Infectious Diseases

No progression of subclinical atherosclerosis in HIV-infected patients starting an initial regimen including tenofovir alafenamide/emtricitabine plus raltegravir, dolutegravir or elvitegravir/ cobicistat during a two-year follow-up

Leonardo Calza, Marco Borderi, Vincenzo Colangeli, Aurora Borioni, Simona Coladonato, Bianca Granozzi & Pierluigi Viale

To cite this article: Leonardo Calza, Marco Borderi, Vincenzo Colangeli, Aurora Borioni, Simona Coladonato, Bianca Granozzi & Pierluigi Viale (2019): No progression of subclinical atherosclerosis in HIV-infected patients starting an initial regimen including tenofovir alafenamide/emtricitabine plus raltegravir, dolutegravir or elvitegravir/cobicistat during a two-year follow-up, Infectious Diseases, DOI: 10.1080/23744235.2019.1707279
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No progression of subclinical atherosclerosis in HIV-infected patients starting an initial regimen including tenofovir alafenamide/emtricitabine plus raltegravir, dolutegravir or elvitegravir/cobicistat during a two-year follow-up

Leonardo Calza, Marco Borderi, Vincenzo Colangeli, Aurora Borioni, Simona Coladonato, Bianca Granozzi and Pierluigi Viale
Department of Medical and Surgical Sciences, Section of Infectious Diseases, “Alma Mater Studiorum”, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy

Raltegravir elvitegravir dolutegravir
intima-media thickness ecocolordoppler

Leonardo Calza [email protected]
Department of Medical and Surgical Sciences, Section of Infectious Diseases, “Alma Mater Studiorum”, University of Bologna, S. Orsola- Malpighi Hospital, via G. Massarenti 11, 40138 Bologna, Italy

The introduction of effective combination antiretroviral therapy (cART) reduced greatly the incidence of acquired immune deficiency syndrome (AIDS) and led to a notable extension of life expectancy in patients with human immunodeficiency virus-1 (HIV-1) infection. Consequently, questions related to long-term non-infec- tious comorbidities have recently emerged. Particularly, concern is mounting about the increased risk of cardio- vascular disease in HIV-positive subjects, which seems multifactorial in origin and related to classical risk factors (such as advancing age, smoking, hypertension), effects of antiretroviral therapy (including hyperlipidaemia and insulin resistance), and systemic inflammation with endo- thelial dysfunction induced by HIV infection itself [1–4].
Cardiovascular disease is the second or third leading cause of non-AIDS-related mortality in the USA and Europe among HIV-positive individuals, and HIV-infected subjects are at a higher risk of developing myocardial infarction even when the risk is controlled for traditional risk factors which have a higher prevalence in this popu- lation (including smoking, hypertension, diabetes, obes- ity and dyslipidaemia) [5–7].
Clinical data about the correlation between antiretro- viral treatment and premature atherosclerosis are con- flicting. In SMART (Strategies for Management of Antiretroviral Therapy) [8] and START (Strategic Timing of Antiretroviral Treatment) [9] randomized trials anti- retroviral therapy significantly reduced the cardiovascu- lar disease risk by suppressing the viral replication. However, in several cohort studies, some antiretroviral drugs were found to be associated with an increased risk of cardiovascular events [10–13], so the real effect of cART on the atherosclerosis progression rate is debated still today.
The association of antiretroviral treatment with pre- mature atherosclerosis was shown in several case-control and cohort studies using carotid ultrasonography to assess the intima-media thickness (IMT) [14–17], even though other published investigations have failed to find an atherogenic effect of antiretroviral treatment [18–20]. Certainly, hyperlipidaemia is a frequent meta- bolic side effect induced by antiretroviral agents, par- ticularly ritonavir- and cobicistat-boosted protease inhibitors (PIs), and it may favour the premature occur- rence of atherosclerosis in HIV-positive individu- als [21,22].
Integrase strand transfer inhibitors (INSTIs) have recently emerged as the preferred first-line treatment for

HIV infection because several randomized trials have established their high efficacy both in treatment-naive and -experienced patients, in association with a favour- able safety profile [23,24]. However, a potential effect of this antiretroviral class on the atherosclerosis progres- sion rate is unknown to date.
An observational study was performed in HIV-infected patients starting an initial antiretroviral therapy including one INSTI (raltegravir, dolutegravir or elvitegravir/cobici- stat) to assess changes in carotid IMT and prevalence of subclinical atherosclerosis after 24 months.

