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Original research article
Influence of nutritional status and
gastrointestinal symptoms on sleep
quality in people living with HIV
Luciana Fidalgo Ramos Nogueira
1
, Thais Carvalho da Fonseca
1
,
Patrick Herman Paterlini
1
, Adriana de Sousa Duarte
1
,
Pollyanna Pellegrino
1
, Claudia Renata dos Santos Barros
1
,
Claudia Roberta de Castro Moreno
2
and
Elaine Cristina Marqueze
1
Abstract
Sleep problems are frequent among people living with HIV (PLWH). Recent studies have found that inadequate
nutritional status and presence of gastrointestinal symptoms are associated with sleep problems. Therefore, the objec-
tive of the present study was to evaluate the influence of nutritional status and gastrointestinal symptoms on sleep
quality in PLWH receiving antiretroviral therapy (ART). A cross-sectional study evaluating the influence of nutritional and
gastrointestinal aspects on the quality of sleep in 307 PLWH (age 18 years) receiving ART seen at the Specialized Care
Service of Santos (SP, Brazil) was carried out. The Pittsburgh Sleep Quality Index (PSQI), body mass index and three
questions from the Self-Reporting Questionnaire (SRQ-20) were used. Generalized linear models adjusted for gender,
age, time in use of antiretrovirals, viral load, CD4þT-lymphocyte cell count and CD4/CD8 ratio were built. Results
showed that body mass index did not affect sleep quality. However, the interaction between poor appetite and not
having poor digestion and uncomfortable feelings in the stomach negatively influenced sleep quality. The interaction of
the three symptoms evaluated also affected sleep quality. Gastrointestinal symptoms were associated with reduced sleep
quality, but there was no influence of BMI. Although the etiology of this relationship is unclear, there seems to be an
important association between sleep quality, immune function and gastrointestinal disorders.
Keywords
Human immunodeficiency virus, sleep-wake disorders, nutritional status, gastrointestinal tract
Date received: 1 November 2018; Revised received 3 April 2019; accepted: 4 April 2019
Introduction
Of the 36.7 million people worldwide living with HIV
in 2016, 53% were on antiretroviral therapy (ART).
In Brazil, also in 2016, despite the free distribution of
medications for HIV treatment by the Unified Health
System (SUS) since 1996, only 62% of the 649,000
people living with HIV (PLWH) were on ART.
1
Among the factors related to the prevalence of ART
use are its adverse effects, which cause physical and
metabolic changes that have been described as risk fac-
tors for chronic diseases.
2
Unlike in the era before
ART, when opportunistic infections were the main
cause of death of PLWH, this population currently
has a higher prevalence of cardiovascular diseases,
dyslipidemias, diabetes and non-AIDS cancers, when
compared to the general population.
3
These changes
also include inadequacy of nutritional status and
1
Department of Epidemiology, Public Health Graduate Program, Catholic
University of Santos, S~
ao Paulo, Brazil
2
Department of Health, Life Cycles and Society, School of Public Health,
University of S~
ao Paulo, S~
ao Paulo, Brazil
Corresponding author:
Elaine Cristina Marqueze, Department of Epidemiology, Public Health
Graduate Program, Catholic University of Santos, 300 Conselheiro
Ne
´bias Avenue, Santos, S~
ao Paulo 11015-001, Brazil.
Email: elaine.marqueze@unisantos.br
International Journal of STD & AIDS
0(0) 1–6
!The Author(s) 2019
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/0956462419846723
journals.sagepub.com/home/std
gastrointestinal symptoms which, in turn, are associat-
ed with poor adherence to ART and HIV progression
to AIDS.
4
With regard to nutritional status, inadequacy is
associated with the pro-inflammatory environment of
HIV infection. Currently, the most important altera-
tions in PLWH are being overweight and obesity.
5
Gastrointestinal symptoms, as well as being overweight
and obesity, may be associated with the occurrence of
sleep problems among adults living with HIV.
Difficulties falling asleep and daytime sleepiness are
the main complaints reported, and both of these prob-
lems persist even in situations of viral replica-
tion control.
