Background

Hypertension is a major global health concern and is estimated to affect 1.13 billion individuals around the world, with approximately two-thirds residing in low- and middle-income nations1. It is currently the most common non-communicable illness among people living with HIV (PLHIV), especially in individuals aged 40 years and older2,3. More than half of the deaths among PLHIV were caused by non-infectious health conditions, with cancer and cardiovascular diseases (CVD) being the most frequent comorbidities4. According to several investigations, PLHIV are twice as likely to develop CVDs as HIV-negative people5,6. The heightened risk is partially linked to HIV-related factors such as long-term antiretroviral therapy (ART) side effects, hypercoagulation, early development of atherosclerosis, immune system activation, and elevated levels of systemic inflammatory markers6,7.

The magnitude of hypertension among PLHIV varies globally8,9. However, Sub-Saharan Africa (SSA) bears the greatest burden of the dual challenge posed by HIV and hypertension, a situation further exacerbated by widespread poverty10,11. A systematic review of articles published between 2000 and 2017 found that the prevalence of hypertension among PLHIV in SSA varied from 6 to 22%12. Studies conducted in East Africa have found that the magnitude of hypertension among PLHIV ranges from 7.98%13 to 43.3%14. In Ethiopia, studies have shown that the magnitude of hypertension in PLHIV varied from 11 to 41.3%15,16,17. Hypertension in PLHIV has been associated with various associated factors, including older age, black ethnicity, being male, and modifiable lifestyle factors like obesity, physical inactivity, smoking, and alcohol consumption11. In addition, some HIV-related health factors, including the specific type of ART regimens used, the prolonged effects of ART treatment, and the duration of HIV/AIDS infection, have also been associated with hypertension in PLHIV18.

Several studies have shown that using some types of ART, especially protease inhibitors and integrase strand transfer inhibitors (INSTIs), may increase the incidence of metabolic syndrome and weight gain, which in turn raises the risk of hypertension19,20,21. Dolutegravir (DTG) is an INSTI that has been linked to cardiometabolic risk21,22, including a possible increased risk of hypertension. The mechanisms underlying the link between DTG and weight gain are not entirely known; however, enhanced adipose tissue activation and renin-angiotensin-aldosterone system (RAAS) modulation may play a role, potentially increasing the risk of hypertension23. The drug suppresses insulin secretion and signaling, possibly via magnesium (Mg2+) chelation, leading to increased insulin resistance and elevated blood glucose levels24. In addition, DTG has been linked to alterations in lipid metabolism, contributing to low high-density lipoprotein cholesterol (HDL-C) and elevated triglyceride and cholesterol levels25. These metabolic disturbances can promote endothelial dysfunction and vascular inflammation, ultimately raising the risk of developing hypertension26.

A cross-sectional study conducted in Uganda among 430 PLHIV on DTG-based ART revealed that the magnitude of hypertension was 27.2%27. An observational multicenter longitudinal study in Ghana reported a hypertension prevalence of 37.3% among PLHIV who were initiated on DTG-based ART28. Since 2018, DTG-based regimens have become the preferred first-line ART in Ethiopia and many other SSA countries29. With the growing use of DTG, concerns about its metabolic side effects have highlighted the need for local evidence. However, most existing studies in Ethiopia either predate the introduction of DTG or do not specifically focus on this drug. To the best of our knowledge, there are no reports on the prevalence of hypertension and its associated factors among PLHIV on DTG-based ART, particularly in the study area. Therefore, this study aimed to determine the prevalence of hypertension and its associated factors among PLHIV on DTG-based ART at Dessie Comprehensive Specialized Hospital (DCSH), Northeast Ethiopia.

Method

Study setting, design, and population

We conducted an institutional-based cross-sectional study among PLHIV receiving DTG-based ART. The study was carried out from February 5 to April 5, 2023, at the ART clinic of DCSH in Northeast Ethiopia. PLHIV aged 18 years or older who had been on DTG-based ART for more than 6 months27 and who volunteered to participate were included. Patients with a diagnosis of hypertension before DTG-based ART initiation, pregnant women, and patients who were seriously ill and unable to respond were excluded.

