Next Article in Journal
Health Communication in Times of Pandemics: A Framework for Increased Community Participation in Infection Prevention
Previous Article in Journal
Patterns of mHealth Engagement and Identification of Facilitators and Barriers to Mobile Health Applications for People Who Use Opioids
Previous Article in Special Issue
Positive Influences: How Provider Actions Affect HIV Care Engagement for Black Women in the Southwest U.S.
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Prolonged Exposure to Antiretroviral Therapy and Risk of Developing Hypertension Among HIV-Infected Clinic Attendees: A Pilot Study in Rural Eastern Cape Province, South Africa

by
Teke Apalata
1,2,*,
Urgent Tsuro
3 and
Olufunmilayo Olukemi Akapo
1
1
Department of Laboratory Medicine and Pathology, Faculty of Medicine and Health Sciences, Walter Sisulu University, Mthatha B-5110, South Africa
2
National Health Laboratory Service, Nelson Mandela Academic Hospital, Mthatha B-5110, South Africa
3
Division of Public Health, Department of Community Medicine, Faculty of Health Sciences, Walter Sisulu University, Mthatha B-5110, South Africa
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2025, 22(9), 1397; https://doi.org/10.3390/ijerph22091397
Submission received: 30 May 2025 / Revised: 24 July 2025 / Accepted: 30 July 2025 / Published: 7 September 2025
(This article belongs to the Special Issue HIV Care Engagement and Quality of Life Among People Living with HIV)

Abstract

Antiretroviral therapy (ART) has significantly improved outcomes in individuals with human immunodeficiency virus (HIV), yet its long-term cardiovascular effects, especially on hypertension risk, remain debated. This pilot study investigated hypertension risk factors in HIV-positive patients undergoing ART and aimed at hypothesis generation rather than drawing definitive causal conclusions. Seventy HIV-infected adults without baseline hypertension were enrolled and followed. Hypertension was defined using the 2017 ACC/AHA guidelines by the South African Hypertension Society. Data on demographic, anthropometric, metabolic, inflammatory, coagulation, and HIV-related variables were collected. Cox regression analysis identified independent predictors of hypertension. Participants had a median age of 37 years (IOR = 10.96), with 84.3% being female. After a median ART exposure of 61.01 months (range: 2–164), 27 individuals (38.6%) developed high blood pressure. In multivariable Cox models adjusting for metabolic syndrome and BMI, age ≥ 35 years was associated with a 2.2-fold higher hypertension risk (Hazard Ratio [HR]: 2.2; 95% Confidence Interval [CI]: 1.04–4.55; p = 0.04). Elevated triglycerides significantly increased risk, with a 7.9-fold higher likelihood of hypertension (HR: 7.9; 95% CI: 1.04–59.5; p = 0.046). ART regimen type, whether initial or current, did not independently predict hypertension. In conclusion, hypertension is prevalent during ART. We hypothesized that traditional cardiovascular risk factors, notably age ≥35 years and hypertriglyceridemia, were key independent predictors, emphasizing the need for routine cardiovascular risk assessment in HIV management.

1. Introduction

According to the United Nations statistics, Eastern and Southern Africa possessed 20.6 million people living with the human immune-deficiency virus (HIV) in 2018, of which 13.8 million were accessing antiretroviral therapy (ART) [1]. Sub-Saharan Africa (SSA) bears the greatest load of the HIV crisis, making up approximately 54% of the global HIV burden [2]. The introduction of ART marked a very big improvement in the life expectancy of people living with HIV [3,4,5]. Hypertension remains a growing health concern globally, with an increase among people living with HIV (PLWH), particularly in low- and middle-income countries. Recent studies highlighted the complex interplay between HIV infection, antiretroviral therapy (ART), and traditional cardiovascular risk factors, underscoring the need for targeted research in underrepresented settings [6,7].
Aging-related diseases including hypertension begin to appear as life expectancy increases [8]. Due to urbanization and westernization, hypertension and other chronic non-communicable diseases (NCDs) are at a rise in SSA [9,10]. Research findings by [11] Nartey et al. (2023) in a study where causal association between ART and hypertension was studied using propensity score showed a prevalence of hypertension was significantly greater among individuals exposed to ART (42.4%) compared to individuals who were not exposed to ART (17.0%). Furthermore, systolic (12.0 mm Hg) and diastolic (6.1 mm Hg) blood pressure elevations were linked to ART usage [11]. ART-treated HIV-positive patients exhibit a much greater morbidity rate for cardiovascular disease (CVD) compared to non-ART-treated patients [12].
Studies have shown that there is a higher risk ratio (RR) with people living with hypertension (PWH) in North America and Europe than those living in Africa with increased incidence of hypertension among HIV-positive people receiving antiretroviral therapy in these regions [13]. Reports have shown that there is an association between elevated blood pressure in people with HIV and dolutegravir-based antiretroviral therapy regimens. There is tendency in men using dolutegravir to show an elevated risk of hypertension [14]. The recent increase in CVD morbidity and mortality may be an indicator of HIV-infection-related risk factors, ART metabolic effects, and chronic inflammation driven by the virus [15]. Recent regional and global studies present a high and growing incidence of hypertension, with low rates of verification, treatment, and management in sub-Saharan Africa (SSA) [16]. A study by [17] S reported that approximately a third (32%) of the people in a study assessing hypertension a year after receiving ART acquired the condition. A higher risk was linked to the use of stavudine and non-nucleoside reverse transcriptase inhibitors (NNRTIs), especially efavirenz. Additionally, a higher risk of hypertension has been associated with conventional characteristics such as advanced age and a higher body mass index (BMI) [17,18]. Prior to the use of ART, hypertension was less prevalent in people with HIV [19,20]. Obesity and older age are increasingly becoming associated with HIV infection as well [21,22]. A 2024 meta-analysis and systematic review reported that overall prevalence of hypertension remained 21.9%; this study evaluated data from 48 studies comprising 193,843 PLWH. Each individual in this study had a CD4 count of at least 200, and prevalence rates were higher in men and those on ART [23]. Ref. [23] investigated the incidence and risk factors of metabolic syndrome (MetS) in people with HIV who were using ART in Ethiopia between 2022 and 2023. The results of the study revealed that a longer ART duration was linked to a higher risk of metabolic problems. Particularly, the prevalence of MetS was 37.6%, and each participant’s average length of time on combination ART was 10 years. Age over 45, female sex, body mass index (BMI) greater than 25 kg/m2, and usage of lopinavir/ritonavir or efavirenz-based ART regimens have been identified as independent risk factors [24]. Another study that was conducted in Kenya noted that there is a high prevalence of obesity and hypertension among HIV-positive people; this high prevalence varied between women and men, however. A systematic review conducted in sub-Saharan Africa by [22] established that the occurrence of lower BP was more prevalent among HIV-positive adults than HIV-negative adults [23,25]. This is supported by a population-based study conducted in South Africa amongst HIV-positive individuals, which pointed out that hypertension was not common among HIV-positive patients [26].
The long-term use of ART in HIV-infected patients results in obesity, immune complications, and drug toxicity [27]. Although there have been recent studies that investigated the prevalence of hypertension and its associated risk factors in HIV-infected people on ART in SSA, there is an urgent need for further research focusing on how HIV and hypertension combine in sub-Saharan Africa, given the region’s high prevalence of both diseases [28,29]. This study focuses on hypertension risk among PLWH in a rural South Africa context, where access to healthcare is often limited and where the dual burden of infectious and non-communicable diseases places additional strain on health systems. By incorporating both anthropometric and metabolic markers, this approach aligns with current public health priorities aimed at integrating chronic disease management within HIV care, especially in resource-constrained environments [30,31].
We conducted this pilot and exploratory study to evaluate the prevalence of hypertension, its risk factors, and generate hypotheses rather than drawing definitive causal conclusions in a cohort of HIV-positive clinic attendees on ART in a rural area of the Eastern Cape province in South Africa, considering the scarcity of data on CVD risk factors in the context of HIV in our setting.

