eISSN: 1732-2707
ISSN: 1730-1270
HIV & AIDS Review. International Journal of HIV-Related Problems
Current issue Archive Manuscripts accepted About the journal Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
Editorial System
Submit your Manuscript
SCImago Journal & Country Rank
2/2020
vol. 19
 
Share:
Share:
Original paper

Blood pressure in relation to the World Health Organization AIDS clinical staging among adults living in rural Kenya

Mikołaj Kamiński
1
,
Piotr Prymas
1
,
Anna Konobrodzka
1
,
Piotr Filberek
1
,
Greta Sibrecht
1
,
Wojciech Sierocki
1
,
Zofia Osińska
1
,
Paweł Bogdański
1

1.
Department of Education and Obesity Treatment and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland
HIV AIDS Rev 2020; 19, 2: 93-98
Online publish date: 2020/06/28
Article file
- HIV-00221-Kaminski.pdf  [0.24 MB]
Get citation
 
PlumX metrics:
 

Introduction

Human immunodeficiency virus (HIV) infection causes the acquired immunodeficiency syndrome (AIDS), a progressively devastating process complicated by malnutrition, wasting, development of other infectious and neoplastic diseases, and shorter life duration [1, 2]. The epidemic of HIV/AIDS is a mayor public health challenge in sub-Saharan Africa, with up to 25 million HIV-positive individuals [3]. Due to efficacy of antiretroviral treatment (ART), HIV-positive patients tend to live longer, and cardiovascular diseases (CVD) became the mayor mortality cause in this population [4, 5]. HIV infection is recognized as an independent CVD risk factor [6]. HIV/AIDS promotes chronic inflammation process resulting in atherosclerosis [7], increases arterial wall stiffness [8], and the risk of arterial hypertension [9]. The risk of CVD in HIV/AIDS is negatively correlated with CD4+ count [10-12]. Moreover, HIV-positive patients are additionally more likely to develop arterial hypertension due to metabolic side effects of ART [13].
In sub-Saharan Africa, both HIV/AIDS and cardiology advanced diagnostics and treatments are limited. Therefore, an early health intervention is crucial among patients with HIV/AIDS and cardiovascular risk living in non-industrialized areas [14]. However, there is a limited data on blood pressure among HIV-positive patients living in rural areas in Africa according to the clinical progress of the disease. Possibly, one of those groups of patients requires more careful monitoring of blood pressure and early health interventions to prevent cardiovascular events, which cannot be efficiently treated in rural areas.
The aim of the study was to compare blood pressure parameters between HIV-positive adults with advanced and non-advanced forms of HIV/AIDS.

Material and methods

We performed prospective, two-center, cross-sectional study in rural Comprehensive Care Clinic (CCC) for HIV patients in Mutomo and Muthale Missionary Hospitals, Kitui County, Kenya. Data was collected in August and September 2016. The study team consisted of local staff and medical volunteers, who participated in the program “Treating with a mission” (leczymyzmisja.pl/en/) under the auspices of the Poznan University of Medical Sciences, Poznan, Poland. The local Bioethical Committee at the Strathmore University in Nairobi, Kenya approved the study protocol (permission reference number SU-IRB 0073/16), and each participant signed an informed consent before participation. In the case of illiteracy, oral informed consent in local language or Swahili was obtained by two CCC workers. In our study, adult HIV-positive patients visiting the outpatient clinic during a routine check-up visit were included and their data anonymized. All patients have been previously diagnosed in the CCC accordingly to the Kenyan HIV diagnostic guidelines [15]. Patients with newly diagnosed HIV-infection, e.g. acute retroviral infection, were excluded. Each participant underwent an interview with a local clinical consultant, clinical examination, anthropometric and blood pressure measurements, and heart rate assessment. Additional data such as World Health Organization (WHO) AIDS clinical stage (WACS), HIV treatment, and time since HIV diagnosis were collected from patients’ data charts.
Anthropometric measurements were collected using body composition analyzer (TANITA BC-601, Illinois, USA), which allows to assess patient’s body mass, body fat percentage, and abdominal fat level. Resting systolic (SBP) and diastolic blood pressure (DBP) were measured after 5 minutes of resting using OMRON M2 basic BP monitor (Omron, Japan) validated according to the international protocol of the European Society of Hypertension [16]. Blood pressure was measured after the participant had rested for at least five minutes and was seated comfortably with his back supported, legs uncrossed, and his feet flat on the floor. Clothing was removed from the arm, in which the cuff was placed. The arm was supported at heart level, with the palm facing up and the elbow slightly flexed. The patient was advised not to speak during the procedure. Different cuff sizes based on the upper arm circumference at the time of each measurement were used. After 2 minutes of rest, second measurement was performed, and the average measurement was used for statistical analysis. Heart rate (HR) was obtained by an AliveCor (AliveCor, USA), a system of electrode and a smartphone application called Kardia, which enables obtaining one-lead ECG from the user [17]. The mean blood pressure (MBP) was calculated according to MBP = 2/3 DBP + 1/3 SBP formula [18]. The pulse pressure (PP) was calculated according to PP = SBP – DBP method. To the final analysis, only completely fulfilled records were included. Abnormal blood pressure was defined as SBP ≥ 140 and/or > DBP ≥ 90.
In order to grade the progression of HIV infection, the WHO recommends using WACS [1], which is a four-grade system designed for developing countries with limited possibility to routinely assess CD4+ count. The WACS grading starts from the asymptomatic patients or with generalized lymphadenopathy (stage 1), through the presence of unexplained moderate to severe weight loss, ranges from mild to severe bacterial, viral and fungal infections (stages 2 and 3), and ends with the development of HIV wasting syndrome, severe generalized infection, and HIV-associated malignancy (stage 4). The clinical staging of HIV patients enrolled in our study was regularly evaluated by medical professionals working in both outpatient clinics. Since we included patients attending routine check-ups, our study group did not include patients with a condition requiring urgent hospitalization. We distinguished group of ART treatment used by each patient for at least one previous month. Additionally, we characterized each combination of ART prescribed.