Sample size determination and sampling technique

The study determined the sample size using a formula for a single population proportion, with certain assumptions: a 5% margin of error (d = 0.05), a 95% confidence interval (Za/2 = 1.96), accounting for a 10% nonresponse rate, and considering the prevalence of hypertension among DTG-treated patients at 50%, as there were no prior studies in the region. This led to a total sample size of 423 individuals. Study participants were selected using a computer-generated simple random sampling technique. A list containing the medical registration numbers of all PLHIV on DTG-based ART (n = 772) who will have follow-up visits at DCSH during the study period was obtained from the Health Management Information System unit of DCSH. Random numbers were generated for each patient using Microsoft Excel, and these numbers were used to randomly select a sample of 423 participants. No stratification was applied during the sampling process.

Data collection procedures

We collected data using a questionnaire adapted from the WHO STEP-wise approach to chronic disease risk factor surveillance30. The questionnaire was translated into the Amharic language and then back into English by another person to check for consistency. The questionnaire was pretested on 5% (21) of the sample size at Boru Meda General Hospital. This questionnaire is divided into three sections: the first focuses on sociodemographic, behavioral, and clinical aspects; the second on physical measurements; and the third on biochemical measurements. All data were gathered by nurse professionals and laboratory technologists under the close supervision of the principal investigator. The data collectors were trained for two days on the purpose of the study, the procedures of data collection, and how to gather information from participants.

Sociodemographic data such as age, sex, education, marital status, monthly income, occupation, and residence, and behavioral characteristics including alcohol drinking status, smoking status, and physical exercise were collected from the patient interview. HIV-related factors such as WHO clinical staging of AIDS, duration of HIV/AIDS infection, duration of ART treatment, duration of DTG-based ART treatment, history of opportunistic infections, and drug adherence levels were extracted from patients’ medical records using a checklist, and other related clinical characteristics [family history of hypertension, CVD, and diabetes mellitus (DM)] were obtained from patient interviews. Body weight and height were measured using a digital balance with a height measurement attached to it. Body mass index (BMI) was calculated by dividing weight in kilograms (kg) by height in meters squared (m2). According to their risk of hypertension, BMI was classified into two categories (< 25 and ≥ 25)31. Waist circumference (WC) and hip circumference (HC) were measured using a flexible, non-elastic tape. The reference ranges were WC > 80 cm for females and > 94 cm for males, as well as a waist-to-hip ratio ≥ 0.85 for females32.

Blood pressure (BP) was measured using a mercury sphygmomanometer BP cuff of appropriate size, covering two-thirds of the upper arm, with the participant in a sitting position. The BP measurement was taken from the left arm, which was supported on a flat surface. Participants were advised to rest for a minimum of 5 min, and if they had consumed caffeinated beverages, they were allowed to rest for 30 min before the measurement. Two measurements were taken 5 min apart, and the average of the two readings was recorded.

Laboratory analysis

About 8 ml of blood was collected from each study participant by a laboratory technologist after an overnight fast. Following serum separation from the whole blood, fasting blood glucose (FBG) and lipid profile levels were measured using the enzymatic method on the Dimension EXL 200 System chemistry analyzer, utilizing a commercially available auto analyzer kit. CD4 count (cells/µl) samples were collected in EDTA containers and analyzed using a Becton Dickinson flow cytometer. Viral load (VL) (copies/mL) samples were also collected in EDTA containers and analyzed with the COBAS® Ampliprep/COBAS® TaqMan PCR analyzer.

Operational definition

Hypertension was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) greater than or equal to 140 mmHg and 90 mmHg, respectively33.

Smoking status was defined as “smoker” for participants who had smoked at least one cigarette within the last one year16.

Alcohol drinking status was defined as “alcohol drinker” for participants who consumed any type of alcoholic beverage more than once per week in the past year regardless of the amount34,35.

