ArticlePDF Available

Weight of Clinical and Social Determinants of Metabolic Syndrome in People Living with HIV

MDPI
Viruses
Authors:
  • Infectious and Tropical Diseases Unit University Hospital of Padua

Abstract and Figures

Background. Comorbidities in people living with HIV (PLWH) represent a major clinical challenge today, and metabolic syndrome (MTBS) is one of the most important. Objective. Our objective was to assess the prevalence of MTBS and the role of both clinical/socio-behavioral risk factors for MTBS in a cohort of PLWH. Methods. All PLWH, over 18 years of age, attending all Infectious Disease Units in Calabria Region (Southern Italy) for their routine checks from October 2019-January 2020 were enrolled. MTBS was defined by NCEP-ATP III criteria. Logistic regression analysis was performed to assess factors significantly associated with the main outcome (MTBS). Results. We enrolled 356 PLWH, mostly males (68.5%), with a mean age of 49 years (standard deviation: 12), including 98 subjects with and 258 without MTBS. At logistic regression analysis, a statistically significant association was found between MTBS and alcohol use, osteoporosis, polypharmacy, and a history of AIDS. Conclusions. Identifying and addressing risk factors, including those that are socio-behavioral or lifestyle-related, is crucial to prevent and treat MTBS. Our results suggest the importance of implementing educational/multidimensional interventions to prevent MTBS in PLWH, especially for those with particular risk factors (alcohol abuse, osteoporosis, previous AIDS events, and polypharmacy). Moreover, alcohol consumption or abuse should be routinely investigated in clinical practice.
Content may be subject to copyright.
Citation: Mazzitelli, M.; Fusco, P.;
Brogna, M.; Vallone, A.; D’Argenio,
L.; Beradelli, G.; Foti, G.; Mangano,
C.; Carpentieri, M.S.; Cosco, L.; et al.
Weight of Clinical and Social
Determinants of Metabolic Syndrome
in People Living with HIV. Viruses
2022,14, 1339. https://doi.org/
10.3390/v14061339
Academic Editor: Sonia Moretti
Received: 10 April 2022
Accepted: 9 June 2022
Published: 20 June 2022
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affil-
iations.
Copyright: © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
viruses
Article
Weight of Clinical and Social Determinants of Metabolic
Syndrome in People Living with HIV
Maria Mazzitelli 1, 2, * , Paolo Fusco 1, Michele Brogna 3, Alfredo Vallone 3, Laura D’Argenio 3,
Giuseppina Beradelli 4, Giuseppe Foti 5, Carmelo Mangano 5, Maria Stella Carpentieri 5, Lucio Cosco 6,
Paolo Scerbo 6, Armando Priamo 6, Nicola Serrao 7, Antonio Mastroianni 8, Chiara Costa 1,
Maria Teresa Tassone 1, Vincenzo Scaglione 1, Francesca Serapide 1, Enrico Maria Trecarichi 1and Carlo Torti 1
1Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences,
“Magna Graecia” University, 88100 Catanzaro, Italy; paolofusco89@gmail.com (P.F.);
costach65@gmail.com (C.C.); mariateresatassone90@gmail.com (M.T.T.);
vincenzo.scaglione91@gmail.com (V.S.); francescaserapide@gmail.com (F.S.); em.trecarichi@unicz.it (E.M.T.);
torti@unicz.it (C.T.)
2Infectious and Tropical Diseases Unit, Padua University Hospital, 35128 Padua, Italy
3Jazzolino Hospital, 89900 Vibo Valentia, Italy; brognam@libero.it (M.B.); alfredo.vallone@aspvv.it (A.V.);
laura.dargenio@aspvv.it (L.D.)
4Unit of Infectious and Tropical Diseases, “Giovanni Paolo II” Hospital, 88046 Lamezia Terme, Italy;
giuseppina.berardelli@asp.cz.it
5
Unit of Infectious and Tropical Diseases, “Bianchi-Melacrino-Morelli” Hospital, 89121 Reggio Calabria, Italy;
fotigiuseppe@tin.it (G.F.); mangano.carmelo@alice.it (C.M.); carpentieri.mariastella@gmail.com (M.S.C.)
6Unit of Infectious and Tropical Diseases, “Pugliese-Ciaccio” Hospital, 88100 Catanzaro, Italy;
lucio.cosco@alice.it (L.C.); scr2002@hotmail.com (P.S.); armando1956@alice.it (A.P.)
7Unit of Infectious and Tropical Diseases, “San Giovanni di Dio” Hospital, 88900 Crotone, Italy;
n.serrao@libero.it
8Unit of Infectious and Tropical Diseases, “Annunziata” Hospital, 87100 Cosenza, Italy;
antoniomastroianni@yahoo.it
*Correspondence: m.mazzitelli88@gmail.com
Abstract: Background.
Comorbidities in people living with HIV (PLWH) represent a major clinical
challenge today, and metabolic syndrome (MTBS) is one of the most important.
Objective.
Our
objective was to assess the prevalence of MTBS and the role of both clinical/socio-behavioral risk
factors for MTBS in a cohort of PLWH.
Methods.
All PLWH, over 18 years of age, attending all
Infectious Disease Units in Calabria Region (Southern Italy) for their routine checks from October 2019–
January 2020 were enrolled. MTBS was defined by NCEP-ATP III criteria. Logistic regression analysis
was performed to assess factors significantly associated with the main outcome (MTBS).
Results.
We enrolled 356 PLWH, mostly males (68.5%), with a mean age of 49 years (standard deviation:
12), including 98 subjects with and 258 without MTBS. At logistic regression analysis, a statistically
significant association was found between MTBS and alcohol use, osteoporosis, polypharmacy, and
a history of AIDS.
Conclusions.
Identifying and addressing risk factors, including those that are
socio-behavioral or lifestyle-related, is crucial to prevent and treat MTBS. Our results suggest the
importance of implementing educational/multidimensional interventions to prevent MTBS in PLWH,
especially for those with particular risk factors (alcohol abuse, osteoporosis, previous AIDS events,
and polypharmacy). Moreover, alcohol consumption or abuse should be routinely investigated in
clinical practice.
Keywords:
HIV; PLWH; metabolic syndrome; non-communicable diseases; diabetes; dyslipidemia; AIDS
1. Introduction
Due to increased life expectancy and efficacy of newer antiretrovirals, the burden
of non-infectious comorbidities in people living with HIV (PLWH) is increasing [
1
,
2
].
Viruses 2022,14, 1339. https://doi.org/10.3390/v14061339 https://www.mdpi.com/journal/viruses
Viruses 2022,14, 1339 2 of 8
Indeed, cardiovascular disease, metabolic complications, cancer, and bone disorders are the
most frequent comorbidities in this population [
3
,
4
]. Among these, metabolic syndrome
(MTBS) is one of the most frequent [
5
]. Therefore, HIV became a chronic disease for which
management of non-communicable diseases (NCDs) remains to date the major clinical
challenge [
6
]. One of the most important issues is the management of the metabolic disease
because MTBS is not only the main drivers of major cardiovascular events, but it is also
associated with an increased risk of respiratory disorders and malignancies [
7
,
8
] and
possible side effects due to polypharmacy [
9
]. This is the reason why dedicated clinics and
services for a multidimensional approach to ageing PLWH have been implemented over
time [10].
Data about prevalence of the metabolic syndrome in people with HIV are not definitive.
Indeed, some data reported the prevalence of MTBS to be about 30%, comparable with the
prevalence of MTBS in the general population, while other studies reported that prevalence
was slightly higher in PLWH than in the general population [
11
,
12
]. Beyond the above-
mentioned criteria, social factors and lifestyle have been identified as contributors to the
risk of MTBS, and control of some social habits was also associated with prevention of
MTBS [
11
]. Moreover, recently it has been demonstrated that socioeconomic and lifestyle
differences between people with and without HIV could lead to a 2.5-fold increased life-
year loss [
13
], and for PLWH, specific factors such as chronic inflammation and type of
antiretroviral therapy could contribute to increases risk of metabolic alterations leading to
other chronic diseases [14,15].
In this study, we aimed at assessing prevalence of MTBS in PLWH in southern Italy
and both clinical and social determinants associated with its presence.
2. Materials and Methods
This observational study was coordinated by the Infectious and Tropical Diseases Unit
of Mater Domini teaching hospital in Catanzaro (Italy) and was conducted in accordance
with the Declaration of Helsinki and the principles of Good Clinical Practice [
16
]. The local
ethical committee (Calabria Region) approved the study protocol on 19 July 2018. Written
informed consent was obtained from all subjects enrolled. Participation in the survey was
proposed to all PLWH older than 18 years, attending the Infectious and Tropical Diseases
Units (ITDUs) in Calabria (cities of Catanzaro—two centers—, Cosenza, Crotone, Lamezia
Terme, Reggio Calabria, and Vibo Valentia) for their routine clinical checks from 1 October
2019 to 31 January 2020. Pregnant women and people aged under 18 years were excluded.
