HIV/AIDS Research and Treatment · Vol. 9, No. 1 · 2023 · pp. 5–13 · e-ISSN 2377-8377

Prevalence and Determinants of Subclinical Atherosclerosis in People Living with HIV on Antiretroviral Treatment in Hospitals in Kinshasa

Murielle Longokolo M, Longo-Mbenza Benjamin, Marcel M. Mambimbi, Hippolyte N-T Situakibanza, Madone M. Ndona, Jean-Robert M. Risassi, Nadine M. Ngongo, Ben Bepouka, Ossam Odio, Jean M. Tshibola, Frédéric T. Tshienda, Eric M. Kasongo, Mamy N. Nzita, Lukiana Tuna, Aimée Lulebo, Donatien M. Sonzi, Christian Kisoka L

DOI: https://doi.org/10.17140/hartoj-9-139 · Published 2023-07-10 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2023 The Author(s)

Abstract

Introduction: The objective of this work was to identify the traditional, emerging, and therapeutic cardiometabolic risk factors for subclinical atherosclerosis in human immunodeficiency virus (HIV)-infected patients under antiretroviral treatment in the era of dolutegravir (DGT) in hospitals in the Kinshasa, Democratic Republic of the Congo (DRC). Methods: This was a descriptive and analytical cross-sectional study held between January 2017 and December 2021 among people living with HIV (PLWHIV) on antiretroviral treatment (ART) for at least 6-months, supported in the structures of the Network Catholic of the Diocesan Office of Medical Works (BDOM) and at the University Clinics of Kinshasa (UCK). Sub clinical atherosclerosis was defined by: pulse pressure (PP)≥60 mm Hg; a carotid intima-media thickness (CIMT)>0.8 mm and a systolic pressure index (SPI)<0.9. Logistic regression was used in the statistical study of associations. Results: A total of 321 PLWHIV on ART were recruited. The average age of PLWHIV was 51±11-years with a female pre dominance of 72% (n=231); the independent determinants of subclinical atherosclerosis were married (aOR: 4, 95% CI 1.5 10.5; p<0.006), low socio-economic status (aOR: 10.7, 95% CI 2.3-48, 7 p<0.002), duration of HIV infection (ORa: 6.6, 95% CI 2.8-16; p<0.0001), duration of antiretroviral treatment ≥9-years (ORa: 0, 3, 95% CI 0.2-0.7; p<0.005) and the total cholesterol/high-density lipoprotein-cholesterol ratio (CT/HDL-C) (ORa: 2, 95% CI 1.1-3.6; p=0.034). Dyslipidaemia (hyper low-density lipoprotein-cholesterol (LDL-C), hyper HDL-c and hypertriglyceridemia) has been identified in PLWHIV on DTG. The prevalence of subclinical atherosclerosis in PLWHIV on ART was 31.1% (n=116/321). Conclusion: Married people, low socioeconomic level, duration of HIV infection, duration of antiretroviral treatment beyond 9-years, and the CT/HDL-C ratio are identified as independent determinants of subclinical atherosclerosis in PLWHIV on ART in Kinshasa hospitals. Dyslipidemia is found in PLWHIV on DTG and the prevalence of subclinical atherosclerosis among PLWHIV on ART is low compared to that of Côte d’Ivoire.

Keywords: Subclinical atherosclerosis; HIV/AIDS; Antiretroviral therapy; Kinshasa/DRC

Introduction

he introduction of highly active antiretroviral treatments (HA- ART) in April 1996 enabled, on the one hand, a substantial T reduction in HIV-related morbidity and mortality and, on the other hand, increased the life expectancy of patients infected with HIV (people living with HIV (PLWHIV)).1-5

As a result, opportunistic infections have given way to chronic complications such as cancers, and metabolic (lipid carbohydrate) abnormalities known as major risk factors for cardiovascular disease (CVD), and chronic kidney disease (CKD). After 2016, the World Health Organization (WHO) proposed dolutegravir (DTG) as a therapeutic alternative for first-line treatment in adults. The National Program for the Fight against human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) (PNLS) in the Democratic Republic of the Congo (DRC) has adopted DTG-based antiretroviral treatment (ART) as first-line treatment. The combination Tenofovir (TDF), Lamivudine (3TC), DTG (TLD) or fixed-dose TLD should be introduced gradually with newly eligible patients.

Thus, the objective of the present study was to identify the traditional, emerging, and therapeutic risk factors for subclinical atherosclerosis in patients living with HIV infection on antiretroviral therapy in the era of DGT in hospital settings, Kinshasa, DRC.

Methods

Design and Framework of the Study

This is a descriptive and analytical cross-sectional study carried out in the structures of the Catholic network of the Diocesan Office of Medical Works (BDOM) and at the University Clinics of Kinshasa (UCK) between January 2017 and December 2021. The BDOM is a network that contains a larger sample of PLWHIV in the city of Kinshasa. On the other hand, the University Clinics of Kinshasa which constitute a tertiary level of care, a level of high technicality was retained as a frame of reference.

Study Population

It concerned PLWHIV aged at least 18-years on ART for at least 6-months and have freely given their consent; were excluded PLWHIV with pregnancy, nephrotic syndrome, hepatic cirrhosis, those using lipid-lowering drugs or insulin, and those who refused to sign informed consent. The sample size was calculated from the Schwartz formula: n=z²p (1-p)/e². The true prevalence of subclinical atherosclerosis among PLWHIV in the DRC is unknown, the prevalence of atherosclerosis of 64.7% in PLWHIV, reported by Djalloh et al7 at the Center Hospitalier Universitaire de Treichville in Côte d’Ivoire served as a baseline. Hence the present study has retained a frequency of 65% for the calculation of the minimum sample size n=(1.96)2×0.65(1-0.65)/(0.05)²=349.58. The calculated sample size was 350 HIV+ subjects.

