In this study of patients with HIV and diabetes or hypertension, increasing HIV-1 RNA was associated with higher HbA1c and higher MAP. This is the first study to demonstrate that poor control of HIV-1 RNA is directly correlated with poor control of diabetes and hypertension, two comorbidities of increasing importance in the management of the patients with HIV infection. We suspect that adherence accounts for our findings, and that poor adherence to antiretroviral therapy correlates with poor adherence to therapy for other medical comorbidities, explaining the relationship between poor control of both conditions.
There are possible alternate explanations for the observed association. Uncontrolled HIV causes systemic inflammation,13
and may contribute to both the development of hypertension and diabetes and to difficulty controlling the conditions. Therapeutic inertia, or failure to increase therapy despite unmet treatment goals, may also hinder control, 14
and may be more pronounced in patients with multiple chronic conditions, especially if they are unrelated chronic conditions.15
Among individuals with HIV, especially those with poor control of their HIV or infectious complications related to immune compromise, less priority may be given to managing their diabetes and hypertension. We found only a weak association between CD4 count and HbA1c, and no association between CD4 count and MAP, suggesting that the level of immunosuppression does not play a significant role. Irrespective of the reason for poor control of both conditions, our study emphasizes the new challenges of multi-morbidity, and suggests that interventions targeting both patients and providers may be needed.
Three prior studies of diabetes control in HIV disease have been conducted. The most recent study by Satlin and colleagues revealed that about one-third of patients in the study sample did not meet American Diabetes Association (ADA) HbA1c goals and over half did not meet blood pressure goals. Similar proportions of patients with adequate and inadequate glycemic control had an undetectable viral load (p=0.21).16
Another study involving 40 HIV-infected diabetics demonstrated that fewer than half of patients attained ADA hemoglobin A1c and blood pressure targets. Undetectable viral load was associated with not meeting LDL and total cholesterol goals.17
A third study examined glycemic, lipid, and blood pressure control among 216 HIV-infected diabetic patients from an urban clinic,18
finding that 54% of patients met the ADA HbA1c target and 65% reached the blood pressure target. The authors noted that an undetectable HIV viral load was associated with being less likely to meet total cholesterol and LDL cholesterol targets, which they attributed to antiretroviral-induced hyperlipidemia. There was no mention of an association between HbA1c at goal or blood pressure at goal and undetectable viral load. Our study expands on prior research by examining the relationship between HIV control and diabetes and hypertension control, with the ultimate goal of understanding how to optimize control of multiple conditions simultaneously.
The prevalence of diabetes in individuals with HIV has been reported as ranging from 2–12%, 6, 19
and diabetes has been associated with antiretroviral therapy, particularly with nucleoside reverse transcriptase inhibitors.20, 21
The overall prevalence of hypertension among HIV-infected individuals was 31.7% (56.4% in men older than 50) in a large cohort study with HIV-uninfected controls,8
with no difference in hypertension prevalence by HIV status. Both conditions contribute to cardiovascular and renal disease and may increase non-HIV related morbidity and mortality in this population.22
Controlling multiple comorbidities is increasingly important as the population of individuals with HIV in the United States ages. In 2008, almost twenty percent of new HIV cases in the U.S. occurred in individuals aged 50 and older.23
An aging population with HIV faces complications from both long-term metabolic toxicities of ART and common medical comorbidities whose prevalence increases with increasing age, such as diabetes and cardiovascular disease.24
Mortality in older individuals with HIV is higher than in younger individuals with HIV,25
the result of both infectious complications and medical comorbidities, and achieving good control of other medical comorbidities in addition to HIV is necessary to decrease mortality in older individuals.
The challenges of multi-morbidity are pronounced for individuals who receive HIV care, as competing priorities make adhering to complex medication regimens difficult. Up to 50% of patients (irrespective of comorbidity) do not take their medications as prescribed, resulting in significant morbidity and cost.26, 27
Despite the importance of adherence in HIV clinical care,13, 28
antiretroviral adherence is suboptimal: a meta-analysis of HIV treatment adherence interventions revealed baseline adherence rates of 55–95% among all participants.29
Similar to HIV, uncontrolled diabetes and hypertension are often caused by poor adherence29
Only about twelve percent of diabetics meet ADA goals for lipid, blood pressure, and glycemic control simultaneously30
and around 35% of hypertensives have controlled blood pressure.31
Self-reported medication adherence is associated with lower HbA1c in diabetes,32, 33
and high adherence to antihypertensive therapy has been associated with blood pressure control.34
Sub-optimal adherence stems from a variety of factors which can be categorized as patient-level barriers, patient-provider barriers, and patient-system barriers.27, 35
Patient-level barriers include low self-efficacy, low literacy, substance abuse and depression.36
These are compounded by patient-provider and patient-system barriers such as poor communication and misunderstanding of treatment instructions, poverty, poor education and housing, lack of insurance and medication costs.37–39
Our study has several potential limitations. Although HbA1c is used clinically in the management of HIV-infected diabetics, it underestimates glycemia.40
This effect should be evenly distributed throughout all study participants, however, and should not affect the associations detected. Blood pressure measurements were part of the routine vital signs measurement done at clinic visits and were not standardized. In addition, we do not have a direct measure of adherence, such as patient self-report, electronic monitoring caps, pill counts, or pharmacy refill data.41
Suppressed viral load is an accepted surrogate for treatment adherence, despite the fact that less than perfect adherence may also result in undetectable viral load.36
Our results demonstrate that poor HIV control is related to poor control of diabetes and hypertension, and we suspect that poor adherence to therapy for HIV is correlated with poor adherence to therapy for other conditions. Research on how patients prioritize medications for their comorbidities in relation to their HIV medications could shape future treatment adherence programs as our patient population ages and more individuals develop comorbid conditions. The most successful adherence programs combine several interventions such as incorporating behavioral interventions with education and increased convenience of care.42
They are typically long-term, individually-tailored interventions focused on practical medication management skills.29, 43
Our results argue that the scope of these programs should be expanded to include both antiretroviral agents and agents for other comorbidities.