2. Materials and Methods

We conducted a pilot study among 70 HIV-infected patients receiving ART attending Ngangelizwe community health centre (NCHC), a government healthcare facility, located at King Sabata Dalindyebo (KSD) local municipality in South Africa’s rural Eastern Cape province between 1 February and 28 February 2019 and there was no loss to follow-up. This pilot study was conducted on a limited number of participants (n = 70) to allow for a strict follow-up mechanism, preventing the occurrence of missing data. The proportional hazards assumption was tested using Schoenfeld residuals and log-log survival plots, and no significant violations were observed. Written informed consent was obtained from the patients. Patients were consecutively enrolled into the study if they were aged 18 years and above and diagnosed with HIV infection but free from hypertension at the initiation of ART (the regimens of ART used are shown in Table 1). The World Health Organization (WHO) STEPwise instrument for data collection and measurement of non-communicable diseases (NCD) risk factors was used [32,33]. Demographic data, medical history (including history of type 2 diabetes mellitus (T2DM), hypertension, tobacco smoking, and alcohol use), and physical examination findings were recorded using the WHO STEPwise tool as shown in Table 2 and Table 3. Blood pressure was measured using a calibrated automated sphygmomanometer following the WHO STEPS protocol. Each participant’s BP was measured three times at 2-min intervals in a seated position after 5 min of rest, and the average of the three readings was used in the analysis. Hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg or self-reported use of antihypertensive medication, in line with South African hypertension guidelines. Abnormal BP refers to any single elevated reading during baseline screening but not meeting the criteria for a confirmed diagnosis of hypertension. Weight and height were measured as shown in Table 2. Body mass index (BMI) was defined as underweight (BMI < 18.5 kg/m2), normal (BMI: 18.5 to 24.9 kg/m2), overweight (BMI: 25.0 to 29.9 kg/m2), and obese (BMI ≥ 30 kg/m2). The presence of metabolic syndrome (MetS) among the study participants was ascertained using criteria developed by the International Diabetes Federation (IDF) and the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III [34,35]. According to IDF criteria, MS was characterized by the presence of central obesity (waist circumference ≥ 94 cm for men or ≥80 cm for women) together with two of the following diagnostic criteria: (1) elevated triglyceride levels (≥150 mg/dL or ≥1.7 mmol/L); (2) low HDL cholesterol (<40 mg/dL or <1.04 mmol/L in men and <50 mg/dL or <1.29 mmol/L in women); (3) hypertension (BP ≥ 140/≥90 mmHg); and (4) fasting hyperglycemia (glucose level ≥ 5.6 mmol/L or ≥100 mg/dL) or previous diagnosis of diabetes. The waist circumference was measured at the belly button using a tailor’s tape. Random blood glucose, glycated hemoglobin (HbA1c), lipid profiles including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides, D-dimmer, and C-reactive protein (CRP) were measured on the Cobas 6000 (Roche, Germany). CD4+ T-cell counts were measured using Partec CyFlow Counter (Cyflow SL, Partec, Munster, Germany), whereas HIV and Hepatitis B measurements were performed using the Multiplex HIV, HCV & HBV nucleic acid test for use on the Cobas® 6800/8800 Systems (Roche, Germany) [36,37]. For HIV testing, at the clinic, a serial algorithm with Determine Rapid HIV-1/2 antibody (Abbott Laboratories, Abbott Park, IL, USA) followed by Unigold Rapid HIV Test (Trinity Biotech, PLC, IDA Business Park, Bray, County Wicklow, Ireland) was used. Cobas m511 integrated hematology analyzer (Roche, Basel, Switzerland) automatically prepared blood samples for immediate testing of platelet counts, erythrocyte sedimentation rate (ESR), and white cell counts. Continuous data were summarized as median (IQR) whilst categorical data were presented as proportions (%). The Chi-square test was used for testing relationships between variables of interest. If the outcome was a continuous variable, we used linear regression. Since the study outcome was ‘time to event’, we used Cox proportional hazard models, with a p-value < 0.05 being significant. IBM SPSS v.23 (Chicago, IL, USA) was used for statistical data analysis.