Patients and methods
We have performed an observational, prospective study involving HIV-1-infected adult patients naïve to anti- retroviral therapy and initiating an antiretroviral treat- ment including one INSTI in our Division of Infectious Diseases from January 2014 through December 2016. Patients starting an initial drug regimen including teno- fovir alafenamide/emtricitabine 25/200 mg daily (TAF/ FTC) plus raltegravir 400 mg twice daily or 1200 mg once
daily (RAL group), TAF/FTC þ elvitegravir/cobicistat
150/150 mg once daily (EVG/c group), or TAF/FTC plus dolutegravir 50 mg once daily (DTG group) were assessed for eligibility and enrolled into the study if they underwent a carotid Doppler ultrasonography at base- line and after 24 months of cART.
Exclusion criteria were: age <40 or >75 years; prior
antiretroviral use for more than two weeks; any changes in current antiretroviral regimen or its discontinuation during the entire follow-up; carotid Doppler ultrasonog- raphy missed at baseline or at 24 months; no clinical or laboratory data of follow-up for at least 24 months; clin- ical history of coronary heart disease, cerebrovascular disease (including transient ischaemic attack, amaurosis fugax or stroke), or peripheric vascular disease; unilat- eral/bilateral carotid occlusion, or stent implantation or endarterectomy; previous endovascular intervention; dia- betes mellitus; current infectious or inflammatory dis- ease; known alcohol abuse or drug addict; hypothyroidism; Cushing’s syndrome; acute or chronic kidney diseases; acute or chronic hepatitis or liver cirrho- sis; pregnancy or lactation; underlying treatment with corticosteroids, anti-inflammatory, or immune-modula- tory agents.
The following demographic, clinical and laboratory data were recorded at the start of therapy and at six- month intervals during the 24-month follow-up: sex, age, race, physical examination, weight, body mass


index (BMI), waist circumference, arterial pressure, clin- ical manifestations; spot urinalysis, plasma lipids (trigly- cerides, total cholesterol, LDL cholesterol and HDL cholesterol), glucose, complete liver and kidney function
tests, CD4þ and CD8þ T lymphocyte count and HIV viral
Arterial hypertension was defined as an arterial pres- sure ≥140/90 mmHg on at least two prior visits, or by a physician diagnosis, or by current use of antihyperten-
sive drugs. Metabolic syndrome was diagnosed when at least three of the following five criteria were present: waist circumference >102 cm for men and >88 cm for
women; fasting triglycerides ≥150 mg/dL; HDL choles-
terol <40 mg/dL for men and <50 mg/dL for women; fasting glucose ≥110 mg/dL; blood pressure
≥130/85 mmHg [25]. The 10-year risk of heart disease or
stroke was estimated by the Atherosclerotic Cardiovascular Disease (ASCVD) algorithm published in 2013 American Heart Association/American College of Cardiology (AHA/ACC) Guideline on the Assessment of Cardiovascular Risk [26].
The HIV RNA viral load was detected using the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (Roche Diagnostics, GmbH, Mannheim, Germany), in accordance with the manufacturer’s instructions, and it was expressed as the number of copies per millilitre of plasma with the lowest detection limit of 20 copies/mL. Virologic failure was defined by a confirmed plasma HIV
RNA >20 copies/mL.
Carotid ultrasonography was made within one month after the beginning of cART and within one month after the end of the 24-month follow-up. The ultrasound investigation of the extracranial carotid arteries (com- mon, internal and external arteries) was performed in our Hospital by the same physician using a Philips HDI 5000 power colour-Doppler with 7.5-MHz probes (Koninklijke Philips Electronics, Eindhoven, the Netherlands). In each ecographic evaluation, the patients were placed in a supine position after at least 10 min of acclimatization in a comfortable room. The common carotid, the bifurcation and at least the first 2 cm of the internal carotid arteries were evaluated in the short and long axis during the tele-diastolic phase. During the investigation, the head of the patient was hyper- extended and extra-rotated from the opposite side. The morphological investigation of the carotid lesions was performed using both ultrasonography and the ultra- sound power colour-Doppler to better characterize the profile of the lesion and the IMT. Subclinical atheroscler-
osis was defined as an IMT ≥0.9 mm at any site, and the

presence of carotid plaque was defined as an IMT
≥1.2 mm at any site, in conformity with the guidelines of the European Society of Cardiology [27].
The adherence to cART was carefully checked on six- monthly outpatient visits by self-reported questionnaires.
Variables were described by using proportions for cat- egorical variables, mean and SD for continuous variables, while comparisons between groups were performed using a Student’s t-test or a Wilcoxon test for normally and non-normally distributed continuous variables, respectively. Group comparisons were made using the Chi-square test for categorical variables. A p value of less than .05 was considered significant. Statistical ana- lysis was performed by XLSTAT 2015.1 Microsoft Excel Statistical Software (Microsoft, Redmond, WA, USA). The study was approved by the Ethical Committee of the S. Orsola-Malpighi Hospital (Bologna, Italy), and all partici- pants signed a written informed consent.