The study population was divided into two groups: PLWH with MTBS and PLWH without
MTBS. According to NCEP-ATP III criteria, metabolic syndrome (MTBS) was defined by
the presence of three or more of the following parameters: waist circumference greater
than 102 cm in males and 88 in females, blood pressure higher than 135/80 mmHg, fasting
blood glucose greater than 100 mg/dL, HDL lower than 50 mg/dL for men and 40 mg for
women, and triglycerides level higher than 150 mg/dL [17].
Data regarding demographics (age, gender, country of origin), clinical history, HIV-
related characteristics (viral load, CD4 + T cell count, AIDS-defining illnesses in the past
medical history) and all comorbidities, co-medications, risk factors and lifestyle-related
characteristics (smoking habit, alcohol consumption, physical exercise), and blood test
results were collected. Data on the level of education were collected, setting up a highest
level of education up to 16 years (primary school, 5 years; secondary school, 3 years; high
school, 5 years; university, 3 or more years). Data on comorbidities were retrieved by
clinical health records. Hypertension was defined by its presence in the medical history or
by anti-hypertensive agents among comedication. Physical activity was assessed by using
WHO definitions according to age [
18
]. Chronic kidney disease was considered if men-
tioned in the medical history or in subject with an estimated glomerular filtration rate below
90 mL/min [
19
]. Excessive alcohol intake was measured by using definitions of Italian
Ministry of Health: intake of 2 or more or 1 or more alcoholic units/day (
1 units = 12 g
of
alcohol) for men and women, respectively, or experiencing episodes of binge drinking (in-
Viruses 2022,14, 1339 3 of 8
take of 5 or more or 4 or more alcoholic units at once for men and women, respectively) [
20
].
Weight and height to calculate body mass index (BMI) and waist circumferences (to estab-
lish MTBS criteria) were measured during clinical check. Polypharmacy was defined as
the intake of 5 or more medications in the same patient [
21
]. Each participant was given a
unique study identification number, and data regarding each patient were transferred onto
an Excel database.
Continuous variables were compared by Student’s t-test for normally distributed
variables and the Mann–Whitney U test for non-normally distributed variables. Categorical
variables were evaluated using the
χ2
or two-tailed Fisher’s exact test. Odds ratios (ORs)
and 95% confidence intervals (CIs) were calculated to evaluate the strength of any asso-
ciation that emerged. Values are expressed as mean (
±
standard deviation) (continuous
variables) or as percentages of the group from which they were derived (categorical vari-
ables). Two-tailed tests were used to determine statistical significance; a p-value of <0.05
was significant. Multivariate analysis was used to explore any possible correlation with the
main outcome (MTBS). For this analysis, we used logistic regression and incorporated vari-
ables found to be significant in univariate testing. All statistical analyses were performed
using the Intercooled Stata program, version 11, for Windows (Stata Corporation, College
Station, TX, USA).
3. Results
Over the study period, we enrolled 356 PLWH, namely 98 (27.5%) subjects with
MTBS, and 258 (72.5%) without MTBS, mainly of male gender (244/356, 68.5%) and with a
mean age of 49 years (standard deviation, SD: 12). Demographics, lifestyle, and clinical
characteristics of the study population are depicted in Table 1according to the presence of
metabolic syndrome (PLWH with MTBS and PLWH without MTBS). In the MTBS group,
PLWH had a mean age of 53 years (SD: 10), were mainly of male gender (76.5%), and
experienced AIDS events in almost 90% cases. PLWH without MTBS had a mean age of
47.6 (SD: 11.6) and were mainly of male gender (65.5%). Prevalence of previous AIDS
events in this groups was 27.5%.
Table 1. Baseline characteristics by presence of metabolic syndrome.
Variable
No. PLWH with
MTBS (%)
98 (100)
No. PLWH without
MTBS (%)
258 (100)
p
Age, mean (SD) 53.1 (10.3) 47.6 (11.6) <0.001
Male gender 75 (76.5) 169 (65.5) 0.04
Country (Italy) 93 (94.9) 217 (84.1) 0.006
Highest level of education 12 (12.1) 54 (20.9) 0.05
Living alone 54 (55.1) 153 (59.3) 0.47
Being retired 15 (15.3) 22 (8.5) 0.05
Being smoker 57 (58.2) 130 (50.4) 0.18
Doing regular exercise 25 (25.5) 89 (34.5) 0.104
Excessive alcohol intake 51 (52) 88 (34.1) 0.019
Chronic kidney disease 10 (10.2) 20 (7.7) 0.45
Cirrhosis 3 (3.1) 5 (1.9) 0.52
COPD 15 (15.3) 17 (6.6) 0.01
Malignancies 3 (3.1) 5 (1.9) 0.52
Psychiatric disorders 24 (24.5) 65 (25.2) 0.89
Neurological disorders 21 (21.4) 19 (7.4) 0.002
Osteoporosis 28 (28.6) 27 (10.5) <0.01
Thyroid diseases 4 (4.1) 11 (4.3) 0.93
HBV coinfection 7 (7.1) 21 (8.1) 0.75
HCV coinfection 27 (27.5) 59 (22.9) 0.35
HBV/HCV coinfection 4 (4.1) 5 (1.9) 0.249
Polypharmacy 18 (18.4) 4 (1.5) <0.01
CD4/CD8 ratio > 1 20 (20.1) 79 (30.6) 0.05
Viruses 2022,14, 1339 4 of 8
Table 1. Cont.
Variable
No. PLWH with
MTBS (%)
98 (100)
No. PLWH without
MTBS (%)
258 (100)
p
Previous AIDS events 88 (89.9) 71 (27.5) <0.01
HIV RNA > 50 copies/mL 5 (5.1) 13 (5.1) 0.98
Years with HIV, mean (SD) 15.9 (0.6) 14.2 (0.6) 0.9
Last CD4 T cell count, mean (SD) 669 (21) 705 (37) 0.8
CD4 T cell count nadir, mean (SD) 310 (15) 277 (23) 0.13
cART *
2NRTI + INI 47 (47.9) 118 (45.7) 0.7
2NRTI + NNRTI 13 (13.2) 53 (20.5) 0.2
2NRTI + PI 18 (18.4) 48 (19.8) 0.9
INI + PI 7 (7.3) 22 (8.5) 0.7
Dual 0 (0) 5 (1.9) 0.2
SD, standard deviation; PLWH, people living with HIV; MTBS, metabolic syndrome; COPD, chronic obstructive
pulmonary disease; cART, combination antiretroviral therapy; NRTI, nucleos(t)ide reverse transcriptase inhibitors;
NNRTI, non-nucleos(t)ide reverse transcriptase inhibitors; INI, integrase inhibitors; PI, protease inhibitors. *, 13
subjects in the MTBS group and 12 in the group without MTBS were receiving cART not present in the listed
combinations.
At the univariate analysis (Table 2), factors significantly associated with MTBS were
age (53.1 vs. 47.6, p< 0.001), male gender (OR: 0.58, 95% CI: 0.3–1.1, p= 0.04), excessive
alcohol intake (OR: 2.1, 95% CI: 1.3–3.5, p= 0.019), chronic pulmonary disease (OR: 2.56, 95%
CI: 1.1–5.7, p= 0.01), neurological diseases (OR: 3.4, 95% CI: 1.6–7.1, p= 0.002), osteoporosis
(OR: 3.42, 95% CI 1.8–6.4, p< 0.01), polypharmacy (OR: 14.3, 95% CI 4.4–59.2, p< 0.01),
and AIDS events in the past medical history (OR: 23.1, 95% CI 11.1–52, p< 0.01). At the
multivariable model, (Table 2), significant association was maintained only for alcohol
consumption (OR: 3.1, 95% CI 1.4–6.6; p< 0.01), osteoporosis (OR: 3.1, 95% CI 1.8–7.3,
p< 0.01
), polypharmacy (OR: 7.1, 95% CI: 1.85–27.6; p< 0.01), and history of AIDS events
(OR: 21, 95% CI 10.9–44.1, p< 0.01).
Table 2.
Univariate and multivariate analyses of risk factors associated with metabolic syndrome
in PLWH.
