ART-treated HIV Research Articles

Increased influenza-specific antibody avidity in HIV-infected women compared with HIV-infected men on antiretroviral therapy.

It is recommended that HIV-infected individuals receive annual influenza vaccination due to their high susceptibility to influenza infection, especially among women. However, there have been few studies investigating sex-related responses to influenza vaccine in antiretroviral therapy (ART)-treated HIV-infected individuals. In this study, 26 aviremic ART-treated HIV-infected individuals and 16 healthy controls were enrolled in the current study. Blood was collected prior to vaccination (D0), on days 7-10 (D7) and on days 14-21 (D14) following administration of the 2013-2014 seasonal influenza vaccine. A series of analyses evaluated the serological and cellular responses following influenza vaccination. Female HIV-infected individuals had increased influenza-specific antibody avidity relative to male HIV-infected individuals, but similar plasma levels of influenza-specific binding antibodies and neutralizing antibodies. Increased cycling B cells and follicular helper CD4 T (Tfh) cells were observed in female HIV-infected individuals pre and postvaccination compared with male HIV-infected individuals, and cycling Tfh cells were directly correlated with influenza-specific antibody avidity. Moreover, plasma testosterone levels were inversely correlated with antibody avidity index. The magnitude of microbial translocation [plasma lipopolysaccharide (LPS)] level was directly correlated with influenza-specific antibody avidity. Circulating 16S rDNA microbiome showed that enrichment of specific species within Proteobacteria was associated with influenza-specific antibody avidity. These results, including differences based on sex and correlations, were only observed in HIV-infected individuals but not in the healthy controls. This study demonstrated sex differences in influenza-specific antibody avidity in ART-treated HIV disease, and provides valuable information on vaccination strategy in the ART-treated HIV-infected population.

T cell senescence predicts subclinical atherosclerosis in HIV-infected patients similarly to traditional cardiovascular risk factors

The main objective of this study is to evaluate the predictive capacity of T cell activation/senescence in subclinical atherosclerosis (SCA) in a group of HIV-infected patients. So, a cross-sectional analysis was performed on 91 long-term triple-ART therapy HIV-infected patients from an observational and prospective cohort. Carotid Intima Media Thickness (cIMT) was measured. Binary logistic regression was used to evaluate independent variables associated with SCA. Compared to patients without SCA, patients with SCA (60.4%) were older (41.33 ± 9.04 vs. 51.73 ± 8.44 years old, p < 0.001) and showed Framingham risk score (2.63 ± 3.127 vs. 7.66 ± 5.84, p = 0.008), as well as higher numbers of CD4+CD8+ double positive T cells (0.50 ± 0.42% vs. 0.81 ± 0.79%, p = 0.037), CD8+CD28− T cells (41.70 ± 16.96% vs. 50.22 ± 16.15%, p = 0.018), higher expression of CD28 on CD8+CD28+ T cells (1865 ± 789 vs. 2243 ± 917 MFI, P = 0.046). In contrast, they showed lower expression of CD38 on CD19+ B cells (65.38 ± 27.47% vs. 42.67 ± 30.26%, P < 0.001). Logistic multivariable analysis showed that Framingham risk score >10% (OR = 14.84, CI95% 1.63–125; p = 0.016) and numbers of CD8+CD28− T cells (OR = 1.032, CI 95% 1–1.065; p = 0.045) were independent factors associated with SCA. Patients with CD8+CD28− T cells ≥59% compared to those <59% had higher risk of SCA (OR = 4, CI95% 1.19–13.3, p = 0.024). Interestingly, 27.4% of patients with low Framingham risk score had elevated levels of CD8+CD28− T cells. In conclusion, immune senescence represented by accumulation of CD8+CD28− T cells may contribute to improve the predictive capacity of the Framingham risk score, especially when the scores are low and can explain, at least in part, the higher prevalence of SCA observed in long-term ART-treated stable HIV infected patients.

An exploration of Prevotella-rich microbiomes in HIV and men who have sex with men

BackgroundGut microbiome characteristics associated with HIV infection are of intense research interest but a deep understanding has been challenged by confounding factors across studied populations. Notably, a Prevotella-rich microbiome described in HIV-infected populations is now understood to be common in men who have sex with men (MSM) regardless of HIV status, but driving factors and potential health implications are unknown.ResultsHere, we further define the MSM-associated gut microbiome and describe compositional differences between the fecal microbiomes of Prevotella-rich MSM and non-MSM that may underlie observed pro-inflammatory properties. Furthermore, we show relatively subtle gut microbiome changes in HIV infection in MSM and women that include an increase in potential pathogens that is ameliorated with antiretroviral therapy (ART). Lastly, using a longitudinal cohort, we describe microbiome changes that happen after ART initiation.ConclusionsThis study provides an in-depth characterization of microbiome differences that occur in a US population infected with HIV and demonstrates the degree to which these differences may be driven by lifestyle factors, ART, and HIV infection itself. Understanding microbiome compositions that occur with sexual behaviors that are high risk for acquiring HIV and untreated and ART-treated HIV infection will guide the investigation of immune and metabolic functional implications to ultimately target the microbiome therapeutically.

Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection

Microbial signals have been linked to autoantibody induction. Recently, we found that purified anti-CD4 autoantibodies from the plasma of chronic HIV-1-infected patients under viral-suppressed antiretroviral therapy (ART) play a pathologic role in poor CD4+ T cell recovery. The purpose of the study was to investigate the association of systemic microbiome and anti-CD4 autoantibody production in HIV. Plasma microbiome from 12 healthy controls and 22 HIV-infected subjects under viral-suppressed ART were analyzed by MiSeq sequencing. Plasma level of autoantibodies and microbial translocation (LPS, total bacterial 16S rDNA, soluble CD14, and LPS binding protein) were analyzed by ELISA, limulus amebocyte assay, and qPCR. We found that plasma level of anti-CD4 IgGs but not anti-CD8 IgGs was increased in HIV+ subjects compared to healthy controls. HIV+ subjects with plasma anti-CD4 IgG > 50 ng/mL (high) had reduced microbial diversity compared to HIV+ subjects with anti-CD4 IgG ≤ 50 ng/mL (low). Moreover, plasma anti-CD4 IgG level was associated with elevated microbial translocation and reduced microbial diversity in HIV+ subjects. The Alphaproteobacteria class was significantly enriched in HIV+ subjects with low anti-CD4 IgG compared to patients with high anti-CD4 IgG even after controlling for false discovery rate (FDR). The microbial components were different from the phylum to genus level in HIV+ subjects with high anti-CD4 IgGs compared to the other two groups, but these differences were not significant after controlling for FDR. These results suggest that systemic microbial translocation and microbiome may associate with anti-CD4 autoantibody production in ART-treated HIV disease.

Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy

Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics. Plasma exosomes were increased in HIV-positive subjects compared to controls, and correlated with increased oxidative stress markers (cystine, oxidized cys-gly) and decreased PUFA (DHA, EPA, DPA). Untargeted proteomics detected markers of exosomes (CD9, CD63, CD81), immune activation (CD14, CRP, HLA-A, HLA-B), oxidative stress (CAT, PRDX1, PRDX2, TXN), and Notch4 in plasma exosomes. Exosomal Notch4 was increased in HIV-positive subjects versus controls and correlated with immune activation markers. Treatment of THP-1 monocytic cells with patient-derived exosomes induced expression of genes related to interferon responses and immune activation. These results suggest that exosomes in ART-treated HIV patients carry proteins related to immune activation and oxidative stress, have immunomodulatory effects on myeloid cells, and may have pro-inflammatory and redox effects during pathogenesis.

CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.

The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA-positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART.

Assays for precise quantification of total (including short) and elongated HIV-1 transcripts

Despite intensive study, it is unclear which mechanisms are responsible for latent HIV infection in vivo. One potential mechanism is inhibition of HIV transcriptional elongation, which results in short abortive transcripts containing the trans-activation response (TAR) region. Because the relative levels of total (including short) and processive transcripts provide measures of HIV transcriptional initiation and elongation, there is a compelling need for techniques that accurately measure both. Nonetheless, prior assays for total transcripts have been semi-quantitative and have seen limited application to patient samples. This manuscript reports the validation of quantitative reverse transcription (RT) droplet digital PCR assays for measurement of total (TAR) and processive (R-U5/gag) HIV transcripts. Traditional RT priming strategies can efficiently detect the TAR region on long HIV transcripts but detect <4% of true short transcripts. The TAR assay presented here utilizes an initial polyadenylation step, which provides an accessible RT priming site and detects short and long transcripts with approximately equal efficiency (70%). By applying these assays to blood samples from 8 ART-treated HIV+ individuals, total HIV transcripts were detected at levels >10-fold higher than elongated transcripts, implying a substantial block to transcriptional elongation in vivo. This approach may be applied to other difficult-to-prime RNA targets.

Elevation of Non-Classical (CD14+/lowCD16++) Monocytes Is Associated with Increased Albuminuria and Urine TGF-β1 in HIV-Infected Individuals on Stable Antiretroviral Therapy.

ObjectiveHigh rates of albuminuria are observed among HIV-infected individuals on stable antiretroviral therapy (ART). Though pro-inflammatory and pro-fibrotic responses are described as components of albuminuria in the general population, it is unclear how these responses are associated to albuminuria in ART-treated chronic HIV. We investigated the relationship of monocyte subsets and urine inflammatory and fibrotic biomarkers to albuminuria in ART-treated HIV-infected participants.Design and MethodsCross-sectional analyses were performed on Hawaii Aging with HIV-cardiovascular disease study cohort participants who were required at entry to be ≥40 years old and on ART ≥3 months. Monocyte subpopulations were determined in banked peripheral blood mononuclear cells (PBMC) using multi-parametric flow-cytometry. Entry random urine samples were assessed for albumin-to-creatinine ratios (UACR). Urine samples were measured for inflammatory and fibrotic biomarkers using Luminex technology.ResultsAmong 96 HIV-infected subjects with measured UACR (87% male, 59% Caucasian, and 89% undetectable HIV RNA with median CD4 of 495.5 cells/μL), 18 patients (19%) had albuminuria. Non-classical (CD14low/+CD16++) monocytes were significantly elevated in subjects with albuminuria (p = 0.034) and were correlated to UACR (r = 0.238, p = 0.019). Elevated non-classical monocyte counts were significant predictors of worsening albuminuria, independent of traditional- and ART-associated risk factors (β = 0.539, p = 0.007). Urine TGF-β1 and collagen-IV were significantly higher in albuminuric compared to non-albuminuric participants (TGF-β1; p = 0.039 and collagen-IV; p = 0.042). Urine TGF-β1 was significantly correlated with non-classical monocyte counts (r = 0.464, p = 0.017).ConclusionAlterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.

CX3CR1+ CD8 T cells in treated HIV infection are functionally impaired by platelet interactions (VIR6P.1171)

Abstract In the era of highly effective antiretroviral therapy (ART), HIV-infected patients have a better long-term prognosis than ever; however, increased inflammation and coagulation in HIV infection is associated with an increased risk of cardiovascular and other morbidities. CD8 T cell expansion is characteristic of HIV infection and has been linked to increased morbidities especially cardiovascular disease in treated HIV infection. Here we have identified a population of circulating memory CD8 T cells that express the vascular endothelium homing receptor CX3CR1 (fractalkine receptor) and is enriched in ART-treated HIV+ patients. CX3CR1+ CD8 T cells have elevated expression of the platelet-binding receptor PSGL-1 and the thrombin-activated receptor PAR-1, suggesting a possible role in cardiovascular disease via endothelial localization and interactions with platelets and mediators of coagulation. We found that even though thrombin stimulation via PAR-1 could directly enhance CD8 T cell responses in vitro, CD8 T cell cytokine production was diminished in the presence of thrombin-activated platelets through mechanisms mediated in part by TGF-β. Thus, we have identified a population of circulating memory CD8 T cells in HIV infection that are activated by thrombin, are susceptible to platelet-mediated regulation, and could contribute to cardiovascular disease risk in ART-treated HIV-infected patients.

Site-specific differences in T cell frequencies and phenotypes in the blood and gut of HIV-uninfected and ART-treated HIV+ adults.

Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV- individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV- adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+ CD4+T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing α4β7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy.

Cryptococcal antigenemia among HIV seropositive patients accessing care in antiretroviral therapy (ART) clinics in Calabar, South Southern Nigeria

Background: Cryptococcus neoformans infection is a life threatening disease especially when associated with immunosupression like HIV/AIDS. The greatest burden of disease occurs in sub-Saharan Africa, where mortality is estimated to be 17%. The finding of cryptococcal antigen in the blood represents a condition of systemic invasion with the fungus. Clinical manifestation of infection with Cryptococcus neoformans in AIDS patients is generally more evident at CD4 cells ≤100 cells/µl. This study was carried out to determine cryptococcal antigenemia among HIV seropositive patients accessing care in ART clinics as patients are not screened routinely despite reports of relatively high co-infection rates with HIV. Methods: This prospective cross-sectional study was carried out on ART-treated and ART-naive HIV positive adult patients attending ART clinics in two tertiary hospitals in Calabar, Nigeria. The sero-prevalence of cryptococcal antigen among the patients was determined using the cryptococcal antigen latex agglutination system (CALAS) (Wampole Laboratories, USA), according to the manufacturer’s instruction. The CD4 count levels of each patient were determined by flow cytometry using the fluorescent activated cell sorter BD FACS Count system (Becton Dickinson). Results: Out of the 272 HIV positive subjects enrolled in the study, 116(42.6%) were ARV-naive and 156(57.4%) were ARV-treated patients. A 5.1% cryptococcal antigenemia prevalence was established in the study. Infection rates were higher among subjects receiving ART 11/156 (7.1%) than in ART-naive subjects 3/116 (2.6%). Infection rates 5(35.7%) peaked at age 25-34 years. The mean CD4 counts of subjects with cryptococcal infection were 100.7±67.8 cells/µl, with a minimum CD4 count of 13.0. All the infections occurred among subjects with CD4 counts ≤200 cells/µl of blood. There was a statistically significant effect of cryptococcal antigenemia on the CD4 counts of the subjects (t=3.7, p=0.002). Conclusion: This study reveals that cryptococcal antigenemia is a health problem among HIV/AIDS patients in our locality. Cryptococcal antigenaemia seem to be more common among HIV patients on ART. The CD4 count levels among the ART treated subjects could have been boosted by administration of ART

Reverse correlation between CD39+CD25+ Treg and activated CD8+ T cells / NK cells in HIV-1- patients with low CD4 cell counts (105.48)

Abstract The role of regulatory T cells (Treg) in HIV has been studied intensely but remains unclear regarding their effect on cellular immune activation. Frequencies of CD4 and CD8 T cells, CD39+CD25+ Treg, Th17 cells, MDSC, B cells, NK cells and the activation status of T cells (CD38+HLADR+) were determined by flow cytometry in 10 healthy controls and 32 HIV-1+ patients. Immunosuppressive functions of single-cell sorted Treg were determined in the CFSE proliferation assay. Cytokine production (IL1b, 2, 4, 5, 6, 8, 10, INFg, TNFa, GM-CSF), C-reactive protein and soluble CD14 were measured in patients’ plasma by Luminex and ELISA. The absolute number of CD39+CD25+ Treg was significantly decreased in HIV-patients compared to normal controls (p=0.001). However, the frequency of Treg (p=0.04) and HLADR+CD38+CD8+ T cells (p=0.05) was increased only in patients with anti-retroviral therapy (ART). HIV+ patients with ART and low CD4+ cell count had the highest level of immune activation (p=0.04), and in this group we observed a significant negative correlation between CD39+CD25+ Treg and activated T cells (r2=0.5) as well as increased numbers of NK-cells. In ART-treated HIV+ patients with CD4+ T cell recovery, the frequency of Treg, NK cells and CD8+ T cell activation normalized. ART restores the frequency of Treg and activated T cells to normal levels. However, in patients whose CD4+ T cell count did not recover during ART, Treg frequency negatively correlated with T cell immune activation.

Effects of Tesamorelin (TH9507), a Growth Hormone-Releasing Factor Analog, in Human Immunodeficiency Virus-Infected Patients with Excess Abdominal Fat: A Pooled Analysis of Two Multicenter, Double-Blind Placebo-Controlled Phase 3 Trials with Safety Extension Data

HIV patients treated with antiretroviral therapy (ART) often develop increased visceral adipose tissue (VAT). Our objective was to perform a pooled analysis of two phase-3 studies of tesamorelin in ART-treated HIV patients with excess abdominal fat. Two multicenter, international studies were conducted; a 26-wk randomized, placebo-controlled primary intervention phase was followed by a 26-wk safety extension. A total of 806 ART-treated HIV patients with excess abdominal fat were randomized in a 2:1 fashion to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) sc daily. At wk 26, patients initially on tesamorelin were rerandomized to 2 mg tesamorelin (T-T group, n = 246) or placebo (T-P, n = 135) for an additional 26 wk, whereas patients on placebo were switched to tesamorelin (P-T, n = 197). Tesamorelin (GHRH(1-44)) at a dose of 2 mg or identical placebo, sc, was given daily. We evaluated percent change in VAT by computed tomography scan at wk 26. At wk 26, VAT decreased significantly in tesamorelin-treated patients (-24 +/- 41 vs. 2 +/- 35 cm(2), tesamorelin vs. placebo, P < 0.001; treatment effect, -15.4%). No significant changes were observed in abdominal sc adipose tissue (-2 +/- 32 vs. 2 +/- 29 cm(2), P = 0.08; treatment effect, -0.6%). Treatment with tesamorelin resulted in significant decreases in triglycerides (-37 +/- 139 vs. 6 +/- 112 mg/dl, P < 0.001; treatment effect, -12.3%) and cholesterol to high-density lipoprotein ratio (-0.18 +/- 1.00 vs. 0.18 +/- 0.94, P < 0.001; treatment effect, -7.2%) vs. placebo. Tesamorelin improved body image [belly appearance distress (P = 0.002)], patient rating of belly profile (P = 0.003), and physician rating of belly profile (P < 0.001). Mean IGF-I increased 108 +/- 112 vs.-7 +/- 64 ng/ml (P < 0.001 vs. placebo). At wk 52, decreases in VAT [-35 +/- 50 cm(2) (-17.5 +/- 23.3%)], waist circumference (-3.4 +/- 6.0 cm), triglycerides (-48 +/- 182 mg/dl), cholesterol (-8 +/- 38 mg/dl), and non-high-density lipoprotein (-7 +/- 38 mg/dl) were maintained (all P < 0.001 vs. original baseline) in the T-T group. Treatment with tesamorelin was generally well tolerated. No clinically meaningful differences were observed between groups in glucose parameters at wk 26 and 52. Treatment with tesamorelin reduces VAT and maintains the reduction for up to 52 wk, preserves abdominal sc adipose tissue, improves body image and lipids, and is overall well tolerated without clinically meaningful changes in glucose parameters.

Influence of antigen exposure on the loss of long-term memory to childhood vaccines in HIV-infected patients

The role of antigen exposure and of CD4 cell deficiency in the long-term persistence of immune memory to childhood vaccines remains uncertain, particularly during HIV infection. We analyzed in vaccinated ART-treated HIV+ patients with undetectable plasma HIV and CD4 cells >250/mm 3 the persistence of two memory cell pools: effector IFNγ-producing and proliferative central memory T cells against two vaccines: (i) vaccinia against the eradicated smallpox virus, and (ii) BCG against Mtb, a persistent pathogen. None of the HIV+ patients had IFNγ-effector cells against VV while the one patient with BCG-specific effector T cells had a recent history of tuberculosis. Proliferative responses were detectable but showed significantly lower frequency and intensity of VV-specific than tuberculin-specific responses, independently of the CD4 nadir. Thus, differential patterns of persistence or recovery of T cell memory pools against childhood vaccines are observed in treated HIV infection that are governed by antigen exposure.

Coronary and peripheral endothelial function in HIV patients studied with positron emission tomography and flow-mediated dilation: relation to hypercholesterolemia

The mechanisms underlying increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) are not known. Our aim was to study the endothelial function of the coronary arteries by cardiac perfusion positron emission tomography (PET), in HIV patients with normal or high cholesterol levels. Flow mediated dilation (FMD) of the brachial artery and circulating endothelial markers were also assessed. HIV patients in ART with total cholesterol <or= 5.5 mmol/L (215 mg/dL; n = 13) or total cholesterol >or= 6.5 mmol/L (254 mg/dL; n = 12) and healthy controls (n = 14) were included. (13)NH(3) perfusion PET, FMD, and measurement of plasma levels of E-Selectin, ICAM-1, VCAM-1, tPAI-1, and hs-CRP were performed. Baseline myocardial perfusion and the coronary flow reserve measured by PET (3.2 +/- 0.3, 3.2 +/- 0.3 and 3.0 +/- 0.3; ns) was similar in HIV patients with normal or high total cholesterol and controls. FMD did not differ between the groups and was 4.6 +/- 1.1%, 5.1 +/- 1.2%, and 4.6 +/- 0.8%, respectively. Increased levels of plasma E-Selectin, ICAM-1, tPAI-1, and hs-CRP were found in HIV patients when compared to controls (p < 0.05). E-Selectin and ICAM-1 levels were higher in HIV patients receiving protease inhibitors (PI) compared to those not receiving PI (p < 0.05). None of the measured endothelial biomarkers differed between the normal and high cholesterol HIV groups. In ART-treated HIV patients with a low overall cardiovascular risk, no sign of endothelial dysfunction was found not even in hypercholesterolemic patients. Also, the increased level of plasma endothelial markers found in HIV patients was not related to hypercholesterolemia.

Autonomic dysfunction in HIV patients on antiretroviral therapy: studies of heart rate variability

The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Introduction of highly active antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis and decreased morbidity. At present it is not known whether introduction of ART also has decreased autonomic dysfunction. To evaluate whether autonomic dysfunction is present in an ART-treated HIV population. HIV patients receiving ART for at least 3 years (n = 16) and an age-matched control group of healthy volunteers (n = 12) were included. All were non-smokers, non-diabetic and had never received medication for dyslipidaemia or hypertension. Following a 10 min resting period a 5 min ECG recording was performed. Heart rate variability (HRV) analysis was performed in accordance with current guidelines and data reported as median (interquartile range). The resting heart rate was higher in HIV patients compared with controls [69 (62-74) versus 57 (52-60); P<0.001]. Total HRV measured as standard deviation of normal-to-normal (SONN) was lower in the HIV group compared with the controls [36 (25-55) versus 74 (57-84) ms; P<0.01] as was parasympathetic activity measured as square root of the mean squared difference of successive normal-to-normal intervals (RMSSD) [22 (9-30) versus 35 (24-62) ms; P<0.05]. Low frequency power was lower in the HIV group compared with the control group [294 (161-602) versus 946 (711-1668) ms(2); P<0.01]. High frequency power as well as systolic and diastolic blood pressure did not differ between the groups. The HIV patients in ART have increased resting heart rate and decreased short-term heart rate variability indicating parasympathetic dysfunction.