Overall, 183 patients were assessed for eligibility. Study inclusion criteria were met by 102 patients who were enrolled in the study. The recruitment plan of the study and patient partition are presented in Figure 1. Demographic, clinical and laboratory characteristics of study patients are summarized in Table 1.
Mean age ± SD was 48.7 ± 7.6 years, 73 patients (71.6%) were men, and 96 (94.1%) were caucasian. Mean CD4 lymphocyte count ± SD was 397 cells/mm3, 29 (28.4%) patients had a CD4 lymphocyte count <200 cells/mm3,
and mean plasma HIV RNA ± SD was 4.3 ± 1.8 log10 cop-
ies/mL. Current smokers were 62 (60.8%), 25 (24.5%) had arterial hypertension, and 36 (35.3%) had metabolic syn- drome. Mean 10-year cardiovascular disease risk ± SD was
7.5 ± 2.6% and mean BMI ± SD was 24.1 ± 4.8 kg/m2. LDL cholesterol >140 mg/dL and triglycerides >200 mg/dL were reported in 57 (55.9%) and 88 (86.3%) patients,
With regard to the antiretroviral regimen, 32, 36 and 34 patients were included in the RAL, EVG/c and DTG groups, respectively. The baseline demographic, clinical and laboratory characteristics of the enrolled patients were comparable across the three groups (Table 1).
At baseline patients with subclinical atherosclerosis were 70 (68.6%) and those with carotid plaques were 33 (32.3%). The prevalence of subclinical atherosclerosis and carotid plaques was comparable across the three groups (Table 1).


Figure 1. Recruitment plan of the study and patient partition according to the current antiretroviral regimen (RAL: raltegravir; DTG: dolute- gravir; EVG/c: elvitegravir/cobicistat).

Table 1. Baseline demographic, epidemiological, clinical and laboratory characteristics of the enrolled patients.
Groups DTG RAL EVG/c
No. of patients 34 32 36
No. of males (%) 24 (70.6) 23 (71.9) 26 (72.2)
No. of Caucasian patients (%) 32 (94.1) 31 (96.8) 33 (91.7)
Mean age ± SD (years) 49.2 ± 7.9 48.4 ± 7.1 48.9 ± 7.4
Homosexuals/heterosexuals/i.v. drug addicts 15/13/6 14/14/4 17/15/4
No. of patients (%) with
current cigarette smoking 20 (58.8) 19 (59.4) 23 (63.9)
arterial hypertension 9 (26.5) 8 (25) 8 (22.2)
Mean CD4 lymphocyte count ± SD (cells/mm3) 388 ± 121 404 ± 159 413 ± 166
Mean plasma HIV RNA ± SD (log10 copies/mL) 4.3 ± 1.7 4.5 ± 1.9 4.2 ± 1.6
Mean serum concentration of glucose ± SD (mg/dL) 84 ± 21 85 ± 16 81 ± 19
Mean serum concentration of total cholesterol ± SD (mg/dL) 215 ± 32 211 ± 36 219 ± 31
Mean serum concentration of LDL cholesterol ± SD (mg/dL) 139 ± 21 142 ± 28 136 ± 25
Mean serum concentration of HDL cholesterol ± SD (mg/dL) 39 ± 11 36 ± 9 38 ± 9
Mean serum concentration of triglycerides ± SD (mg/dL) 237 ± 42 231 ± 38 225 ± 36
Mean weight ± SD (kg) 72.6 ± 15.8 74.5 ± 17.3 73.4 ± 17.6
Mean waist circumference ± SD (cm) 90.5 ± 12.4 91.4 ± 11.7 90.2 ± 14.6
Mean BMI value ± SD (kg/m2) 24.3 ± 4.1 23.8 ± 5.1 24.2 ± 4.6
No. of patients (%) with metabolic syndrome 12 (35.3) 10 (31.2) 14 (38.9)
Mean 10-year cardiovascular disease risk ± SD (%) 7.2 ± 2.6 7.6 ± 2.9 7.3 ± 2.5
No. of patients with subclinical atherosclerosis (%) 24 (70.6) 22 (68.7) 24 (66.7)
No. of patients with carotid plaques (%) 10 (29.4) 10 (31.2) 13 (36.1)
DTG: dolutegravir; RAL: raltegravir; EVG/c: elvitegravir/cobicistat; LDL: low-density lipoprotein; HDL: high-density lipoprotein; BMI: body mass index.

