglycemia and progression to diabetes.28 Among the most commonly used contemporary antiretroviral medications is tenofovir disiproxil fumarate, which is associated with nephrotoxicity, particularly among those with preexisting risk factors, such as untreated hypertension or diabetes.
Several large cohort studies that tracked acute and chronic disease among HIV-infected people and documented substantial morbidity primarily followed patients receiving care in tertiary research centers. Our study found a high rate of hypertension (more than one-third of HIV-infected patients). The Women's Interagency HIV Study reported that HIV-infected women at baseline had a prevalence of hypertension of 26%, which is similar to the prevalence among demographically matched HIV-uninfected women.28
Factors associated with hypertension include increasing age, African American race, smoking, low education levels, and obesity (BMI >30 kg/m2) and, in HIV-infected patients, particularly those using protease inhibitors, an increased likelihood of metabolic syndrome.29 More recent data suggest that hypertension rates increased among HIV-infected patients between 2003 and 2013, with the highest prevalence found among Medicare recipients (65.1%; who would tend to be older) compared with those who used commercial insurance (25.0%).30 The higher prevalence of hypertension in HIV-infected Community Health Applied Research Network patients compared with locally selected HIV-uninfected controls is notable, given that they tended to be younger and were less likely to be African American than patients followed in other cohort studies.27-29
Rates of insulin resistance appear to be higher in HIV-infected people than in HIV-uninfected people.31-33 The Multicenter AIDS Cohort Study found that HIV-infected men using antiretroviral therapy had approximately a 5-fold increase in risk of diabetes compared with HIV-uninfected controls and that antiretroviral therapy use conferred a 2-fold to 3-fold increased risk of hyperglycemia compared with HIV-infected, untreated controls.31 Hepatitis C coinfection, which is common in HIV infection and was more prevalent among HIV-infected patients in this Community Health Applied Research Network sample compared with HIV-uninfected patients in this sample, is an independent risk factor for developing diabetes.34-37 The increased rates of opiate use disorder among HIV-infected patients in our cohort may reflect higher rates of injection drug use as the mechanism for the higher prevalence of hepatitis C.
HIV-uninfected patients who are obese or have excess abdominal fat have a higher risk of developing diabetes than the general US population.38 The higher risk of diabetes among HIV-infected patients than among HIV-uninfected patients in our study was particularly notable given the large number of HIV-uninfected Asian Pacific Islanders who received primary care in several of the participating Community Health Applied Research Network community health centers and who would have a greater genetic predisposition to glucose intolerance.39
The propensity toward diabetes for HIV-infected patients was robust; it persisted even after adjustment for BMI. Our study found significant excess risk of chronic kidney disease among HIV-infected patients, also noted in other studies.40-42 The reasons for the excess renal morbidity in HIV-infected patients include HIV disease itself, as well as several of the medications used to treat HIV, particularly tenofovir disiproxil fumarate, one of the most common treatments. 43 The increasing age of HIV-infected patients also contributes to renal morbidity; rates of chronic kidney disease are <1% in patients aged <40 and increase to >6% among patients aged >60.44 The excess risk for chronic kidney disease in HIV-infected patients was particularly high among younger patients: a relative risk of 4.6 in those aged <40, but a nonsignificant difference among those aged >60 (ie, aging HIV-uninfected patients acquire chronic kidney disease from many other causes).45 The North American AIDS Cohort Collaboration on Research and Design found that race was also independently associated with chronic kidney disease among HIV-infected people; black HIV-infected patients had a 46% increased risk of progressive chronic kidney disease than white HIV-infected patients.46 The results of our study also underscore the need to carefully control for potential confounders, such as race and age, because the prevalence of chronic kidney disease was only slightly higher among HIV-infected patients, but the difference in Ors was much greater. In this community-based sample, the finding of excess chronic kidney disease in HIV-infected patients was particularly striking, given that HIV-infected patients tended to be younger and were less likely to be from a racial/ethnic minority group than other community health center patients, highlighting the importance of adjusted analyses.
Lipid abnormalities are common among HIV-infected people and are seen in both untreated people and those using highly active antiretroviral therapy.47-50 In our study, both HIV-infected patients and HIV-uninfected patients frequently took medication for dyslipidemia and/or had a laboratory test indicating dyslipidemia (ie, elevated plasma low-density lipoprotein cholesterol or triglyceride levels).
Severe dyslipidemia in HIV-infected patients—hypertriglyceridemia in particular—is increased in patients who use protease inhibitors, especially ritonavir-containing regimens.51 The effect of various antiretroviral medications on lipids varies considerably. Recent recommendations for initial highly active antiretroviral therapy regimens included initiating treatment with 2 nucleoside reverse transcriptase inhibitors and an integrase strand transfer inhibitor,51 regimens that are less likely to cause dyslipidemia in patients without other risk factors than previously recommended options. The high prevalence of dyslipidemia in HIV-infected patients and HIV-uninfected patients in this sample may reflect that this condition is increasingly common in the general population but may also suggest that most patients accessing primary care services in safety-net community health centers could benefit from lifestyle interventions that might decrease their risk of complications from untreated dyslipidemia (eg, exercise, diet, and medication).
HIV-infected patients have been known to be at increased risk for malignancies associated with immunodeficiency since the beginning of the epidemic, although the spectrum has changed in the current era of highly active antiretroviral therapy.52 In recent years, the prevalence of Kaposi's sarcoma and central nervous system lymphomas has declined, whereas the prevalence of Hodgkins and non-Hodgkins lymphoma has increased.53 The rates of other cancers have also increased, particularly liver, anal, laryngeal, and lung cancers. 54-56 The increased prevalence of liver cancer may reflect the high rates of chronic hepatitis B and hepatitis C infection in HIV-infected patients, and the increasing rate of anal cancer may reflect high levels of concomitant oncogenic HPV infection. The high rates of lung cancer may reflect excess rates of cigarette smoking among HIV-infected patients,55-59 and rates of laryngeal cancer may be affected by both excess smoking and HPV exposure. In the Community Health Applied Research Network population, lymphomas and HPV-related cancers were much more prevalent among HIV-infected patients than among HIV-uninfected patients, consistent with other epidemiological studies, but
excess risk for other cancers was also seen. Thus, astute clinicians will need to be alert for a wide range of oncogenic outcomes as their HIV-infected patients age.
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