6
Sleep architecture is organized in cycles in which
NREM (non-rapid eye movement) and REM (rapid
eye movement) stages alternate successively and
repeat five to seven times per sleep session.
7
This orga-
nization, however, can be altered by factors such as
diseases and medication use, impairing cognitive capac-
ity, memory consolidation and immune function.
9
It is noteworthy that the presence of sleep disorders
is associated not only with chronic diseases, but also
with risk factors for their development, such as smok-
ing, alcoholism and inadequate eating habits.
10
In addi-
tion, it is a bidirectional relationship, since chronic
diseases may cause changes in the sleep-wake cycle,
with consequent impacts on physical and mental recov-
ery. Thus, the presence of gastrointestinal symptoms
and changes in body weight are also strongly associated
with poor sleep quality.
6
PLWH experience significant changes in sleep
patterns after infection, especially reduction in total
sleep time, increased sleep fragmentation due to fre-
quent awakenings, increased latency and poor sleep
quality.
11,12
These modifications may occur due to
pain, gastrointestinal disorders and respiratory prob-
lems.
13
In a systematic review performed by Low
et al.,
14
prevalence of poor sleep quality in PLWH
ranged from 29 to 97%, much higher than the 33%
prevalence estimated for the general population. This
broad range was due to the different evaluation meth-
ods, which ranged from subjective questionnaires to
polysomnography. However, many of the studies that
evaluated the occurrence of sleep problems among
PLWH were carried out more than 10 years ago, with
different ART regimens.
15
Therefore, the objective of the present study was to
evaluate the influence of nutritional status and gastroin-
testinal symptoms on sleep quality in PLWH on ART.
Methods
The study population consisted of 2000 PLWH on
ART aged 18 years, seen at the Specialized Care
Service (SAE) in the city of Santos (SP, Brazil) in
2014. The sample was calculated in 2014, the year in
which the proposal was submitted to the funding
agency. The data collection took place in 2016, after
approval of both the proposal and the project by the
ethics committee.
Based on a prevalence of poor sleep quality of 29%,
a generalized linear model test with a significance level
of 5%, sample error of 0.05 and assuming variations of
5% and loss of 10%, the selected sample comprised
322 patients (G*Power). Fifteen questionnaires, which
were either incomplete or inconsistent, were excluded,
giving a final sample of 307 PLWH.
The questionnaire was applied between February
and June 2016 in the form of an interview conducted
by trained graduate students. Data for the biochemical
indicators were obtained from the Control System for
Laboratory Tests of CD4/CD8 and Viral Load (Siscel,
a computer system managed by the Ministry of
Health). Only the results of the exams closest to the
interview date of each participant were used, and the
range of time did not exceed six months. This range
was established based on the Clinical Protocol and
Therapeutic Guidelines for Management of HIV
Infection in Adults,
13
which recommends that the bio-
chemical indicators for monitoring PLWH in clinical
follow-up should be performed every six months.
The dependent variable was sleep quality, assessed
by the validated Brazilian Portuguese version of the
Pittsburgh Sleep Quality Index (PSQI). Individuals
who obtained a global PSQI >5 were classified as
having poor sleep quality.
16
The independent variables were nutritional status
and gastrointestinal symptoms. Nutritional status was
assessed by the body mass index (BMI), obtained from
self-reported weight and height. It is important to
emphasize that the participants were interviewed on
the same day as their monthly medical visit at the
SAE, and that their weight was also measured. These
measures are considered valid and accurate for cross-
sectional epidemiological studies.
17
BMI score was
classified as underweight (<18.5 kg/m
2
), normal
(18.5–24.9 kg/m
2
), overweight (25.0–29.9 kg/m
2
)or
obese (30.0 kg/m
2
).
18
Gastrointestinal symptoms were assessed by three
questions taken from the validated version of the
Self-Reporting Questionnaire (SRQ-20).
19
The ques-
tions were: “Do you have uncomfortable feelings in
the stomach?”, “Do you have poor appetite?” and
“Do you have poor digestion?”