Carotid IMT values at baseline and after 24 months are summarized in Table 2. Overall, after 24 months the
mean IMT change ± SD was þ0.025 ± 0.017 mm in com- mon carotid artery, þ0.028 ± 0.019 mm in carotid bifurca- tion, and þ0.033 ± 0.024 mm in internal carotid artery. Changes in mean IMT compared with respective base-
line values were not significant in each arterial district (p ¼ .093, .134 and .309, respectively).
Particularly, in common carotid artery the mean IMT
change ± SD was þ0.026 ± 0.014 mm in DTG group,
þ0.019 ± 0.015 mm in RAL group and þ0.029 ± 0.024 mm

in EVG/c group. Mean increases were not significant in comparison with respective baseline values and compar- able across the three groups.
In carotid bifurcation the mean IMT change ± SD was þ0.031 ± 0.023 mm in DTG group, þ0.026 ± 0.018 mm in RAL group and þ0.029 ± 0.021 mm in EVG/c group. Mean changes were not significant in comparison with
respective baseline values and comparable across the three groups.
In internal carotid artery the mean change ± SD was
þ0.032 ± 0.023 mm in DTG group, þ0.031 ± 0.022 mm in
Table 2. Carotid intima-media thickness values at baseline and after 24 months.


in EVG/c group (p ¼ .096). The mean change ± SD from baseline to month 24 in triglycerides was þ16 ± 10 mg/dL

Baseline IMT
Groups (mm)
Common carotid artery DTG

24-month IMT

pω in DTG group (p ¼ .078), þ11 ± 7 mg/dL in RAL group (p ¼ .108) and þ19 ± 11 mg/dL in EVG/c group (p ¼ .063).
Mean increases in weight and BMI at month 24 were

Right artery 0.719 ± 0.211 0.743 ± 0.217 0.024 ± 0.011 .277
Left artery 0.716 ± 0.215 0.742 ± 0.305 0.028 ± 0.016 .317 RAL
Right artery 0.713 ± 0.238 0.731 ± 0.244 0.018 ± 0.014 .409
Left artery 0.717 ± 0.321 0.739 ± 0.222 0.021 ± 0.015 .281
Right artery 0.709 ± 0.198 0.736 ± 0.311 þ0.027 ± 0.019 .182
Left artery 0.709 ± 0.198 0.741 ± 0.255 þ0.033 ± 0.027 .248
Carotid bifurcation DTG
Right artery 0.722 ± 0.218 0.752 ± 0.244 0.029 ± 0.017 .191
Left artery 0.719 ± 0.245 0.743 ± 0.275 0.033 ± 0.026 .313 RAL
Right artery 0.719 ± 0.242 0.745 ± 0.281 0.027 ± 0.017 .382
Left artery 0.723 ± 0.267 0.748 ± 0.331 0.026 ± 0.019 .276
Right artery 0.717 ± 0.251 0.744 ± 0.301 þ0.028 ± 0.018 .177
Left artery 0.722 ± 0.195 0.751 ± 0.335 þ0.031 ± 0.024 .216
Internal carotid artery DTG
Right artery 0.726 ± 0.317 0.757 ± 0.317 þ0.031 ± 0.023 .098

0.032 ± 0.024
Right artery 0.719 ± 0.244 0.759 ± 0.323 þ0.041 ± 0.028 .077
Left artery 0.723 ± 0.261 0.761 ± 0.371 þ0.037 ± 0.027 .118
IMT: intima-media thickness; DTG: dolutegravir; RAL: raltegravir; EVG/c: elvitegra- vir/cobicistat.
All values are expressed ad mean ± SD.
pω ¼ p-value month 24 versus baseline value.