3. Results

Of the 70 HIV-infected patients, 27 (38.6%) developed abnormal BP, 13/27 (48.10%) within the initial 5 years of ART exposure; 10 (37.04%) between 5 and 10 years of ART exposure; and the remaining 4 (14.81%) developed abnormal BP after 10 years of ART exposure.
Table 2 displays patients’ characteristics as well as factors associated with the development of high BP following univariate/bivariate analysis. Table 2, Table 3 and Table 4 showed the associations between selected variables of interest and the occurrence of hypertension among HIV positive patients during ART. Univariate/bivariate analyses (Table 2 and Table 3) showed that patients aged ≥35 years, overweight or obese, with high blood levels of triglyceride, and diagnosed with MS using NCEP criteria. Figure 1 and Figure 2 shown that multivariable Cox models adjusting for metabolic syndrome and BMI, age ≥ 35 years was associated with a 2.2-fold higher hypertension risk (Hazard Ratio [HR]: 2.2; 95% Confidence Interval [CI]: 1.04–4.55; p = 0.04). Elevated triglycerides significantly increased risk, with a 7.9-fold higher likelihood of hypertension (HR: 7.9; 95% CI: 1.04–59.5; p = 0.046).
Figure 1 shows that older individuals (≥35 years) have a higher cumulative risk of the event than younger individuals, particularly as ART duration lengthens.
Figure 2 above presents over the course of ART 2 times (Hazard Ratio: 2.2; 95% CI: 1.04–4.55; p = 0.04) and 8 times (Hazard Ratio: 7.9; 95% CI: 1.04–59.5; p = 0.046) higher likelihood of developing hypertension, respectively. Variables in the Cox proportional hazards model are displayed.

4. Discussion

Studies have shown that high levels of triglyceride contribute to the thickening of the artery walls (arteriosclerosis), resulting in increased risk of hypertension, stroke, heart attack, and other cardiovascular diseases. In the present study, we expanded our comparison to include findings from similar African cohorts, particularly those conducted in rural and peri-urban populations in East and Southern Africa. Our findings align with previous studies from East Africa, such as research from rural Uganda and Kenya, which reported comparable rates of hypertension among PLWH, underscoring the growing burden of non-communicable diseases (NCDs) in these traditionally underserved settings [38,39]. Similarly, data from rural South Africa have highlighted a rising prevalence of hypertension in HIV-positive populations, driven by a combination of long-term ART exposure, aging, and the increasing prevalence of traditional risk factors such as obesity and dyslipidemia [40]. Most patients in this study were either obese or overweight, consistent with findings by [40] that weight reduction through dietary interventions improves BMI and enhances glucose and lipid metabolism, including lowering triglyceride levels. This supports the recommendation for weight loss to reduce excess calories that contribute to elevated triglycerides [41]. Furthermore, most of the patients in this study who had high blood pressure were drinking alcohol; however, this was not statistically significant. While alcohol was not significantly associated with the outcome in our analysis, this finding should be interpreted with caution and does not preclude a possible association in larger or more diverse populations. The latter is high in calories and sugar, and previous studies have demonstrated that regular consumption of alcohol had a potent effect on levels of triglycerides [42]. It is evident from this study that traditional risk factors (not HIV- and ART-related factors) were key players in the development of hypertension among HIV-infected patients on chronic medication; therefore, policies on healthy eating habits should be promoted. The use of healthier fats such as fat found in plants, vegetables, and fish, which are high in omega-3, should be recommended. Regular exercise along with reducing sugar and processed carbohydrates are additional healthy lifestyle choices that patients can make to prevent elevated blood triglyceride levels [43].
Study has established a link between age and triglyceride levels. Triglyceride levels in men’s blood have been found to progressively rise until the age of 50, at which point it begins to lightly decrease. Nonetheless, as women age, their triglyceride levels continue to rise, mild hypertriglyceridemia is reported in women from the age of 60 years and 30 years in men [42]. Although age influences blood levels of triglycerides, it has been previously reported as being an independent risk factor for hypertension [44]. Prior research suggests that older adults typically have much higher blood pressure, but not everyone will experience this age-related rise in blood pressure, regardless of their HIV status or ART regimen [45]. Early identification of elevated blood pressure and metabolic abnormalities among people living with HIV (PWH) on ART highlights the need to integrate routine cardiovascular risk screening, including BMI, waist circumference, and lipid profiles, into existing ART monitoring protocols. This could improve early detection and management of hypertension and reduce long-term morbidity. Our findings in this study report traditional risk factors such as being older than 35 and having an elevated triglyceride, which suggest significant, independent, and highly associated risk factors in hypertension. The incidence of hypertension is also high among HIV-infected patients receiving chronic ART medication in this study. We acknowledge that this finding could be attributed to several factors: the relatively small sample size, which may have limited the statistical power to detect significant associations, the homogeneity of ART regimens among participants, with a large proportion receiving similar fixed-dose combinations, and the possibility of a true absence of effect in this specific population. We consider this result as clinically significant since the magnitude of effect is meaningful in practice, regardless of whether 95% CIs are wider; hence, we plan a further study with a large sample size and appropriate controls, including HIV-negative patients.
The limitations in this study include the pilot study not being powered to make definitive causal inferences due to a small sample size. It is, however, exploratory in nature for generating hypotheses. Although the proportional hazards assumption holds, we did not perform the Correction for Multiple Comparisons (FDR and Bonferroni). The pilot study was also conducted in one community health center only, limiting the possibility of generalization of our results There is need for future research with larger, more diverse cohorts and which employs longitudinal or randomized designs to better isolate regimen effects to be used.

