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Abstract

Patients with perinatally acquired HIV may be at risk for the development of age-related non-AIDS diseases. The primary aim of this study was to describe patterns of systemic hypertension among a cohort of adults (≥18 years) with perinatally acquired HIV. A retrospective cohort study was conducted among adults (≥18 years) with perinatally acquired HIV infection. Primary outcomes included documentation of systemic hypertension as well as several additional non-AIDS-associated illnesses. Systemic hypertension incidence rates and rate ratios (RRs) were calculated among groups aged ≥18 and <18 years at the time of hypertension diagnosis. The overall prevalence of hypertension in the cohort (N = 109) was 26.6%, and the incidence rate of hypertension was significantly higher among those aged ≥18 years compared to those who are aged <18 years at the time of diagnosis (RR: 10.0, CI: 7.29-13.71). By multivariable analysis, only coexisting renal disease was associated with an increased risk of hypertension diagnosis.

Keywords

HIV hypertension perinatal adult

Introduction

In the United States, perinatal HIV transmission has declined 96% since 1992, with nearly 10 000 cumulative cases, and 161 reported cases in 2012.¹ International rates of maternal-to-child transmission of HIV have recently begun to decline as well, though nearly 220 000 new HIV infections were reported in 2014, the majority occurring in sub-Saharan Africa.² A large number of perinatally infected HIV-positive individuals are now aging through adolescence into adulthood.

In the adult population with nonperinatally acquired HIV, the success of combination antiretroviral therapy (cART) has yielded a dramatic decline in AIDS-associated morbidity and mortality.^3
–5 In concert with this decline has been an increase in non-AIDS diseases including cardiovascular and renal disease.^5
–7 Though antiretroviral toxicity and traditional risk factors such as tobacco use may partially account for these findings, HIV infection itself appears to play a significant role through its immune-inflammatory-modulating effects.⁸

Similar trends have been witnessed among younger perinatally infected HIV-positive children, where mortality rates have declined as non-AIDS conditions have increased.^9,10 Small cohort studies have demonstrated increasing organ-specific non-AIDS-associated disease among younger perinatally infected HIV-positive children in the modern cART era, including renal disease,¹¹ and markers of cardiovascular risk such as carotid stiffness and cardiovascular strain.^12

–15 Importantly, the majority of these cohort studies were composed of younger populations (9-11 years), and many non-AIDS illnesses appear to increase with age.^12,13,16,17 The prevalence and patterns of systemic hypertension among adult aged (≥18 years) members of this risk group remain largely unexplored.

Methods

This retrospective cohort study was conducted among patients with perinatally acquired HIV infection who received care within the University of Maryland Hospital System. Inclusion criteria comprised documentation of HIV infection detected by HIV-1 virologic testing on 2 separate occasions in infancy, or anti-HIV-1 antibodies persisting beyond 18 months of age in a child documented to have been born to a mother with HIV infection. Participants were only included if they had reached at least 18 years of age as of September 30, 2013. Exclusion criteria included those <18 years of age by September 30, 2013, and/or those with documented or suspected nonperinatally acquired HIV infection.

The objectives of this study were to characterize the incidence, prevalence, and patterns of systemic hypertension among the cohort of perinatally infected HIV-positive patients. As this cohort had adults aged at least 18 years, incidence rates of new systemic hypertension diagnoses were further examined based on age at diagnosis within 1 of the 2 groups: ≥18 or <18 years. Primary outcomes included provider documentation of systemic hypertension as well as several additional non-AIDS-associated illnesses, including renal disease. Systemic hypertension was defined as any of the following: (1) provider documentation of systemic hypertension diagnosis or (2) receipt of antihypertensive medications specifically for blood pressure management. Additional end points included provider-documented CD4 count and CD8 count patterns, HIV RNA levels, antiretroviral therapy (ART) exposure history, and sociodemographic data. Covariates of interest included CD4 count, HIV viral copy-years, coexistent renal disease, and several demographic characteristics. Data were collected from birth (or earliest available time point) to September 30, 2013, or latest available encounter prior to this date.

