World Journal of AIDS, 2011, 1, 182-184
doi:10.4236/wja.2011.14026 Published Online December 2011 (http://www.SciRP.org/journal/wja)
Zinc Status in Virological Controlled Human
Immunodeficiency Virus Type 1 Infected
Patients
Carlos Tornero, Consuelo Lapuebla, Ana Ventura, Julian Diaz, Maricarmen Mafe
Internal Medicine Department and Laboratory, Hospital Gandia, Valencia, Spain.
Received August 1st, 2011; revised September 12th, 2011; accepted September 24th, 2011.
ABSTRACT
Zinc (Zn) is a key micronutrient for correct immune function and its deficiency correction has been shown to be useful
in HIV-infected but most of the studies included a significant proportion of patients without adequate virological con-
trol. It would be interesting to establish the prevalence, associated factors and clinical repercussions of Zn deficiency in
patients with good virological to assessing the usefulness of Zn monitoring in the routine follow-up of well controlled
HIV-infected patients, based on the colorimetric techniques commonly used in daily clinical practice. We included the
first 100 patients that met the requirements of HAART and viremia levels under 200 copies for at least 6 consecutive
months, with no active illicit drug use, active infections or weight loss of any cause during the previous 6 months. Se-
rum Zn concentration was measured using a colorimetric assay (Sentinel Diagnostics®) adapted to the Cobas 8000
analyzer (Roche Diagnostics). The Zn values showed a normal distribution with a mean concentration of 88.7 µg/dl
(SD 23.3) and were found to b e decreased in 13 patients and in 6 subjects were below 61 µg/dl. Both the simple statis-
tical analysis and the multivariate regression model only identified a significant effect for age and alcoho l consumption.
In sum an important number of HIV-infected with effective and prolonged HAART and no evidence of active infections
or other associated factor show diminished serum Zn concentrations. The inclusion of at least occasional Zn determi-
nations should be considered in the regular follow-up evaluations of HIV-infected patients.
Keywords: Zinc, Micronutrients, HAART
1. Introduction
Zinc (Zn) is a key micronutrient for correct immune
function. Zinc deficiency is not uncommon, and its cor-
rection has been shown to be useful in a number of clini-
cal contexts [1]. HIV-infected patients often present Zn
deficiency, and normalization of the levels of this ele-
ment likewise offers benefit for such individuals [2].
However, most of the studies conducted in these subjects
were published before highly active antiretoviral therapy
(HAART) were available, and included a significant
proportion of patients without adequate virological con-
trol, illicit drug users, and patients with active infections
or malnutrition of different origins. It would be interest-
ing to establish the prevalence, associated factors and
clinical repercussions of Zn deficiency in patients with
good virological control and without the aforementioned
factors, with a view to assessing the usefulness of Zn
monitoring in the routine follow-up of well controlled
HIV-infected patients, based on the colorimetric tech-
niques commonly used in daily clinical practice.
2. Material and Methods
The systematic determination of Zn was introduced in all
patients followed-up on in a center specialized in the
management of HIV-infected individuals. We included
the first 100 patients that met the requirements of
HAART and viremia levels under 200 copies for at least
6 consecutive months, with no active illicit drug use,
active infections or weight loss of any cause during the
previous 6 months. Anthropometric data were collected,
together with information relating to alcohol consump-
tion, the presence of diarrhea, lipodystrophy, skin lesions,
nadir and present CD4+ lymphocytes counts, transami-
nases levels and antecedents of decompensated liver cir-
rhosis. A total of 13 4 patients were seen until the planned
00 subjects were recruited (Table 1). 1

Zinc Status in Virological Controlled Human Immunodeficiency Virus Type 1 Infected Patients183
Table 1. Baseline characteristics.
Age, mean years ± SD 44.5 ± 10.05
Sex, % males 64
CD4 cell count, mean years ± SD
Nadir 218.1 ± 172.1
Current 640 ± 357
Alcohol use % participans 13
BMI, mean kg/m2 ± SD 25.3 ± 4.6
Receiving ART and with undetectable viral load (<200 copies/mL) 100%
Serum zinc levels mean mcgr/dl , mean ± SD 88.7 ± 23.3
Serum Zn concentration was measured using a colori-
assay (Sentinel Diagno stics®) adapted to the Cobas 8000
analyzer (Roche Diagnostics). The adult serum reference
values were 66 - 150 µg/dl. The SPSS version 13.0 sta-
tistical package was used to analyze the results, based on
the Student t-test and Mann-Whitney U-test for categ ori-
cal variables and using the Pearson correlation coeffi-
cient for quantitative variables. For the multivariate
analysis we constructed a multivariate regression model
with the Zn concen tratio ns as response variable.