5. Conclusions

The observed patterns of elevated blood pressure and metabolic abnormalities among people living with HIV on ART suggest a potential need to explore the integration of routine cardiovascular risk screening into existing ART monitoring protocols. While this pilot study is not powered to make definitive causal inferences, the preliminary findings underscore the value of further research. These exploratory results may provide a foundation for future studies that could support broader efforts to align HIV care with national strategies for managing HIV–NCD comorbidities.
There is a need for robust and expanded study throughout the province with comparable data among various settings to establish the findings from this study.

6. Future Research

Future research showing the sample size calculation of a new study that age-matches general population, taking into account the HIV-negative control group, will be considered.
The pilot study aimed at generating hypotheses for further research, which should have a sample size that allows for drawing conclusions. The sample size of the further study must allow for the following:
Formula (Schoenfeld Method)
To estimate the required number of events (n) to achieve 80% power at a 5% significance level in a Cox proportional hazards model, Schoenfeld formula will be used:
n = [(Z1−α/2 + Z1−β)2]/[p(1 − p) × (log(HR))2]
where
  • n: Number of events required;
  • Z1−α/2: Z-value for significance level (e.g., 1.96 for 5%);
  • Z1−β: Z-value for desired power (e.g., 0.84 for 80%);
  • HR: Hazard Ratio to detect;
  • p: Proportion of individuals in the treatment/exposure group.

Author Contributions

T.A., U.T. and O.O.A., methodology; T.A., U.T. and O.O.A., validation; T.A., U.T. and O.O.A., formal analysis; U.T. and T.A., investigation; T.A., U.T. and O.O.A., resources; T.A. and U.T., data curation; T.A., writing—original draft preparation; T.A., U.T. and O.O.A., visualization; T.A., U.T. and O.O.A., project administration; T.A. and U.T. All authors have read and agreed to the published version of the manuscript.

Funding

This study was financed by the South African Medical Research Council (SAMRC) with grant number MRC-RFA-CC-01-2024.

Institutional Review Board Statement

This study was approved by the Research Ethics and Biosafety Committee of the Faculty of Health Sciences in Walter Sisulu University, bearing the protocol number 073/15. Permissions to conduct the study were obtained from the Eastern Cape Department of Health and the health district office. Written informed consents were obtained from all study participants, and confidentiality was observed throughout the study. To protect privacy and confidentiality of patients, no names were recorded and, instead, a personalized research number was used for each patient and only investigators had access to the collected data.

Informed Consent Statement

Written Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Data from this study will be made available from the corresponding author upon request.

Acknowledgments

The work reported herein was made possible through funding by the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the SAMRC Research Strengthening & Capacity Development Initiative (RCDI) Programme. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the SAMRC.

Conflicts of Interest

The authors declare no conflicts of interest. The funders had no role in the design of to study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Abbreviations

The following abbreviations are used in this manuscript:
ACCAmerican College of Cardiology
AHAAmerican Heart Association
ARTAnti-retroviral therapy
ANOVAAnalysis of variance
BMIBody mass index
CD4Cluster of differentiation 4
CIConfidence interval
CRPC-reactive protein
DBPDiastolic blood pressure
HDLHigh-density lipoprotein
HIVHuman immunodeficiency virus
LDLLow-density lipoprotein
NCDNon-communicable diseases
NHLSNational Health Laboratory Services
SBPSystolic blood pressure
SDStandard deviation
SSASub-Saharan Africa
TCTotal cholesterol
WHOWorld Health Organization
NRTINucleoside Reverse Transcriptase Inhibitor
NNRTINon-Nucleoside Reverse Transcriptase Inhibitor
TDTTenofovir Disoproxil Fumarate
3TCLamivudine
FTCEmtricitabine
EFVEfavirenz
NVPNevirapine
d4TStavudine