Variable
No. PLWH
with MTBS (%)
98 (100)
No. PLWH without
MTBS (%)
258 (100)
Univariable Analysis Multivariable Analysis
Odds Ratio
(95% CI) pOdds Ratio
(95% CI) p
Age, mean (SD) 53.1 (10.3) 47.6 (11.6) - <0.001
Male gender 75 (76.5) 169 (65.5) 0.58 (0.3–1.1) 0.04
Country (Italy) 93 (94.9) 217 (84.1) 3.5 (1.32–11.7) 0.006
Highest level of education 12 (12.1) 54 (20.9) 0.52 (0.24–1.1) 0.05
Living alone 54 (55.1) 153 (59.3) 0.84 (0.51–1.4) 0.47
Being retired 15 (15.3) 22 (8.5) 1.9 (0.88–4.1) 0.05
Being smoker 57 (58.2) 130 (50.4) 1.36 (0.8–2.25) 0.18
Doing regular exercise 25 (25.5) 89 (34.5) 0.66 (0.36–1.1) 0.104
Excessive alcohol intake 51 (52) 88 (34.1) 2.1 (1.3–3.5) 0.019 3.1 (1.4–6.6) <0.01
Chronic kidney disease 10 (10.2) 20 (7.7) 1.35 (0.54–3.2) 0.45
Cirrhosis 3 (3.1) 5 (1.9) 1.59 (0.24–8.4) 0.52
COPD 15 (15.3) 17 (6.6) 2.56 (1.1–5.7) 0.01
Malignancies 3 (3.1) 5 (1.9) 1.59 (0.24–8.4) 0.52
Psychiatric disorders 24 (24.5) 65 (25.2) 0.96 (0.53–1.7) 0.89
Neurological disorders 21 (21.4) 19 (7.4) 3.4 (1.6–7.1) 0.002
Osteoporosis 28 (28.6) 27 (10.5) 3.42 (1.8–6.4) <0.01 3.6 (1.8–7.3) <0.01
Thyroid diseases 4 (4.1) 11 (4.3) 0.95 (0.21–3.3) 0.93
HBV coinfection 7 (7.1) 21 (8.1) 0.86 (0.3–2.1) 0.75
HCV coinfection 27 (27.5) 59 (22.9) 1.28 (0.7–2.24) 0.35
HBV/HCV coinfection 4 (4.1) 5 (1.9) 2.1 (0.41–10.2) 0.249
Polypharmacy 18 (18.4) 4 (1.5) 14.3 (4.4–59.2) <0.01 7.1 (1.85–27.6) <0.01
CD4/CD8 ratio > 1 20 (20.1) 79 (30.6) 0.58 (0.31–1.1) 0.05
Previous AIDS events 88 (89.9) 71 (27.5) 23.1 (11.1–52) <0.01 21 (10.9–44.1) <0.01
Viruses 2022,14, 1339 5 of 8
Table 2. Cont.
Variable
No. PLWH
with MTBS (%)
98 (100)
No. PLWH without
MTBS (%)
258 (100)
Univariable Analysis Multivariable Analysis
Odds Ratio
(95% CI) pOdds Ratio
(95% CI) p
HIV RNA > 50 copies/mL 5 (5.1) 13 (5.1) 1.01 (0.27–3.13) 0.98
Years with HIV, mean (SD) 15.9 (0.6) 14.2 (0.6) - 0.9
Last CD4 T cell count, mean (SD) 669 (21) 705 (37) - 0.8
CD4 T cell count nadir, mean (SD) 310 (15) 277 (23) - 0.13
cART *
2NRTI + INI 47 (47.9) 118 (45.7) 1.1 (0.66–1.78) 0.7
2NRTI + NNRTI 13 (13.2) 53 (20.5) 0.5 (0.3–1.2) 0.2
2NRTI + PI 18 (18.4) 48 (19.8) 0.9 (0.5–1.8) 0.9
INI + PI 7 (7.3) 22 (8.5) 0.8 (0.3–2.1) 0.7
Dual 0 (0) 5 (1.9) 0 (0–2) 0.2
SD, standard deviation; PLWH, people living with HIV; MTBS, metabolic syndrome; COPD, chronic obstructive
pulmonary disease; cART, combination antiretroviral therapy; NRTI, nucleos(t)ide reverse transcriptase inhibitors;
NNRTI, non-nucleos(t)ide reverse transcriptase inhibitors; INI, integrase inhibitors; PI, protease inhibitors.
*, 13 subjects in the MTBS group and 12 in the group without MTBS were receiving cART not present in the listed
combinations.
4. Discussion
We found that approximately one-third (27.5%) of PLWH in our cohort from southern
Italy had MTBS. This result in the middle of the range of prevalence of MTBS in the general
population, which is from 15% to 29% in Italy [
22
24
]. As for PLWH, in comparison with
other cohorts from Mediterranean area, (i.e., Spain), where the prevalence was 11.4%, our
prevalence of MTBS was higher [
25
], while it was lower than that recently described by
a multicenter Italian cohort reporting a prevalence of MTBS of 29.3–35% in PLWH over
10 years [
12
]. According to the latter study, prevalence of MTBS in PLWH residing in
Italy decreased from 2005 to 2015. However, since then, a new class of antiretroviral, the
integrase inhibitors, which are strictly associated with weight gain, is available. Whether
the advent of this new class influenced the prevalence of MTBS in PLWH across Italy
remains to be investigated.
Due to the residency of our patients in the Mediterranean area, we would have
expected a far lower prevalence of MTBS, similar to that found in other Mediterranean
cohorts (15–21%) [
22
,
23
]. A plausible explanation for this discrepancy could be the indirect
effect of globalization that has also changed people’s eating habits (increased consumption
of “junk food “and sweet/carbonated drinks) [
26
]. On the other hand, more likely, it could
be due to social determinants recently identified as determinants of MTBS in the Italian
Obesity Barometer Report 2019 [
27
]. Herein, it is demonstrated that 30% of Italians are
overweighted/obese and that proportions of obese/overweighted people is greater in the
south compared to the north of Italy [
27
]. This difference is due to sedentary lifestyle, lower
level of education, and high caloric intake [27].
This risk factors are represented also in PLWH [
28
,
29
] and confirmed by our results.
Moreover, in PLWH, some lifestyle behaviors increasing the risk of MTBS (such as alcohol
abuse) are overrepresented, increasing the risk of metabolic disorders further [
30
32
]. In
our cohort, people with excessive alcohol intake were 3.1-fold more likely to have MTBS
when compared to those who did not report any alcohol consumption. Moreover, alcohol
consumption is a part of the nutritional habit; hence, it is likely that these factors may
influence each other. Therefore, educational interventions to avoid and control alcohol
abuse should be promoted.
Another crucial tool to prevent MTBS is performing regular exercise, which also
prevents other comorbidities such as bone disorders, specifically osteoporosis, and could
contribute to keeping ageing people fit.
Polypharmacy was significantly associated with MTBS in our cohort, and this could
be easily explained by the fact that polypharmacy is a proxy of comorbidities. Moreover,
the use of specific medications (protease inhibitors, antidepressants agents, corticosteroids,
oral contraceptives) may increase the risk of the development of the metabolic syndrome
Viruses 2022,14, 1339 6 of 8
by either promoting weight gain or altering lipid or glucose metabolism [
33
,
34
]. Healthcare
providers should promptly recognize, systematically review, and assess the risk associated
with some medications more than others and appropriately change/switch off medications
contributing to the burden of metabolic disease. Moreover, careful attention to the drug
choices should be paid in patients who are overweight or have other risk factors for diabetes
or cardiovascular disease.
Our data showed a significant association between MTBS and previous AIDS events.
Furthermore, in our analysis, a trend to significance was found for CD4/CD8 ratio: PLWH
with a low CD4/CD8 ratio (<1) were more likely to have MTBS (p= 0.05). A low CD4/CD8
ratio has been linked to ageing and acts both as a predictor of mortality in the general
population and a biomarker of inflammation in PLWH [
35
]. It would therefore seem that
both inflammation and immunosuppression play a role in metabolic diseases.
It should be noted that our analysis shows that (even if not statistically) the most
educated people tend to have half the risk of developing MTBS. A possible explanation is
that highly educated people take much more care regarding quality of food and lifestyles;
by contrast, people with lower levels of education may eat larger amounts of unhealthy,
calorically dense food than those with a higher education level [
36
]. This result is also in
line with data from the general Italian population previously mentioned.
This study is somewhat limited by its cross-sectional nature, by the lack of a control
group, by the low number of participants, and by the possible bias connected with a
retrospective collection of data from clinical health records (missing information such as
underreporting of comedications and comorbidities, etc.). Furthermore, categorizations
of some variables in a dichotomous way could have had an impact on our results [
37
].
Moreover, it is well-recognized that there are prominent sex differences in MTBS [
38
,
39
].
Given the prominent sex differences in the pathogenesis of metabolic syndrome, it is
possible that the risk factors associated with MTBS may also be altered by different gender
distribution, and this can also be seen as a limitation of our study in terms of generalizability
of results.
Our study suggests that prevalence of MTBS in our cohort is high (27.5%); therefore, it
is important to both identify risk factors and implement educational/multidimensional
interventions to prevent MTBS in PLWH, especially for those with particular risk factors
(previous AIDS events or polypharmacy). Moreover, some behaviors, such as alcohol
consumption, should be routinely investigated in clinical practice, and campaigns should
be implemented to promote a change in the lifestyle of patients by promoting healthy diets,
weight loss, and physical activity. Lastly, since available data are still debated, more recent
and updated data are necessary to establish the actual prevalence of MTBS in PWLH.