Collection of Data

It was based on an ad hoc data collection sheet containing sociodemographic characteristics (age, sex, marital status, and socioeconomic level), clinical data (clinical stages of infection by HIV, duration of infection, duration of HIV treatment and treatment regimen), anthropometry recorded weight, height, waist circumference (WC), hip circumference (HC), body mass index (BMI=weight, kg/height in m ) using standard methods in par- 1-5 ticipants with light clothing and without shoes, using an OMRON BF214 type BODY Composition Monitor impedance scale and tape measure and a measuring board. Blood pressure (BP), including systolic blood pressure (SBP), diastolic blood pressure (DBP) 1-5 and pulse pressure (PP) (SBP-DBP) after the participant rested for 10-minutes seated in a quiet room, was measured in the left arm with the elbow flexed at the level of the heart at the using an Omron HEM 705 electronic manometer (Omron Life Science Co. Ltd, Tokyo, Japan).

Laboratory tests included: C-reactive protein (CRP), glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), serological tests for HIV, uric acid, 6 and serum creatinine. Viral load values dating back no more than 3-months were collected from participants’ medical records. All the analyzes (hematology and biochemistry) were carried out in the Laboratory of Biochemistry and Hematology of the University Clinics of Kinshasa. The HIV serological test was carried out on each blood sample (according to the algorithm of the National Program for the Fight against HIV/AIDS (PNLS)/DRC in force to confirm the seropositivity of the HIV cases included. The medical imaging data were including the systolic pressure index (SPI) or ankle brachial index (ABI) determined using an 8 MHz continuous wave Doppler device probe, brand HUNTLEIGH, held 6 7 in the hand as described by Kwiatkowska et al6 and Olalla et al7 and measurement of the carotid intima-media thickness (CIMT) performed using a Doppler ultrasound device equipped with a 7.5 MHZ linear probe from PHILIPS brand. Scanning was done first at the level of the right common carotid then the left. The areas of interest were defined as a distance of 0.5 cm, 1 cm and 2 cm from the bifurcation.

On each area of interest, the near and far wall thicknesses were measured; the maximum values of the intima-media thickness (IMT) measurements were used if there was an atherosclerotic plaque. The ABI (IPS) value was determined by dividing the higher pressure of the two arteries at the ankles by the higher brachial systolic blood pressure. Using the formula below, SPI was calculated as follows: SPI=Ankle peripheral arterial stiffness (PAS)/ Arm PAS. With PAS ankle (the systolic pressure of the posterior tibial artery or the dorsum of the foot artery).

Working Definitions

Arterial hypertension was defined by SBP≥140 mmHg and 8,9 DBP≥90 mm Hg or current intake of antihypertensives. Body mass index (BMI) was defined by the ratio of weight expressed in kg to height in m², with total obesity being defined by a value >30 kg/m². Diabetes mellitus was defined by fasting blood glucose ≥126 mg/dL or taking antidiabetics.10 An increase in HDL-C≥75 10,11 mg/dL was considered a cardiovascular risk factor. Subclinical (preclinical) atherosclerosis was defined by: PP≥60 mmHg; an

carotid IMT (cIMT)>0.8 mm and an ABI<0.9. A suppressed viral load was defined by a plasma HIV-ribonucleic acid (RNA) level≤1000 copies/mL and an undetectable viral load was <50 copies/mL.15 CRP>3 mg/L was considered a cardiovascular risk factor.16 Chronic kidney disease was defined by a ClCr<60 ml/min with reference to the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) classification. Hyperuricemia was defined as uricemia≥7 mg/dL.19 The TG/ Glucose (TyG) ratio was calculated by ln (TG (mg/dL)×FG (mg/ dL)/2), which allows to determine insulin resistance, it is a more effective biomarker than its separate components to identify abnormalities glucose metabolism.20 Its normal value is set at 4.49. Non-HDL-C was calculated by the differential between TC and HDL-C. In patients considered at high cardiovascular risk, the non-HDL cholesterol level is <130 mg/dL. In patients considered to be at very high cardiovascular risk, this rate is <100 mg/dL. The CT/HDL-C ratio is used to measure cardiovascular risk. Its normal value must be <5. Low-density lipoprotein (LDL)/HDL atherogenic coefficient was considered to predict cardiovascular risk if the ratio was >3.323; The TG/HDL-C ratio ≥3 was considered to be a marker of insulin resistance. Uric acid/HDL-C ratio ≥10.9% was considered a predictor of metabolic syndrome.25

Statistical Analysis

Data were entered using Excel 2013 software, exported, and ® analyzed using IBM statistical package for the social sciences ® (SPSS ) 26 software. Statistical analyses considered a descriptive (mean±standard deviation, frequency, proportion), univariate comparative approach for associated factors and multivariate analysis of the binary logistic regression type to identify the independent determinants predisposing to subclinical atherosclerosis (dependent variable) after adjustment for confounding variables (Adjusted odds ratio (ORa); 95% confidence interval (95% CI)). A value of p<0.05 was considered statistically significant.

Ethical Considerations

All participants provided written informed consent before participating in the study. However, patient records/information were anonymized and anonymized before analysis. The protocol for this study was submitted and approved by the ethics committee of the School of Public Health of the University of Kinshasa under the Helsinki recommendations (App No: ESP/CE/101/2020).

Results

Sociodemographic, Clinical and Therapeutic Characteristics of the Study Population

A total of 321 HIV-infected patients on ART were enrolled in this study.