Khat chewing status was defined as “chewer” for participants who consumed any amount of khat in the last one year; otherwise, they were classified as “non-chewer”36.

Participants were classified as engaging in regular physical activity if they reported performing at least 30 min of intense exercise once a week or more16.

Comorbid disease was defined as a chronic disease with a confirmed diagnosis of the disease other than HIV infection, like cardiovascular disease, mental health disorders, TB, etc37.

Statistical analysis

Data were checked for completeness and entered in Epi-Data version 4.6 and analyzed using SPSS version 26.0. Categorical data were presented using frequency distribution, while continuous data were expressed as the median ± interquartile range (IQR). Logistic regression analysis was used to evaluate the associations between the correlates and hypertension. Variables with p-values less than 0.25 in the bivariate logistic regression analysis were included in a multivariable logistic regression model to account for potential confounding factors. Crude and adjusted odds ratios with 95% confidence intervals (CI) are reported, and a p-value of less than 0.05 was considered statistically significant. Multicollinearity between the independent variables was assessed, and the variance inflation factor (VIF) was determined to be within an acceptable range (since the VIF was < 2 in this study). In addition, the model’s fit was assessed using the Hosmer and Lemeshow test.

Ethics approval and consent to participate

An ethical clearance letter was obtained from Debre Markos University, School of Medicine, ethical review committee with reference number SOM/229/44/23 and date 20/01/2023. A collaboration letter for data collection was also obtained from DCSH. It was confirmed that the study met the ethical and scientific standards outlined in national and international guidelines. Written informed consent was obtained from all participants, or from legal guardian in cases where participants were unable to read or write, prior to the start of the study.

Result

Sociodemographic and behavioral characteristics

A total of 415 participants were included in this study, achieving a 98.1% response rate. Of these, the majority (60.2%) are females, with a median age of 42 years (IQR: 38, 50), 60.7% residing in rural areas, and 29.9% being farmers. Concerning behavioral characteristics, about 58.6% didn’t do regular physical exercise, 12.8% were alcohol drinkers, and 5.1% were cigarette smokers (see Table 1).

Table 1 Sociodemographic and behavioral characteristics of the study participants.
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Clinical characteristics of the study participants

Over half of the study participants (56.1%) had CD4 counts below 500 cells/mm³; almost half (50.6%) of participants had been living with HIV for more than 10 years; and 57.8% had been using a DTG-based regimen for more than 2 years. Approximately 8% of participants had a history of opportunistic infections in the last 6 months, and 11.3% had a family history of hypertension (see Table 2).

Table 2 Clinical characteristics of the study participants.
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Anthropometric characteristics of the study participants

About 37.6% of participants were classified as having excessive body weight (overweight/obese), 35.2% had a raised waist circumference, and 40.2% had elevated waist-to-hip ratios (Table 3).

Table 3 Anthropometric characteristics of the study participants.
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Biochemical characteristics of the study participants

More than half of the study participants (57.3%) had low HDL-C levels, and 13% exhibited hyperglycemia (Table 4).

Table 4 Biochemical characteristics of the study participants.
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Prevalence of hypertension among PLHIV taking DTG-based ART

The prevalence of hypertension was found to be 63 cases (15.2%), with a 95% CI ranging from 11.9 to 19% (see Fig. 1). Among hypertensive study participants, the mean values of SBP and DBP were 149.4 ± 15.3 mmHg and 96.8 ± 9.2 mmHg, respectively, whereas those among the normotensive study participants were 117.4 ± 9 mmHg and 75.26 ± 7.3 mmHg, respectively.

Fig. 1
figure 1

Prevalence of hypertension among PLHIV taking DTG-based ART at DCSH.

