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HIV & Aging Clinical Recommendations
Hypertension (HTN) remains one of the more common chronic diseases in the general population, affecting nearly 75 million adults in the United States . Global estimates of hypertension in persons living with HIV (PLWH) show an overall prevalence of 25%, increasing with age and treatment experience . Studies comparing HIV-treated to HIV-uninfected individuals are inconsistent in determining a difference in the prevalence of HTN ; . Recent studies have attempted to address the potential relationship between HIV infection, antiretroviral therapy (ART), and HTN. These reports      confirm that while HTN is common, there is little evidence to suggest that HIV or specific antiretroviral medications independently cause HTN. Rather, as the population with HIV ages, the prevalence of HTN increases, just as it does in the general population. Recently, the American Heart Association highlighted the importance of cardiovascular disease (CVD) in PLWH, discussing the association of HTN with CVD .
Several mechanisms have been proposed as the potential cause of HTN in PLWH, including chronic inflammation from gut bacterial translocation leading to blood vessel stiffening, activation of the renin-angiotensin-aldosterone system, and chronic sympathetic activation . But as mentioned above, there is no concrete evidence that PLWH are at an increased risk of developing HTN, though they are likely at an increased risk of suffering the consequences of uncontrolled HTN. Thankfully, the clinical awareness of HTN in PLWH seems to be increasing .
Ambulatory blood pressure monitoring has become an important tool in the diagnosis of HTN and monitoring of HTN control , and is now a strongly recommended practice for diagnostic confirmation . This has also been shown to be useful in PLWH. On one hand, there may be an overestimation of HTN using in-clinic measurements alone, at least with older definitions of HTN . However, it may also be helpful as PLWH seem to have abnormal diurnal blood pressure, where the blood pressure does not fall at night as in most uninfected individuals, which may also be diagnosed by ambulatory measurements , and may result in underdiagnosis if only in-clinic measurements are used. Furthermore, the appropriate office method of blood pressure measurement also needs to be implemented, including avoiding causes of elevated BP such as recent caffeine or tobacco use, full bladder, talking, clothing under the cuff, with back and feet unsupported .
As the number of individuals living with HIV has grown, many of them have begun to utilize healthcare services outside of HIV clinics (Patel 2016). The number of comorbidities has increased, particularly in those over the age of 50, and treatment for HTN has become common. These findings underscore the need for increased coordination of services, particularly for older individuals living with HIV (Patel 2016).
Blood Pressure Goals
There are several clinical guidelines for management of HTN, including guidelines published by the American College of Physicians (ACP) and the American Academy of Family Medicine (AAFP), the Eighth Joint National Committee (JNC8), and the AHA/ACC guidelines published by the American Heart Association and American College of Cardiology (Kansagara 2017; James 2014; Rosendorff 2015a). Recommendations have also been published for target BP goals in the setting of different comorbid conditions, such as diabetes and CKD (ADA 2017; KDIGO 2013). These guidelines differ slightly in their recommendation for when to initiate therapy and the target BP for older adults diagnosed with HTN. The JNC8, AAFP and ACP advocate for target BP goals of less than 150/90 mmHg for adults age 60 or older. The AHA/ACC recommend a patient-centered target of <130/80 for those with clinical CVD (e.g. ischemic heart disease or stroke) or are at high risk of CVD (≥10% 10-year risk using a risk assessment calculator such as the ASCVD risk score), or a goal of 140/90 in those without CVD or low risk of developing CVD (<10% 10-year risk).
Similarly, the American Diabetes Association generally recommends a goal of 130/80, and recommendations from KDIGO (Kidney Disease: Improving Global Outcomes) suggest that individuals with an eGFR less than 60 ml/min and urinary albumin excretion greater than 300 mg/day should have a target BP of less than 130/80 mmHg.
The Systolic Blood Pressure Intervention Trial (SPRINT) assessed if lowering systolic BP to less than 120 mmHg versus less than 140 mmHg was associated with improved outcomes in community dwelling adults age 50 or older. Data from this trial suggests that lower systolic BP may be beneficial for some individuals, such as those with pre-existing cardiovascular disease (Wright 2015). However, a more recent meta-analysis suggests that there is still limited evidence on the benefit of more intensive BP control in the general population (Weiss 2017). The recommendation that older persons should have a higher target systolic BP (150 vs 140 mmHg in younger persons) grew out of the recognition that older persons were more susceptible to orthostatic hypotension, changes in kidney function, and other side effects when attempts were made to adjust drug doses to achieve target goals (Wright 2015).
As noted in the JNC8 report, guidelines are not a substitute for careful clinical judgment, particularly in complex patients with competing risks. Target goals may not be achieved in individuals who develop complications of treatment.
There are no specific guidelines for the management of HTN in PLWH that differ from those recommendations for the general population, but variations in guidelines for older individuals and those with CKD must be considered where appropriate (Nguyen 2015). Since the prevalence of CKD in PLWH is common, and inadequately treated BP is both a complication of CKD and a contributor to the rate of loss of kidney function, special attention to blood pressure management is usually required in this population.
Lifestyle modification is the clear first step in managing HTN. This includes making dietary recommendations such as the DASH diet, decreasing sodium intake, increasing potassium intake. It also includes recommending weight loss and at least 30 minutes of aerobic activity daily. Finally, substance abuse, a common comorbid condition in PLWH , should also be addressed, specifically tobacco cessation and alcohol moderation.
JNC8, with the concurrence of the ACC/AHA guidelines, recommend either thiazide diuretics, calcium channel blockers, and angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) as appropriate first line choices. Both also recommend avoiding the use of ACEI and ARB in African Americans unless there is another compelling comorbid condition to choose one of those agents  . In the setting of chronic kidney disease, there is evidence that the use of ACEI or ARB provide reno-protective benefits beyond lowering of blood pressure. This supports arguments that ACEI or ARB be considered as first-line choices in the treatment of hypertension in HIV-infected individuals with CKD  ). Although the risk for hyperkalemia is increased with their use, particularly in individuals with reductions in GFR, with appropriate monitoring, they are safe and effective in most individuals.
When choosing the appropriate therapy for PLWH, care must be taken with regards to potential drug-drug interactions between antiretroviral medications and anti-hypertensive agents, primarily in the calcium channel blocker and beta blocker classes. However, most anti-hypertensive medications can be dose adjusted as needed . Beyond this concern, there is no specific recommendation for initial and subsequent choice of anti-hypertensive in PLWH.
Despite efforts to control HTN, standard therapies can fail to achieve target goals, particularly in complex patients with multiple co-morbidities. In patients where goal blood pressures are not achieved, clinicians should consider and assess for possible causes such as non-adherence to prescribed therapies or existence of secondary causes of hypertension (such as obstructive sleep apnea or primary aldosteronism). Recent studies have demonstrated the existence of benefits from the use of mineralocorticoid antagonists (spironolactone), particularly in refractory hypertension, superior to other 4th line treatments (Glicklich 2015).
Clinical trials evaluating the safety and efficacy of renal nerve ablation for the treatment of HTN where pharmacological management was not possible or ineffective have been instituted. Initial reports appeared promising, however additional experience is needed before recommendations regarding this therapy can be made for the management of refractory HTN (Chen 2016).
Rosendorff C, Lackland DT, Allison M, Aronow WS, Black HR, Blumenthal RS, et al. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Hypertension 2015; 65(6):1372-1407.