Women were in the majority at 72% (n=231); the mean age of the patients was 51±11-years; the age group of 43-59-years was the most encountered in 49.2% (158); 243 (75.7%) were married; 269 (83.8%) had a low socio-economic level; 101 (31.5) patients were at WHO stage 3; 224 (69.8%) of the patients were on the TDF+3TC+Efavirenz (EFV) combination; 110 (34.3%) had a 12-14 duration of HIV infection of fewer than 8-years; 137 (42.7%) of the patients had a duration of antiretroviral treatment of fewer than 5-years (Table 1).

Table 1. Sociodemographic, Clinical and Therapeutic Characteristics of the Study Population 17,18

Variables N=321(100%) Sociodemographic Data

Sex 90(28%) • Male 231(72%) • Feminine 51±11

Average Age (years)

Age range (years) ≥60 92(28.7) 43-59 158(49.2) <43 71(22.1)

Marital Status

21,22 • Married 243(75.7) • Single 78(24.3)

Socio-Economic Level

24 • Down 269(83.8) • Pupil 52(16.2)

Clinical and Therapeutic Data

WHO clinical stages • 1 90(28) • 2 77(24) • 3 101(31.5) • 4 53(16.5)

Therapeutic Diet

• TDF+3TC+EFV 224(69.8) • TDF+3TC+DTG 76(23.6) • TDF+3TC+LPV/r 14(4.4) • AZT+3TC+NVP 7(2,2)

Duration of Infection (years)

• ≥14 103(32.1) • 8-13 108(33.6) • <8 110(34.3)

Duration of Antiretroviral Treatment (years)

• ≥9 107(33.3) • 5-8 77(24) • <5 137(42.7%) TDF(Tenofovir); 3TC (lamivudine); EFV(Efavirenz); DTG(Dolutegravir); LPV/r(lopinavir/ritonavir); AZT(Zidovudine); NVP(Nevirapine)

Comparisons across Antiretroviral Therapy Regimens

According to traditional variables: Except for diastolic BP (p>0.05), there was an unequal and highly significant variation (p=0.000) in mean values for age, SBP, PP, WC, HC, WC/HC, BMI, blood sugar, LDL-cholesterol (LDL-C), HDL-C, TG and TC from DTG to LPV/r (Table 2).

According to emerging variables: Except for LDL-C/HDL- C (p>0.05), there was an unequal and very significant variation (p=0.000) in the mean values of creatinine, uric acid, CRP, SPI, cIMT, TyG ratio, non-HDL-C, TG/HDL-C ratio and TC/HDL-C ratio from DTG to LPV/r (Tables 3 and 4).

Extent of Subclinical Atherosclerosis

The overall extent of subclinical atherosclerosis was estimated at

Table 2. Comparisons of Mean Values of Traditional Subclinical Atherosclerosis

Statistical Characteristics/ Independent Variables

Age (years) 46±10.3 52.9±10.6 68±9.4 75.3±0.8 <0.0001 SBP (mm Hg) 124.3±19.3 131±19.9 131.3±14.1 177.9±13.1 <0.0001 DBP (mm Hg) 78.5±12.2 79.6±12.1 73.7±6.5 78.2±17.5 0.565 PP (mm Hg) 45.4±13.6 51±16.2 Waist circumference (cm) 86.2±13.6 89.2±12.2 115.7±10.7 130.2±4.9 <0.0001 Hip circumference (cm) 97.5±14.1 101.5±11 114.8±11.5 128.3±10.2 <0.0001 Waist/Hip Circumference 0.9±0.7 0.9±0.7 BMI (Kg/m ) 24.3±4.9 25.5±5.1 34.4±2.6 34.4±2.8 <0.0001 Blood glucose (m/dL) 94.3±26.3 91.6±20.6 115.6±7.7 177.7±78.6 <0.0001 LDL-C (mg/dL) 107.2±37 92.7±33.5 58.4±13.5 36±14.4(SE) <0.0001 HDL-C (mg/dL) 47.3±6.3 34.5±16.2 15.5±6 8.1±1.7 <0.0001 TG (mg/dL) 92.8±34.5 84±33.8 Total cholesterol (mg/dL) 155.6±15.6 200.3±58.4 243.4±67 279.5±70.2 <0.0001 DTG: Dolutegravir, EFV: Efavirenz, NVP: Nevirapine, LPV/r: Lopinavir/ritonavir, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, PP: Pulse pressure, BMI: Body mass index, LDL-C: Low-density lipoprotein-cholesterol, HDL-C: High-density lipoprotein-cholesterol,TG:Triglycerides, Analysis of variance (ANOVA).

Table 3. Comparisons of Mean Values of Subclinical Atherosclerosis Emergent Variables across ART Groups

Statistical Characteristics/ Independent Variables

Creatinine (md/dL) 0.94±0.21 1.02±0.26 1.37±0.77 3.12±1.44 <0.0001 Uric acid (mg/dL) 5.6±1.7 6.4±2.2 CRP (mg/L) 2.2±0.4 8.3±7.6 SPI 0.99±0.1 1.01±0.2 Mean cIMT (mm) 1.14±0.24 2.2±1.2 TyG after 4.5±0.27 4.5±0.26 Front TyG 9.29±0.27 9.9±0.26 No HDL-C (mg/dL) 110.6±17.7 143±51.7 145.6±38 284.9±79.7 <0.0001 TG/HDL-C 1.95±0.79 2.30±1.06 3.11±1.20 2.31±0.31 0.007 LDL-c/HDL-C 2.25±0.79 2.43±0.81 2.58±0.58 2.65±12.7 0.179 CT/HDL-C 3.32±0.56 5.24±2.75 7.47±1.79 36.58±12.7 <0.0001 Uric acid/HDL-C (%) 11.6±0.04 36.4±32.1 76.7±24.9 154.2±53.8 <0.0001 DTG: Dolutegravir, EFV: Efavirenz, NVP: Nevirapine, LPV/r: Lopinavir/ritonavir, cIMT: Carotid Intima-media Thickness,TyG:Triglyceride/glucose, No HDL-c: No High-density lipoprotein-cholesterol, LDL-C/HDL-C: low-density lipoprotein cholesterol/High-density lipoprotein-cholesterol, CT/HDL-C:Total cholesterol/High density lipoprotein-cholesterol