Data analysis

A statistical analysis was performed using STATISTICA 12.0 (StatSoft, USA). Normality of variables distribution was tested using Kolmogorov-Smirnov test with Lilliefors correction. Due to lack of normality, non-parametric tests were performed. We divided patients into two groups: patients with non-advanced form of HIV disease (stage 1 in WACS) and with advanced form of HIV disease (stage 2, 3, or 4 in WACS). Comparison of non-advanced with advanced HIV was made by Mann-Whitney test, and results shown as median and 25th-75th percentiles. In order to compare study groups in the presence of abnormal blood pressure, treatment 2 test was used. To assess associations between blood pressure parameters and clinical features in study groups, Spearman rank correlation test was performed. Differences with p value < 0.05 were considered statistically significant. The figure was generated by using ggplot2 and ggthemes R packages [19].

Results

Out of 268 patients, we excluded 23 patients due to uncompleted records, which resulted in the total of 245 (female, 192; 78%) participants included in the study, aged 46 (range, 39-53), in the final analysis. All patients were using ART. The prescribed antiretroviral drugs were: nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) – lamivudine, abacavir, and zidovudine; non-nucleoside reverse transcriptase inhibitors (NNRTI) – efavirenz and nevirapine; reverse transcriptase inhibitor (RTI) – tenofovir; protease inhibitors (PI) – lopinavir and atazanavir. We noted following ART combinations: NRTI + NNRTI + RTI (n = 123), NRTI + NRTI + NNRTI (n = 97), NRTI + NRTI + PI (n = 22), NRTI + RTI + PI (n = 2), and NRTI in monotherapy (n = 1). General characteristics of the group is summarized in Table 1. One hundred and two patients presented with non-advanced HIV disease (WACS = 1), whereas 83 had advanced disease (WACS > 1): 23 had WACS = 2, 52 had WACS = 3, and eight had WACS = 4. Both groups did not differ significantly in sex, age, time since HIV diagnosis, age at HIV diagnosis, body mass index (BMI), waist circumference, fat tissue percentage, abdominal fat level, HR, use of antiretroviral drugs, nor presence of abnormal blood pressure (Table 1). The comparison of blood pressure parameters of each group is presented in Figure 1. There were significant differences between patients with non-advanced HIV and advanced HIV in DBP [71 (64-77) vs. 81 (75-88); p < 0.0001], MBP [87 (80-94) vs. 95 (88-102); p < 0.0001], and PP [48 (42-56) vs. 43 (35-50); p < 0.0001]. A tendency, but not significant difference among study groups in SBP [119 (109-129) vs. 122 (114-133); p = 0.07] was observed. We found significant associations between blood parameters and age, age at HIV diagnosis, abdominal fat level, and WACS of participants (Table 2).