The normality of the variables was tested by the
Shapiro–Wilk test. The internal consistency and reli-
ability of the PSQI were determined by Cronbach’s
Alpha (p ¼0.70). Initially, the generalized linear
model (GLM) was built to evaluate the relationship
2International Journal of STD & AIDS 0(0)
between sleep quality and each independent variable
(BMI, uncomfortable feelings in the stomach, poor
appetite and poor digestion). Subsequently, a multiple
model was constructed that included only statistically
significant independent variables (p <0.05). All models
used gender, age, time in use of ART, viral load quan-
tification, CD4 lymphocyte cell count and CD4/CD8
ratio as covariates. The significance level for all tests
was 5%. Statistical analyses were performed using the
Statistica 7.0 and Stata 12.0 software packages.
Ethical issues related to human research were fully
respected and participants provided written informed
consent. The study was authorized by the Municipal
Health Department of Santos and approved by the
Research Ethics Committee of the Catholic
University of Santos (number 1.237.142).
Results
Participants had a mean age of 48 years (SD 12.1 years)
and 52.4% were female. Regarding gender, 59.4%
identified themselves as women. Most subjects had con-
cluded high school (50.5%), had no partner (73.0%)
and no paid work activity (60.3%). Mean time since
HIV diagnosis was 12.9 years (SD 8.1 years) and 95.8%
were on ART for an average of 9.4 years (SD
7.6 years). Concerning biochemical indicators, 71.4%
had undetectable viral load (<50 copies/mL), 89.7%
had CD4 lymphocyte cell count 200 cells/mm
3
and
73.3% had CD4/CD8 ratio <1.0.
Of the total number of participants, 49.5% had poor
sleep quality. Regarding gastrointestinal symptoms,
32.8% reported uncomfortable feelings in the stomach,
30.6% had poor appetite and 23.4% poor digestion.
Almost a third of the sample was classified as overweight
(30.5%), and 14.3% as obese. Only 20.7% reported
changes in body weight after HIV diagnosis. Of these,
14.5% reported a median loss of 12.5 kg (IQR 8.5–
20.0 kg) and 5.6% had a median gain of 11.0 kg (IQR
5.0–19.0 kg). However, 47.1% reported weight changes
over the preceding 12 months, of which 30.3% had a
median loss of 6.0 kg (IQR 3.0–12.0 kg) and 16.8% had
a median gain of 6.0 kg (IQR 3.0–12.0 kg).
Nutritional status did not influence sleep quality
(F ¼1.404 and p ¼0.237). By contrast, all three gastro-
intestinal symptoms negatively influenced sleep quality
(Figure 1). The multiple model revealed an interaction
effect between poor appetite and poor digestion on
those who had poor sleep quality (Figure 2(a)), and
between poor appetite and uncomfortable feelings in
the stomach, on poor sleep quality (Figure 2(b)).
(a) (b)
(c)
F=32.467 p< 0.001
Vertical bars represent 95 % CI
seYoN
Poor appetite
-5
0
5
10
15
PSQI score
F=8.4973 p= 0.004
Verti cal bars repres ent 95% C I
seYoN
Poor digestion
-5
0
5
10
15
PSQI sco re
F=18.385 p< 0.001
Vertical bars represent 95% CI
seYoN
Uncomf ort able feelin
g
s in the stomach
-5
0
5
10
15
PSQI score
Figure 1. Generalized linear models of gastrointestinal symptoms and sleep quality of PLWH. (a) 䊏; (b) 䊏; (c) 䊏.
Nogueira et al. 3
F=4.8575 p= 0.028
Vertical bars rep resent 9 5% CI
Poor digestion: no
Poor digestion: yes
seYoN
Poor app etite
-5
0
5
10
15
PSQI score
F=4.8606 p= 0.028
Vertical bars represent 95% CI
Uncomfortable feelings inthestomach: no
Uncomfort able feelings in the st omach: y es
seYoN
Poor appetite
-5
0
5
10
15
PSQI score
F=0.4450 p =0.505
Verti cal b ars repr esent 95% C I
Uncomfortable feelings in the stomach: no
Uncomfortable feelings in the stomach: yes
seYoN
Poor digestion
-5
0
5
10
15
PSQI score
F=4.0309 p =0.046
Vertical bars represent 95% CI
Poor digestion: no
Poo r di
g
estion:
y
es
Uncomfortable feelings in the stomach:
no
No Yes
-5
0
5
10
15
PSQI score
Uncomfortable feelings in the stomach:
yes
No Yes
Poor appetite Poor appetite
(a) (b)
(c)
(d)
Figure 2. Multiple model of gastrointestinal symptoms and sleep quality of PLWH. (a) 䊏; (b) 䊏; (c) 䊏; (d) 䊏.
