Circulating mycobacterial-reactive CD4+ T cells with an immunosuppressive phenotype are higher in active tuberculosis than latent tuberculosis infection.

BACKGROUND: Previous studies suggest that control of Mycobacterium tuberculosis infection is compromised by the activity of regulatory T cells, including those that express CD39, an ectonucleotidase with immunosuppressive properties. Here, we examine the role of CD39 on CD4+ T cells reacting to M. tuberculosis antigens. METHODS: Cryopreserved PBMC from patients with active TB (n = 31) or individuals with LTBI (n = 30) were cultured with PPD, ESAT-6 or CFP-10 and antigen-reactive CD4+ T cells assessed by: A) intracellular expression of interferon-gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) and interleukin (IL)-2, B) co-expression of CD25 and CD134 with or without CD39, and C) production of IFN-γ, TNF-α and IL-10 in culture supernatants. RESULTS: Active TB patients were not differentiated from individuals with LTBI by intracellular expression of IFN-γ, TNF-α or IL-2 (alone or together), nor by co-expression of CD25 and CD134. However, active TB patients exhibited higher proportions of CD25+, CD134+, CD4+ T cells expressing CD39 in response to all antigens (p ≤ 0.022). Furthermore, in response to PPD, CD39 expression on CD25+, CD134+, CD4+ T cells correlated with IL-10 production (r = 0.41, p = 0.005) and inhibition of CD39 decreased IL-10 production. CONCLUSIONS: Antigen-reactive CD4+ T cells expressing CD39 are more abundant in active TB than LTBI and are associated with production of the immunosuppressive cytokine IL-10. Modulating the effects of CD39 might enhance cellular immune responses against M. tuberculosis.

Immune reconstitution disorders in patients with HIV infection: from pathogenesis to prevention and treatment.

An immune reconstitution disorder occurs in up to 40 % of severely immunodeficient HIV patients who commence antiretroviral therapy (ART), with an immune reconstitution inflammatory syndrome (IRIS) being encountered most commonly. Differences in the immunopathogenesis of an IRIS associated with different types of pathogen have become apparent but common features have also been defined. These include severe immunodeficiency prior to commencing ART associated with a high pathogen load and 'compensatory' immune responses, particularly innate immune responses, which inadequately control the pathogen and increase the risk of immunopathology as the immune system recovers on ART. Prevention of an IRIS may be achieved by optimising therapy for opportunistic infections before ART is commenced, delaying ART or using immunomodulatory therapy to prevent or suppress the immune response that causes the immunopathology. However, further clinical studies are required to examine these options in a systematic manner for the various types of IRIS.

Role of monocytes in mediating HIV-specific antibody-dependent cellular cytotoxicity.

Antibodies (Abs) that mediate antibody-dependent cellular cytotoxicity (ADCC) activity against HIV-1 are of major interest. A widely used method to measure ADCC Abs is the rapid and fluorometric antibody-dependent cellular cytotoxicity (RFADCC) assay. Antibody-dependent killing of a labelled target cell line by PBMC is assessed by loss of intracellular CFSE but retention of membrane dye PKH26 (CFSE-PKH26+). Cells of this phenotype are assumed to be derived from CFSE+PKH26+ target cells killed by NK cells. We assessed the effector cells that mediate ADCC in this assay. Backgating analysis and phenotyping of CFSE-PKH26+ revealed that the RFADCC assay's readout mainly represents CD3-CD14+ monocytes taking up the PKH26 dye. This was confirmed for 53 HIV+plasma-purified IgG samples when co-cultured with PBMC from three separate healthy donors. Emergence of the CFSE-PKH26+ monocyte population was observed upon co-culture of targets with purified monocytes but not with purified NK cells. Image flow cytometry and microscopy showed a monocyte-specific interaction with target cells without typical morphological changes associated with phagocytosis, suggesting a monocyte-mediated ADCC process. We conclude that the RFADCC assay primarily reflects Ab-mediated monocyte function. Further studies on the immunological importance of HIV-specific monocyte-mediated ADCC are warranted.

Novel sensitive real-time PCR for quantification of bacterial 16S rRNA genes in plasma of HIV-infected patients as a marker for microbial translocation.

We developed a real-time PCR to quantify 16S rRNA gene levels in plasma from HIV-infected patients as a marker of microbial translocation. The assay uses shrimp nuclease (SNuc) to eliminate DNA contamination, giving high sensitivity and low variability. The 16S rRNA gene levels measured in plasma from HIV patients correlated significantly with lipopolysaccharide levels.

Synthesis of specific fatty acids contributes to VLDL-triacylglycerol composition in humans with and without type 2 diabetes.

AIMS/HYPOTHESIS: It is recommended that patients with diabetes reduce their intake of saturated fat and increase their intake of monounsaturated fat or carbohydrate. However, high-carbohydrate diets may result in higher saturated fatty acids in VLDL-triacylglycerol. This is attributed to de novo lipogenesis, although synthesis of specific fatty acids is rarely measured. The objective of this study was to examine the contribution of de novo fatty acid synthesis to VLDL-triacylglycerol composition. It was hypothesised that levels of total and de novo synthesised fatty acids would increase with increased carbohydrate intake in diabetic participants. METHODS: Seven individuals with type 2 diabetes mellitus and seven matched non-diabetic controls consumed two diets differing in fat energy (lower fat <25%, higher fat >35%) for 3 days in a randomised crossover design. Blood samples were drawn before and 24 h after the ingestion of (2)H-labelled water. RESULTS: In the control participants, the higher-fat diet resulted in a 40% reduction in VLDL-triacylglycerol fatty acids because of decreases in myristic, palmitic, palmitoleic and linoleic acids, but the opposite trend occurred in participants with diabetes. The lower-fat diet increased the fractional synthesis rate by 35% and 25% in the control and diabetes participants, respectively (range: 0-33%). Palmitate accounted for 71% of fatty acids synthesised (range: 44-84% total de novo synthesised fatty acids). CONCLUSIONS/INTERPRETATION: (2)H incorporation was used for the first time in humans showing variability in the synthesis rate of specific fatty acids, even palmitic acid. A lower-fat diet stimulated saturated fatty acid synthesis at high rates, but no net stimulation of synthesis of any fatty acid occurred in the diabetes group. The implications of this finding for our understanding of lipid metabolism in diabetes require further investigation.

The frequency of high-grade intraepithelial neoplasia in anal/perianal warts is higher than previously recognized.

A retrospective review of the prevalence of intraepithelial neoplasia (IN) in surgically removed perianal/anal warts from December 1995 to December 2004 was undertaken in patients referred to the Sexual Health Clinic at Royal Perth Hospital. Data were analysed from 115 men and 38 women, 29 of whom had HIV infection (27 men and two women). Perianal/anal IN within the warts was found in 78% (52% high grade) of men with HIV infection. In men without HIV infection, the overall rate of IN within warts was 33% (20% high grade). The IN rate was 8.3% for HIV-negative women (2.8% high grade). Rates of IN within perianal/anal warts in men with or without HIV infection are higher than previously reported, and suggest the likelihood of a substantial increase in the future incidence of anal cancer. The association between IN and genital warts needs to be further studied.

Cholesterolaemic influence of palmitic acid in the sn-1, 3 v. the sn-2 position with high or low dietary linoleic acid in healthy young men.

Healthy young men were fed four diets for 2 weeks each providing natural fats containing palmitic acid (16 : 0) predominantly in the sn-1, 3 position of dietary TAG or containing 16 : 0 predominantly in the sn-2 position with low or high levels of linoleic acid (18 : 2n-6). Two treatments supplied 16 : 0 in the sn-1, 3 positions from palmstearin with low (3 % energy) or high (>7 % energy) 18 : 2n-6 and two treatments supplied 16 : 0 in the sn-2 position from lard with high or low levels of 18 : 2n-6. Diets contained 30-35 % energy as fat, 7-11 % energy as 16 : 0 and moderate levels of cholesterol. Fasting serum cholesterol and lipoprotein concentrations were measured. Cholesterol fractional synthesis rate (FSR) was determined by 2H incorporation. Diets providing 16 : 0 in the sn-2 position resulted in lower fasting serum total cholesterol (TC) and a lower TC:HDL ratio than diets providing 16 : 0 in the sn-1, 3 positions. Diets with high levels of 18 : 2n-6 significantly decreased the TC:HDL ratio, reaffirming the well-known cholesterol-reducing effect of 18 : 2n-6. A lower non-esterified cholesterol FSR was observed with low dietary levels of 18 : 2n-6. No differences between dietary treatments were found for serum HDL-cholesterol, LDL-cholesterol or TAG. It is concluded that dietary fats containing 16 : 0 in the sn-2 position may result in slightly lower fasting TC than diets providing 16 : 0 in the sn-1, 3 positions, while the level of n-6 polyunsaturated fat influences endogenous cholesterol synthesis.

Cytomegalovirus (CMV)-specific CD8+ T cells in individuals with HIV infection: correlation with protection from CMV disease.

CD8+ cytotoxic T cells play a key role in immunological protection from clinical cytomegalovirus (CMV) disease. Numbers of CMV-specific CD8+ T cells are increased in untreated and antiretroviral-treated HIV patients compared with healthy controls. Accumulation of CMV-specific CD8+ T cells during HIV infection may reflect persistent reactivation of CMV owing to suboptimal immune control and/or oligoclonal expansion of the limited populations of CMV-specific CD8+ T cells present before antiretroviral therapy (ART). CD8+ T cells directed against the CMV immediate early (IE)-1 protein may play an important role in preventing CMV replication to pathogenic levels. However, immunological protection from CMV disease in HIV-infected individuals on ART does not appear to depend on total numbers of CMV-specific CD8+ T cells but rather on the presence of both effector-memory and effector CMV-specific CD8+ T cells that produce interferon-gamma and/or perforin in response to CMV antigens.

The effect of combination antiretroviral therapy on CD5 B- cells, B-cell activation and hypergammaglobulinaemia in HIV-1-infected patients.

OBJECTIVES: This study assessed B-cell activation, CD5 B-cells and circulating immunoglobulin levels in HIV-infected patients treated with combination antiretroviral therapy (CART). METHODS: Measurement of plasma immunoglobulin levels and electrophoresis of plasma proteins, and analyses of total numbers of B-cells and B-cells expressing CD 38 and CD5 in whole blood, were undertaken in 47 consecutive HIV-1-infected patients attending an out-patient clinic. RESULTS: All HIV-infected patients had similar percentages and numbers of B-cells. Proportions of CD5 B-cells in all HIV-infected patients were significantly lower than those in HIV-negative controls. Aviraemic HIV-infected patients on CART had lower percentages of CD5, CD 38 and CD5 CD 38 B-cell subsets and lower plasma levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) than viraemic HIV-infected patients (untreated or on CART). However, 33-37% of aviraemic HIV-infected patients had IgG and IgA levels above the 95th percentile of the normal range defined in HIV-seronegative donors. In aviraemic HIV-infected patients, plasma IgA levels correlated only with proportions of activated (CD 38) B-cells. IgG levels did not correlate with the proportions of B-cell subsets or any marker of HIV disease activity. Monoclonal immunoglobulins were not detected in any plasma sample. CONCLUSIONS: Aviraemic HIV-infected patients on CART have lower plasma levels of IgG and IgA than viraemic HIV-infected patients, but levels are often above the normal range. CD5 B-cell numbers are depressed, so these cells are unlikely to contribute to hypergammaglobulinaemia in HIV-infected patients.

Dysregulation of CD28 and CTLA-4 expression by CD4 T cells from previously immunodeficient HIV-infected patients with sustained virological responses to highly active antiretroviral therapy.

OBJECTIVES: Current guidelines recommend commencing highly active antiretroviral therapy (HAART) in HIV-infected patients when CD4 T-cell counts reach 350 cells/microL. However, late-presenting HIV-infected patients with CD4 T-cell counts<50 cells/microL are still common. The ability of long-term HAART to normalize immune dysregulation in severely immunodeficient HIV-infected patients remains unclear. Here we address indices of immune dysregulation in previously severely immunocompromised HIV-infected patients treated with long-term HAART who had achieved increased CD4 T-cell counts and complete suppression of HIV viraemia. METHODS: We examined expression of CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and intracellular perforin by CD4 and CD8 lymphocytes from 25 highly selected HIV-infected patients [nadir CD4 T-cell counts <50 cells/microL, >4 years on HAART and >6 months of complete viral suppression (<50 HIV-1 RNA copies/mL)] and 18 HIV-seronegative age- and sex-matched controls. RESULTS: HIV-infected patients had lower percentages of CD28-expressing CD4 lymphocytes and higher percentages of CTLA-4-expressing CD4 lymphocytes than controls. The percentage of CTLA-4-expressing CD4 lymphocytes correlated inversely with that of CD28-expressing CD4 lymphocytes. The proportion of CD4 lymphocytes expressing perforin was generally low. However, more HIV-infected patients than controls had >1% of CD4 lymphocytes expressing perforin [11 of 25 (44%) vs. one of 18 (5.5%)]. The percentage of CD8 lymphocytes expressing perforin did not differ between HIV-infected patients and controls. Amongst HIV-infected patients, the percentage of perforin-expressing CD8 lymphocytes correlated inversely with nadir but not current CD4 T-cell count. CONCLUSIONS: Expression of CD28, CTLA-4 and perforin by CD4 lymphocytes remain dysregulated in HIV-infected patients with previous severe immunodeficiency, despite increased CD4 T-cell counts and control of HIV viraemia by HAART.

Randomized, placebo-controlled, phase I/IIa evaluation of the safety and immunogenicity of fowlpox virus expressing HIV gag-pol and interferon-gamma in HIV-1 infected subjects.

We conducted a randomized, placebo-controlled double-blind trial to examine the safety and immunogenicity of a candidate HIV therapeutic vaccine based upon a recombinant fowl pox virus capable of coexpressing the human cytokine interferon-gamma and/or genes from HIV-1. Thirty-five eligible subjects were randomized (12 placebo, 11 fowlpox + HIV genes, 12 fowl pox + HIV genes + interferon gamma). All but one subject (placebo group) received three immunizations (by intramuscular injection on day 0, week 4 and week 12) and all completed 52 weeks of follow-up. All subjects continued to take combination antiretroviral therapy for the duration of study. There were no significant toxicity or safety concerns and the distribution of adverse events and their severity was consistent across each randomly assigned vaccine group. Comparison of placebo recipients with the combined recipients of the two vaccine constructs, in terms of anti-HIV gag ELISpot or lymphoproliferative responses, tended to favour the placebo group, but were not significantly different (difference in time-weighted mean change from baseline = 56 Spot forming units (sfu)/10(6) PBMC; p = 0.062 and 4.4 SI; p = 0.337). There were no significant changes in CTL responses by standard Cr(51) release assay. Anti-FPV antibodies were detected by week 14 in 0 placebo and 20 (87%) vaccine recipients. Although safe, neither vaccine construct appeared to possess detectable T-cell mediated anti-HIV immunogenic properties in HIV infected individuals, as measured by standard T cell assays.

Restoration of CD4 T-cell responses to cytomegalovirus is short-lived in severely immunodeficient HIV-infected patients responding to highly active antiretroviral therapy.

OBJECTIVES: To define the level of pathogen-specific immune reconstitution persisting over 3 to 5 years of highly active antiretroviral therapy (HAART) in HIV-infected patients who began therapy with CD4 T-cell counts below 50 cells/microL. METHODS: Cytomegalovirus (CMV)-specific T-cell responses were analysed in adult HIV-1-infected patients with nadir CD4 T-cell counts below 50 cells/microL before HAART. CMV-specific CD4 T-cell responses were measured by interferon-gamma enzyme-linked immunospot assay (ELISpot assay), lymphoproliferation and interferon-gamma levels in cell culture supernatants. RESULTS: CD4 T-cell responses to CMV were low in untreated patients and remained low during the first year on HAART, but increased progressively to levels similar to those found in HIV-seronegative CMV-seropositive controls at 3 years. Responses then declined markedly and at 5 years were lower than controls. This could not be explained by changes in CD4 or CD8 T-cell counts or plasma HIV RNA levels. Interferon-gamma and interleukin-5 responses to a mitogen were maintained or elevated. CONCLUSIONS: CMV-specific CD4 T-cell responses were found to decline after 3-5 years on HAART and may provide inadequate long-term protection against CMV disease in patients who are severely immunodeficient prior to treatment.

Persistent HIV-1 replication does not explain low levels of T-cell interferon-gamma mRNA and elevated serum NO(2) (-)/NO(3) (-) in patients with stable CD4 T-cell responses to HAART.

HIV-1 infected patients adherent to HAART and displaying stable increases in CD4 T-cell counts differ in their control of HIV replication and one might expect this to reflect depressed immune function. The importance of virological control in functional immune reconstitution was investigated in HIV-1 infected patients who maintained high or undetectable plasma HIV RNA levels over 2-4 years on HAART (discordant and complete responders, respectively). Immunocompetence and immune activation were assessed directly ex vivo and after a short period of culture, as HIV replication in cultures from viraemic patients may artificially depress responses. Expression of cytokine (interferon-gamma, interleukin-5) and chemokine receptor (CCR5, CRTH2) mRNA were determined and soluble CD30 and NO(2) (-)/NO(3) (-) were measured in sera. Unstimulated cells from all patients had low levels of IFNgamma mRNA relative to uninfected controls. Discordant responders had more IFNgamma, IL-5 and CCR5 mRNA in mitogen-stimulated PBMC than complete responders, where the difference could be attributed to CD8-T-cells. Serum NO(2) (-)/NO(3) (-) levels were significantly higher in all patients than controls, with no difference between complete and discordant responders. Serum CD30 levels were significantly higher in discordant responders. These data indicate a persistent immune deficit in immune reconstituted patients irrespective of HIV viral load and associate persistent viral replication with lymphocyte activation, probably involving CD8 T-cells.

Peyronie's disease in men with HIV responding to highly active antiretroviral therapy.

The pathogenesis of Peyronie's disease (induratio penis plastica) is unclear, but immune phenomena appear likely to be involved. Two cases are presented where the condition developed in temporal association with a virological response to highly active antiretroviral therapy (HAART) in men with HIV infection. It is suggested that this may represent another manifestation of immune restoration disease.

Graves' disease during immune reconstitution after highly active antiretroviral therapy for HIV infection: evidence of thymic dysfunction.

A patient with HIV infection who experienced immune reconstitution after highly active antiretroviral therapy (HAART) [increase in CD4 T cell count from <1/microl to >600/microl] presented with severe Graves' disease 32 months after commencing HAART. A comprehensive clinical and laboratory study demonstrated pronounced regional lymphadenopathy and thymic enlargement at presentation, and that the onset of thyrotropin receptor antibody production was associated with increased production of soluble CD30 (a marker of type 2 immune responses). Blood naive CD8 T cell counts and TREC levels in both CD4 and CD8 T cells were increased at multiple time points compared with carefully selected controls. We conclude that the Graves' disease in this patient was associated with abnormally high blood counts of thymus-derived T cells, and propose that Graves' disease after HAART in this and other HIV patients may result from failure to delete autoreactive T cell clones in the regenerating thymus.

Endothelial function in HIV-infected patients receiving protease inhibitor therapy: does immune competence affect cardiovascular risk?

BACKGROUND: The use of HIV protease inhibitors (PIs) as a component of combination antiretroviral therapy in HIV-infected patients has been associated with dyslipidaemia, but its significance as a risk factor for cardiovascular disease is unclear. Endothelial dysfunction is an early phase of atherogenesis that may be assessed non-invasively with ultrasonography in vivo. AIM: To evaluate vascular function and investigate potential determinants of endothelial dysfunction of the peripheral circulation in PI-treated, HIV-infected men with dyslipidaemia. DESIGN: Observational, case-control study. METHODS: We studied 24 HIV-infected, PI-treated men with dyslipidaemia and 24 normolipidaemic, healthy male controls matched for age and body mass index. Brachial artery endothelial function was studied using high-resolution ultrasound and computerized edge-detection software. This non-invasive technique measured post-ischaemic flow-mediated dilatation (FMD), and the endothelium-independent vasodilatory response to glyceryl trinitrate (GTN). RESULTS: Within the HIV patient group, FMD was significantly associated with percentage of 'naïve' CD4 + 45RA + T cells (p = 0.03), while plasma lipid/lipoprotein and insulin levels, body mass, and smoking status did not correlate with endothelial function. FMD was not significantly different between the study group and the controls. CONCLUSIONS: The atherogenic potential of PI-associated dyslipidaemia may be attenuated in HIV-infected patients with decreased immune competence, reflecting a possible contribution of cell-mediated immune responses to the pathogenesis of atherosclerosis.

Combined analysis of two-year follow-up from two open-label randomized trials comparing efficacy of three nucleoside reverse transcriptase inhibitor backbones for previously untreated HIV-1 infection: OzCombo 1 and 2.

PURPOSE: To compare inhibition of HIV replication, improvements in CD4+ T-cell counts, metabolic parameters, and body shape changes after 2 years of assigned therapy in OzCombo patients. METHOD: Study participants were those who were recruited into the open-label OzCombo 1 (1996/1997) and OzCombo 2 (1997/1998) trials. Patients in OzCombo 1 were randomized to receive indinavir in combination with zidovudine+lamivudine (AZT+3TC; n = 35), stavudine (d4T)+3TC (n = 34), or d4T+didanosine (ddI) (n = 37). OzCombo 2 patients were randomized to the same nucleoside reverse transcriptase inhibitor (NRTI) backbones with nevirapine (n = 20, 22, 23, respectively). The mean time-weighted changes from baseline in CD4 T-cell count/mL, HIV RNA (log copies/mL plasma), and proportions with detectable viral load (<500 copies plasma HIV RNA/mL) between NRTI arms over 2 years were compared by formal meta-analysis. A cross-sectional study of metabolic and body shape complications was also undertaken. RESULTS: For the comparison of d4T+3TC and d4T+ddI to AZT+3TC, mean differences in time-weighted change from baseline in CD4 T-cell count/microL and log copies HIV RNA/mL adjusted for baseline CD4+ T-cell and HIV RNA counts were: -44 (p =.08) and -14 (p =.56) cells/microL and -0.1 (p =.40) and -0.1 (p =.6) copies/mL. Odds ratios for detectable viral load in the last study quarter were 0.6 (p =.44) and 1.0 (p =.95). The mean percent leg fat was lower in the d4T+3TC and d4T+ddI than the AZT+3TC arm (mean difference 5.1% [p =.07] and 7.6% [p =.02], respectively). CONCLUSION: For all regimens, virological control and immunological response were maintained over 2 years. Regimens containing d4T and particularly d4T+ddI were significantly associated with increased peripheral fat loss compared with AZT+3TC.

Distribution of human CD30 gene promoter microsatellite alleles in healthy and human immunodeficiency virus-1 infected populations.

The human CD30 gene, found on chromosome 1; 1p36, contains a microsatellite of the type [(CCAT)2-12CCACTTATGCAT]n within the promoter. As the microsatellite has been shown to be both polymorphic and involved in the transcriptional regulation of this gene, it is of potential interest with respect to interindividual differences in CD30 expression. Here we describe a method for determining length variation of this repeat region and determine the frequency and distribution of alleles of the CD30 microsatellite within the Western Australian population. As soluble CD30 levels are predictive for disease associated with human immunodeficiency virus (HIV)-1 infection, we also determined allele frequencies in an HIV+ cohort.

Levels of IL-6 and soluble IL-6 receptor are increased in HIV patients with a history of immune restoration disease after HAART.

OBJECTIVES: We have previously described immune restoration diseases (IRD) associated with asymptomatic opportunistic infections presenting in immunodeficient HIV patients responding to highly active antiretroviral therapy (HAART). Here we address the question of whether patients with a history of IRD exhibit persistent immune activation, shown by elevated levels of interleukin-(IL)-6 and soluble IL-6 receptor (sIL-6R). METHODS: Peripheral blood mononuclear cells (PBMCs) and plasma were collected from HIV patients with nadir CD4 T cell counts of < 80/microL and who had achieved immune reconstitution after HAART with (n=14) or without (n=15) experiencing IRD, severely immunodeficient (SID) patients with < 80 CD4 T cells/microL (n=8) and HIV seronegative controls (n=15). PBMC production and plasma levels of IL-6, sIL-6R and interferon (IFN)-gamma (PBMC only) were measured by enzyme linked immunosorbent assay (ELISA). Intracellular flow cytometry was used to determine the predominant cellular source of IL-6 in HIV patients and controls. RESULTS: Unstimulated PBMC from IRD patients produced significantly higher amounts of IL-6 and sIL-6R than non-IRD patients and HIV seronegative controls. The sIL-6R concentration was also significantly higher in supernatants from mitogen-stimulated PBMC from IRD patients compared to non-IRD patients. The production of IFN-gamma did not differ between IRD and non-IRD patients. IRD patients had significantly higher plasma levels of IL-6 compared to non-IRD patients, SID patients and controls. Monocytes were the predominant source of IL-6 in both HIV patients and controls. CONCLUSIONS: Patients with a history of IRD after HAART have elevated levels of IL-6 and sIL-6R.

An evaluation of serum soluble CD30 levels and serum CD26 (DPPIV) enzyme activity as markers of type 2 and type 1 cytokines in HIV patients receiving highly active antiretroviral therapy.

This study evaluates serum CD26 (dipeptidyl peptidase IV, DPPIV) enzyme activity and serum levels of soluble CD30 as markers of T1 and T2 cytokine environments in HIV patients who achieved immune reconstitution after highly active antiretroviral therapy (HAART). Patients who had experienced inflammatory disease associated with pre-existent opportunistic infections after HAART (immune restoration diseases, IRD) were considered separately. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were compared with IFN-gamma production by PBMC cultured with cytomegalovirus (CMV) antigen in controls and patient groups. High sCD30 levels were associated with low IFN-gamma production after antigenic stimulation in control subjects and, to a lesser extent, in immune reconstituted HIV patients. There was no association between serum CD26 (DPPIV) enzyme activity and IFN-gamma production or sCD30 levels. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were significantly increased in immune reconstituted patients with high HIV viral loads. Patients who had experienced CMV retinitis as an IRD had significantly higher sCD30 levels than all other patient groups. Hence, high sCD30 levels may be a marker of a T2 cytokine environment in HIV patients with immune reconstitution and are associated with higher HIV viral loads and a history of CMV associated IRD.