Author Contributions:
Conceptualization, M.M. and C.T.; methodology, M.M., C.T. and E.M.T.;
software, E.M.T.; formal analysis, E.M.T.; investigation, M.M.; data curation, M.B.; A.V.; L.D.; G.F.;
C.C.; M.T.T.; C.M.; M.S.C.; V.S.; P.F.; F.S.; L.C.; A.P.; A.M.; N.S.; P.S.; G.B.; writing—original draft
preparation, M.M.; writing—review and editing, M.M. and C.T.; project administration, M.M. All
authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement:
The study was conducted according to the guidelines of the
Declaration of Helsinki and approved by the Ethics Committee of Calabria Region on 19 July 2018
(n. 201).
Informed Consent Statement:
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement: All data of interest are herein reported.
Acknowledgments:
We want to thank all our patients for their participation in this study and the
CalabrHIV Study Group. We want to also thank Peter Reiss (Netherlands) for his support and advice
in manuscript draft preparation.
Viruses 2022,14, 1339 7 of 8
Conflicts of Interest:
The authors declare no conflict of interest. Maria Mazzitelli was supported as a
Ph.D. student by the European Commission (FESR FSE 2014–2020) and by the Calabria region (Italy).
The European Commission and Calabria region cannot be held responsible for any use that may be
made of information contained therein. She was also supported in developing this research by the
EACS mentorship program 2021 (Peter Reiss, The Netherlands). Results of this paper were presented
in part during a poster session at the EACS conference 2021, in London.
References
1.
Deeks, S.G.; Lewin, S.R.; Havlir, D.V. The End of AIDS: HIV Infection as a Chronic Disease. Lancet
2013
,382, 1525–1533. [CrossRef]
2. Bonnet, F.; Le Marec, F.; Leleux, O.; Gerard, Y.; Neau, D.; Lazaro, E.; Duffau, P.; Caubet, O.; Vandenhende, M.A.; Mercie, P.; et al.
Evolution of comorbidities in people living with HIV between 2004 and 2014: Cross-sectional analyses from ANRS CO
3
Aquitaine
cohort. BMC Infect. Dis. 2020,20, 850. [CrossRef] [PubMed]
3.
Touloumi, G.; Kalpourtzi, N.; Papastamopoulos, V.; Paparizos, V.; Adamis, G.; Antoniadou, A.; Chini, M.; Karakosta, A.;
Makrilakis, K.; Gavana, M.; et al. Cardiovascular risk factors in HIV infected individuals: Comparison with general adult control
population in Greece. PLoS ONE 2020,15, e0230730. [CrossRef] [PubMed]
4.
Robbins, H.A.; Pfeiffer, R.M.; Shiels, M.S.; Li, J.; Hall, H.I.; Engels, E.A. Excess cancers among HIV-infected people in the United
States. J. Natl. Cancer Inst. 2015,107, dju503. [CrossRef]
5.
Li Vecchi, V.; Maggi, P.; Rizzo, M.; Montalto, G. The metabolic syndrome and HIV infection. Curr. Pharm. Des.
2014
,20, 4975–5003.
[CrossRef]
6.
Kansiime, S.; Mwesigire, D.; Mugerwa, H. Prevalence of non-communicable diseases among HIV positive patients on antiretroviral
therapy at joint clinical research centre, Lubowa, Uganda. PLoS ONE 2019,14, e0221022. [CrossRef]
7.
Esposito, K.; Chiodini, P.; Colao, A.; Lenzi, A.; Giugliano, D. Metabolic syndrome and risk of cancer: A systematic review and
meta-analysis. Diabetes Care 2012,35, 2402–2411. [CrossRef]
8.
Baffi, C.W.; Wood, L.; Winnica, D.; Strollo, P.J., Jr.; Gladwin, M.T.; Que, L.G.; Holguin, F. Metabolic Syndrome and the Lung. Chest
2016,149, 1525–1534. [CrossRef]
9.
Mazzitelli, M.; Milinkovic, A.; Pereira, B.; Palmer, J.; Tong, T.; Asboe, D.; Boffito, M. Polypharmacy and evaluation of anticholiner-
gic risk in a cohort of elderly people living with HIV. AIDS 2019,33, 2439–2441. [CrossRef]
10.
Pereira, B.; Mazzitelli, M.; Milinkovic, A.; Casley, C.; Rubio, J.; Channa, R.; Girometti, N.; Asboe, D.; Pozniak, A.; Boffito, M.
Evaluation of a Clinic Dedicated to People Aging with HIV at Chelsea and Westminster Hospital: Results of a 10-Year Experience.
AIDS Res. Hum. Retrovir. 2022,38, 188–197. [CrossRef]
11.
Nguyen, K.A.; Peer, N.; Mills, E.J.; Kengne, A.P. A Meta-Analysis of the Metabolic Syndrome Prevalence in the Global HIV-Infected
Population. PLoS ONE 2016,11, e0150970. [CrossRef] [PubMed]
12.
Taramasso, L.; Bonfanti, P.; Ricci, E.; Maggi, P.; Orofino, G.; Squillace, N.; Menzaghi, B.; Madeddu, G.; Molteni, C.; Vichi, F.; et al.
Metabolic syndrome and body weight in people living with HIV infection: Analysis of differences observed in three different
cohort studies over a decade. HIV Med. 2022,23, 70–79. [CrossRef] [PubMed]
13.
Pourcer, V.; Groumelen, J.; Bouee, S. Comorbidities in people living with HIV: An epidemiologic and economic analysis using a
claims database in France. PLoS ONE 2020,15, e0243529.
14.
Nou, E.; Lo, J.; Grinspoon, S.K. Inflammation, immune activation, and cardiovascular disease in HIV. AIDS
2016
,30, 1495–1509.
[CrossRef] [PubMed]
15.
Alvi, R.M.; Neilan, A.M.; Tariq, N.; Awadalla, M.; Afshar, M.; Banerji, D.; Rokicki, A.; Mulligan, C.; Triant, V.A.; Zanni, M.V.; et al.
Protease Inhibitors and Cardiovascular Outcomes in Patients with HIV and Heart Failure. J. Am. Coll. Cardiol.
2018
,72, 518–530.
[CrossRef] [PubMed]
16.
World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving
human subjects. JAMA 2013,310, 2191–2194. [CrossRef]
17.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third
Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001,285, 2486–2497. [CrossRef]
18.
Physical Activity—WHO. Available online: https://www.who.int/news-room/fact-sheets/detail/physical-activity#:~{}:
text=WHO%20defines%20physical%20activity%20as,part%20of%20a%20person\T1\textquoterights%20work (accessed on
27 March 2022).
19.
Levey, A.S.; Eckardt, K.U.; Tsukamoto, Y.; Levin, A.; Coresh, J.; Rossert, J.; De Zeeuw, D.; Hostetter, T.H.; Lameire, N.; Eknoyan, G.
Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes
(KDIGO). Kidney Int. 2005,67, 2089–2100. [CrossRef]
20.
Consiglio Per la Ricerca in Agricoltura e L’analisi Dell’economia Agraria (CREA)—Guidelines for Healthy Nutrition—2018
Revision. Available online: https://www.salute.gov.it/imgs/C_17_pubblicazioni_2915_allegato.pdf (accessed on 27 March 2022).
21.
Gleason, L.J.; Luque, A.E.; Shah, K. Polypharmacy in the HIV-infected older adult population. Clin. Interv. Aging
2013
,8, 749–763.
22.
Miccoli, R.; Bianchi, C.; Odoguardi, L.; Penno, G.; Caricato, F.; Giovannitti, M.G.; Pucci, L.; Del Prato, S. Prevalence of the
metabolic syndrome among Italian adults according to ATP III definition. Nutr. Metab. Cardiovasc. Dis.
2005
,15, 250–254.
[CrossRef]
Viruses 2022,14, 1339 8 of 8
23.
Novelletto, B.F.; Guzzinati, S.; Avogaro, A. Prevalence of metabolic syndrome and its relationship with clinically prevalent
cardiovascular disease in the Veneto region, northeastern Italy. Metab. Syndr. Relat. Disord.
2012
,10, 56–62. [CrossRef] [PubMed]
24.
Cicero, A.F.; Nascetti, S.; Noera, G.; Gaddi, A.V.; Massa Lombarda Project Team. Metabolic syndrome prevalence in Italy. Nutr.
Metab. Cardiovasc. Dis. 2006,16, e5–e6. [CrossRef] [PubMed]
25.