Table 4. Comparison of Mean Values of Traditional and Emerging Cardiometabolic Risk Markers in Women

Variables HIV+ Naive HIV+ HIV+/DTG HIV+EFV HIV+/NVP VIH+/LPV/r

Creatinine (md/dL) 1.2±0.8 2.2±1.1 Glycemia (mg/dL) 80.3±4.4 104.3±47.6 LDL-c (mg/dL) 115.8±28 149±10.5 HDL-c (mg/dL) 49±15 59.6±34.7 Triglyceride (mg/dL) 114±43 276.2±66 TC (mg/dL) 161.9±21.8 68.2±9.2 Non HDL (mg/dL) 112.9±21.7 8.6±38.6 TG/HDL 2.7±1.5 8±5.9 LDL/HDL 2.6±1 3.8±2.9 CT/HDL 3.6±1.3 1.9±1.6 ABI 1.2±0.1 2.1±0.2 CIMT (mm) 0.7±0.4 0.5±0.1 LDL: Low-density lipoprotein; HDL: High-density lipoprotein;TC:Total ABI: ankle-brachial index; Non-HDL: CT-HDL Variables across ART Groups

DTG+other ARTs EFV+other ART NVP+other ARTs LPV/r+other ART p-value

57.5±15.8 99.7±15.8 <0.0001

1.01±0.12 1.02±0.11 <0.0001

69.7±25.4 19.4±4.8 <0.0001

DTG+other ARTs EFV+other ART NVP+other ARTs LPV/r+other ART p-value

5.9±2.2 9±3.5 <0.0001 65.8±12.2 72.1±1.5 0.565 1.23±0.3 1.49±0.1 <0.0001 3.07±1.2 3.91±0.72 <0.0001 4.54±0.20 4.9±0.45 <0.0001 10.24±0.20 10.8±0.45 <0.0001

CRP: C-reactive protein, SPI: Systolic Pressure Index,

1±0.7 1.1±0.7 1.6±1.9 3.8±1 95.8±26 90.2±21 82.3±23 157.2±72 112±41.3 112.2±38 106.3±36 172±20 44.9±14.4 45±13 58.5±19 9±2 96±34 90.6±34 87.5±35 139.4±65.3 159±19.3 196.5±77.4 176.7±32.2 291±89 115.2±22 146.3±73.5 118.2±43.1 282±89 2.5±1.4 2.5±2.1 1.8±1.2 16.6±9.9 2.8±1.4 2.8±1.4 2.1±1.3 20±5.2 4±1.4 4.9±3.8 3.4±1.5 33.8±14.5 1.3±0.2 2.4±0.2 2.4±0.1 2.6±0.2 1.2±0.1 2.3±1.1 3±1.3 4±0.9 cholesterol; CIMT: Carotid intima-media thickness test;

over 1/3 (36.14%) of patients (n=116/321).

Independent Determinants of Traditional, Emerging and Therapeutic Cardiometabolic Risk of Subclinical Atherosclerosis in PLWHIV on ART

Considering all the traditional and emerging biomarkers of significant cardiovascular risk in univariate analysis, only married people (ORa: 4, 95% CI 1.5-10.5; p<0.006), the low socioeconomic level (ORa: 10.7, 95% CI 2.3-48.7 p<0.002), duration of HIV infection (ORa: 6.6, 95% CI 2.8-16; p<0.0001), duration of antiretroviral treatment ≥9-years (ORa: 0.3, 95% CI: 0.2-0.7; p<0.005) and CT/ HDL-C ratio (ORa: 2, IC 95% 1.1-3.6; p=0.034) were retained as independent determining biomarkers in the multivariate analysis of the binary logistic regression type (Table 5).

Discussion And Conclusion

The present study identified the traditional, emerging, and therapeutic risk factors for subclinical atherosclerosis in PLWHIV infection on antiretroviral treatment in the era of DGT in a hospital setting in Kinshasa.

The population of this study was characterized by an advanced age. The mean age was 51±11-years. We observe senility in PLWHIV (oxidative stress) linked to contamination beyond the age of 50, but also to antiretroviral treatment, which keeps patients alive and healthy for a long time. The female gender was twice as common in the study population. That is 28% (n=90) men against 72% (n=231) women. This feminization of HIV infection is observed in all countries and more markedly in those where heterosexual transmission is very predominant, particularly in Sub- Saharan Africa.28 Sixty-nine point eight percent (69.8%) (n=224) of PLWHIV were on EFV. The initial therapeutic choice is an essential decision for the therapeutic future of the patient.

Except for peripheral artery disease (PAD) and LDL-C/ HDL-C, all traditional and emerging markers in this study were elevated in the LPV/r group, except LDL-C, HDL-C, and TG which were higher in the DTG group, TG/HDL-C in the EFV group.

