Controversies of Arterial Hypertension in People Living with HIV on Antiretroviral Treatment

Introduction: Antiretroviral therapy (ART) in HIV carriers increased the life expectancy of this population, favoring the emergence of cardiovascular and metabolic diseases and cancer as the main causes of death. Objective: to review the literature on the prevalence of arterial hypertension (AH) and associated factors in HIV carriers using ART. Methods: The literature of the last ten years was been reviewed, using the PubMed, SciELO, IBECS and LILACS databases and the descriptors: antiretroviral therapy highly active ; acquired immunodeficiency syndrome; hypertension and HAART (highly active antiretroviral therapy) . Review articles, case reports, letters to the editor, studies with HBV / HCV co-infected and experimental studies were been excluded. Results: Nineteen studies were been selected, totaling 47,753 patients. The prevalence of HA ranged from 8.0% to 45.0%. The studies identified high body mass index, advanced age, male sex, smoking, high cholesterol, low HDL cholesterol, hypertriglyceridemia, diabetes mellitus, central obesity, family history of hypertension, previous cardiovascular event, time of HIV diagnosis, ART, time of ART use, ART with protease inhibitors (PIs) and CD4 ≥ 200 cells / ml as factors associated with HA. Multivariate analyzes reported associations with family history of HA, aging, various antiretroviral regimens, male gender, previous cardiovascular event, time of HIV diagnosis, central obesity, diabetes, metabolic syndrome, and time of ART. Conclusion: The prevalence of AH in HIV patients varies widely according to the population studied. In these individuals, in addition to the association with classic risk factors, AH is also related to viral infection and the use of ART.


Introduction
According to UNAIDS, in 2017, 36 million people in the world were living with HIV (PLWHA) and due to the rapid increase in antiretroviral therapy (ART) coverage, more than 20 million (54.0%) had access to adequate treatment. In Latin America in 2016, 58.0% of the population with HIV received ART [1].
The expansion of antiretroviral therapy markedly increased the life expectancy of PLWHA. On the other hand, the lengthening of life for a longer time facilitated the appearance of diseases related to increasing age, among which we can include cardiovascular and metabolic diseases and cancer, which now emerge as the main causes of death in this population [2]. In addition to this, HIV infection became a disease of chronic course, with uncertain long-term complications that justify the investigation of the effects of the same infection, as of the treatment on the health of the carriers [3].
The possible association between ART and arterial hypertension (AH) has been a focus of attention by the scientific community. However, several studies that have been published regarding the association, their results are controversial [4,5]. It is suspected that factors such as time of infection with HIV, time of ART use, exposure

Results
The search returned 209 articles. After applying the filters by period, language, delimitation of studies in humans and abstracts, 91 articles were been excluded for having more than 10 years of publication and 61 for not meeting the inclusion criteria or being duplicated. 57 articles were selected, four were review articles and 34 with content irrelevant for the purpose of this study, including other diseases and HIV/HCV/HBV coinfection among others, 25 articles were included in this review totaling 41,306 patients ( Figure 1). Table 1 shows the prevalence of AH and associated factors reported in the selected articles, showing a variation ranging from 12.7% in the study with the Ethiopian population to 45.6% in the Malaysian study. The majority (64.0%) of the studies were been done in Africa.
to different types of therapeutic regimens, and PIs may be considered risk factors for arterial hypertension [6][7][8][9]. A systematic review published on the subject points to classic risk factors for high blood pressure such as obesity, advanced age, smoking, among others, they behave in the same way in the person with HIV [5].
Given the above, the objective of this study was to review the literature of the last 10 years on the prevalence of arterial hypertension (AH) and associated factors, in patients living with HIV using ART.

Methods
A narrative review has been carried out using the data banks of Pubmed, Scientific Electronic Library Online (Scielo), IBECS and LILACS. The articles published in English, Portuguese and Spanish were included between 2010 and 2020. The descriptors were initially verified on the Virtual Health Library site (http://decs. bvs.br/) and at the National Center for Biotechnology Information (https://www.ncbi.nlm.nih.gov/mesh) and thus defined: antiretroviral therapy highly active (HAART); acquired immunodeficiency syndrome; hypertension and HAART (Medical Subject Heading).  By separately analyzing the articles that used multivariate analysis, it is possible to observe a positive association between arterial hypertension and the variables, family history of AH [12], aging [12,15,18,28,29,38], number of different antiretroviral regimens [34], male gender [8,18], previous cardiovascular event [12], family history of cardiovascular disease [12], time of diagnosis with HIV [12,38], central obesity [12,15,18,31,39], diabetes [12], metabolic syndrome [12] and time of ART [12].
It is worth highlighting that the associations of AH with the different therapeutic regimens, time of HIVdiagnosis and time of ART are closely related to age, which is an important risk factor for AH [40]. In other words, the longer the HIV carrier lives, the greater the exposure to ART and the greater the possibility of using different therapeutic regimens, being older, a fact that increases the risk of arterial hypertension. Furthermore, the age variable deserves special attention in this scenario before we can conclude on the relationships of HIV infection and its treatment with arterial hypertension [41].

Conclusion
In conclusion, the prevalence of AH in HIV/AIDS carriers is slightly higher when we compare those without infection and is associated with known classical risk factors. However, the results are controversial; there is evidence in favor of the association with factors related to HIV-infection and antiretroviral therapy, deserving to highlight the role of age in this relationship.

Human and Animal Rights
No animals were used in this research.

Funding
This study had no external funding sources.

Conflict of Interest
I declare no relevant conflict of interest.

Discussion
This review showed that the prevalence of arterial hypertension (AH) in HIV carriers has a wide range from 8.0% to 45.0% , a result that will depend on the population studied. The prevalence of pre-hypertension was reporting in two studies 42.0% [8] and 34.0% [10].
Regarding the factors associated with AH in this population, the results can be divided into two groups, association with classic risk factors, such as age, family history of AH, obesity, among others, and those related to HIV infection and ART [14,15]. Many studies showed that patients with HIV behave in a similar way to those without infection, and regarding the association between HA and risk factors, they are already known.
Furthermore, several studies are favorable to the association between AH and HIV-infection or ART. Palacios et al, in a longitudinal study observed an increase in blood pressure after 48 weeks of ART [30]. Bernardino, et al. [34], studying PLWHA, in a hospital in Spain, reported a prevalence of 15.0% of AH with ambulatory monitoring and 39.0% of isolated AH and concluded that this last measure is useful for screening hypertensive patients in that population [34]. In those patients who switch to ART [7,9,17,34], time of HIV disease [11,28], type of antiretroviral treatment, especially those taking PIs [14] and have CD4 ≥ 200 cells/ ml [9][10][11]34], were associated with AH [35]. Nüesch, et al. [35], reported an increase in systolic blood pressure with cumulative exposure to NNRI , PIs and triple treatments, in addition to the association with cardiovascular events [22,35]