Descriptive statistics, including mean, median, standard deviation, and quartiles for continuous measures, were used to characterize the study population. Incidence rates and rate ratios (RRs) (with 95% confidence intervals [95% CIs]) were calculated among groups aged ≥ 18 and < 18 years. Measures of association were assessed using χ² and t-tests, along with logistic regression for multivariate analysis. Univariate analyses were done using the χ² test, and the Fisher exact test, as appropriate. Multivariable logistic regression was used to evaluate independent predictors of hypertension.

Results

Charts were abstracted from 109 patients. Figure 1 describes the incidence rate of systemic hypertension diagnoses by age. Overall, a provider diagnosis of systemic hypertension was documented in 29 (26.6%) patients, with a mean age of onset of 19.0 years. Of these 29 patients, 17 (59%) had a documented prescription for antihypertension at the most recent provider visit. Among those with a provider diagnosis of hypertension and not on antihypertensive therapy, 2 (17%) had a documented blood pressure of >140/90 mm Hg at the most recent visit.

Figure 1.

Incidence rate of hypertension by age.

Compared to those who are of <18 years of age, patients who had reached ≥18 years demonstrated a significantly higher rate of systemic hypertension (incidence rate ≥18 years versus <18 years: 4.59/100 person-years versus 0.46/100 person years, respectively; RR: 10.0, 95% CI: 7.29-13.71; Figure 1). Demographic and clinical characteristics of the cohorts with and without hypertension diagnoses are presented in Table 1. The mean age of the overall cohort was 22.8 years (range: 18.5-30.2 years). The majority (93%) was African American, and 55% were female. These characteristics did not differ between those with and without hypertension diagnoses. Patients with a diagnosis of hypertension had numerically lower rates of contemporary and/or previously sustained HIV RNA suppression (≥12 months as well as ≥3, 5, and/or 10 years) though these findings did not reach statistical significance. Median nadir CD4 count and CD4/CD8 ratio among those with a hypertension was 176 cells/mm³ and 0.2, respectively, and did not significantly differ from those without a hypertension diagnosis. Finally, the total burden of nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, and protease inhibitor exposure did not differ between those with and without a systemic hypertension diagnosis.

Table 1.

Cohort Demographic and Clinical Characteristics.

	Hypertension Cohort, n = 29	Nonhypertension Cohort, n = 80
Gender	Male: 13 (45%),^a Female: 16 (55%)	Male: 36 (45%),^a Female: 44 (55%)
Ethnicity	AA: 27 (93%),^a W: 1 (4%), NR: 1 (4%)	AA: 76 (95%),^a W: 4 (5%), NR: 0
Age as of September 30, 2013 (years)	Mean: 23.2,^a Median: 22.6	Mean: 22.6,^a Median: 22.0
Past durable HIV RNA suppression of ≥12 months (%)	15 (51.7%)^a	55 (61.1%)^a
Past durable HIV RNA suppression of ≥3 years (%)	9 (31%)^a	35 (38.9%)^a
Past durable HIV RNA suppression of ≥5 years (%)	6 (20.7%)^a	24 (26.7%)^a
Past durable HIV RNA suppression of ≥10 years (%)	2 (6.9%)^a	7 (7.8%)^a
HIV RNA suppression most recent visit (%)	13 (44.8%)^a	36 (40%)^a
Nadir CD4 count (cells/mL, median) (%)	176^a	179^a
Nadir CD4/CD8 ratio	0.2^a	0.3^a
Mean rate of NRTI Use (per 100 PY)	13.96^a	15.70^a
Mean rate of NNRTI use (per 100 PY)	2.81^a	2.69^a
Mean rate of PI use (per 100 PY)	4.42^a	4.04^a

Abbreviations: AA, African American; NR, not recorded; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; PY, person-years; W, white.

^a P = NS.

Sixteen (55%) patients with a diagnosis of hypertension had at least 1 diagnosis of renal disease, compared to 12 (15%) patients without a diagnosis of hypertension. Restricted only to diagnoses of chronic (vs self-limited) renal disease, prevalence was 45% among patients with a diagnosis of hypertension compared to 10% among patients without a diagnosis of hypertension. However, coincident renal disease/hypertension diagnoses were less prevalent among those newly diagnosed at ≥18 years compared to those newly diagnosed at <18 years (38.1% versus 87.5%, respectively).

By multivariable analysis, proximate CD4 count and nadir, viral load copy-years, obesity, race, gender, and tobacco use were not found to be associated with a hypertension diagnosis. By contrast, a concomitant renal disease diagnosis was found to be associated with a hypertension diagnosis (odds ratio: 4.93, 95% CI: 1.79-13.62).

Discussion

We found a high prevalence (nearly 27%) of systemic hypertension among our cohort of adult-aged patients with perinatally acquired HIV. Further, rates of systemic hypertension increased as patients reached ≥18 years. Normative data from the National Health and Nutrition Examination survey demonstrated a hypertension prevalence among 18- to 39-year-olds of only 7.3%.¹⁸ Further, in the Johns Hopkins Precursors Study, a prospective cohort of 1132 white males, the cumulative incidence of hypertension at 25 years of age was only 0.3%.¹⁹ Hypertension (variably defined) is well described in older HIV-infected patients, with several cohort studies with mean ages of 40 to 50 years quoting prevalence rates of 8% to 33%.^{20

–28} By contrast, patterns of hypertension in younger adults with HIV have been largely unknown. The high rate of hypertension diagnoses among young adults in our study needs to be confirmed in a larger population.

There is a growing understanding that HIV infection may engender risk for early age-related comorbidities, but it is unclear how this relationship unfolds among adults with perinatally acquired HIV. The dynamics of HIV-associated pathogenesis, cART toxicity, and the natural aging process are uniquely aligned in perinatally infected HIV-positive adults, a population which has undergone growth and development in the presence of HIV disease and antiretroviral exposure. Traditional risk factors, such as body mass index (BMI), tobacco use, and family history may play a role as well and these risk factors may differ geographically. As these patients enter adulthood, adolescent and adult providers will need to understand the unique clinical patterns emerging in this population so that screening and prevention efforts can be targeted effectively.

Traditional risk factors for hypertension in older adults, including BMI, gender, and ethnicity, were not associated with an increased risk of hypertension diagnosis in our cohort. In addition, HIV viremia copy-years and CD4 nadir were not associated with increased risk for hypertension. Importantly, small sample size may have limited the ability to detect such associations. However, a renal disease diagnosis was significantly associated with the risk for systemic hypertension. Of note, prevalence of systemic hypertension remained high (15%) even among those without a renal disease diagnosis. Though these findings need confirmation, providers should carefully screen and follow patients with or without existing or prior renal disease diagnoses for the development of hypertension.

Limitations to our study include its retrospective nature, reliance on clinical documentation as part of routine care where differences in provider assessments would be expected, relatively small sample size, a single geographic site (limiting broad extrapolation of findings), and lack of a comparative matched cohort. In addition, chronicity of specific diseases was difficult to ascertain due to retrospective data collection.

Given the persistently high rate of perinatal HIV transmission worldwide and the extension of life with ART, this group will continue to age into adulthood. Providers caring for HIV-infected adults will need to tailor their care to this unique population. Based on the results of our study, adult providers may need to closely screen and monitor the development of hypertension and renal disease in perinatally infected patients as they age into adulthood. These findings will need to be examined in larger cohorts, with special attention to developing countries where perinatal HIV transmission remains a significant concern.

Footnotes

Authors’ Note

All authors have contributed equally to the work.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Patterns of Systemic Hypertension among Adults with Perinatally Acquired HIV