Protease inhibitors are mainly implicated in cardiovascular risk, through their ability to induce dyslipidemia and insulin resistance.29 In contrast, integrase inhibitors have so far not shown consistent lipid abnormalities when used in antiretroviral-naïve patients.30

It has also been noted in the literature that non-nucleoside reverse transcriptase inhibitors (NNRTIs) cause dyslipidemia, including total hypercholesterolemia and hypertriglyceridemia.

Except for DBP and blood glucose (p>0.05), all mean values of traditional and emerging risk factors as well as viral load and duration of treatment were significantly higher in the old regimen than in the new one diet.

Indeed, there is a relationship between antiretrovirals and the presence of a major level of cardiovascular risk. Exposure to the lopinavir/ritonavir combination (protease inhibitors) is a factor increasing this risk. Marrakchi et al34 made the same observation. Blumer et al35 have shown that protease inhibitors only increase the risk of the onset of insulin resistance and possibly the risk of a cardiovascular event if they are combined with zidovudine and lamivudine. Several studies have found links between exposure to 14,35-37 different classes of antiretrovirals and cardiovascular risk.

On the other hand, dyslipidemia in this study was frequent in patients on DTG. Several studies have shown the opposite Kamdem et al.13 Two randomized studies carried out in Africa, the New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-income countries (NAMSAL) trial Blümer et al38 and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial Mingou et al39 reported that people taking DGT-based treatment, mainly women, experienced significant weight gain. A new study, based on a cohort from 12 sites, African Cohort Study (AFRICOS), supported by the President’s Emergency Plan for AIDS Relief (PEP- FAR) (the United States Presidential Program for the Fight against HIV/AIDS) in Kenya, Nigeria, Tanzania, and Uganda confirms that a treatment based on DGT poses a significant risk of overweight to patients.40 Viral load suppression was significant in the 30,38-40 DTG arm. Several studies have also confirmed this.

The duration of exposure to ART greater than or equal to 9-years (p=0.013) was significantly associated with the presence of 26,27 7 12 atherosclerosis as in the AM study Djalloh et al in Ivory Coast.

Some recent studies report that newer ART decrease the prevalence of insulin resistance in HIV-infected patients compared 41-43 to older ARVs. The duration of exposure to ART is a determining factor in atherosclerosis.12 On the other hand, the duration of DTG is short compared to other ART (deterministic and cumulative effect). Only married people, low socioeconomic level, duration of infection, duration of antiretroviral treatment beyond 9-years, and CT/HDL-C ratio were retained as independent determinants of atherosclerosis in multivariate analysis of the logistic 7 12 regression type. On the other hand, Djalloh et al7 in Côte d’Ivoire12 found the duration of exposure to ART, age, and hypertension as determinants of atherosclerosis in PLWHIV on ART.13

Despite the existence of a very effective treatment allowing PLWHIV to lead a relatively normal life, the chronic inflammation persists and is at the origin of the premature development of comorbidities related to age, such as CVD such as atherosclerosis. The low socio-economic level not only limits access to education, care, and training on the means of prevention against transmissible diseases44 but also increases the risk of adopting risky sexual be- 31-33 44-48 havior. The CT/HDL-C ratio has been suggested as a statisti- 23,24 cally significant atherogenic risk. The present study reported an overall hospital prevalence (frequency) of subclinical atherosclerosis in PLWHIV on ART of 36.1%. This frequency seems lower 7 12 than the study conducted by Djalloh et al7 in Côte d’Ivoire12 which found a prevalence of 64.7% according to SPI and cIMT.

The results obtained cannot be generalized to all hospitals in the DRC and the hospital nature of the study does not

Table 5. Independent Determinants of Cardiometabolic Risk of Overall Subclinical Atherosclerosis in the Population of People Living with HIV on Antiretroviral Therapy

Variables OR 95% CI p-value ORaj 95% CI p-value Sex

Male 1.2(0.7-2) 0.303 Female 1

Age (years)

≥60 43-59 0.001 <43

Marital Status

Married 10(4.2-23.7) 4(1.5-10.5) <0.0001 0.006 Bachelor 1 1

Socio-Economic Level

Down 18.4(4.4-77.1) 10.7(2.3-48.7) <0.0001 0.002 Pupil 1 1

Duration of Infection (years)

≥14 7.6(3.8-15) 6.6(2.8-16) <0.0001 8-13 5.5(2.8-10) <0.0001 4.1(1.9-9.2) <0.0001 <8 1 1

Duration of Treatment (years)

≥9 0.3(0.2-0.7) 0.005 5-8 0.013 0.7(0.3-1.5) 0.248 <5 1

Waist Circumference (cm)

≥85 1.8(1.1-2.9) 0.012 <85 1

Hip Circumference (cm)

≥100 1.7(1-3) 0.017 <100 1

BMI (Kg/m )

≥25 1.6(1-2.6) 0.024 <25 1

CRP (mg/L)

High≥3 3(1.9-4.9) <0.0001 Down <3 1

Creatinine (mg/dL)

≥1.5 3(1.8-5) <0.0001 <1.5 1

Tg/Hdl-C

≥2.2 2(1.3-3) 0.002 <2.2 1

LDL-c/HDL-C

≥2.52 1.5(0.9-2.3) 0.07 <2.52 1

Ct/Hdl-C

≥4 4(2.3-7) <0.0001 2(1,1-3,6) 0.034 <4 1 0.002

allow the conclusions to be generalized to the entire Congolese population in general. This constitutes the limits of our study. On the other hand, the present study has the merit of having identified the determinants of subclinical atherosclerosis in PLWHIV on ART without DTG, dyslipidemia under the diet with dolutegravir and having used the measurement of pulse pressure, SPI, and cIMT among PLWHIV in Kinshasa. Early screening for subclinical atherosclerosis in naïve PLWHIV and those on ART would be necessary; to conduct studies to determine the role of DTG in dyslipidemia in adults.