Bernal, E.; Masiá, M.; Padilla, S.; Martín-Hidalgo, A.; Gutiérrez, F. Prevalence and characteristics of metabolic syndrome among
HIV-infected patients from a Mediterranean cohort. Med. Clin. 2007,128, 172–200. [CrossRef] [PubMed]
26.
Costa-Font, J.; Mas, N. ‘Globesity’? The effects of globalization on obesity and caloric intake. Food Policy
2016
,64, 121–132.
[CrossRef]
27.
1st Italian Obesity Barometer Report. 2019. Available online: http://www.ibdo.it/pdf/OBESITY-REPORT-2019.pdf (accessed on
27 March 2022).
28.
Vancampfort, D.; Mugisha, J.; De Hert, M.; Probst, M.; Stubbs, B. Sedentary Behavior in People Living With HIV: A Systematic
Review and Meta-Analysis. J. Phys. Act. Health 2017,14, 571–577. [CrossRef] [PubMed]
29.
Fitch, K.; Abbara, S.; Lee, H.; Stavrou, E.; Sacks, R.; Michel, T.; Hemphill, L.; Torriani, M.; Grinspoon, S. Effects of lifestyle
modification and metformin on atherosclerotic indices among HIV-infected patients with the metabolic syndrome. AIDS
2012
,26,
587–597. [CrossRef]
30.
Pool, E.; Winston, A.; Bagkeris, E.; Vera, J.H.; Mallon, P.; Sachikonye, M.; Post, F.A.; Pozniak, A.; Boffito, M.;
Anderson, J.; et al.
Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study team. High-risk behaviours, and their associations
with mental health, adherence to antiretroviral therapy and HIV parameters, in HIV-positive men who have sex with men. HIV
Med. 2019,20, 131–136. [CrossRef]
31.
Duko, B.; Ayalew, M.; Ayano, G. The prevalence of alcohol use disorders among people living with HIV/AIDS: A systematic
review and meta-analysis. Subst. Abus. Treat. Prev. Policy 2019,14, 52. [CrossRef]
32.
Johnston, P.I.; Wright, S.W.; Orr, M.; Pearce, F.A.; Stevens, J.W.; Hubbard, R.B.; Collini, P.J. Worldwide relative smoking prevalence
among people living with and without HIV. AIDS 2021,35, 957–970. [CrossRef]
33.
Flint, O.P.; Noor, M.A.; Hruz, P.W.; Hylemon, P.B.; Yarasheski, K.; Kotler, D.P.; Parker, R.A.; Bellamine, A. The role of protease
inhibitors in the pathogenesis of HIV-associated lipodystrophy: Cellular mechanisms and clinical implications. Toxicol. Pathol.
2009,37, 65–77. [CrossRef]
34.
Pasquali, R.; Vicennati, V. Steroids and the metabolic syndrome. J. Steroid Biochem. Mol. Biol.
2008
,109, 258–265. [CrossRef]
[PubMed]
35.
McBride, J.A.; Striker, R. Imbalance in the game of T cells: What can the CD4/CD8 T-cell ratio tell us about HIV and health? PLoS
Pathog. 2017,13, e1006624. [CrossRef] [PubMed]
36.
van Bussel, L.M.; van Rossum, C.T.; Temme, E.H.; Boon, P.E.; Ocké, M.C. Educational differences in healthy, environmentally
sustainable and safe food consumption among adults in the Netherlands. Public Health Nutr.
2020
,23, 2057–2067. [CrossRef]
[PubMed]
37.
MacCallum, R.C.; Zhang, S.; Preacher, K.J.; Rucker, D.D. On the practive of dichotomization of quantitative variables. Psychol.
Methods 2002,7, 19–40. [CrossRef] [PubMed]
38.
Pradhan, A.D. Se differences in the metabolic syndrome: Implications for cardiovascular health in women. Clin. Chem.
2014
,60,
44–52. [CrossRef]
39.
Rochlani, Y.; Pothineni, N.V.; Mehta, J.L. Metabolic Syndrome: Does it differ between women and men? Cardiovasc. Drugs Ther.
2015,29, 329–338. [CrossRef]
... We also included a list of the following comorbidities: malignancy, chronic renal disease (defined as an estimated glomerular filtration rate of <60 mL/min) [20], dyslipidemia, ischemic heart disease, hypertension, obesity (defined as a body mass index of >30 kg/m 2 ) [21], cirrhosis, diabetes, osteoporosis, chronic obstructive pulmonary diseases, mood disorders, and neurological disorders. For each participant, we considered the median number of comorbidities and recorded the prevalence of multimorbidity (defined as the presence of 2 or more noninfectious comorbidities in the same person) and polypharmacy (defined as the intake of 5 or more non-antiretroviral medications in the same person) [7,[22][23][24][25]. ...
... The median age was 66 years (IQR: 65-70), and 87/112 (77.6%) were male at birth; 97.3% PLWH were of Caucasian ethnicity. The median time living with HIV was 25 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) years. The median CD4+ T cell count at nadir was 233 (122-345) cells/mm 3 , while 24.1% of PLWH had experienced at least one AIDS-defining condition according to their past medical history. ...
... As for people who switched, HIV was very well controlled; 100% of such persons had HIV RNA levels of <50 copies/mL, and the median CD4+ T cell count was 645 (466-872) cell/mm 3 . The median duration of HIV infection was 25 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) years, and the median CD4+ T cell count at nadir was 233 cell/mm 3 . Almost one out of four (24.1%) individuals had experienced an AIDS event in their past medical history. ...
Article
Full-text available
Background: Clinical trials and real-life studies have granted the efficacy and safety of dolutegravir and lamivudine (DTG/3TC) in naïve and experienced people living with HIV (PLWH), but there are no long-term data in elderly people. We herein describe our real-life cohort of PLWH who were ≥65 years of age (PLWH ≥ 65) who started or were switched to DTG/3TC, single-tablet regimen, or DTG plus 3TC. Methods: We considered laboratory/clinical parameter changes from the baseline to the last follow-up time point available for each person by the paired Wilcoxon test and analyzed factors associated with virological failure (VF) and discontinuation. Results: We included 112 PLWH with a median age of 66 (IQR: 65-70) years, 77.6% males; 84.8% of people had multimorbidity, 34.8% were on polypharmacy, and only 5.4% were naïve to treatment. Reasons to be switched to DTG/3TC were: abacavir removal (38.7%), treatment simplification (33.1%), and PI discontinuation (28.2%). The median treatment durability was 6 (IQR: 5.4-7) years. No significant changes were detected in metabolic, renal, immunological, or cardiovascular biomarkers during follow-up. HIV RNA undetectability was maintained in 104 (92.8%) individuals for whom follow-up evaluation was available. We observed eight discontinuations (two deaths, two VFs, two early intolerances, one significant weight gain, and one switch to long-acting therapy). No factors were significantly associated with VF or discontinuation. Conclusions: This is the first study on DTG/3TC in PLWH ≥ 65 with a follow-up longer than 5 years. DTG/3TC was found to be safe and effective, neutral on metabolic parameters, and with a low discontinuation rate for toxicity or VF.
... 26 One of which is advanced disease stage (AIDS), which has been reported in studies in white population to be significant determinants of MetS. 27 Another study also showed that disease severity indicators, such as the level of CD4 + counts, the duration of diagnosed HIV infection, exposure to ART, and type of regimen used, were strong predictors of MetS in PLHA. 11 However, available evidence regarding the determinants of MetS in PLHA populations is inconsistent and inconclusive. ...
Article
Full-text available
Purpose Scaling up antiretroviral treatment (ART) reduces morbidity and mortality among people living with HIV/AIDS (PLHA). This success is challenged by the constellation of interrelated metabolic disorders such as metabolic syndrome (MetS). Given the changing ART regimens and schedules, increasing patient age and methodological limitations, existing evidence regarding the determinants of MetS remains inconclusive. Therefore, in the current study, we aimed to identify the determinants of MetS in patients receiving ART at a tertiary hospital in central Ethiopia. Patient and Methods We conducted an unmatched case–control study that included 393 patients with a case-to-control ratio of 1 to 2. Data were collected by interviewing patients, reviewing charts, physical examinations, and laboratory testing. The data were entered into Epi-Info version 7.2 and analyzed using SPSS version 26. A binary logistic regression analysis was used to identify the determinants of MetS. The adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to estimate the strength of the association between MetS and its determinants. Statistical significance was set at p-value < 0.05. Results In this study, higher odds of developing MetS were identified among patients aged 40–60 years (AOR 3.75; 95% CI: 1.66–8.49) and those older than 60 years (AOR 6.18; 95% CI: 2.12–17.95) than among those aged < 40 years. Similarly, higher odds were observed among patients who frequently consumed animal source foods than among those who consumed cereals or vegetables (AOR, 1.94; 95% CI, 1.03–3.63), those who had HIV lipodystrophy (AOR 1.73; 95% CI: 1.05–2.86), those who were treated with stavudine (AOR 3.08; 95% CI: 1.89–5.04), and those who were treated with zidovudine (AOR 1.71, 95% CI: 1.02–2.88) compared to their counterparts. Conclusion Older age, diet from animal sources, exposure to zidovudine or stavudine, and the presence of lipodystrophy were independent determinants of MetS.