References

  1. UNAIDS. Fact Sheet—World AIDS Day 2019 Geneva: Global HIV Statistics. 2019. Available online: https://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf (accessed on 28 May 2025).
  2. The Global HIV/AIDS Epidemic. The Global HIV/AIDS Epidemic USA: KFF. 2019. Available online: https://www.kff.org/global-health-policy/fact-sheet/the-global-hiv-aids-epidemic/ (accessed on 28 May 2025).
  3. Kooij, K.W.; Zhang, W.; Trigg, J.; Cunningham, N.; Budu, M.O.; Marziali, M.E.; Lima, V.D.; Salters, K.A.; Barrios, R.; Montaner, J.S.G.; et al. Life expectancy and mortality among males and females with HIV in British Columbia in 1996–2020: A population-based cohort study. Lancet Public Health 2025, 10, e228–e236. [Google Scholar] [CrossRef] [PubMed]
  4. Appiedu-Addo, S.N.A.; Appeaning, M.; Magomere, E.; Ansa, G.A.; Bonney, E.Y.; Quashie, P.K. The urgent need for newer drugs in routine HIV treatment in Africa: The case of Ghana. Front. Epidemiol. 2025, 5, 1523109. [Google Scholar] [CrossRef] [PubMed]
  5. Moyo, R.C.; Sigwadhi, L.N.; Carries, S.; Mkhwanazi, Z.; Bhana, A.; Bruno, D.; Davids, E.L.; Van Hout, M.C.; Govindasamy, D. Health-related quality of life among people living with HIV in the era of universal test and treat results from a cross-sectional study in KwaZulu-Natal, South Africa. HIV Res. Clin. Pract. 2023, 25, 2298094. [Google Scholar] [CrossRef]
  6. Bigna, J.J.; Ndoadoumgue, A.L.; Nansseu, J.R.; Tochie, J.N.; Nyaga, U.F.; Nkeck, J.R.; Foka, A.J.; Kaze, A.D.; Noubiap, J.J. Global burden of hypertension among people living with HIV in the era of increased life expectancy: A systematic review and meta-analysis. J. Hypertens. 2020, 38, 1659–1668. [Google Scholar] [CrossRef]
  7. Dzudie, A.; Hoover, D.; Kim, H.Y.; Ajeh, R.; Adedimeji, A.; Shi, Q.; Pefura Yone, W.; Nsame Nforniwe, D.; Thompson Njie, K.; Pascal Kengne, A. Hypertension among people living with HIV/AIDS in Cameroon: A cross-sectional analysis from Central Africa International Epidemiology Databases to Evaluate AIDS. PLoS ONE 2021, 16, e0253742. [Google Scholar] [CrossRef]
  8. Okyere, J.; Ayebeng, C.; Owusu, B.A.; Dickson, K.S. Prevalence and factors associated with hypertension among older people living with HIV in South Africa. BMC Public Health 2022, 22, 1684. [Google Scholar] [CrossRef] [PubMed]
  9. Gafane-Matemane, L.F.; Craig, A.; Kruger, R.; Alaofin, O.S.; Ware, L.J.; Jones, E.S.; Kengne, A.P. Hypertension in sub-Saharan Africa: The current profile, recent advances, gaps, and priorities. J. Hum. Hypertens. 2025, 39, 95–110. [Google Scholar] [CrossRef]
  10. Zhou, B.; Perel, P.; Mensah, G.A.; Ezzati, M. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat. Rev. Cardiol. 2021, 18, 785–802. [Google Scholar] [CrossRef]
  11. Nartey, E.T.; Tetteh, R.A.; Anto, F.; Sarfo, B.; Kudzi, W.; Adanu, R.M. Risk of hypertension in adult patients on antiretroviral therapy: A propensity score matching analysis. Health Sci. Investig. J. 2023, 4, 540–549. [Google Scholar] [CrossRef]
  12. Ghandakly, E.; Moudgil, R.; Holman, K. Cardiovascular disease in people living with HIV: Risk assessment and management. Clevel. Clin. J. Med. 2025, 92, 159–167. [Google Scholar] [CrossRef]
  13. Davis, K.; Perez-Guzman, P.; Hoyer, A.; Brinks, R.; Gregg, E.; Althoff, K.N.; Justice, A.C.; Reiss, P.; Gregson, S.; Smit, M. Association between HIV infection and hypertension: A global systematic review and meta-analysis of cross-sectional studies. BMC Med. 2021, 19, 105. [Google Scholar]
  14. Hirigo, A.T.; Yilma, D.; Astatkie, A.; Debebe, Z. The association between dolutegravir-based a3tiretrovirals and high blood pressure among adults with HIV in southern Ethiopia: A cross-sectional study. Ther. Adv. Infect. Dis. 2024, 11, 20499361241306942. [Google Scholar] [PubMed]
  15. Mugisha, N.; Ghanem, L.; Komi, O.A.; Noureddine, R.; Shariff, S.; Wojtara, M.; Nanehkeran, M.M.; Uwishema, O. Addressing Cardiometabolic Challenges in HIV: Insights, Impact, and Best Practices for Optimal Management—A Narrative Review. Health Sci. Rep. 2025, 8, e70727. [Google Scholar] [CrossRef] [PubMed]
  16. Derick, K.I.; Khan, Z. Prevalence, awareness, treatment, control of hypertension, and availability of hypertension services for patients living with human immunodeficiency virus (HIV) in sub-Saharan Africa (SSA): A systematic review and meta-analysis. Cureus 2023, 15, e37422. [Google Scholar] [CrossRef] [PubMed]
  17. Siddiqui, M.; Moore, T.J.; Long, D.M.; Burkholder, G.A.; Willig, A.; Wyatt, C.; Heath, S.; Muntner, P.; Overton, E.T. Risk factors for incident hypertension within 1 year of initiating antiretroviral therapy among people with HIV. AIDS Res. Hum. Retroviruses 2022, 38, 735–742. [Google Scholar] [CrossRef]
  18. Tsuro, U.; Oladimeji, K.E.; Pulido-Estrada, G.A.; Apalata, T.R. Risk factors attributable to hypertension among HIV-infected patients on antiretroviral therapy in selected rural districts of the Eastern Cape Province, South Africa. Int. J. Environ. Res. Public Health 2022, 19, 11196. [Google Scholar] [CrossRef]