Discussion

In our study, we found that patients with advanced form of HIV infection had a higher DBP and MBP and lower PP than patients with non-advanced form of HIV. Moreover, a tendency in difference between both groups in SBP was noted. Most likely, the differences between study groups in MBP and PP were secondary to difference in DBP, while SBP did not differ significantly. There was no significant difference between both groups in the presence of abnormal blood pressure.
The development of arterial hypertension in HIV/AIDS is multifactorial. HIV infection as such leads to endothelial dysfunction, inflammatory state, dyslipidemia, and insulin resistance [10]. In individuals with developed immunosuppression, inflammatory foci may accelerate in endothelial and metabolic changes caused by HIV [11, 12]. Finally, ART was reported to cause endothelial dysfunction, dyslipidemia, and worsen glucose tolerance [10, 13]. All those outcomes may result in an escalation of atherosclerosis, which in consequence increases a CV risk in HIV-positive people [7]. An increase of arterial stiffness in HIV-positive individuals was associated with advanced form of infection, presence of metabolic syndrome, and age [8]. Since the risk of metabolic syndrome is augmented by HIV infection, both non-HIV inflammatory foci and ART indirectly influence arterial stiffness, which has a sequential effect on the development of arterial hypertension in HIV-positive population [9].
Njekela et al. reported negative association between progression of HIV/AIDS (assessed by CD4+ count and advanced WACS) and risk of hypertension among ART-naïve patients living in Tanzania [20]. Moreover, the study showed that clinical stage of the disease alone may result in arterial hypertension. In another study performed on Kenyan population, Bloomfield et al. demonstrated that low blood pressure (SBP < 100, DBP < 60 mm Hg) carries the highest mortality risk among HIV-positive patients [21]. High SBP was also significantly associated with increased mortality, but only among patients without advanced form of HIV/AIDS [21]. Nadir of CD4+ count during the history of HIV/AIDS was correlated negatively with WACS [22] and nadir of CD4+ was characterized as an independent predictor of sustained hyper¬tension [23]. Additionally, Manner et al. concluded that delaying ART initiation in ART-naïve patients may cause additional risk of arterial hypertension [23]. Since CD4+ count is negatively correlated with risk of hypertension, we speculate that poor adherence to ART therapy may result in the progression of disease, decrease of CD4+, promotion of chronic inflammation leading to an increase of arterial wall stiffness [8] and consequently, an increase of DBP.
To exclude potential influence of ART on blood pressure, both groups were compared according to prescribed treatment and no significant difference was observed. However, the compliance of patient is unknown. It is possible that patients with advanced form of infection resulted in worse compliance than those of non-advanced group, which could lead to a lack of clinical improvement or progression of HIV/AIDS.
Interestingly, WACS alone had significant associations with DBP, MBP, and PP. Moreover, age, age at HIV diagnosis, and abdominal fat level were positively associated with BP parameters. Abdominal fat level correlates with visceral adiposity measured by magnetic resonance imaging [24]. Visceral adiposity was associated with renin-angiotensin-aldosterone (RAA) system activation in HIV-positive population [25]. Therefore, the observed association between abdominal fat level and DBP, MBP, and PP may reflect on activation of RAA system by visceral fat tissue.
Unexplained weight loss and HIV wasting syndrome are the criteria of advanced HIV infection [1]. However, no significant differences in BMI, waist circumference, and fat tissue between both groups were observed. We suppose that most of the patients were assigned to the advanced HIV infection group due to occurrence of at least one viral, bacterial, or fungal infection, unexplained fever, etc.
We analyzed data of 245 HIV-positive adults, mostly middle-aged females living in rural areas of Kenya. All individuals were on ART. Asymptomatic and symptomatic groups did not differ significantly in sex, age, BMI, time since HIV diagnosis, and HIV treatment. The only differences between both groups appeared in DBP, MBP, and PP. The results of our study suggest that HIV/AIDS clinical stage may be associated with DBP as well as MBP and PP. Individuals with advanced-HIV infection living in rural Kenya may require more clinical attention for early diagnosis of hypertension.
Our study has several limitations. Firstly, we collected data cross-sectionally without a follow-up. Secondly, the collected data was limited. We have not collected data on hypertension risk factors, e.g. family history of smoking, alcohol, diet, physical activity, and type of occupation. This would require an engagement of additional CCC workers, which was practically impossible. Data on comorbidities in patients’ records were sparse. Information found in medical charts included only two patients who were previously diagnosed as hypertensive and one suffered from diabetes. However, we speculate that these numbers may be underestimated. HIV-positive patients are encouraged to disclose all health-related problems in CCC, but some may not admit their comorbidities due to a lack of sense of necessity or fear of shame (e.g. alcohol problems). Data on anti-hypertensive treatment were not collected due to lack of information in patients’ data charts. Arterial hypertension is a multifactorial disease, and the limitation of data is a flaw of this study. Nevertheless, the possible factors influencing BP may be related to HIV/AIDS progression. HIV-positive patients with arterial hypertension may likely characterize with poor adherence to treatment, leading to an increase of blood pressure and progression of the infection, which is reflected by a higher stage of WACS. Regardless of the limitation, our study underlines the necessity of vigilant monitoring of BP in patients with an advanced stage of HIV infection living in African rural areas.

Conclusions

HIV-positive patients with advanced form of HIV disease have higher DBP and MBP and lower PP than individuals with non-advanced HIV living in rural Kenya.

Acknowledgement

The authors want to express their gratitude to all workers of Comprehensive Care Clinical in Muthale and Mutomo Missionary Hospitals.

Conflict of interest

The authors declare no conflict of interest with respect to the research, authorship, and/or publication of this article.

References

1. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. Geneva: World Health Organization; 2007.
2. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992; 41 (RR-17): 1-19.
3. UNAIDS DATA 2018. Available at: http://www.unaids.org/sites/default/files/media_asset/unaids-data-2018_en.pdf.
4. Lohse N, Hansen AB, Gerstoft J, Obel N. Improved survival in HIV-infected persons: consequences and perspectives. J Antimicrob Chemother 2007; 60: 461-463.
5. Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853-860.
6. Grunfeld C, Delaney JAC, Wanke C, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS 2009; 23: 1841-1849.
7. Hsue PY, Hunt PW, Schnell A, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 2009; 23: 1059-1067.
8. Leite LHM, Cohen A, Boccara F. HIV infection and aortic stiffness. Arch Cardiovasc Dis 2017; 110: 495-502.
9. Ucciferri C, Falasca K, Vecchiet J. Hypertension in HIV: management and treatment. AIDS Rev 2017; 19: 198-211.
10. Demir OM, Candilio L, Fuster D, et al. Cardiovascular disease burden among human immunodeficiency virus-infected individuals. Int J Cardiol 2018; 265: 195-203.
11. Kaplan RC, Kingsley LA, Gange SJ, et al. Low CD4+ T-cell count as a major atherosclerosis risk factor in HIV-infected women and men. AIDS 2008; 22: 1615-1624.
12. Lichtenstein KA, Armon C, Buchacz K, et al. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis 2010; 51: 435-447.
13. Nduka CU, Stranges S, Sarki AM, Kimani PK, Uthman OA. Evidence of increased blood pressure and hypertension risk among people living with HIV on antiretroviral therapy: a systematic review with meta-analysis. J Hum Hypertens 2016; 30: 355-362.
14. Dzudie A, Rayner B, Ojji D, et al. Roadmap to achieve 25% hypertension control in Africa by 2025. Glob Heart 2018; 13: 45-59.
15. National AIDS and STI Control Programme, Ministry of Public Health and Sanitation, Kenya. Guidelines for HIV Testing and Counselling and Kenya. Nairobi: NASCOP; 2008.
16. Coleman A, Freeman P, Steel S, Shennan A. Validation of the Omron MX3 Plus oscillometric blood pressure monitoring device according to the European Society of Hypertension international protocol. Blood Press Monit 2005; 10: 165-168.
17. User Manual for Kardia™ by AliveCor®. 2011. Available at: https://www.alivecor.com/previous-labeling/kardia/08LB12.3.pdf.
18. Cywinski J, Tardieu B, Heiss HW. Essentials in pressure monitoring blood and other fluids. Clin Cardiol 1982; 5: 446-A36.
19. Wickham H. ggplot2: elegant graphics for data analysis. 2 ed. Cham: Springer; 2016.
20. Njelekela M, Muhihi A, Aveika A, et al. Prevalence of hypertension and its associated risk factors among 34,111 HAART naïve HIV-infected adults in Dar es Salaam, Tanzania. Int J Hypertens 2016; 2016: 5958382.
21. Bloomfield GS, Hogan JW, Keter A, et al. Blood pressure level impacts risk of death among HIV seropositive adults in Kenya: a retrospective analysis of electronic health records. BMC Infect Dis 2014; 14: 284.
22. Ilovi CS, Lule GN, Obel AO, Irimu HM. Correlation of WHO clinical staging with CD4 counts in adult HIV/AIDS patients at Kenyatta National Hospital, Nairobi. East Afr Med J 2011; 88: 65-70.
23. Manner IW, Trøseid M, Oektedalen O, Baekken M, Os I. Low nadir CD4 cell count predicts sustained hypertension in HIV-infected individuals: nadir CD4 predicts hypertension in HIV. J Clin Hypertens 2013; 15: 101-106.
24. Browning LM, Mugridge O, Chatfield MD, et al. Validity of a new abdominal bioelectrical impedance device to measure abdominal and visceral fat: comparison with MRI. Obesity (Silver Spring) 2010; 18: 2385-2391.
25. Srinivasa S, Fitch KV, Wong K, et al. RAAS activation is associated with visceral adiposity and insulin resistance among HIV-infected patients. J Clin Endocrinol Metab 2015; 100: 2873-2882.
1. WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. Geneva: World Health Organization; 2007.
2. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992; 41 (RR-17): 1-19.
3. UNAIDS DATA 2018. Available at: http://www.unaids.org/sites/default/files/media_asset/unaids-data-2018_en.pdf.
4. Lohse N, Hansen AB, Gerstoft J, Obel N. Improved survival in HIV-infected persons: consequences and perspectives. J Antimicrob Chemother 2007; 60: 461-463.
5. Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853-860.
6. Grunfeld C, Delaney JAC, Wanke C, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS 2009; 23: 1841-1849.
7. Hsue PY, Hunt PW, Schnell A, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 2009; 23: 1059-1067.
8. Leite LHM, Cohen A, Boccara F. HIV infection and aortic stiffness. Arch Cardiovasc Dis 2017; 110: 495-502.
9. Ucciferri C, Falasca K, Vecchiet J. Hypertension in HIV: management and treatment. AIDS Rev 2017; 19: 198-211.
10. Demir OM, Candilio L, Fuster D, et al. Cardiovascular disease burden among human immunodeficiency virus-infected individuals. Int J Cardiol 2018; 265: 195-203.
11. Kaplan RC, Kingsley LA, Gange SJ, et al. Low CD4+ T-cell count as a major atherosclerosis risk factor in HIV-infected women and men. AIDS 2008; 22: 1615-1624.
12. Lichtenstein KA, Armon C, Buchacz K, et al. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis 2010; 51: 435-447.
13. Nduka CU, Stranges S, Sarki AM, Kimani PK, Uthman OA. Evidence of increased blood pressure and hypertension risk among people living with HIV on antiretroviral therapy: a systematic review with meta-analysis. J Hum Hypertens 2016; 30: 355-362.
14. Dzudie A, Rayner B, Ojji D, et al. Roadmap to achieve 25% hypertension control in Africa by 2025. Glob Heart 2018; 13: 45-59.
15. National AIDS and STI Control Programme, Ministry of Public Health and Sanitation, Kenya. Guidelines for HIV Testing and Counselling and Kenya. Nairobi: NASCOP; 2008.
16. Coleman A, Freeman P, Steel S, Shennan A. Validation of the Omron MX3 Plus oscillometric blood pressure monitoring device according to the European Society of Hypertension international protocol. Blood Press Monit 2005; 10: 165-168.
17. User Manual for Kardia™ by AliveCor®. 2011. Available at: https://www.alivecor.com/previous-labeling/kardia/08LB12.3.pdf.
18. Cywinski J, Tardieu B, Heiss HW. Essentials in pressure monitoring blood and other fluids. Clin Cardiol 1982; 5: 446-A36.
19. Wickham H. ggplot2: elegant graphics for data analysis. 2 ed. Cham: Springer; 2016.
20. Njelekela M, Muhihi A, Aveika A, et al. Prevalence of hypertension and its associated risk factors among 34,111 HAART naïve HIV-infected adults in Dar es Salaam, Tanzania. Int J Hypertens 2016; 2016: 5958382.
21. Bloomfield GS, Hogan JW, Keter A, et al. Blood pressure level impacts risk of death among HIV seropositive adults in Kenya: a retrospective analysis of electronic health records. BMC Infect Dis 2014; 14: 284.
22. Ilovi CS, Lule GN, Obel AO, Irimu HM. Correlation of WHO clinical staging with CD4 counts in adult HIV/AIDS patients at Kenyatta National Hospital, Nairobi. East Afr Med J 2011; 88: 65-70.
23. Manner IW, Trøseid M, Oektedalen O, Baekken M, Os I. Low nadir CD4 cell count predicts sustained hypertension in HIV-infected individuals: nadir CD4 predicts hypertension in HIV. J Clin Hypertens 2013; 15: 101-106.
24. Browning LM, Mugridge O, Chatfield MD, et al. Validity of a new abdominal bioelectrical impedance device to measure abdominal and visceral fat: comparison with MRI. Obesity (Silver Spring) 2010; 18: 2385-2391.
25. Srinivasa S, Fitch KV, Wong K, et al. RAAS activation is associated with visceral adiposity and insulin resistance among HIV-infected patients. J Clin Endocrinol Metab 2015; 100: 2873-2882.
Copyright: © 2020 Polish AIDS Society. This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2024 Termedia Sp. z o.o.
Developed by Bentus.