... Individual characteristics, such as older age, marital status, family history of diabetes, heavy alcohol consumption, higher BMI, higher LDL-C, and higher total cholesterol, were associated with the risk of MetS, and this result was consistent with previous studies [16][17][18]. However, heavy alcohol consumption, family history of diabetes mellitus, higher BMI, and higher total cholesterol levels were cited as risk factors independently associated with MetS after adjusting for possible confounding factors. ...
Article
Full-text available
Introduction The incidence of metabolic syndrome (MetS) in people living with HIV is significantly higher than in people without HIV. MetS is not only a major driver of cardiovascular disease (CVD) but is also closely related to the development of chronic kidney disease (CKD). The aim of this study was to investigate the prevalence of and risk factors for MetS and to further understand the degree of damage to target organs. Methods This was a cross‐sectional descriptive study conducted at Chongqing Public Health Medical Center, China. Information was collected via questionnaire survey, physical examination, and laboratory tests. We used the China Diabetes Society guidelines to define MetS. Pooled cohort equations were calculated to compare CVD risk in the next 10 years in people living with HIV aged ≥40 years with or without MetS. We used Student's t‐test, the chi‐squared test, Fisher's exact test, binary logistic regression, and multiple linear regression in the statistical analysis. Results The study included 979 people living with HIV, including 13 who have experienced CVD, receiving antiretroviral therapy (ART). The median age was 43.0 years, 20.9% were female, and the median ART time was 45.0 months. The prevalence of MetS was 33.9%. The components of MetS criteria were hyperglycaemia (50.4%), hypertriglyceridaemia (48.4%), hypertension (46.8%), low concentrations of high‐density lipoprotein cholesterol (28.2%), and abdominal obesity (25.0%). Higher body mass index (odds ratio [OR] 1.266; 95% confidence interval [CI] 1.203–1.333), higher total cholesterol (OR 1.267; 95% CI 1.011–1.588), high alcohol consumption (OR 1.973; 95% CI 1.009–3.859), and family history of diabetes (OR 1.726; 95% CI 1.075–2.770) were independent risk factors for MetS. Compared with the non‐MetS group, the MetS group had a higher rate of urine albumin (23.8% vs 14.8%, p = 0.001), and the estimated glomerular filtration rate <90 mL/min/1.73 m² (18.37% vs. 12.8%, p = 0.020) and β2‐microglobin (p = 0.004) increased more markedly in the MetS group. Regarding the risk of developing CVD events in the next 10 years, 38.5% of those in the MetS group were at high or very high risk, which was significantly higher than in the non‐MetS group (p < 0.001). In addition, age (p < 0.001) and sex (p = 0.002) are independent risk factors for developing CVD events in the next 10 years. Conclusions The prevalence of MetS in people living with HIV on ART is high in Chongqing, China. Risk factors for the development of MetS are high alcohol consumption, family history of diabetes, higher body mass index, and higher total cholesterol levels. In addition, MetS is associated with a risk of CKD and the incidence of 10‐year CVD.
... Since the introduction of antiretroviral treatment (ART), HIV infection has become a chronic condition, and people living with HIV (PWH) could have life expectancies close to those of the general population [1,2]. This implies that PWH are becoming older, with an increase in the comorbidity burden that HIV specialists have to manage [3][4][5][6][7][8][9][10][11][12]. However, despite ART, many people do not have a complete CD4 recovery [13][14][15][16], and PWH with low CD4 cell count have an estimated life expectancy of 30 years lower than the general population [1]. ...
Article
Full-text available
After 40 years of its appearance, human immunodeficiency virus (HIV) infection remains a leading public health challenge worldwide. Since the introduction of antiretroviral treatment (ART), HIV infection has become a chronic condition, and people living with HIV could have life expectancies close to those of the general population. People with HIV often have an increased risk of infection or experience more severe morbidity following exposure to vaccine-preventable diseases. Nowadays, several vaccines are available against bacteria and viruses. However, national and international vaccination guidelines for people with HIV are heterogeneous, and not every vaccine is included. For these reasons, we aimed to perform a narrative review about the vaccinations available for adults living with HIV, reporting the most updated studies performed for each vaccine among this population. We performed a comprehensive literature search through electronic databases (Pubmed—MEDLINE and Embase) and search engines (Google Scholar). We included English peer-reviewed publications (articles and reviews) on HIV and vaccination. Despite widespread use and guideline recommendations, few vaccine trials have been conducted in people with HIV. In addition, not all vaccines are recommended for people with HIV, especially for those with low CD4 cells count. Clinicians should carefully collect the history of vaccinations and patients’ acceptance and preferences and regularly check the presence of antibodies for vaccine-preventable pathogens.
... Third, although INSTI drugs, particularly DTG, showed better efficacy, safety and durability compared to PI drugs in improving lipid profiles [5,36,37], we did not evaluate metabolic and cardiological toxicities linked to this drug class [22,38]. These adverse events need to be evaluated in the near future by larger studies, in order to implement educational and multidimensional interventions to prevent metabolic alterations in PLWH, especially for those with particular risk factors such as alcohol abuse, osteoporosis, previous AIDS events, and polypharmacy [39]. Further, we did not assess changes of specific drugs in the study regimens, types of drugs in the regimens to which the participants were switched, or the outcome of these regimens after the switch; more studies are needed to address these points. ...
Article
Full-text available
Background: Dolutegravir (DTG) is recommended by international guidelines as a main component of an optimal initial regimen of cART (combination antiretroviral treatment) in people living with HIV (PLWH) and in case of switching for failure or optimization strategies. However, studies on the performance of DTG-containing regimens and indications for switching therapies in the long term are sparse. The purpose of this study was to evaluate prospectively the performance of DTG-based regimens, using the metrics of “efficacy”, “safety”, “convenience” and ‘’durability”, among a nationally representative cohort of PLWH in Italy. Methods: We selected all PLWH in four centers of the MaSTER cohort who initiated a DTG-based regimen either when naïve or following a regimen switch between 11 July 2018 and 2 July 2021. Participants were followed until the outcomes were recorded or until the end of the study on 4 August 2022, whichever occurred first. Interruption was reported even when a participant switched to another DTG-containing regimen. Survival regression models were fitted to evaluate associations between therapy performance and age, sex, nationality, risk of HIV transmission, HIV RNA suppression status, CD4+ T-cell count, year of HIV diagnosis, cART status (naïve or experienced), cART backbone and viral hepatitis coinfection. Results: There were 371 participants in our cohort who initiated a DTG-based cART regimen in the time frame of the study. The population was predominantly male (75.2%), of Italian nationality (83.3%), with a history of cART use (80.9%), and the majority initiated a DTG-based regimen following a switch strategy in 2019 (80.1%). Median age was 53 years (interquartile range (IQR): 45–58). Prior cART regimen was based mostly on a combination of NRTI drugs plus a PI-boosted drug (34.2%), followed by a combination of NRTIs plus an NNRTI (23.5%). Concerning the NRTI backbone, the majority comprised 3TC plus ABC (34.5%), followed by 3TC alone (28.6%). The most reported transmission risk factor was heterosexual intercourse (44.2%). Total interruptions of the first DTG-based regimen were registered in 58 (15.6%) participants. The most frequent reason for interruption was due to cART simplification strategies, which accounted for 52%. Only 1 death was reported during the study period. The median time of total follow-up was 556 days (IQR: 316.5–722.5). Risk factors for poor performance of DTG-containing-regimens were found to be: a backbone regimen containing tenofovir, being cART naïve, having detectable HIV RNA at baseline, FIB-4 score above 3.25 and having a cancer diagnosis. By contrast, protective factors were found to be: higher CD4+ T-cell counts and higher CD4/CD8 ratio at baseline. Conclusion: DTG-based regimens were used mainly as a switching therapy in our cohort of PLWH who had undetectable HIV RNA and a good immune status. In this type of population, the durability of DTG-based regimens was maintained in 84.4% of participants with a modest incidence of interruptions mostly due to cART simplification strategies. The results of this prospective real-life study confirm the apparent low risk of changing DTG-containing regimens due to virological failure. They may also help physicians to identify people with increased risk of interruption for different reasons, suggesting targeted medical interventions.
... In the last EACS guidelines, INSTIs represent the preferred class for first-line therapy and as an option for optimization in experienced PWH due to their high efficacy, genetic barrier, and tolerability [12,13,[17][18][19][20][21][22]. However, in the last few years, the scientific community focused on this class's possible role in weight gain, particularly dolutegravir (DTG) [11,21,23,24]. Regarding Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI), only rilpivirine (RPV) and doravirine (DOR) are recommended by EACS guidelines, thanks to their excellent efficacy and safety [14,[25][26][27][28]. ...
