Excessive cardiovascular morbidity and mortality among people living with HIV – preventable with better services?

Editor’s notes: Opportunities to prevent mortality among people living with HIV also include careful attention to risk factors for modifiable cardiovascular health risk factors such as smoking, cholesterol levels, weight and exercise.  In an interesting study from Canada, Jeon and colleagues used the Ontario administrative databases to look at differences between 259 475 people being admitted with acute myocardial infarction according to their HIV status.  Overall, people living with HIV who had heart attacks were around 15 years younger and more than twice as likely to die within 30 days following discharge from the hospital compared to HIV-negative people.  This was not because people living with HIV had received care that was obviously different, with similar rates of revascularisation procedures and follow up visits to the cardiology services.  The study highlights the ongoing uncertainty about the reasons for increased morbidity and mortality among people living with HIV.  However, it is clear that we do have several well proven tools with which to reduce cardiovascular morbidity, so we should ensure that they are incorporated into HIV treatment services.

The relationship between known indicators of cardiovascular risk and HIV were also studied in 67 black South Africans living with HIV.  Borkum and colleagues demonstrate that HIV infection in black South Africans living with HIV was generally well controlled with 84% being virally suppressed and that they had a median CD4 count of over 500 cells per microlitre.  Nonetheless, most had a variety of characteristics that suggest that they were at high risk of cardiovascular events.  Markers of inflammation were raised in 68% and “non-dipping” blood pressure, which is a measure of excessive stiffness of the arteries, was present in 65%.  Straightforward measures that could be made even at the most peripheral ART clinic also demonstrated risk, with 67% being classified as overweight and 76% having an increased waist circumference, both well recognized independent risk factors for cardiovascular disease.  Worryingly this sample, which was largely female (91%), had an average age of only 42 years.  It is clear that intervention on cardiovascular risks is something for all ART providers to consider in every setting.

The Australian Positive and Peers Longevity Evaluation study (beautifully given the acronym of APPLES) also points out the importance of making valid comparisons between people living with HIV and their HIV negative peers.  In Australia, almost half of all people living with HIV are now over the age of 50 years.  Petoumenos and colleagues show that among gay and bisexual men older than 55 years, recruited in Sydney, those living with HIV were more likely to report noncommunicable comorbidities including heart disease and diabetes. However, some of the more obvious risk factors, such as smoking status, were not different between the groups and people living with HIV drank less alcohol than their HIV negative peers.  The relationships between HIV, lifestyle and noncommunicable disease risk are complex but probably important as the population of people living with HIV continues to age.

In a study from the Cohorte de la Red de Investigación en Sida (CoRIS) in Spain, Masiá and colleagues have also explored long term outcomes of almost 9000 people living with HIV and their experience of non-AIDS defining events.  They show that mortality rates are considerably higher in people living with HIV who have any non-AIDS event, even if these are traditionally considered less severe, such as bacterial pneumonia, psychiatric diseases, bone fractures, or diabetes. In addition to standard indicators (such as low CD4 count at ART initiation), we should take the development of non-AIDS events as a warning to intensify management efforts and more targeted prevention of complications.

In the UK, Molloy and colleagues conducted an audit of clinical services provided at different sites.  They show that systems need to catch up with the changes in life experience of people living with HIV.  While sexual health screening was almost universally available, only 71.4% of sites were able to offer cervical cytology despite the increased risk of cervical cancer in women living with HIV.  Less than half of people taking ART had their risk for cardiovascular disease documented.  Regular audit of appropriate services, even with simple checklists for service providers is a strong tool to improve care for people living with HIV and should have a direct impact on mortality.

 

Mortality and health service use following acute myocardial infarction among persons with HIV: a population-based study

 

Jeon C, Lau C, Kendall CE, Burchell AN, Bayoumi AM, Loutfy M, Rourke SB, Antoniou T. AIDS Res Hum Retroviruses. 2017 Sep 14. doi: 10.1089/AID.2017.0128. [Epub ahead of print]