Conflicts Of Interest

The authors declare that they have no conflicts of interest.

References

  1. HsuePYWatersD. HIV infection and coronary heart disease: Mechanisms and management. Nat Rev Cardiol. 2019; 16(12): 745- 759. doi: 10.1038/s41569-019-0219-910.1038/s41569-019-0219-9 https://doi.org/10.1038/s41569-019-0219-9
  2. Serrano-VillarSGutiérrezFMirallesC. Human immunodeficiency virus as a chronic disease: Evaluation and management of nonacquired immune deficiency syndrome-defining conditions. Open Forum Infect Dis. 2016; 3: ofw097. doi: 10.1093/ofid/ofw09710.1093/ofid/ofw097 https://doi.org/10.1093/ofid/ofw097
  3. DeeksSGLewinSRHavlirDV. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013; 382(9903): 1525-1533. doi: 10.1016/S0140-6736(13)61809-710.1016/s0140-6736(13)61809-7 https://doi.org/10.1016/s0140-6736(13)61809-7
  4. LegarthRAAhlstromMGKronborgG. Long-term mortality in HIV-infected individuals 50 years or older: A nationwide, population-based cohort study. J Acquir Immune Defic Syndr. 2016; 71(2): 213-218. doi: 10.1097/QAI.000000000000082510.1097/qai.0000000000000825 https://doi.org/10.1097/qai.0000000000000825
  5. Pillay-vanWVMsemburiWLaubscherR. Mortality trends and differentials in South Africa from 1997 to 2012: Second National Burden of Disease Study. Lancet Glob Health. 2016; 4(9): e642-e653. doi: 10.1016/S2214-109X(16)30113-910.1016/s2214-109x(16)30113-9 https://doi.org/10.1016/s2214-109x(16)30113-9
  6. Programme National de Lutte contre le VIH/SIDA (PNLS). Guide de prise en charge intégrée du VIH en République Démocratique du Congo. 2020. Website. https://hivpolicywatch. org/duremaps/data/guidelines-rename/DemocraticRepublicof-CongoARTguidelines2013.pdf. Accessed July 21, 2022
  7. Djalloh A-MA, Soya E, Ekou A, et al. Prévalence et déterminants de l’athérosclérose chez les patients infectés par le virus de l’immunodéficience humaine (VIH) et traités par les anti-rétroviraux. [In: French]. JMV-J Médecine Vasc. 2018; 43(2): 115. doi: 10.1016/j.jdmv.2017.12.090 https://doi.org/10.1016/j.jdmv.2017.12.090
  8. KwiatkowskaWKnyszBArczynskaK. Peripheral arterial disease and ankle-brachial index abnormalites in young and middle-aged HIV-positive patients in Lower Silesia, Poland. PLoS One. 2014; 9(12): e113857. doi: 10.1371/journal.pone.011385710.1371/journal.pone.0113857 https://doi.org/10.1371/journal.pone.0113857
  9. Olalla J, Salas D, De La Torre J, Del Arco A, Prada JL, Alegría JG. Ankle-brachial index in the assessment of cardiovascular risk among HIV infected patients. Rev Med Chil. 2011; 139(8): 1039- 1045
  10. GeeMECampbellNSarrafzadeganN. Standards for the uniform reporting of hypertension in adults using population survey data: Recommendations from the World Hypertension League Expert Committee. J Clin Hypertens (Greenwich). 2014; 16(11): 773- 781. doi: 10.1111/jch.1238710.1111/jch.12387 https://doi.org/10.1111/jch.12387
  11. DesormaisIAmidouSAHouehanouYC. The prevalence, awareness, management and control of hypertension in men and women in Benin, West Africa: The TAHES study. BMC Cardiovasc Disord. 2019; 19 (1): 303. doi: 10.1186/s12872-019-01273-710.1186/s12872-019-01273-7 https://doi.org/10.1186/s12872-019-01273-7
  12. Mukeba-TshialalaDNachegaJBMutombo-TshingwaliMArendtVGilsonGMoutschenM. Obesity, high blood pressure, hypercholesterolaemia, and untreated diabetes in HIV-infected and HIV-uninfected Adults in Mbuji-Mayi (Democratic Republic of Congo). Bull Soc Pathol Exot. 2017; 110(5): 301-309. doi: 10.1007/ s13149-017-0561-2
  13. Longo-MbenzaBApalataTLongokoloM. Association of Helicobacter pylori infection with the metabolic syndrome among HIV-infected black Africans receiving highly active antiretroviral therapy. Cardiovasc J Afr. 2015; 26(2): 52-56. doi: 10.5830/ CVJA-2015-012
  14. KamdemFMapoureYHamadouB. Prevalence and risk factors of peripheral artery disease in black Africans with HIV infection: A cross-sectional hospital-based study. Vasc Health Risk Manag. 2018; 14: 401-408. doi: 10.2147/VHRM.S16596010.2147/vhrm.s165960 https://doi.org/10.2147/vhrm.s165960
  15. AguCEUchenduIKNsonwuACOkwuosaCNAchukwuPU. Prevalence and associated risk factors of peripheral artery disease in virologically suppressed HIV-infected individuals on antiretroviral therapy in Kwara state, Nigeria: A cross sectional study. BMC Public Health. 2019; 19(1): 1143. doi: 10.1186/s12889-019- 7496-410.1186/s12889-019-7496-4 https://doi.org/10.1186/s12889-019-7496-4