RAL group and þ0.038 ± 0.027 mm in EVG/c group. Mean variations were not significant in comparison with respective baseline values and comparable across the
three groups (Table 2).
After 24 months, the change in prevalence of subclin- ical atherosclerosis was not significant in each group: from 24/34 (70.6%) to 26/34 (76.5%) in DTG group (p ¼ .087), from 22/32 (68.7%) to 23/32 (71.9%) in RAL
group (p ¼ .116) and from 24/36 (66.7%) to 27/36 (75%)
in EVG/c group (p ¼ .069).
Similarly, the prevalence of carotid plaques after 24 months showed no significant changes in each group: from 10/34 (29.4%) to 11/34 (32.3%) in DTG group (p ¼ .255), from 10/32 (31.2%) to 11/32 (34.4%) in RAL
group (p ¼ .109), and from 13/36 (36.1%) to 15/36
(41.7%) in EVG/c group (p ¼ .96).
With regard to metabolic parameters, mean changes in total cholesterol and triglycerides during the 24- month follow-up were not significant in all groups. The mean change ± SD from baseline to month 24 in total
cholesterol was þ9 ± 4 mg/dL in DTG group (p ¼ .781), þ6 ± 3 mg/dL in RAL group (p ¼ .884) and þ11 ± 5 mg/dL

statistically significant in comparison with respective baseline values in each group, but comparable across the three groups. The mean change ± SD from baseline
to month 24 in weight was þ5.1 ± 2.2 kg in DTG group (p ¼ .028), þ4.3 ± 1.9 kg in RAL group (p ¼ .044) and þ4.1 ± 1.7 kg in EVG/c group (p ¼ .035). The mean
change ± SD from baseline to month 24 in BMI was þ0.73 ± 0.29 kg/m in DTG group (p ¼ .038), þ0.67 ± 0.24 kg/m in RAL group (p ¼ .026) and
þ0.63 ± 0.31 kg/m in EVG/c group (p ¼ .035). However,
mean increases in waist circumference at month 24 were not significant in comparison with respective base- line values in each group and comparable across the three groups. The mean change ± SD from baseline to
month 24 in waist circumference was þ1.9 ± 0.8 cm in DTG group (p ¼ .218), þ2.2 ± 1.1 cm in RAL group (p ¼ .097) and þ2.1 ± 1 cm in EVG/c group (p ¼ .099).
There were no statistically significant differences at month 24 across the three groups in percentage of patients with plasma HIV RNA <20 copies/mL: 32/34
(94.1%) in DTG group, 31/32 (96.9%) in RAL group and
33/36 (91.7%) in EVG/c group. Mean changes ± SD in CD4þ T lymphocyte counts at month 24 were compar- able across the three groups: DTG, þ139 ± 88 cells/mm3; RAL, þ125 ± 74 cells/mm3; EVG/c, þ119 ± 66 cells/mm3.
Clinical data about a correlation between specific anti- retroviral agents and a faster atherosclerosis progression are lacking. A potential role of boosted PI in accelerating the progression of atherosclerosis has emerged in some observational studies.
In a longitudinal cohort study of 211 adult HIV-infected patients, progression of atherosclerotic disease was assessed by carotid IMT and coronary artery calcium (CAC) measurements over six years. Carotid IMT and CAC increases were significantly associated with age, smoking, baseline triglycerides and total cholesterol, diabetes, cART duration, HIV viral load and nadir CD4 T-lymphocyte count. Moreover, PI use was significantly associated with IMT increase [28]. A cross-sectional study evaluating 80 HIV-positive patients and 65 HIV-negative controls showed a significantly higher prevalence of