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Factors associated with hypertension among PLHIV taking DTG-based ART

Factors such as age, sex, physical exercise, alcohol drinking status, CD4 T-cell counts, duration of living with HIV, duration of taking ART, duration of taking DTG-based ART treatment, family history of hypertension, family history of DM, comorbidities, BMI, waist circumference, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and FBG were associated with hypertension in bivariable logistic regression. In multivariable logistic regression, sex (AOR = 3.01, 95% CI: 1.56–5.79, p = 0.001), duration of taking DTG-based therapy (AOR = 3.61, 95% CI: 1.72–7.59, p = 0.001), family history of hypertension (AOR = 3.51, 95% CI: 1.54–8.04, p = 0.003), BMI (AOR = 1.92, 95% CI: 1.02–3.64, p = 0.044), and FBG level (AOR = 2.33, 95% CI: 1.01–5.39, p = 0.047) were significantly associated with hypertension among PLHIV taking DTG-based ART (see Table 5).

Table 5 Factors associated with hypertension among PLHIV taking DTG-based ART at DCSH.
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Discussion

The purpose of this study was to look at the prevalence of hypertension and its associated factors in PLHIV taking DTG-based ART. In this study, the prevalence of hypertension among PLHIV on DTG-based ART was 15.2% (95% CI: 11.9–19). We also found that sex, duration of taking DTG-based ART, family history of hypertension, BMI, and FBG levels were significant correlates of hypertension among PLHIV on DTG-based ART.

The prevalence in our study is in line with the findings from Benin (16.8%)38 and southern Ethiopia (17.3%)39. However, this prevalence is higher than that reported in a previous study conducted in Northwest Ethiopia (7.21%)40. In addition, the prevalence in our study was higher compared to the ADVANCE clinical study conducted in South Africa reported the prevalence of hypertension after 192 weeks was 10.5%41. On the other opposing, the prevalence in this study was lower than that reported in previous studies conducted in Uganda (27.2%)27, Northwest Ethiopia (42%)17, Kenya (24.2%)42, and Ghana (21%)43. In addition, an observational multicenter longitudinal study was undertaken from 2020 to 2022 in Ghana to investigate the prevalence of hypertension among PLHIV taking DTG-based ART, and the prevalence rate was 37.3%, which is higher than the current result28. Furthermore, the prevalence of hypertension in our study was lower compared to a study in Tanzania conducted among 430 participants, 99.3% of whom were on DTG-based ART, which reported a prevalence of 24.8%44. Moreover, the NASMAL clinical study conducted in Cameroon showed that the prevalence of hypertension among PLHIV taking DTG-based ART was 33.33% after 192 weeks, which is higher than the current study41. Within the general population of Ethiopia, the pooled prevalence of hypertension was found to be 20.63%45. This result indicates that the prevalence of hypertension among PLHIV on DTG-based ART is lower than that observed in the general population of Ethiopia. This inconsistency might be because of variations in socioeconomic and demographic conditions, lifestyle factors, genetic predispositions, study methodologies (differences in study populations, inclusion criteria, and sample size), comorbidity prevalence, local ART guidelines, and duration of HIV infections and ART treatment. For instance, the studies done in Northwest Ethiopia40 and Ghana28 were cohort studies, whereas our study used an institutional-based cross-sectional study design. In addition, a study conducted in Tanzania44 included those who were ART-naïve individuals; however, our study included those who were ART-experienced individuals. Furthermore, a study conducted in Uganda27 included higher proportions of participants with a BMI ≥ 25 kg/m² (59.6% vs. 37.6%) and a history of alcohol use (20% vs. 12.8%) compared to our study. Moreover, a study conducted in Northwest Ethiopia40 included 30.8% of participants with comorbidities, compared to 10.8% in our study. These factors may account for the difference.

Sex, duration of taking DTG-based ART, family history of hypertension, BMI, and FBG levels were significantly associated with hypertension among PLHIV taking DTG-based ART. Accordingly, male participants were 3.01 times more likely to have hypertension as compared to female participants. Similar findings were reported in Uganda27 and Kenya42. This difference in sex may be explained by hormonal differences that protect women from hypertension. It is possible that female hormones, especially estrogen, may play a role in protecting them from developing hypertension due to their vasodilatory effect on the blood vessels46. In men, androgens raise blood pressure through activation of the renin-angiotensin system (RAS). This triggers oxidative stress, resulting in the production of vasoconstrictive substances and a decrease in nitric oxide availability47. Furthermore, men are more susceptible to behavioral factors such as alcohol consumption, smoking, and other substance use, which are directly associated with a higher risk of developing hypertension compared to women.