  19. Mivumbi, J.P.; Gbadamosi, M.A. Hypertension Prevalence and Associated Factors in HIV Positive omen at Kicukiro, Kigali, Rwanda: A Cross-Sectional Analysis. medRxiv 2025. [Google Scholar]
  20. Bailin, S.S.; Koethe, J.R.; Rebeiro, P.F. The pathogenesis of obesity in people living with HIV. Curr. Opin. HIV AIDS 2024, 19, 6–13. [Google Scholar] [CrossRef]
  21. Fanfair, R.; Cheever, L.; Mermin, J. September 18 Is National HIV/AIDS and Aging Awareness Day CDC Encourages People Aged 50 or Older to Get Tested for HIV at a Glance; National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention: Atlanta, GA, USA, 2024. [Google Scholar]
  22. Chen, A.; Chan, Y.K.; Mocumbi, A.O.; Ojji, D.B.; Waite, L.; Beilby, J.; Codde, J.; Dobe, I.; Nkeh-Chungag, B.N.; Damasceno, A.; et al. Hypertension among people living with human immunodeficiency virus in sub-Saharan Africa: A systematic review and meta-analysis. Sci. Rep. 2024, 14, 16858. [Google Scholar] [CrossRef]
  23. Abdela, A.A.; Yifter, H.; Reja, A.; Shewaamare, A.; Ofotokun, I.; Degu, W.A. Prevalence and risk factors of metabolic syndrome in Ethiopia: Describing an emerging outbreak in HIV clinics of the sub-Saharan Africa–a cross-sectional study. BMJ Open 2023, 13, e069637. [Google Scholar] [CrossRef]
  24. Saito, A.; Karama, M.; Kamiya, Y. HIV infection, and overweight and hypertension: A cross-sectional study of HIV-infected adults in Western Kenya. Trop. Med. Health 2020, 48, 224. [Google Scholar] [CrossRef]
  25. Galaviz, K.I.; Patel, S.A.; Siedner, M.J.; Goss, C.W.; Gumede, S.B.; Johnson, L.C.; Ordóñez, C.E.; Laxy, M.; Klipstein-Grobusch, K.; Heine, M.; et al. Integrating hypertension detection and management in HIV care in South Africa: Protocol for a stepped-wedged cluster randomized effectiveness-implementation hybrid trial. Implement. Sci. Commun. 2024, 5, 115. [Google Scholar] [CrossRef] [PubMed]
  26. Spach, D.H. National HIV Curriculum. Adverse Effects of Antiretroviral Medications. 2025. Available online: https://www.hiv.uw.edu/go/antiretroviral-therapy/adverse-effects/core-concept/all?utm_source (accessed on 29 May 2025).
  27. Denu, M.K.; Revoori, R.; Buadu, M.A.E.; Oladele, O.; Berko, K.P. Hypertension among persons living with HIV/AIDS and its association with HIV-related health factors. AIDS Res. Ther. 2024, 21, 5. [Google Scholar] [CrossRef] [PubMed]
  28. World Health Statistics 2023. Available online: https://cdn.who.int/media/docs/default-source/gho-documents/world-health-statistic-reports/2023/world-health-statistics-2023_20230519_.pdf (accessed on 29 May 2025).
  29. Sun, S.; Zhou, S.; Huang, Q.; Sun, J. The unique relationship between body mass index and metabolic syndrome in AIDS patients. Sci. Rep. 2025, 15, 13915. [Google Scholar] [CrossRef] [PubMed]
  30. Lam, J.O.; Leyden, W.A.; Alexeeff, S.; Lea, A.N.; Hechter, R.C.; Hu, H.; Marcus, J.L.; Pitts, L.; Yuan, Q.; Towner, W.J.; et al. Changes in body mass index over time in people with and without HIV infection. In Open Forum Infectious Diseases; Oxford University Press: New York, NY, USA, 2024; Volume 11, p. ofad611. [Google Scholar]
  31. Fryar, C.D.; Kit, B.; Carroll, M.D.; Afful, J. Hypertension Prevalence, Awareness, Treatment, and Control Among Adults Ages 18 and Older: United States, August 2021—August 2023. In NCHS Data Briefs; National Center for Health Statistics: Hyattsville, MD, USA, 2024. [Google Scholar]
  32. Demissie, B.M.; Girmaw, F.; Amena, N.; Ashagrie, G. Prevalence of metabolic syndrome and associated factors among patient with type 2 diabetes mellitus in Ethiopia, 2023: Asystematic review and meta analysis. BMC Public Health 2024, 24, 1128. [Google Scholar] [CrossRef]
  33. Jamali, Z.; Ayoobi, F.; Jalali, Z.; Bidaki, R.; Lotfi, M.A.; Esmaeili-Nadimi, A.; Khalili, P. Metabolic syndrome: A population-based study of prevalence and risk factors. Sci. Rep. 2024, 14, 3987. [Google Scholar] [CrossRef]
  34. WHO. Global HIV Programme. Available online: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/treatment/advanced-hiv-disease (accessed on 29 May 2025).
  35. Ren, Q.W.; Teng, T.H.K.; Ouwerkerk, W.; Tse, Y.K.; Tsang, C.T.W.; Wu, M.Z.; Tse, H.-F.; Voors, A.A.; Tromp, J.; Lam, C.S.P.; et al. Triglyceride levels and its association with all-cause mortality and cardiovascular outcomes among patients with heart failure. Nat. Commun. 2025, 16, 1408. [Google Scholar] [CrossRef]
  36. Virani, S.S.; Newby, L.K.; Arnold, S.V.; Bittner, V.; Brewer, L.C.; Demeter, S.H.; Dixon, D.L.; Fearon, W.F.; Hess, B.; Johnson, H.M.; et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J. Am. Coll. Cardiol. 2023, 82, 833–955. [Google Scholar] [CrossRef]
  37. Kwarisiima, D.; Atukunda, M.; Owaraganise, A.; Chamie, G.; Clark, T.; Kabami, J.; Jain, V.; Byonanebye, D.; Mwangwa, F.; Balzer, L.B.; et al. Hypertension control in integrated HIV and chronic disease clinics in Uganda in the SEARCH study. BMC Public Health 2019, 19, 511. [Google Scholar] [CrossRef] [PubMed]