atherosclerosis among HIV-infected patients and a higher value of carotid IMT among those treated with PIs [29].
A meta-analysis of 57 clinical studies investigated the relationship between HIV infection, cART and markers of endothelial damage, and showed a significant associ- ation of PI exposure with elevated carotid IMT and increased pulse wave velocity (PWV) [30]. The PREVALEAT (Premature Vascular Lesions and Antiretroviral Therapy) II cohort study evaluated changes in carotid IMT in 119 advanced naïve HIV-positive
patients (with less than 200 CD4þ T-lymphocytes/mm3)
starting an initial cART including efavirenz, atazanavir/ ritonavir or darunavir/ritonavir. During a 12-month fol- low-up, patients receiving darunavir/ritonavir were at higher risk of developing pathological IMT than those treated with efavirenz or atazanavir/ritonavir [31].
In the A5260s randomized trial, progression of carotid IMT was assessed over three years in 328 naïve HIV-posi- tive subjects without known cardiovascular disease or diabetes and starting an initial regimen including teno- fovir/emtricitabine plus atazanavir/ritonavir, darunavir/ ritonavir or raltegravir. Carotid IMT progressed more fastly on darunavir/ritonavir than atazanavir/ritonavir, while changes with raltegravir were intermediate. A slow carotid IMT progression rate was significantly associated with higher levels of bilirubin and non-high-density lipo- protein cholesterol [32].
In the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM), the relationship between HIV-related characteristics and carotid IMT was assessed in 538 HIV-infected patients. Among the HIV- related factors, tenofovir use was associated with a lower common carotid IMT and a slower progression of atherosclerosis, while no associations between IMT pro- gression rate and other antiretroviral agents were found [33].
In the Swiss HIV Cohort Study, the association between individual antiretroviral agents and the preva- lence and extent of subclinical atherosclerosis was inves- tigated by coronary TC angiography and CAC measurement. This study enrolled 403 HIV-positive patients and showed an increased risk of non-calcified/ mixed plaque only in subjects exposed to abacavir, while tenofovir and efavirenz were negatively associated with any plaque and calcified plaque, respectively [34]. On the other hand, in the Multicenter AIDS Cohort Study, 450 men with HIV infection (81% with virological suppression) underwent coronary TC angiography to search subclinical atherosclerosis. In this study, no con- sistent associations between use of specific antiretroviral

compounds and both coronary plaque presence and extent were found [35].
Furthermore, to date, there is no agreement about the best non-invasive method to diagnose subclinical atherosclerosis in HIV-infected patients with moderate- to-high cardiovascular disease risk. In a single-centre observational study, 100 consecutive HIV-positive adults underwent a carotid B-mode ultrasonography to assess both IMT and segmental PWV as indicator of arterial stiffness. IMT and PWV were discordant for 21 of 100 subjects enrolled, and a high risk of discordance was sig- nificantly associated with dyslipidaemia, male gender and hypertension. So, in patients with significant cardio- vascular disease risk factors (dyslipidaemia, hyperten- sion), the use of both IMT and PWV may improve the identification of high-risk patients who should be addressed to further cardiovascular evaluation [36]. In another observational study, the ankle-brachial index (ABI) was compared with estimation of IMT for screening of peripheral arterial disease in 102 HIV-infected individ- uals. The authors found a poor correlation between ABI and traditional cardiovascular disease risk factors (other than BMI) or carotid IMT, so in this study, ABI did not seem valuable as a screening tool for subclinical athero- sclerosis in HIV population [37].
In our study, after 24 months of an INSTI-based triple regimen the mean IMT changes in common carotid artery, carotid bifurcation and internal carotid artery were not significant in each group in comparison with respective baseline values and were comparable across the three groups. Similarly, changes in prevalence of subclinical atherosclerosis and carotid plaques were not significant in comparison with baseline values in each group and they were comparable across the three groups.
After 24 months, all INSTI-based regimens did not produce significant variations in lipid parameters. However, there was a statistically significant increase in weight and BMI in each group compared to respective baseline values, and increases in weight and BMI were comparable in subjects MK-0518  treated with RAL, DTG or EVG/c. On the other hand, mean changes in waist circumfer- ence at month 24 were not significant in comparison with respective baseline values in each group and com- parable across the three groups.
This is the first study, to the best of our knowledge, to compare the atherosclerosis progression rate in HIV- positive, antiretroviral therapy-naive patients starting an INSTI-based treatment.


Obviously, several limitations are present in our study, so the results must be interpreted with caution. First, the study has an observational design, and some con- founding factors could potentially influence the choice of treatment, even though the baseline characteristics of patients were comparable across all treatment groups. We have not included a control group without HIV infection. The limited sample size, the short duration of the observation period and the data extraction from the medical records can be occasionally incomplete or inaccurate. Finally, there are many differences in diet, exercise and lifestyle among the enrolled subjects which were not evaluated, and they could probably influence the observed changes in some parameters.
To conclude, in our study, the initial antiretroviral therapy with tenofovir alafenamide/emtricitabine plus raltegravir, dolutegravir or elvitegravir/cobicistat for 24 months has led to a comparable and not significant effect on the progression rate of subclinical atheroscler- osis assessed by carotid Doppler ultrasonography. Further, enlarged studies are needed in order to better investigate the effect of specific antiretroviral agents on the atherosclerotic process.

Disclosure statement
No potential conflict of interest was reported by the authors.

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