  16. TaharbouchtSGuermazR. L’index de pression systolique et la Non Alcoholic Fatty Liver Disease (NAFLD): Une étude cas-témoins. JMV-J Médecine Vasc. 2020; 45: S41. doi: 10.1016/j. jdmv.2020.01.09910.1016/j.jdmv.2020.01.099 https://doi.org/10.1016/j.jdmv.2020.01.099
  17. Organisation Mondiale de la Santé (OMS). Lignes directrices consolidées sur l’utilisation des médicaments antirétroviraux pour le traitement et la prévention de l’infection à VIH: Recommandations pour une approche de santé publique. [In: French]. nd 2 ed. 2016. Website. https://www.ncbi.nlm.nih.gov/books/ NBK374294/pdf/Bookshelf_NBK374294.pdf. Accessed July 21, 2022
  18. Cardio-online. Une athérosclérose infraclinique et une CRP élevée simultanées associées à un risque accru d'infarctus et d’AVC. [In: French]. 2018. Website. https://www.cardio-online.fr/Actualites/Depeches/Une-atherosclerose-infraclinique-et-une-CRPelevee-simultanees-associees-a-un-risque-accru-d-infarctus-et-d-AVC. Accessed July 21, 2022
  19. Kidney International Supplements. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease, Official Journal of the International Society of Nephrology, 2013. Website. https://kdigo.org/wp-content/ uploads/2017/02/KDIGO_2012_CKD_GL.pdf. Accessed July 21, 2022
  20. TiaWMNdaJKKouameGRKobenanRDainguiDOuattaraB. Insuffisance rénale chronique: Aspects épidémiologique, diagnostique, thérapeutique et évolutif au CHU de Bouaké de 2016 à 2020. [In: French]. Revue Africaine de Médecine Interne. 2022; 9 (2-2): 60-66. de Gercourt TGJ. Prise en Charge de I’hyper Uricémie en Médecine Générale: Approche Qualitative. [In: French]. [master’s thesis]. Médecine Humaine et Pathologie: 2018. Website. https://dumas.ccsd. cnrs.fr/dumas-01901630v1/file/Girou%20Jayet%20de%20Gercourt%20Thibault.pdf. Accessed July 21, 2022
  21. Hong S, Han K, Park C-Y. The triglyceride glucose index is a simple and low-cost marker associated with atherosclerotic cardiovascular disease: A population-based study. BMC Med. 2020; 18(1): 361. doi: 10.1186/s12916-020-01824-2 https://doi.org/10.1186/s12916-020-01824-2
  22. Thérapeutique. NOUVEAUTÉS 2016 EN DYSLIPIDÉMIE. [In: French]. 2016. Website. https://www.louvainmedical.be/fr/ article/nouveautes-2016-en-dyslipidemie. Accessed July 21, 2022
  23. BelalcazarSAcostaEJMedina-MurilloJJSalcedo-CifuentesM. Conventional biomarkers for cardiovascular risks and their correlation with the castelli risk index-indices and TG/HDL- C. Archivos de Medicina (Col). 2020; 20(1): 11-22. doi: 10.30554/ archmed.20.1.3534.2020
  24. Olamoyegun MA, Oluyombo R, Asaolu SO. Évaluation de la dyslipidémie, des ratios lipidiques et de l’indice athérogène en tant que facteurs de risque cardiovasculaire chez les habitants semi-urbains au Nigeria. [In: French]. Ann Afr Med. 2016; 15(4): 194-199. doi: 10.4103/1596-3519.194280 https://doi.org/10.4103/1596-3519.194280
  25. PatilSRojulpoteCGonuguntlaK. Association of triglyceride to high density lipoprotein ratio with global cardiac microcalcification to evaluate subclinical coronary atherosclerosis in non-diabetic individuals. Am J Cardiovasc Dis. 2020; 10(3): 241-246
  26. KocakMZAktasGErkusESincerIAtakBDumanT. Serum uric acid to HDL-cholesterol ratio is a strong predictor of metabolic syndrome in type 2 diabetes mellitus. Rev Assoc Med Bras (1992). 2019; 65(1): 9-15. doi: 10.1590/1806-9282.65.1.910.1590/1806-9282.65.1.9 https://doi.org/10.1590/1806-9282.65.1.9
  27. PsomasKCDixneufM. VIH et vieillissement—Vivre avec le VIH à 50 ans et plus. [In: French]. vih.org. 2014. Website. https:// vih.org/20130205/vivre-avec-le-vih-a-50-ans-et-plus/. Accessed February 22, 2023
  28. HaddadNRobertAPopovicN. Cas de VIH nouvellement diagnostiqués chez les personnes de 50 ans et plus, comparativement aux personnes de moins de 50 ans: 2008 à 2017. [In: French]. Relevé Mal Transm Au Can. 2019; 45(11): 311-317. doi: 10.14745/ccdr.v45i11a02f10.14745/ccdr.v45i11a02f https://doi.org/10.14745/ccdr.v45i11a02f
  29. The Joint United Nations Programme on HIV/AIDS (UN-AIDS). Global AIDS Monitoring 2023: Indicators and questions for monitoring progress on the 2021 Political
  30. AgbekoDKToyiTLihanimpoD. Troubles lipidiques et glucidiques à risque cardio-vasculaires chez les personnes vivant avec le virus d’immunodéficience humaine sous traitement antirétroviral: cas du centre de prise en charge médicale de l’ONG Espoir-Vie-Togo à Lomé. [In: French]. Pan Afr Med J. 2019; 34: 203. doi: 10.11604/pamj.2019.34.203.2060010.11604/pamj.2019.34.203.20600 https://doi.org/10.11604/pamj.2019.34.203.20600
  31. Tougouma J-B, Yaméogo AA, Yaméogo NV, et al. Fréquence élevée de l´ischémie myocardique asymptomatique dans une population de patients infectés par le VIH à Bobo-Dioulasso, Burkina Faso. [In: French]. Pan Afr Med J. 2021; 38: 173. doi: 10.11604/ pamj.2021.38.173.9509
  32. O’HalloranJASatchellCSMallonPW. Dyslipidemia, atherosclerosis and cardiovascular disease: An increasingly important triad in an aging population living with HIV. Future Virol. 2013; 8(10): 1021-1034. doi: 10.2217/fvl.13.8710.2217/fvl.13.87 https://doi.org/10.2217/fvl.13.87
  33. CrestaMBrunAMerletP. Cardiopathie ischémique silencieuse chez les patients sous ARV: Prévalence et facteurs de risque. [In: French]. Médecine et Maladies Infectieuses Formation. 2022; 1(2 Suppl), S134-S135. doi: 10.1016/j.mmifmc.2022.03.29310.1016/j.mmifmc.2022.03.293 https://doi.org/10.1016/j.mmifmc.2022.03.293
  34. European AIDS Clinical Society. EACS guidelines 9.0. 2017. Website. https://www.eacsociety.org/media/2017_guidelines_9.0english_rev-20181024.pdf. Accessed February 22, 2023
  35. ErginHEIngaEEMaungTZJavedMKhanS. HIV, antiretroviral therapy and metabolic alterations: A review. Cureus. 2020; 12(5): e8059. doi: 10.7759/cureus.805910.7759/cureus.8059 https://doi.org/10.7759/cureus.8059
  36. Marrakchi W, Kooli I, Harzallah G, Aouam A, Chakroun M. Évaluation du risque cardiovasculaire des personnes vivant avec le VIH en Tunisie: Un nouveau challenge pour améliorer la qualité de vie. [In: French]. Annales d’Endocrinologie. 2018; 79(4): 502. doi: 10.1016/j.ando.2018.06.1020 https://doi.org/10.1016/j.ando.2018.06.1020
  37. BlümerRMvan VonderenMGSutinenJ. Zidovudine/ lamivudine contributes to insulin resistance within 3 months of starting combination antiretroviral therapy. AIDS Lond Engl. 2008; 22(2): 227-236. doi: 10.1097/QAD.0b013e3282f3355710.1097/qad.0b013e3282f33557 https://doi.org/10.1097/qad.0b013e3282f33557
  38. MingouJSAwFSarrSA. Dyslipidemia of patients living with HIV in DAKAR transversal study, case-wi tnesses, multicentric. PARIPEX-INDIAN JOURNAL OF RESEARCH. 2018; 7(1): 117-121
  39. AlviRM. Protease inhibitors and cardiovascular outcomes in patients with HIV and heart failure. J Am Coll Cardiol. 2018; 72: 518-530. doi: 10.1016/j.jacc.2018.04.08310.1016/j.jacc.2018.04.083 https://doi.org/10.1016/j.jacc.2018.04.083
  40. NAMSAL ANRS 12313 Study Group, Kouanfack C, Mpoudi-Etame M, Bassega PO, et al. Dolutegravir-based or low-dose efavirenz-based regimen for the treatment of HIV-1. N Engl J Med. 2019; 381(9): 816-826. doi: 10.1056/NEJMoa1904340 https://doi.org/10.1056/nejmoa1904340
  41. VenterWF. Comparaison de 3 traitements de 1re ligne pour l’infection VIH en Afrique du Sud (essai ADVANCE). [In: French]. th Paper presented at: 10th IAS Conference on HIV Science; 2019; Mexico City, Mexico, USA
  42. Abstract Supplement Oral Abstracts from the 23rd International AIDS Conference, 6-10 July 2020. J Int AIDS Soc. 2020; 23(Suppl 4): e25547. doi: 10.1002/jia2.25547 https://doi.org/10.1002/jia2.25547
  43. KrikkeMHoogeveenRCHoepelmanAIMVisserenFLJArendsJE. Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models. HIV Med. 2016; 17(4): 289-297. doi: 10.1111/hiv.1230010.1111/hiv.12300 https://doi.org/10.1111/hiv.12300
  44. TsengZHMoffattEKimA. Sudden cardiac death and myocardial fibrosis, determined by autopsy, in persons with HIV. N Engl J Med. 2021; 384(24): 2306-2316. doi: 10.1056/NEJ-Moa191427910.1056/nej-moa1914279 https://doi.org/10.1056/nej-moa1914279
  45. DeguenonvoGNCGayeAMThiamIDialCMMWoto-GayeG. Athérosclérose aortique et coronarienne au Sénégal: À propos d’une série autopsique de 116 patients d’origine africaine au CHNU Aristide Le Dantec (Dakar-Sénégal). [In French]. Ann Pathol. 2019; 39(1): 2-8. doi: 10.1016/j.annpat.2018.06.00110.1016/j.annpat.2018.06.001 https://doi.org/10.1016/j.annpat.2018.06.001
  46. FontaineJ. Impact de la situation socio-économique sur l’observance des personnes vivant avec le VIH. [In: French]. 2021. Website. https://dumas.ccsd.cnrs.fr/dumas-03239445/document. rd Accessed February 22, 2023
  47. IzizagBBSituakibanzaHKiazayawokoF. Déterminants de la non-observance au traitement antirétroviral chez l´adulte à Kinshasa. [In: French]. Pan Afr Med J. 2020; 37: 157. doi: 10.11604/ pamj.2020.37.157.13261