  38. Hickey, M.D.; Ayieko, J.; Owaraganise, A.; Sim, N.; Balzer, L.B.; Kabami, J.; Atukunda, M.; Opel, F.J.; Wafula, E.; Nyabuti, M.; et al. Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda. PLoS Med. 2021, 18, e1003803. [Google Scholar] [CrossRef]
  39. Kamkuemah, M. The Epidemiology of Chronic Non-Communicable Diseases (NCDS) and NCD Risk Factors in Adolescents & Youth Living with HIV in Cape Town, South Africa. Ph.D. Thesis, University of Cape Town, Cape Town, South Africa, 2021. [Google Scholar]
  40. Ma, Y.; Sun, L.; Mu, Z. Effects of different weight loss dietary interventions on body mass index and glucose and lipid metabolism in obese patients. Medicine 2023, 102, e33254. [Google Scholar] [CrossRef] [PubMed]
  41. Banović Fuentes, J.; Beara, I.; Torović, L. Regulatory Compliance of Health Claims on Omega-3 Fatty Acid Food Supplements. Foods 2024, 14, 67. [Google Scholar] [CrossRef] [PubMed]
  42. Mikkelsen, M.; Wilsgaard, T.; Grimsgaard, S.; Hopstock, L.A.; Hansson, P. Associations between postprandial triglyceride concentrations and sex, age, and body mass index: Cross-sectional analyses from the Tromsø study 2015–2016. Front. Nutr. 2023, 10, 1158383. [Google Scholar] [CrossRef]
  43. Suzuki, T.; Fukui, S.; Shinozaki, T.; Asano, T.; Yoshida, T.; Aoki, J.; Mizuno, A. Lipid profiles after changes in alcohol consumption among adults undergoing annual checkups. JAMA Netw. Open 2025, 8, e250583. [Google Scholar] [CrossRef]
  44. Li, Y.; He, S.; Jian, W.; Liu, Y.; Cheng, Z.; Peng, H. Triglyceride-glucose index predicts adverse cardiovascular events in patients with H-type hypertension combined with coronary heart disease: A retrospective cohort study. Cardiovasc. Diabetol. 2025, 24, 45. [Google Scholar] [CrossRef]
  45. Hirigo, A.T.; Yilma, D.; Astatkie, A.; Debebe, Z. Prevalence and Determinants of Metabolic Syndrome among Adults Living with HIV on First-Line Antiretroviral Treatment in Southern Ethiopia: A Cross-Sectional Study. Ther. Adv. Chronic Dis. 2025, 16, 20406223251346289. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Cumulative hazard of event by age group over duration of ART.
Figure 1. Cumulative hazard of event by age group over duration of ART.
Ijerph 22 01397 g001
Figure 2. Hypertriglyceridemia as an independent risk factor for the development of abnormal BP over the course of ART in HIV-infected patients (n = 70).
Figure 2. Hypertriglyceridemia as an independent risk factor for the development of abnormal BP over the course of ART in HIV-infected patients (n = 70).
Ijerph 22 01397 g002
Table 1. ART regimen coding system definitions.
Table 1. ART regimen coding system definitions.
CodeComponents (Drugs)Full NamesDrug Class
1T3ETenofovir + Lamivudine + EfavirenzTenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) + Efavirenz (EFV)NRTI + NRTI + NNRTI
1TFETenofovir + Emtricitabine + EfavirenzTenofovir disoproxil fumarate (TDF) + Emtricitabine (FTC) + Efavirenz (EFV)NRTI + NRTI + NNRTI
1S3EStavudine + Lamivudine + EfavirenzStavudine (d4T) + Lamivudine (3TC) + Efavirenz (EFV)NRTI + NRTI + NNRTI
1S3NStavudine + Lamivudine + NevirapineStavudine (d4T) + Lamivudine (3TC) + Nevirapine (NVP)NRTI + NRTI + NNRTI
1T3NTenofovir + Lamivudine + NevirapineTenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) + Nevirapine (NVP)NRTI + NRTI + NNRTI
Table 2. Characteristics of the study participants and univariate/bivariate analysis of factors associated with the occurrence of abnormal blood pressure among the HIV-positive clinic attendees. The table reveals the factors associated with high blood pressure in the study.
Table 2. Characteristics of the study participants and univariate/bivariate analysis of factors associated with the occurrence of abnormal blood pressure among the HIV-positive clinic attendees. The table reveals the factors associated with high blood pressure in the study.
Variables of InterestTotal
N (%)
Blood PressureChi-Squarep-Value
NormalHigh
Non-modifiable risk factors:
Age, years 4.580.032
   <3532 (45.71%)24/32 (75%)8/32 (25%)
   ≥3538 (54.29%)19/38 (50%)19/38 (70.4%)
Gender 2.290.130
   Male11 (15.70%)9/11 (81.8%)2/11 (18.2%)
   Female59 (84.30%)34/59 (57.6%)25/59 (42.4%)
Modifiable risk factors:
Alcohol consumption
   Yes26 (37.1%)15/26 (57.7%)11/26 (42.3%)0.240.621
   No44 (62.9%)28/44 (63.6%)16/44 (36.%)
Cigarette smoking 0.410.521
   Yes13 (18.6%)9/13 (20.9%)4/13 (30.8%)
   No57 (81.4%)34/57 (59.1%)23/57 (40.4%)
History of type 2 diabetes mellitus 0.160.686
   Yes4 (6.2%)3/4 (75.0%)1/4 (25.0%)
   No61 (93.8%)39/61 (63.9%)22/61 (36.1%)
Body mass index 9.740.008
   Normal29 (41.4%)24/29 (82.8%)5/29 (17.2%)
   Overweight20 (28.6%)10/20 (50.0%)10/20 (50%)
   Obesity21 (30%)9/21 (42.9%)12/21 (57.1%)
Table 3. Univariate and bivariate analysis of lipid profiles, glucose levels, coagulation and inflammatory markers, metabolic syndrome, HIV parameters, and ART regimens associated with hypertension among HIV-positive clinic attendees.