Duration of taking DTG-based ART treatment was significantly associated with hypertension. Patients who had been on DTG-based ART for longer than 2 years were 3.61 times more likely to have hypertension as compared to those who had been on DTG-based ART for less than or equal to 2 years. This finding is consistent with previous studies from Uganda27, Ethiopia46, and Tanzania10. The relationship between the duration of ART treatment and hypertension might be directly influenced by alterations in endothelial function, or it could be associated with longevity and age-related conditions, including ART-induced changes in body composition and weight gain48,49.

The findings of the current study reveal that having a family history of hypertension is significantly associated with hypertension. Participants with a family history of hypertension were 3.51 times more likely to develop hypertension compared to those without a similar history. This is similar to previous studies in South Africa50, Rwanda51, and Ethiopia52. This association might be explained by the family members sharing genes that increase susceptibility to elevated blood pressure and stroke. In addition, this could be because of family members sharing similar lifestyle habits, such as dietary habits, exercise, and alcohol consumption, which can negatively impact health53,54.

BMI was another factor significantly associated with hypertension among PLHIV on DTG-based ART. Participants with a BMI of ≥ 25 kg/m2 were 1.92 times more likely than their counterparts to develop hypertension. This finding is consistent with studies conducted in Benin38, Ghana43, Burundi55, and Ethiopia53. Several mechanisms have been proposed to explain the association between obesity and hypertension. It is commonly believed that the buildup of visceral and ectopic fat in various tissues and organs disrupts metabolic and hemodynamic processes56. Furthermore, insulin resistance and inflammation may contribute to changes in vascular function in obese individuals, leading to the development of hypertension57. Although the mechanism of interaction between DTG and obesity is not fully understood, multiple studies have identified a link between DTG use and excess body weight21,58. This indicates that preventive strategies focused on weight management and a healthy diet are essential for reducing excess body weight in PLHIV who are taking DTG27.

Moreover, FBG level was found to be significantly associated with hypertension. Individuals who had a FBG level ≥ 110 mg/dl were 2.33 times more likely to develop hypertension as compared to those who had FBG level < 110 mg/dl. This result is consistent with findings from Southern Ethiopia59 and Northeast Ethiopia60. This association could be attributed to elevated blood glucose levels, which lead to plaque formation that obstructs normal blood flow and may, in turn, raise blood pressure61,62. In addition, as blood glucose levels rise, widespread damage to blood vessels occurs. This results in a loss of blood vessel elasticity and an increase in body fluid volume, both of which may elevate the risk of hypertension63.

Strengths and limitations of the study

This is one of the first studies to assess hypertension in PLHIV taking DTG-based ART in Ethiopia, providing the framework for future research. Despite its strength, this study has certain weaknesses. Since we excluded patients with known hypertension prior to DTG initiation, the prevalence estimate may be skewed downward. Data collection relied on a questionnaire with self-reported variables, which may have led participants to provide desirable responses. In addition, as the study sample came from a single institution, the results should be interpreted carefully. Furthermore, the study lacked data on participants’ renal function, dietary intake, and salt consumption, which could potentially confound the observed prevalence of hypertension. Moreover, due to its cross-sectional design, this study cannot establish a temporal link between hypertension and associated factors.

Conclusion

Hypertension is not uncommon in PLHIV taking DTG-based ART. Sex, duration of taking DTG-based ART, family history of hypertension, BMI, and FBG levels were significant correlates of hypertension among PLHIV on DTG-based ART. These findings highlight the need for routine hypertension screening and lifestyle interventions for PLHIV on DTG, particularly among males, those with prolonged use of DTG-based ART, a family history of hypertension, elevated BMI, or increased FBG. In addition, we suggest that researchers conduct a prospective cohort study to investigate the effect of DTG-based ART on hypertension.