3. Results
The Zn values showed a normal distribution with a mean
concentration of 88.7 µg/dl (SD 23.3). The levels were
found to be decreased in 13 patients (13%; 95% CI 6 -
19), and in 6 subjects were below 61 µg/dl. Both the
simple statistical analysis and the multivariate regression
model only identified a significant effect (R: 0.114, p <
0.01) for age (Cr : 0.15 ; 95% CI 0.04 - 0.25 , p < 0.01) an d
alcohol consumption (Cr: 14.67 ; 95%CI 1.49 - 27.85, p =
0.03), no differences being observed with respect to the
nadir CD4+ lymphocytes count, present CD4+ lympho-
cytes count, body mass index, presence of diarrhea, li-
podystrophy, transaminase elevation or diagnosis of liver
cirrhosis. Zinc replacement therapy or dietary recom-
mendations were provided in these subjects.
4. Comments
Zinc is a microelement obtained mainly from meat and
legumes, and is absorbed in the jejunum and to a lesser
extent in the large bowel, in relation to the plasma levels
reached. Pancreatic enzyme alterations and diarrhea re-
duce Zn absorp tion, though the levels of this element are
also found to be decreased in acute inflammatory proc-
esses, nutritional deficiencies, alcoholism, chronic liver
disease and in intravenous drug abusers [1]. In view of
the relationship between Zn and correct immune function,
this element has been extensively studied in HIV-in-
fected individuals, where Zn deficiency is common—
probably due to a coincidence of many of the above
mentioned factors: lack of control of the infection [3],
nutritional deficiency particularly in intravenous drug
abusers [4], alcoholism and terminal liver diseases [5],
diarrhea [3], etc. In turn, Zn deficiency in HIV-infected
patients has been associated to increased viral replication
and a poorer diag nosis [3,6], and correction of such defi-
ciency has been correlated to improvements in survival
and immune recovery [3,6-8].
Studies in the HAART era have reported Zn defi-
ciency in over 30% of all patients, with immunological
benefits once the problem is corrected. However, in these
studies the percentage of patients with virological control
and the absence of other confounding factors is low [3,9].
The interest of our study is that it involves a group of
patients with effective and prolonged HAART and no
evidence of active infections or other associated factors,
in which the Zn deficiency rate was found to be 13% -
with severe deficiency in 6%. Among the mentioned
factors associated to Zn deficiency, only at least moder-
ate alcohol consumption was associated to diminished
levels of the element—no correlation being observed
with transaminase elevation, liver cirrhosis, lipodystro-
phy, diarrhea or CD4+ counts. Although we cannot rule
out specific nutritional deficiencies, the latter were not
clinically evident, since we did not include patients with
recent weight loss, and the body mass index of the sub-
jects with Zn deficiency was 25.3 kg/m2 (SD 4.6). In
contrast, we observed an inverse correlation to age not
previously d e scribed in the literature, and which might be
attributable to dietary differences. Possibly other factors,
e.g., non-evident active infections such as hepatitis C,
persistent immune activation phenomena inherent to HIV
disease, or dietary or genetic factors co nditioning absorp-
tion could explain some case of Zn deficiency [10]. The
direct colorimetric method used in this study offers the
advantages of being technically easier, automatically

Zinc Status in Virological Controlled Human Immunodeficiency Virus Type 1 Infected Patients 184
performed and less costly than the atomic absorption
spectrophotometric techniques used in other studies, and
as such is the method usually employed in clinical labo-
ratories. As has been commented, the clinical relevance
of Zn deficiency and the benefits derived from correcting
the problem are difficult to establish in our case, because
most of the patients had high CD4+ counts (640
cells/mm3, SD 357)—with no differences versus patients
without Zn deficiency.
In sum, an important number of HIV-infected patients
in the HAART era show diminished serum Zn concentra-
tions. In a large percentage of cases the underlying cause
cannot be identified, since these subjects have good vi-
rological control, with no liver disease or malnutrition.
Further studies are needed to establish the causes and
corroborate the usefulness of Zn replacement therapy—
though given the high prevalence of Zn deficiency even
in patients with good nutritional status and virological
control, the inclusion of at least occasional Zn determi-
nations should be considered in the regular follow-up
evaluations of HIV-infected patients.
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