People with HIV have higher rates of acute myocardial infarction (AMI) than HIV-negative individuals. We compared mortality risk and health service use following AMI among people with and without HIV between January 1, 2002, and March 31, 2015. We conducted a population-based study using Ontario's administrative databases. Our primary outcomes were risk of inpatient death and death at 30 days following hospital discharge. In secondary analyses, we compared use of revascularization procedures within 90 days of AMI, as well as readmission or emergency department visits for heart disease and cardiology follow-up within 90 days of discharge. We studied 259 475 AMI patients, of whom 345 (0.13%) were people with HIV. AMI patients with HIV were younger than HIV-negative patients (mean age ± standard deviation: 54.4 ± 10.5 years vs. 69.3 ± 14.3 years). Following multivariable adjustment, the odds ratios for inpatient death and death at 30 days following discharge were 1.04 [95% confidence intervals (CI) 0.64-1.56] and 2.42 (95% CI 1.00-4.92), respectively. In secondary analyses, no differences were observed in receipt of revascularization procedures (hazard ratio (HR) 0.98; 95% CI 0.85-1.12), readmission or emergency department visit for heart disease (HR 1.18; 95% CI 0.85-1.62), or cardiology follow-up (HR 0.88; 95% CI 0.76-1.01). People with HIV experience AMI at younger ages and may be at higher risk of death in the 30 days following hospital discharge, underscoring the importance of targeting modifiable cardiovascular disease risk factors in these patients.

Abstract access [1]

High prevalence of "non-dipping" blood pressure and vascular stiffness in HIV-infected South Africans on antiretrovirals

Borkum MS, Heckmann JM, Manning K, Dave JA, Levitt NS, Rayner BL, Wearne N. PLoS One. 2017 Sep 20;12(9):e0185003. doi: 10.1371/journal.pone.0185003. eCollection 2017.

Background: HIV-infected individuals are at increased risk of tissue inflammation and accelerated vascular aging ('inflamm-aging'). Abnormal diurnal blood pressure (BP) rhythms such as non-dipping may contribute to an increased risk of cardiovascular and cerebrovascular events in HIV infected individuals. However, little data exists on ambulatory blood pressure (ABP) and measures of vascular stiffness in the black African HIV infected population.

Methods: This is a cross-sectional analysis of otherwise well, HIV infected outpatients on ART for >5 years. Study assessments included: 24hr ABP monitoring, pulse wave velocity (PWV) and central aortic systolic pressure (CASP) using a AtCor Medical Sphygmocor device, fasting lipogram, oral glucose tolerance test, high-sensitivity C-reactive protein (hsCRP) and anthropometric data. Patients completed a questionnaire of autonomic symptoms. CD4+ counts and viral loads were obtained from the National Laboratory results system.

Results: Sixty-seven black participants were included in the analysis of whom 91% (n = 61) were female with a mean age of 42.2 ± 8.6 years. The median duration on ART was 7.5 years (IQR = 6-10), 84% were virally supressed and the median CD4 count was 529.5cells/mm3 (IQR = 372.0-686.5). The majority (67%) were classified as overweight and 76% had an increased waist circumference, yet only 88% of participants were normotensive. A hsCRP level in the high cardiovascular risk category was found in 68% of participants. The prevalence of non-dipping BP was 65%. Interestingly, there was no association on multivariable analysis between dipping status and traditional risk factors for non-dipping BP, such as: obesity, autonomic dysfunction and older age.

Conclusion: This relatively young cross-sectional sample of predominantly normotensive, but overweight black women on effective ART >5 years showed: a high prevalence of non-dipping BP, inflammation and vascular stiffness. Causality cannot be inferred but cardiovascular risk reduction should be emphasized in these patients.  

Abstract [2]  Full-text [free] access [3]

Prevalence of self-reported comorbidities in HIV positive and HIV negative men who have sex with men over 55 years—The Australian Positive & Peers Longevity Evaluation Study (APPLES)

Petoumenos K, Huang R, Hoy J, Bloch M, Templeton DJ, Baker D, Giles M, Law MG, Cooper DA. PLoS One. 2017 Sep 8;12(9):e0184583. doi: 10.1371/journal.pone.0184583. eCollection 2017.

In Australia, almost half of HIV-positive people are now aged over 50 and are predominately gay and bisexual men (GBM). Compared to the general HIV-negative population, GBM engage more in behaviours that may increase the risk of age-related comorbidities, including smoking, high alcohol consumption and recreational drug use. The objective of APPLES was to compare comorbidities and risk factors in HIV-positive older GBM with an appropriate control group of HIV-negative GBM. We undertook a prospectively recruited cross-sectional sample of HIV-positive and HIV-negative GBM ≥ 55 years. Detailed data collection included clinic data, a health and lifestyle survey, and blood sample collection. We report key demographic, laboratory markers and self-reported comorbidities by HIV status. For selected comorbidities we also adjust HIV status a priori for age, smoking and body mass index. Over 16 months 228 HIV-positive and 218 HIV-negative men were recruited. Median age was 63 years (IQR: 59-67). Although more HIV-positive men reported having ever smoked, smoking status was not statistically different between HIV positive and HIV negative men (p = 0.081). Greater alcohol use was reported by HIV-negative men (p = 0.002), and recreational drug use reported more often by HIV-positive men (p<0.001). After adjustment, HIV-positive men had significantly increased odds of diabetes (adjusted Odds ratio (aOR): 1.97, p = 0.038), thrombosis (aOR: 3.08, p = 0.007), neuropathy (aOR: 34.6, P<0.001), and non-significantly increased odds for heart-disease (aOR: 1.71, p = 0.077). In conclusion, HIV-positive GBM have significantly increased odds for key self-reported comorbidities. This study underscores the importance of an appropriate HIV-negative control group for more accurate evaluation of the risk and attribution of age-related comorbidities in HIV-positive people.

Abstract [4]  Full-text [free] access [5]

Prediction of long-term outcomes of HIV-infected patients developing non-AIDS events using a multistate approach

Masiá M, Padilla S, Moreno S, Barber X, Iribarren JA, Del Romero J, Gómez-Sirvent JL, Rivero M, Vidal F, Campins AA, Gutiérrez F; Cohorte de la Red de Investigación en Sida (CoRIS). PLoS One. 2017 Sep 8;12(9):e0184329. doi: 10.1371/journal.pone.0184329. eCollection 2017.

Objectives: Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013.

Design: Prospective multicenter cohort study.

Methods: Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced ("NAE development"); from alive and NAE-experienced to death ("Death after NAE"); and from alive and NAE-free to death ("Death without NAE"). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition "Death after NAE".

Results: 8789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80-30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition "Death after NAE" was 12.1 (95%CI, 4.90-29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45-6.57) for intermediate-severity; and 9.85 (5.45-17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11-3.84), age >50 years (1.78, 1.08-2.94), hepatitis C-coinfection (2.52, 1.38-4.61), lower CD4 cell count at cohort entry (HR 2.49; 95%CI 1.20-5.14 for CD4 cell count below 200 and HR 2.16; 95%CI 1.01-4.66 for CD4 cell count between 200-350, both compared to CD4 cell count higher than 500) and concomitant CD4 <200 cells/mL (2.22, 1.42-3.44) were associated with death after NAE. CD4 count and HIV-1 RNA at engagement, previous AIDS and hepatitis C-coinfection predicted mortality in NAE-free persons.

Conclusion: NAEs, including low-severity events, increase prominently the risk for mortality in PLWH. Prognostic factors differ between NAE-experienced and NAE-free persons. These findings should be taken into account in the clinical management of PLWH developing NAEs and may permit more targeted prevention efforts.

Abstract [6]  Full-text [free] access [7]

Routine monitoring and assessment of adults living with HIV: results of the British HIV Association (BHIVA) national audit 2015

Molloy A, Curtis H, Burns F, Freedman A; BHIVA Audit and Standards Sub-Committee. BMC Infect Dis. 2017 Sep 13;17(1):619. doi: 10.1186/s12879-017-2708-y.

Background: The clinical care of people living with HIV changed fundamentally as a result of the development of effective antiretroviral therapy (ART). HIV infection is now a long-term treatable condition. We report a national audit to assess adherence to British HIV Association guidelines for the routine investigation and monitoring of adult HIV-1-infected individuals.

Methods: All UK sites known as providers of adult HIV outpatient services were invited to complete a case-note review and a brief survey of local clinic practices. Participating sites were asked to randomly select 50-100 adults, who attended for specialist HIV care during 2014 and/or 2015. Each site collected data electronically using a self-audit spreadsheet tool. This included demographic details (gender, ethnicity, HIV exposure, and age) and whether 22 standardised and pre-defined clinical audited outcomes had been recorded.

Results: Data were collected on 8258 adults from 123 sites, representing approximately 10% of people living with HIV reported in public health surveillance as attending UK HIV services. Sexual health screening was provided within 96.4% of HIV services, cervical cytology and influenza vaccination within 71.4% of HIV services. There was wide variation in resistance testing across sites. Only 44.9% of patients on ART had a documented 10-year CVD risk within the past three years and fracture risk had been assessed within the past three years for only 16.7% patients aged over 50 years.

Conclusions: There was high participation in the national audit and good practice was identified in some areas. However, improvements can be made in monitoring of cardiovascular risk, bone and sexual health.

Abstract [8]  Full-text [free] access [9]

Africa [15], Europe [16], Northern America [17], Oceania [18]
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