4International Journal of STD & AIDS 0(0)
There was no interaction effect of poor digestion and
uncomfortable feelings in the stomach on sleep quality
(Figure 2(c)). In addition, there was an interaction
between poor appetite, uncomfortable feelings in the
stomach and poor digestion, as well as an interaction
between poor appetite, uncomfortable feelings in the
stomach and no poor digestion, on those who had
poor sleep quality (Figure 2(d)).
Discussion
In the present study, regardless of gender, age,
time in use of ART, viral load quantification, CD4
T-lymphocyte cell count or CD4/CD8 ratio, the pres-
ence of gastrointestinal symptoms was associated with
worse sleep quality in PLWH. Although the etiology of
this relationship is not yet fully understood, there seems
to be an important association between sleep, immune
function and gastrointestinal disorders.
20
Persistent
inflammation, which is caused by HIV and can also
be induced by long-term use of ART, promotes chronic
activation of the immune system. One of the mecha-
nisms involved in this process is the homeostatic imbal-
ance of lymphoid tissue associated with the intestine.
4
Although the present study did not observe differences
related to the immune system and time in use of ART,
it is important to emphasize that sleep problems regu-
late and are regulated by cytokines which contribute to
chronic inflammation and, consequently, to gastroin-
testinal tract impairment.
21
No previous studies associating nutritional status
with sleep quality in this population were found.
However, in the study conducted by Lee et al.
22
inves-
tigating sleep problems in adults living with HIV,
no association was found between sleep fragmentation
and anthropometry. This result suggests, according to
the authors, that factors other than body weight may
play a more critical role in determining the sleep quality
in PLWH, as evidenced in the present study.
In the current HIV epidemic situation, however, it is
noteworthy that being overweight and obesity repre-
sent the main nutritional status among PLWH.
5
Furthermore, previous studies found similar prevalence
of being overweight and obesity both among ART-
naı
¨ve and PLWH who had been on treatment for
more than 10 years.
3,23,24
These data indicate that its
development can be accelerated and exacerbated by
factors independent of ART, which include inadequate
lifestyle and poor sleep quality.
4,25
The results of the present study are corroborated by
other authors who report a high prevalence of poor
sleep quality,
6,11,26,27
being overweight and greater pre-
disposition to the development of gastrointestinal
symptoms in PLWH.
5,28
Since the advent of ART, HIV infection has
assumed the characteristics of a chronic disease.
Complex life changes, imposed by both the disease
and the treatment, highlight the importance of non-
pharmacological interventions as an integral part of
the clinical follow-up of PLWH. Gastrointestinal dis-
orders and sleep problems in this population are often
underdiagnosed and inadequately treated. In this con-
text, comprehensive healthcare and sleep assessment by
specialized care services can contribute significantly to
better clinical outcomes.
Conclusion
Gastrointestinal symptoms were associated with
reduced sleep quality, but there was no influence of
BMI. The results highlight the importance of complete
nutritional assessment of PLWH which, in addition to
determining nutritional status, should also include
counseling for gastrointestinal symptoms reported by
patients. These measures can contribute more effective-
ly to the prevention and treatment of adverse effects
associated with HIV infection and ART, and conse-
quently promote better sleep and quality of life in
this population.
Acknowledgements
The authors extend thanks to the Municipal Health
Department of Santos – Department of Surveillance –
Coordination of Control of Infectious Diseases, for support-
ing the research, and to all the volunteers who participated in
the study for their valuable contribution.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of
this article.
Funding
This study was supported by the National Council for
Scientific and Technological Development – CNPq (grant
number 455046/2014–0).
ORCID iD
Elaine Cristina Marqueze https://orcid.org/0000-0002-
4987-7757
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