Article
Full-text available
In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the last 20 years. We merged data of eight cohorts of the SCOLTA project: lopinavir/r (LPV), atazanavir/r (ATV), darunavir/r or /c (DRV), rilpivirine (RPV), raltegravir (RAL), elvitegravir/c (EVG), dolutegravir (DTG) and bictegravir (BIC). We included 4405 people with HIV (PWH). Overall, 664 (15.1%), 489 (11.1%), and 271 (6.2%) PWH interrupted the treatment in the first, second, and third years after starting a new ART. Looking at the interruption in the first year, the most frequent causes were adverse events (3.8%), loss to follow-up (3.7%), patients’ decisions (2.6%), treatment failure (1.7%), and simplification (1.3%). In the multivariate analysis regarding experienced patients, treatment with LPV, ATV, RPV or EVG/c, having less than 250 CD4 cells/mL, history of intravenous drug use, and HCV positivity were associated with an increased risk of interruption. In naive people, only LPV/r was associated with an increased risk of interruption, while RPV was associated with a lower risk. In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in the first year of ART (3.84%). Treatment discontinuations were more frequent during the first year of follow-up and decreased thereafter. First-generation PI in both naïve and experienced PWH, and EVG/c, in experienced PWH, were associated with a higher risk of treatment interruptions.
Article
Full-text available
Background: Cardiometabolic health has become crucial, especially for women with HIV (WWH). We assessed the achievement of targets for hypertension, dyslipidemia, and diabetes (H/Dy/DT) in primary prevention in a WWH cohort. Methods: Cross-sectional analysis including all WWH in our clinic, excluding those who had a myocardial infarction. H/Dy/DT achievement was assessed by both EACS guidelines and individual cardiovascular risk, CVR (measured by ESC calculator), using logistic regression to evaluate differences in H/Dy/DT achievement between migrant and Italian women. Results: We included 292 WWH, 55.5% Italian and 44.5% migrant women; the median age was 50 (IQR:42–58) years, 94.5% had undetectable HIV-RNA, 55.1% had a high level of education, 27.1% were smokers, and 19.2% did regularly physical exercise. Overall, 76%, 19%, and 5% of women presented a low, a high, and a very high CVR, respectively. Among Italians, 28.4% and 6.2% women presented a high and a very high CVR, respectively. Considering migrants, 7.7% and 3.8% women presented a high and a very high CVR, respectively. Overall, among migrant women, those with a high CVR were more likely to be not at target than those with a low risk (especially for LDL-c and blood pressure among people on treatment), despite the fact that we did not detect a statistically significant difference. By contrast, migrants were more likely to achieve glycemic targets than Italians (p = 0.032). Conclusions: H/Dy/DT target achievement is suboptimal, especially in migrants. A more aggressive pharmacological treatment, also assessing adherence to medical prescriptions, and promotion of healthy lifestyle should be urgently implemented, possibly redrawing the current model of care.
Article
Background People with HIV (PWH) may be at risk for more severe COVID-19 outcomes. We compared risk for severe COVID-19 in PWH with matched individuals without HIV. Methods We identified adults in Massachusetts with a positive SARS-CoV-2 test, March 2020–July 2022, using electronic medical record data from 3 large clinical practice groups. We then used regression models to compare outcomes among PWH versus propensity score–matched people without HIV (matched 20:1) for severe COVID-19 (pneumonia or acute respiratory distress syndrome), hospitalization, and hospital length of stay. Results We identified 171,058 individuals with COVID-19; among them, 768 PWH were matched to 15,360 individuals without HIV. Overall, severe COVID-19 and hospitalization were similar in PWH and those without HIV (severe COVID-19: 3.8% vs 3.0%, adjusted odds ratio [OR] 1.27, 95% confidence interval [CI]: 0.86–1.87; hospitalization: 12.1% vs 11.3%, adjusted OR: 1.08, 95% CI: 0.87 to 1.35). Compared with people without HIV, PWH with low CD4 T-cell counts (<200 cells/mm ³ ) had more severe COVID-19 (adjusted OR: 3.99, 95% CI: 2.06 to 7.74) and hospitalization (adjusted OR: 2.26, 95% CI: 1.35 to 3.80), but PWH with high CD4 counts had lower odds of hospitalization (adjusted OR: 0.73, 95% CI: 0.52 to 1.03). Conclusions PWH with low CD4 T-cell counts had worse COVID-19 outcomes compared with people without HIV, but outcomes for those with high CD4 counts were similar to, or better than, those without HIV. It is unclear whether these findings are generalizable to settings where PWH have less access to and engagement with health care.
Article
Full-text available
Objectives The aim of this study was to assess the incidence of being overweight and metabolic syndrome (MS) among people living with HIV (PHIV) in three different cross‐sectional studies conducted over three different periods: 2005, 2011 and 2015. Methods This was a multi‐centre, nationwide study. Data were collected in three studies from the CISAI group – SIMOne, HIV‐HY and STOPSHIV – and included a total of 3014 PHIV. Logistic regression [odds ratio (OR), 95% confidence interval (CI)] was used to account for age and gender difference among three groups when comparing MS prevalence and being overweight; potential confounders were accounted for by including them in the regression equation. Results Overall, the mean age was 46.9 ± 10.2 years, and men comprised 73.3% of participants. Comparing 2005, 2011 and 2015, MS was present in 34.5%, 33.0% and 29.3% of PHIV, respectively. Adjusted OR for MS was 0.64 (95% CI: 0.52–0.78) in 2011 and 0.56 (95% CI: 0.46–0.69) in 2015 compared with 2005, while BMI (kg/m²) increased from 23.6 in 2005, 24.5 in 2011 and 24.5 in 2015, with a concomitant increase of being overweight from 29.4% to 39.5% to 39.6% (p < 0.0001). Conclusions In recent years, PHIV have had a significantly improved metabolic profile compared with previously, despite increasing weight and BMI.
Article
Full-text available
Objective and design: People living with HIV (PLH) suffer disproportionately from the chronic diseases exacerbated by smoking tobacco. We performed a systematic review and meta-analysis to establish the relative prevalence of smoking among PLH. Methods: We included observational studies reporting current smoking rates among PLH and comparators without HIV. We searched Medline, EMBASE, LILACS and SciELO from inception to 31 August 19. We excluded studies that recruited participants with smoking related illness. We used a random effects model to estimate the odds ratio for current smoking in PLH and people without HIV. We used the Newcastle--Ottawa scale to assess methodological bias. We performed subgroup analysis based on sex and WHO region. We quantified heterogeneity with meta-regression and predictive distributions. PROSPERO registration:CRD42016052608. Results: We identified 6116 studies and included 37. Of 111 258 PLH compared with 10 961 217 HIV-negative participants pooled odds of smoking were 1.64 [(95% confidence interval, 95% CI: 1.45-1.85) (95% prediction interval: 0.66-4.10, I2 = 98.1%)]. Odds for men and women living with HIV were 1.68 [(95% CI: 1.44-1.95) (95% prediction interval: 0.71-3.98, I2 = 91.1%)] and 2.16 [(95% CI: 1.77-2.63) (95% prediction interval: 0.92-5.07, I2 = 81.7%)] respectively. Conclusion: PLH are more likely to be smokers than people without HIV. This finding was true in subgroup analyses of men, women and in four of five WHO regions from which data were available. Meta-regression did not explain heterogeneity, which we attribute to the diversity of PLH populations worldwide. Smoking is a barrier to PLH achieving parity in life expectancy and an important covariate in studies of HIV-associated multimorbidity.
Article
Full-text available
Objectives As people living with HIV (PLHIV) age, the burden of non-HIV related comorbidities increases resulting in additional healthcare costs. The present study aimed to describe the profile, the prevalence and the incremental costs of non-HIV related comorbidities in PLHIV compared to non-HIV matched controls (1:2 ratio) in France.Methods The French permanent sample of health beneficiaries (Echantillon généraliste de bénéficiaires [EGB]), a claims database representative of the national population, was used to assess comorbidities in PLHIV which were identified by the ICD-10 diagnosis codes of hospitalization, full healthcare coverage, and drug reimbursements between 2011 and 2014. The control group was matched by year of birth, gender, region of residence, and economic status. Total costs of outpatient care and hospitalizations were analysed from a societal perspective. A general linear model was used to assess the incremental cost per patient in PLHIV.ResultsA total of 1,091 PLHIV and 2,181 matched controls were identified with a mean ± standard deviation age of 46.7 ± 11.5 years. The prevalence of alcohol abuse (5.8% vs 3.1%; p
Article
Full-text available
Background The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management. Methods The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment. Results 2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the “high” or “very high” risk groups of the disease risk scores for CKD, CVE and bone fracture score. Conclusions Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.
Article
Full-text available
Background Although combined antiretroviral therapy has substantially improved the prognosis of people living with HIV (PLHIV), mortality remains higher compared to the general population, mainly due to higher prevalence of non-HIV-related comorbidities, including cardiovascular diseases (CVD). We assessed the prevalence of CVD risk and its contributing factors in adult PLHIV versus general population controls in Greece. Settings Cross-sectional comparison of PLHIV (Athens-Multicenter-AIDS-Cohort-Study; AMACS) versus general population controls (National health examination survey; EMENO). Methods All HIV-infected adults with ≥1 measurement of interest (blood pressure, lipids, glucose, weight, height) between 2012–2014 and all EMENO participants (2014–2016) were included. Ten-year total CVD risk was estimated using the Framingham (FRS) or the Systematic Coronary Risk Evaluation (SCORE) equations. Results 5839 PLHIV (median age:41.6 years, 85.4% males) and 4820 controls (median age:48 years, 48.4% males) were included. Adjusting for age, sex and origin, PLHIV were more likely to be current smokers (adjusted OR:1.53 [95% CI:1.35–1.74]) and dyslipidemic (aOR:1.18; [1.04–1.34]), less likely to be obese (aOR:0.44 [0.38–0.52], with no differences in hypertension, diabetes or high (≥20%) FRS but with greater odds of high (≥5%) SCORE (aOR:1.55 [1.05–2.30]). Further adjustment for educational level, anti-HCV positivity and BMI showed higher prevalence of hypertension in PLHIV. Conclusions Despite the relative absence of obesity, PLHIV have higher prevalence of traditional CVD risk factors and higher risk of fatal CVD compared to general population. Regular screening and early management of CVD risk factors in PLHIV should be of high priority for CVD prevention.
Article
Full-text available
Background: Alcohol use disorder (AUD) is common among people living with HIV/AIDS (PLWHA) and associated with a greater risk of poor medication adherence, unsafe sexual behaviors as well as poor quality of life. To our knowledge,there is no previous systematic review and meta-analysis that reported the pooled prevalence estimate of AUD among PLWHA. Therefore, this review aimed to systematically review the available studies on the prevalence of AUD among PLWHA and forward possible recommendations for future clinical practice and research. Methods: PubMed, EMBASE, Psych INFO and SCOPUS databases were searched to identify the relevant studies. We have also scanned the reference lists of the eligible studies to supplement our electronic search. We used the Comprehensive Meta-analysis software versions 3.0 to conduct a meta-analysis. Subgroup and sensitivity analysis were performed and Cochran’s Q- and the I2- test were employed to see the heterogeneity. The presence of publication bias was explored by utilizing Egger’s test and visual inspection of the symmetry in funnel plots. Results: A total of 25 studies with 25,154 participants across developed and developing countries were included in the final analysis. Our meta-analysis revealed that the pooled prevalence estimate of AUD among PLWHA was found to be 29.80% (95% CI; 24.10–35.76). The prevalence of AUD was higher in males (26.90%) than female (13.37%) HIV patients. In this study, the pooled prevalence of AUD was considerably higher (31.52%) when measured by Alcohol Use Disorders Identification Test (AUDIT) as compared to Composite International Diagnostic Interview (CIDI) (13.51%). In addition, the pooled prevalence of AUD was higher in the developed countries (42.09%) while lower for developing countries (24.52%). Conclusion: n the current study, the pooled prevalence estimates of AUD among PLWHA was considerably high(29.80%). Screening and appropriate management of AUD among PLWHA are recommended.
Article
Full-text available
Introduction: Antiretroviral therapy (ART) has changed the course of HIV/AIDs by enabling patients to live longer, raising concern of the co- existence of HIV with other chronic illnesses, notably non-communicable diseases (NCDs). NCDs are on the rise in developing countries and evidence shows higher occurrence among people living with HIV (PLHIV). In Uganda, the burden of NCDs among PLHIV remains largely unquantified. Objective: To determine the prevalence of hypertension, osteoporosis, diabetes mellitus, renal impairment, asthma, cardiomyopathy and multi-morbidity among HIV positive patients, receiving Anti-Retroviral Therapy at Joint Clinical Research Centre, Lubowa, Uganda. Methods: This was a cross-sectional study conducted among 387 systematically sampled patients, receiving ART at the Joint Clinical Research Centre, Lubowa, between March and April 2017. The study used data extracted from routine care patient files to identify individuals with non-communicable diseases. Prevalence of the NCDs was estimated and reported with 95% confidence intervals. Prevalence was also reported at various levels of socio- demographic, behavioural and clinical factors. Results: The overall prevalence of having at least one NCD was 20.7% (95% CI: 16.7-24.5). The prevalence of hypertension was 12.4% (95% CI: 9.1-15.7), osteoporosis 6.5% (95% CI: 4.0-8.9), diabetes mellitus 4.7% (95% CI: 2.6-6.8), renal impairment 1.6% (95% CI: 0.3-2.8), asthma 1.6% (95% CI: 0.3-2.8), and cardiomyopathy 1.3% (95% CI: 0.2-2.4). Prevalence of multi-morbidity was 4.7% (95% CI: 2.6-6.8). Prevalence was significantly higher among older participants, widowed participants and individuals with an opportunistic infection. Conclusion: Non-communicable diseases are common among people living with HIV. There is need to encourage early diagnosis and treatment of non-communicable diseases in PLHIV in Uganda.
Article
Successful management of HIV infection as a chronic condition has resulted in a demographic shift where the proportion of people living with HIV (PLWH) older than 50 years is steadily increasing. A dedicated clinic to PLWH older than 50 years was established at Chelsea and Westminster Hospital in January 2009 and then extended to HIV services across the directorate. We report the results of a service evaluation reviewing 10 years of activities of this clinic between January 2009 and 2019. We aimed to estimate the prevalence of major noninfectious comorbidities, polypharmacy (≥5 medications), and multimorbidity (≥2 non-HIV-related comorbidities) and describe algorithms devised for use in HIV outpatient clinics across the directorate. A cohort of 744 PLWH older than 50 years attending this service were analyzed (93% male; mean age of 56 ± 5.5 years; 84% white ethnicity); 97.7% were on antiretroviral treatment and 95.9% had undetectable HIV-RNA at the time of evaluation. The most common comorbidities diagnosed were dyslipidemia (50.1%), hypertension (21.5%), mental health disorders (depression and/or anxiety disorders, 15.7%), osteoporosis (12.2%), obesity (11.9%), chronic kidney disease (7.5%), and diabetes (5.8%). Low vitamin D levels were found in 62% of patients [43% with vitamin D deficiency (<40 mmol/liter) and 57% with vitamin D insufficiency (40-70 mmol/liter)]. The overall prevalence of polypharmacy and multimorbidity was 46.6% and 69.3%, respectively. This study showed significant rates of non-HIV-related comorbidities and polypharmacy in PLWH older than 50 years, leading on to the implementation of clinical care pathways and new joint HIV/specialty clinics (cardiology, nephrology, neurology, metabolic, menopause, and geriatric) to improve prevention, diagnosis, and management of major comorbidities in people aging with HIV.
Article
Objective To assess the differences in healthy, environmentally sustainable and safe food consumption by education levels among adults aged 19–69 in the Netherlands. Design This study used data from the Dutch National Food Consumption Survey 2007–10. Food consumption data were obtained via two 24-h recalls. Food consumption data were linked to data on food composition, greenhouse gas emissions (GHGe) and concentrations of contaminants. The Dutch dietary guidelines (2015), dietary GHGe and dietary exposure to contaminants were used as indicators for healthy, environmentally sustainable and safe food consumption, respectively. Setting The Netherlands. Participants 2106 adults aged 19–69 years. Results High education groups consumed significantly more fruit (+28 g), vegetables (men +22 g; women +27 g) and fish (men +6 g; women +7 g), and significantly less meat (men –33 g; women –14 g) compared with low education groups. Overall, no educational differences were found in total GHGe, although its food sources differed. Exposure to contaminants showed some differences between education groups. Conclusions The consumption patterns differed by education groups, resulting in a more healthy diet, but equally environmentally sustainable diet among high compared with low education groups. Exposure to food contaminants differed between education groups, but was not above safe levels, except for acrylamide and aflatoxin B1. For these substances, a health risk could not be excluded for all education groups. These insights may be used in policy measures focusing on the improvement of a healthy diet for all.
Article
: As a consequence of ageing, the number of prescribed medications for people living with HIV (PLWH) is increasing. Concomitant use of different drugs and their potential interactions may increase anticholinergic exposure and escalate the risk for side effects. We conducted an analysis in our cohort of PLWH over 50 years of age to evaluate the overall anticholinergic risk, as it is useful to identify, prevent, and manage increased side effect risks.