Table 3. Univariate and bivariate analysis of lipid profiles, glucose levels, coagulation and inflammatory markers, metabolic syndrome, HIV parameters, and ART regimens associated with hypertension among HIV-positive clinic attendees.
Variables of InterestTotal
N (%)
Blood Pressure Chi-Squarep-Value
NormalHigh
Lipid profile:
Total cholesterol, mmol/L 2.320.128
   Desirable60 (93.8%)38/60 (63.3%)22/60 (36.7%)
   High4 (6.3%)1/4 (25.0%)3/4 (75%)
LDL, mmol/L 1.600.205
   Desirable45 (97.8%)28/45 (62.2%)17/45 (37.8)%
   High1 (2.2%)0/1 (0%)1/1 (100%)
HDL, mmol/L 1.440.230
   Desirable45 (70.3%)26/45 (57.8%)19/45 (42.2%)
   Low19 (29.7%)14/19 (35%)5/19 (20.8%)
Triglyceride, mmol/L 13.150.0002
   Desirable46 (82.1%)33/46 (77.1%)13/46 (28.3%)
   High10 (17.9%)1/10 (10.0%)9/10 (90.0%)
Ratio total cholesterol/HDL 2.830.024
   <456 (88.9%)36/56 (64.3%)20/56 (83.3%)
   4–66 (9.5%)2/6 (33.3%)4/6 (66.7%)
   >61/1 (1.6%)1/1 (100%)0/1 (0%)
Blood glucose tests
Random blood glucose, mmol/L 0.640.424
   Normal69 (98.6%)42/69 (60.9%)27/69 (39.1%)
   Abnormal1 (1.4%)1/1 (100%)0/1 (0%)
Glycated Hb, mmol/L 3.400.065
   Normal48 (68.6%)26/48 (60.5%)22/48 (81.5%)
   Abnormal22 (31.4%)17/22 (77.3%)5/22 (22.72%)
Coagulation disorders
   D-dimmer 1.580.208
   Positive30 (46.2%)16/30 (53.3%)14/30 (46.6%)
   Negative35 (53.8%)24/35 (68.5%)11/35 (31.4%)
Metabolic syndrome
MS by NCEP 3.070.080
   Present31 (44.3%)15/31 (48.4%)16/31 (51.6%)
   Absent39 (55.7%)28/39 (71.7%)11/39 (28.2%)
MS by IDF 1.580.209
   Present31 (44.3%)16/31 (51.6%)15/31 (48.4%)
   Absent39 (55.7%)27/39 (69.2%)12/39 (30.8%)
HIV-associated risk factors
WHO staging at ART initiation 1.960.58
   Stage 134 (49.3%)20/34 (58.8%)14/34 (41.2%)
   Stage 215 (21.7%)8/15 (53.3%)7/15 (46.7%)
   Stage 318 (26.1%)12/18 (66.7%)6/18 (33.3%)
   Stage 42 (2.9%)2/2 (100%)0/2 (0%)
Current HIV viral load, copies/mL 1.000.32
   Detectable39 (58.2%)22/39 (56.4%)17/39 (43.6%)
   Undetectable28 (41.8%)20/28 (71.4%)8/28 (28.6%)
Level of immunosuppression 0.380.943
   Severe4 (6%)3/4 (75.0%)1/4 (25.0%)
   Advanced10 (14.9%)6/10 (60.0%)4/10 (40.0%)
   Mild7 (10.4%)4/7 (57.1%)3/7 (42.8%)
   Normal46 (68.7%)29/46 (63.0%)17/46 (36.9%)
ART-associated risk factors
Initial ART regiments ** 2.140.71
   1T3E25 (35.7%)15/25 (60.0%)10/25 (40.0%)
   1TFE33 (47.1%)20/33 (60.9%)13/33 (39.4%)
   1S3E3 (4.3%)3/3 (100%)0/3 (0%)
   1S3N5 (7.1%)3/5 (60.0%)2/5 (40.0%)
   1T3N4 (5.7%)2/4 (50.0%)2/4 (50.0%)
Current ART regiments 6.020.019
   1T3E16 (23.2%)10/16 (62.5%)6/16 (37.5%)
   1TFE48 (69.6%)30/48 (62.5%)18/48 (37.5%)
   1S3E2 (2.9%)2/2 (100.0%)0/2 (0%)
   1S3N1 (1.4%)0/1 (0%)1/1 (100.0%)
   1T3N2 (2.9%)0/2 (0%)2/2 (100%)
ART duration, years 0.200.91
   <5 years36 (51.4%)23/36 (63.5%)13/36 (36.1%)
   5–10 years24 (34.3%)14/24 (58.3%)10/24 (41.7%)
   >10 years10 (14.3%)6/10 (60.0%)4/10 (40.0%)
Table 4. Multivariate Cox-regression analysis displaying independent risk factors for the development of hypertension over the duration of ART exposure.
Table 4. Multivariate Cox-regression analysis displaying independent risk factors for the development of hypertension over the duration of ART exposure.
Risk FactorsHazard Ratio (HR)
(95% CI for HR)
B-CoefficientSEWald Chi-Squarep-Value
Age, Years2.169 (1.035–4.546)0.7740.3784.2060.04 *
Triglyceride, mmol/L7.855 (1.037–59.469)2.0611.0333.9820.046 *
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Apalata, T.; Tsuro, U.; Akapo, O.O. Prolonged Exposure to Antiretroviral Therapy and Risk of Developing Hypertension Among HIV-Infected Clinic Attendees: A Pilot Study in Rural Eastern Cape Province, South Africa. Int. J. Environ. Res. Public Health 2025, 22, 1397. https://doi.org/10.3390/ijerph22091397

AMA Style

Apalata T, Tsuro U, Akapo OO. Prolonged Exposure to Antiretroviral Therapy and Risk of Developing Hypertension Among HIV-Infected Clinic Attendees: A Pilot Study in Rural Eastern Cape Province, South Africa. International Journal of Environmental Research and Public Health. 2025; 22(9):1397. https://doi.org/10.3390/ijerph22091397

Chicago/Turabian Style

Apalata, Teke, Urgent Tsuro, and Olufunmilayo Olukemi Akapo. 2025. "Prolonged Exposure to Antiretroviral Therapy and Risk of Developing Hypertension Among HIV-Infected Clinic Attendees: A Pilot Study in Rural Eastern Cape Province, South Africa" International Journal of Environmental Research and Public Health 22, no. 9: 1397. https://doi.org/10.3390/ijerph22091397

APA Style

Apalata, T., Tsuro, U., & Akapo, O. O. (2025). Prolonged Exposure to Antiretroviral Therapy and Risk of Developing Hypertension Among HIV-Infected Clinic Attendees: A Pilot Study in Rural Eastern Cape Province, South Africa. International Journal of Environmental Research and Public Health, 22(9), 1397. https://doi.org/10.3390/ijerph22091397

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop