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Current
HIV Research
ISSN: 1570-162X
Current HIV Research
Volume 5, Number 2, March 2007
Contents
Review Articles
Disease Progression in Children with Vertically-Acquired
HIV Infection in Sub-Saharan Africa: Reviewing the Need for
HIV Treatment Pp. 139-153
Kirsty Little, Claire Thorne, Chewe Luo, Madeleine Bunders,
Ngashi Ngongo, Peter McDermott and Marie-Louise Newell
[Abstract]
What Strategies to Boost Production of Affordable
Fixed-Dose Anti-Retroviral Drug Combinations for Children
in the Developing World? Pp. 155-187
Daniele Dionisio, Robert Gass, Peter McDermott, Vincenzo
Racalbuto, Marina Madeo, Giuseppe Braghieri, Siobhan Crowley,
Eloan Dos Santos Pinheiro, Peter Graaff, Ashwin Vasan, Achara
Eksaengsri, Helene Moller, Arun Kumar Khanna, Krisana Kraisintu,
Sandeep Juneja, Stavros Nicolaou, Aloka Sengupta, Francesco
Esperti and Daniela Messeri
[Abstract]
Original Research Papers
Cloning and Characterization of Functional Subtype
A HIV-1 Envelope Variants Transmitted Through Breastfeeding
Pp. 189-197
Stephanie M.J. Rainwater, Xueling Wu, Ruth Nduati, Rebecca
Nedellec, Donald Mosier, Grace John-Stewart, Dorothy Mbori
Ngacha and Julie Overbaugh
[Abstract]
Reduction of Anti-HIV-1 Gag Immune Responses
During Co-Immunization: Immune Interference by the HIV-1 Envelope
Pp. 199-209
Franklin R. Toapanta, Jodi K. Craigo, Ronald C. Montelaro
and Ted M. Ross
[Abstract]
Synergistic Effect of Combined HIV/HCV Immunogens:
A Combined HIV-1/HCV Candidate Vaccine Induces a Higher Level
of CD8+ T Cell-Immune Responses in HLA-A2.1 Mice
Pp. 211-219
Ali Azizi, Masoud Ghorbani, Catalina Soare, Majid Mojibian
and Francisco Diaz-Mitoma
[Abstract]
Evidence for Predominance of CCR5-Using HIV-1 Strains
During Highly Active Antiretroviral Therapy Pp. 221-234
Yuan Min Wang, Bin Wang, Wayne B. Dyer, Kishen Lachireddy,
Ng Kee Peng and Nitin K. Saksena
[Abstract]
Drug Resistance and Viral Evolution in Plasma and
Peripheral Blood Cells During Structured Treatment Interruption
(STI) and Non-Interrupted HAART Pp. 235-250
Yuan Min Wang, Wayne B. Dyer, Cassy Workman, Bin Wang,
Ng Kee Peng, Kishen Lachireddy, Choo Beng Chew, John Sullivan
and Nitin K. Saksena
[Abstract]
Interclade Crossreactivity of HIV 1 Specific T Cell
Responses in Human Immunodeficiency Virus Type 1 Infection
in China Pp. 251-259
Shuguang Zhao, Song Zhai, Yan Zhuang, Shaoyang Wang, Dedong
Huang, Whenzhen Kang, Xinhong Li, Xu G. Yu, Bruce D. Walker,
Marcus A. Altfeld and Yongtao Sun
[Abstract]
Anti-IgG Antibodies from Sera of Healthy Individuals
Neutralize HIV-1 Primary Isolates Pp. 261-265
Radmila Metlas, Tanja Srdic and Veljko Veljkovic
[Abstract]
A Study of Tryptophan Metabolism via Serotonin
in Ventricular Cerebrospinal Fluid in HIV-1 Infection
Using a Neuroendoscopic Technique
Pp. 267-272
Pierluigi Longatti, Alessandro Perin, Stefano Comai, Antonella
Bertazzo, Vittoria Rizzo, Carlo Virgilio Luigi Costa and Graziella
Allegri
[Abstract]
Fatal Disseminated Toxoplasmosis During Primary HIV
Infection Pp. 273-274
Liana Signorini, Maurizio Gulletta, Davide Coppini, Carla
Donzelli, Roberto Stellini, Nino Manca, Giampiero Carosi and
Alberto Matteelli
[Abstract]
Epicardial Adipose Tissue is Related to Carotid Intima-Media
Thickness and Visceral Adiposity in HIV-Infected Patients
with Highly Active Antiretroviral Therapy-Associated Metabolic
Syndrome Pp. 275-279
Gianluca Iacobellis, Arya M. Sharma, Adriano M. Pellicelli,
Benvenuto Grisorio, Giorgio Barbarini and Giuseppe Barbaro
[Abstract]
Abstracts
[Back to top]
Disease Progression in Children with
Vertically-Acquired HIV Infection in Sub-Saharan Africa: Reviewing
the Need for HIV Treatment
Kirsty Little, Claire Thorne, Chewe Luo, Madeleine Bunders,
Ngashi Ngongo, Peter McDermott and Marie-Louise Newell
Approximately 700,000 children become newly infected
with HIV annually, mainly through mother-to-child transmission
(MTCT), making paediatric HIV a leading cause of morbidity
and mortality worldwide. The substantial interest in preventing
MTCT (PMTCT) has generated information on rates of transmission
and associated factors, but there is a lack of information
on disease progression and mortality in vertically-infected
children, especially from resource-poor settings. Peer-review
journals with titles or abstracts containing reference to
the review’s themes were selected using widely available
search engines. We review relevant literature on mortality
in children born to HIV infected mothers; morbidity and mortality
associated with paediatric HIV infections; eligibility to
and efficacy of antiretroviral therapy (ART). Child mortality
is independently associated with maternal HIV status and maternal
death, with paediatric infection resulting in ~4 fold increase
in mortality by age 2 years. Morbidities seen in infected
children were similar to those seen in uninfected children,
although the rates and recurrences of illness were greater.
There is some evidence that progression to AIDS may be more
rapid in resource poor settings, although data on this are
very limited. PMTCT and paediatric ART have been shown to
be highly successful in resource-limited settings, but are
not universally applied. Further efforts to increase coverage
of both PMTCT and paediatric ART could substantially reduce
the numbers of children becoming infected and improve survival
of those infected. Additionally, improvements in health infrastructures
could improve care provision, not only through improved detection
and monitoring but also through treatment of co-morbidities
and nutritional support.
[Back to top]
What Strategies to Boost Production of Affordable
Fixed-Dose Anti-Retroviral Drug Combinations for Children
in the Developing World?
Daniele Dionisio, Robert Gass, Peter McDermott, Vincenzo
Racalbuto, Marina Madeo, Giuseppe Braghieri, Siobhan Crowley,
Eloan Dos Santos Pinheiro, Peter Graaff, Ashwin Vasan, Achara
Eksaengsri, Helene Moller, Arun Kumar Khanna, Krisana Kraisintu,
Sandeep Juneja, Stavros Nicolaou, Aloka Sengupta, Francesco
Esperti and Daniela Messeri
Background: No more than 8% of HIV positive children
needing treatment in low- and middle-income countries have
access to antiretroviral drugs (ARVs). Children presently
account for about 4% of all treated patients, while for equitable
access they should make up at least 13%.
Aims: This study explores key issues, implications
and interaction dynamics to boost production of easy-to-use
and affordable fixed-dose combination (FDC) ARVs for children
in the developing world. Potentials for equitable solutions
are examined including priority steps and actions, appropriate
treatment options and reliable forecasting methods for paediatric
ARVs, as well as combination incentives to generic companies
against market unattractiveness and enforced intellectual
property (IP) rights. Moreover, implementation strategies
to enhance the development and production of affordable ARV
paediatric formulations and appropriate supply systems to
ensure availability are investigated.
Results: The current market for FDC paediatric ARVs
is already substantial and will only grow with improved and
scaled up diagnosis and monitoring of children. This provides
an argument for immediate increase of production and development
of FDC ARVs for children. These formulations must be low cost
and included in the list of Essential Medicines to avoid children
continuing to lag behind in access to treatment. Access-oriented,
long-term drug policy strategies with the ability to pass
muster of governments, the UN system, as well as generic and
research-based enterprises are needed to let children gain
expanded and sustained access to FDC ARVs. Under the requirements
listed above, IP-bound Voluntary License (VL) flexibilities
do appear, if coupled with substantial combination incentives
to generic firms, as a fitting tool into the needs. Policies
must consider enhancing human resource capacity in the area
of caregivers and social and health workers aiming to spread
correct information and awareness on effectiveness and rationale
of FDC ARVs for children. Policies should urge that paediatric
ARV treatment programmes entwine with extant interventions
on prevention of mother-to-child transmission, as well as
with HIV treatment initiatives focused on mothers and household
members. Policies, again, should consider centralising functions
and pooling resources to help overcome drug supply barriers.
WHO’s brokering role in VL-based agreements between
wealthy and developing country industries, as well as its
technical guidance in setting international standards should
not be waived while looking for sustained access to optimised
ARV treatments for children. Strategies discussed in this
paper, while taking unavoidability of marketing and profit
rules into account, look closely into the trade and drug policy
directions of China and India according to frontier crossing
implications of their IP management trends as well as their
multi-faceted penetration strategies of both the wealthy and
under-served markets the world over.
[Back to top]
Cloning and Characterization of Functional Subtype
A HIV-1 Envelope Variants Transmitted Through Breastfeeding
Stephanie M.J. Rainwater, Xueling Wu, Ruth Nduati, Rebecca
Nedellec, Donald Mosier, Grace John-Stewart, Dorothy Mbori
Ngacha and Julie Overbaugh
Previous studies of HIV-1 variants transmitted from mother-to-infant
have focused primarily on computational analyses of partial
envelope gene sequences, rather than analyses of functional
envelope variants. There are very few examples of well-characterized
functional envelope clones from mother-infant pairs, especially
from envelope variants representing the most prevalent subtypes
worldwide. To address this, we amplified the envelope variants
present in 4 mother-infant transmission pairs, all of whom
were infected with subtype A and three of whom presumably
transmitted HIV-1 during the breastfeeding period. Functional
envelope clones were constructed, either encoding full-length
envelope sequences from the mother and baby or by making chimeric
envelope clones in a common backbone sequence. The infant
envelope sequences were genetically homogeneous compared to
the maternal viruses, and pseudoviruses bearing these envelopes
all used CCR5 as a coreceptor. The infant viruses were generally
resistant to neutralization by maternal antibodies present
near the time of transmission. There were no notable differences
in sensitivity of the mother and infant envelope variants
to neutralization by heterologous plasma or monoclonal antibodies
2G12 and b12, or to inhibition by sCD4, PSC-RANTES or TAK779.
This collection of viral envelopes, which can be used for
making pseudotyped viruses, may be useful for examining the
efficacy of interventions to block mother-infant transmission,
including sera from vaccine candidates, purified antibodies
under consideration for passive immunization and viral entry
inhibitors.
[Back to top]
Reduction of Anti-HIV-1 Gag Immune Responses
During Co-Immunization: Immune Interference by the HIV-1 Envelope
Franklin R. Toapanta, Jodi K. Craigo, Ronald C. Montelaro
and Ted M. Ross
Immunization with more than one immunogen (co-immunization)
is an efficient regimen to induce immunity to multiple antigens.
However, immune interference has been reported using multi-plasmid
DNA immunizations. HIV-1 envelope (Env) and Gag gene products
are the predominant immunogens used in current AIDS vaccines,
although, few studies have evaluated possible immune interference
when these two antigens are co-administered. Therefore, in
this study, immune interference during co-inoculation was
examined using DNA vaccines expressing lentiviral Envs and
Gag from gene sequences optimized for efficient expression
in mammalian cells (codon-optimized). BALB/c mice vaccinated
in separate hind legs with each plasmid individually elicited
high titer immune responses, however, when HIV-1 Envgp120
and HIV-1 Gagp55 DNA plasmids were co-inoculated,
there was a reduction in the immune responses elicited to
HIV-1 Gagp55. To determine if the anti-HIV-1 Gagp55
immune interference was specific to HIV-1 Envgp120,
mice were co-immunized with plasmids expressing the surface
envelope protein from two additional lentiviruses, Envgp130-SIV
or Envgp90-EIAV, or a soluble form of hemagglutinin
(sHA) from influenza virus and HIV-1 Gagp55- or
SIV Gagp55-DNA. Interestingly, there was no reduction
in anti-HIV-1 Gagp55 immune responses using other
lentiviral envelopes or the influenza sHA. Also, none of the
lentiviral envelopes reduced anti-SIV Gagp55 immune
responses during co-immunization. Therefore, anti-HIV-1 Gag
immune interference appears specific to co-immunizations with
HIV-1 Envgp120 and may involve a yet undefined
immunological mechanism(s).
[Back to top]
Synergistic Effect of Combined HIV/HCV Immunogens:
A Combined HIV-1/HCV Candidate Vaccine Induces a Higher Level
of CD8+ T Cell-Immune Responses in HLA-A2.1 Mice
Ali Azizi, Masoud Ghorbani, Catalina Soare, Majid Mojibian
and Francisco Diaz-Mitoma
Dual infections with HIV-1 and Hepatitis C virus (HCV) may
proceed in concert to cause severe disease. HIV positive individuals
that become infected with HCV advance more rapidly to AIDS
than those that are infected with HIV-1 alone. In this study,
HLA-A2.1 mice were immunized with a combination vaccine including
HIV and HCV immunogens (polycistronic DNA + proteins) or vaccine
containing either HIV or HCV immunogens. Mice immunized with
the combined HIV/HCV regimen had similar antibody titers as
the group receiving either the HIV-1 or HCV only regimen.
Proliferative immune responses showed that mice receiving
the combined HIV/HCV vaccine exhibited a three fold higher
stimulation index (SI) to gp120 than mice immunized with the
vaccine containing HIV alone. To determine whether our vaccine
strategy induced Th1 or Th2 immune responses, IFN-γ
and IL-4/IL-5 were measured. The combined HIV/HCV vaccine
induced a higher level of Th1 responses to HIV-1 gag protein
compared with the other groups, as measured by IFN-γ
production. Interestingly, detection of IFN-γ
by ELISPOT assay demonstrated that the combined HIV/HCV vaccine
group had increased numbers of spot forming cells (SFC) to
HIV-gp120 peptides when compared to that of the HIV-1 only
vaccine group. The combined HIV/HCV vaccine group also showed
an increase in SFC to HCV-core peptides in comparison with
the group receiving the HCV only vaccine. Intracellular IFN-γ
staining confirmed the ELISPOT results and demonstrated that
the combined HIV/HCV group had significantly higher percentages
of HIV and HCV-specific CD8+T cells in comparison to the groups
receiving the HIV or HCV vaccines. These results suggest a
new approach to maximize vaccine efficacy against HIV and
HCV.
[Back to top]
Evidence for Predominance of CCR5-Using HIV-1 Strains
During Highly Active Antiretroviral Therapy
Yuan Min Wang, Bin Wang, Wayne B. Dyer, Kishen Lachireddy,
Ng Kee Peng and Nitin K. Saksena
Background: Very little is known about the influence
of Highly Active Antiretroviral Therapy (HAART) on the surface
expression of CCR5 and CXCR4 with respect to receptor tropism
and replication kinetics of autologous HIV strains, during
continuous therapy and structured treatment interruption (STI)
regimens.
Objectives: The main objectives of this study were
to assess whether continuous therapy and STI regimens had
any modulatory effects on expression of CCR5 and CXCR4 on
T lymphocytes.
Study Design: We studied 6 patients on continuous
HAART, 4 patients on STI and 1 treatment-naïve patient.
Sequential peripheral blood mononuclear cells (PBMC) samples
were analyzed to determine viral replication kinetics, the
genotype influencing tropism of the autologous strain, in
vitro co-receptor usage patterns in relation to the surface
expression of each co-receptor.
Results: Our data suggest that predominant CCR5 expression
and tropism, during therapy, but significant down-modulation
of CXCR4 expression. During the off-therapy phases of STI,
CXCR4 expression increased, which correlated with increased
CXCR4 tropism of isolates from these time points. In-vitro
tropism during therapy was consistent with the HIV-1 V3 genotype,
which was characteristic of CCR5 using strains.
Conclusions: These results suggest that certain HAART
regimens influence the surface expression of CXCR4, which
may have profound implications for antiretroviral treatment.
[Back to top]
Drug Resistance and Viral Evolution in Plasma and
Peripheral Blood Cells During Structured Treatment Interruption
(STI) and Non-Interrupted HAART
Yuan Min Wang, Wayne B. Dyer, Cassy Workman, Bin Wang,
Ng Kee Peng, Kishen Lachireddy, Choo Beng Chew, John Sullivan
and Nitin K. Saksena
Background: Highly active antiretroviral therapy
(HAART) can successfully reduce plasma and tissue levels of
HIV-1 RNA and results in reductions in HIV-related morbidity
and mortality, but the slow viral evolution during therapy
in cellular reservoirs is a continuing problem. In addition,
little remains known how viral evolutionary process may differ
between cell-free and cell-associated compartments, over time,
in vivo in patients receiving HAART or STI.
Objectives: The main objectives of this study were
to assess viral replication kinetics, drug resistance and
viral evolution during HAART and STI.
Study design: We have conducted a longitudinal study
of virus culture kinetics in vitro, molecular analysis
of uncultured HIV-1 variants from plasma and PBMC of 6 patients
on HAART, 4 patients on STI, and 6 from treatment-naïve
patients.
Results: Our data suggest that drug resistance mutations
remained compartmentalized between plasma and PBMC. The divergent
distribution of resistance mutations between plasma and PBMC
coincided with divergent env gene evolution in these
compartments. In contrast, the HIV strains from therapy-naive
patients showed tight genetic and phylogenetic concordance
between plasma and PBMC. Both STI and non-STI groups showed
the presence of resistance mutations to both RT and protease
inhibitors, which correlated with inadequate suppression of
viremia and partially with the virus culture isolation
in vitro.
Conclusions: Overall, STI for HIV patients has no
added advantage over regular HAART at the virologic level
and in the diminution of resistance mutations that result
in therapy failure. Under both forms of anti-retroviral therapies,
virus could be isolated in vitro from the PBMC showing
continuing low-level viral replication under suppressive therapy.
Overall, these data may be useful in predicting the late emergence
of drug resistance mutations via the latent integrated provirus.
[Back to top]
Interclade Crossreactivity of HIV 1 Specific T Cell
Responses in Human Immunodeficiency Virus Type 1 Infection
in China
Shuguang Zhao, Song Zhai, Yan Zhuang, Shaoyang Wang, Dedong
Huang, Whenzhen Kang, Xinhong Li, Xu G. Yu, Bruce D. Walker,
Marcus A. Altfeld and Yongtao Sun
To determine the degree of HIV-1-specific cytotoxic-T-lymphocyte
(CTL) cross-responses to the clade B and C consensus sequences
at the single peptide level. We assessed CTL responses in
46 HIV-1 clade B chronically infected individuals using an
interferon-γ
Elispot assay with a total of 826 overlapping peptides spanning
HIV-1clade B and C consensus sequences. In general, 583 peptides
were recognized by HIV-1-specific T cells in the study subjects
(292 clade B, 291 clade C respectively), of which 204 peptides
in both clades were recognized simultaneously. The HIV-1-specific
CTL responses to both clade peptides contributed 54.23% (954/1759)
to the total responses. No significant difference was observed
between the overall magnitude or frequency of CTL responses
to clade B proteins and those to clade C proteins. According
to the profiles of CTL magnitude and CTL frequency, the top
44 and 35 synthetic peptides were identified as immunodominant
regions in the clade B and C consensus sequences respectively
and 27 corresponding peptides in two immunodominant regions
were cross-reactive. These peptides with cross-reactivity
had a significantly higher ability to elicit CTL responses
(P< 0.01) and preferentially had a trend of lower entropy
and higher inter-clade homology. A wide degree of cross-clade
reactivity of HIV-1-specific T cells exist in clade B and
clade C variants. Most of immunodominant peptides with cross-reactivity
are vigorous to elicit CTL responses and preferentially be
conservative. This result may make future HIV-1 vaccines including
multiple copies of CTL epitopes in these immunodominant peptides
effective for this population.
[Back to top]
Anti-IgG Antibodies from Sera of Healthy Individuals
Neutralize HIV-1 Primary Isolates
Radmila Metlas, Tanja Srdic and Veljko Veljkovic
Immunoglobulins (Ig) of pooled healthy human sera were purified
by affinity chromatography based on their reactivity with
human IgG. This Ig fraction represent connected, natural antibodies
(NAbs) and here are denoted as anti-IgG antibodies. The data
revealed that IgG, IgA and IgM isotypes are constituents of
anti-IgG fraction. The ability of anti-IgG antibodies to prevent
infection of PBMC by HIV-1 was demonstrated. They exhibited
different neutralizing activity depending on the phenotype
of the tested virus. The efficacy of neutralization was comparable
to monoclonal antibodies (MAbs) IgG1b12 at least for the HIV-192HT593B
strain. These studies suggest that connected antibodies thus,
constituents of immune network, could prevent infection by
HIV-1. NAbs as essential components of therapeutic molecules
of intravenous Ig (IVIg) have a beneficial effect on variety
of immunological disorders by affecting the structure, function
and dynamics of the immune network. Since, hallmark of HIV-1
infection are immunological disorders we hypothesizes that
they might be corrected to some extend by anti-IgG antibodies.
[Back to top]
A Study of Tryptophan Metabolism via Serotonin
in Ventricular Cerebrospinal Fluid in HIV-1 Infection
Using a Neuroendoscopic Technique
Pierluigi Longatti, Alessandro Perin, Stefano Comai, Antonella
Bertazzo, Vittoria Rizzo, Carlo Virgilio Luigi Costa and Graziella
Allegri
In this paper we report the study of tryptophan metabolism
via serotonin in ventricular CSF in HIV-1 infection
in order to investigate the origin of tryptophan metabolites
in the human brain. The patients (n=4) were affected with
non-communicating hydrocephalus. One of these also was suffering
from HIV-1 infection. The CSF was withdrawn from different
sites of the cerebral cavity with a neuroendoscopic procedure
which allows an accurate exploration of all the cerebral ventricles.
The measurement of tryptophan, 5-hydroxytryptophan, serotonin,
5-hydroxyindoleacetic acid, and melatonin was carried out
by HPLC with fluorometric detection. In HIV-1 infection the
highest concentration of tryptophan is present in the CSF
of the choroid plexus; however, the levels are markedly lower
than those in hydrocephalic individuals (control group). 5-Hydroxytryptophan
CSF content is higher in HIV-1 infection than in hydrocephalic
controls in all districts examined. Regarding serotonin, a
great difference appears in the choroid plexus and in the
pituitary recess between the HIV-1 infected patient and the
control group. The values of 5-hydroxyindoleacetic acid are
much lower in the CSF of the HIV-1 infected patient than in
hydrocephalic controls. Melatonin levels appear to fluctuate
largely but, in the HIV-1 infection, a great variability is
present among the sites of CSF withdrawal. The third ventricle
contains the highest concentration of melatonin and the choroid
plexus and the pituitary recess the lowest. All the melatonin
concentrations in HIV-1 infection are largely different than
in hydrocephalic controls. This is the first report on the
measurement of tryptophan metabolites via serotonin
in ventricular CSF in HIV-1 infection.
[Back to top]
Fatal Disseminated Toxoplasmosis During Primary HIV
Infection
Liana Signorini, Maurizio Gulletta, Davide Coppini, Carla
Donzelli, Roberto Stellini, Nino Manca, Giampiero Carosi and
Alberto Matteelli
Toxoplasmosis is a well recognized manifestation of AIDS,
but the disseminated disease is a rare condition and it has
not been associated to HIV seroconversion to our knowledge.
We describe a fatal episode of disseminated T. gondii
acute infection with massive organ involvement during primary
HIV infection. The serological data demonstrate primary T.
gondii infection. The avidity index for HIV antibodies
supports recent HIV-1 infection.
[Back to top]
Epicardial Adipose Tissue is Related to Carotid Intima-Media
Thickness and Visceral Adiposity in HIV-Infected Patients
with Highly Active Antiretroviral Therapy-Associated Metabolic
Syndrome
Gianluca Iacobellis, Arya M. Sharma, Adriano M. Pellicelli,
Benvenuto Grisorio, Giorgio Barbarini and Giuseppe Barbaro
Background: High cardiovascular risk and
accelerated atherosclerosis are associated with human immunodeficiency
virus (HIV). Recently, the use of highly active antiretroviral
therapy (HAART) for the treatment of HIV infection is correlated
with the development of HAART-associated metabolic syndrome
and lipodystrophy (LDS). Detection of epicardial fat thickness,
new index of visceral adiposity in non HIV-infected patients,
might be important as diagnostic tool in HIV-infected patients
on HAART.
Objective: Primary objective of this study was to
evaluate whether echocardiographic epicardial adipose tissue
is related to visceral adipose tissue (VAT) and Carotid Intima-Media
Thickness (IMT), index of atherosclerosis in HIV-infected
patients on HAART with LDS
Design: We studied 60 consecutive HIV-infected subjects
with HAART-associated metabolic syndrome and LDS and 45 HIV-infected
subjects on HAART without LDS.
Main Outcomes Measures: Epicardial fat thickness
and IMT were measured by ultrasonography in both study and
control groups. Magnetic resonance imaging (MRI) was used
to calculate VAT in HIV-infected subjects on HAART with LDS.
Results: Epicardial adipose tissue thickness showed
an excellent correlation with MRI-VAT (r=0.85; P<0.001)
and IMT (r=0.78;P<0.001) in HIV-infected patients on HAART-with
LDS. Multiple regression analysis showed that epicardial fat
thickness was best predicted by MRI-VAT and IMT (R2=0.57,
p<0.001 and p<0.01, respectively). HIV-infected patients
with HAART-associated metabolic syndrome and LDS showed higher
epicardial fat thickness and IMT (8 vs 6.5 mm; 0.71
vs 0.66 mm, respectively, p<0.01 for both) than
HIV-infected subjects on HAART without LDS.
Conclusion: Echocardiographic assessment of epicardial
fat may have the potential to be a simple and reliable marker
of visceral adiposity and increased cardiovascular risk in
HIV-infected patients with HAART-associated metabolic syndrome
and LDS.
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