Markers Of HIV Disease Progression Research Articles

Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection.

Our understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children. We enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata. Children had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively). The gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.

Cannabis Use and Body Composition in People Living with HIV (PLWH) From the Miami Adult Studies on HIV (MASH) Cohort

ObjectivesCannabis is the most prevalently used substance in the United States and among people living with HIV (PLWH). Underserved minorities living with HIV suffer from high rates of obesity. Yet, little is known about the implications of cannabis use on body composition in PLWH. Thus, we sought to determine the association between cannabis use and body composition PLWH.MethodsIn this cross-sectional study, participants were selected from the ongoing Miami Adult Studies on HIV (MASH) cohort. Cannabis use was self-reported and confirmed with urinalysis for cannabis along with other illicit drugs (American Bio Medica Corp, Kinderhook, NY). Participants were selected if they did not use any illicit drugs and excluded if they used illicit drugs other can cannabis. Informed consent, demographics, and anthropometrics were collected by trained personnel. HIV viral load (VL, copies/mL), and CD4+ cells (cells/mL) were abstracted from medical records. Descriptive statistics were used to analyze demographics, cannabis use, overweight (BMI ≥ 25 kg/m2) and VL (suppressed VL < 50 copies/mL). SPSS 26 was used to analyze the linear association between cannabis use and BMI. Logistic regression calculated the odds ratio (OR) of cannabis use and overweight status. Independent sample t-test compared CD4+ cell count and VL between the cannabis-using and non-using groups.ResultsParticipants’ mean age was 53.6 ± 8.3 years (n = 346), 42.5% were female, 57.5% were Black, and 73.1% had a BMI ≥ 25 kg/m2 (overweight). Cannabis users accounted for 34.1% of the sample. The frequency of participants with a suppressed VL was 80.3%. No significant differences in CD4+ count or VL between the cannabis users and non-users (p > .05). Cannabis use was associated with a lower BMI adjusted for age, sex, race and ethnicity, CD4+ count, and VL (b = −1.8 SE = 0.83, p = .03). Also, cannabis use was associated with reduced odds of being overweight after adjusting for age, sex, race and ethnicity, CD4+ count, and VL (OR: 0.44, 95% CI: 0.23–0.83; p = 0.01).ConclusionsThe use of cannabis was associated with lower BMI and decreased odds of being overweight or obese. Cannabis use did not significantly affect crucial markers of HIV disease progression (CD4+ count and VL) negatively. Longitudinal research is needed to further assess these associations and determine its medicinal efficacy in weight management.Funding SourcesNIDA.

Dietary Components and Metabolites Are Associated with Liver Fibrosis in People Living with HIV (PLWH) in the MASH cohort

Abstract Objectives Distinct dietary components and microbiome metabolites may affect liver disease progression, a common comorbidity among people living with HIV (PLWH). Similarly, diet composition, including micronutrients, have been associated with markers of HIV disease progression (CD4 cell count). The objective of this study was to investigate the associations between dietary components, plasma metabolites, and liver fibrosis in PLWH. Methods A cross-sectional pilot study that enrolled 50 PLWH on antiretroviral therapy from the Miami Adult Studies on HIV (MASH) cohort. Diet quality was measured with the USDA Healthy Eating Index (HEI) and liver fibrosis was measured via the Fibrosis-4 Index (FIB-4). Microbiome metabolites were measured from plasma samples via metabolomics-non-targeted gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Statistical analysis included T-test, Chi-square, Spearman correlation, and Partial Least Squares Discriminant Analysis (PLS-DA). Results The participants’ mean age was 55 ± 6.81, 58% were male, and 68% were African Americans. FIB-4 and HEI seafood/plant protein score were inversely correlated (rho = -0.320, P = 0.022). There were also trends towards significance between CD4 cell count and seafood/plant protein score (rho = 0.251; P = 0.078), and CD4 cell count and greens/beans HEI score (rho = 0.269; P = 0.059). Microbiome metabolites that differed between the high and the low FIB-4 group using PLS-DA included 3-methylhistidine and phosphatidylcholine (PC) metabolites, often associated with meat consumption. Conclusions Lower liver fibrosis and higher CD4 cell count, a measure of HIV disease progression, were associated with consumption of foods typically high in micronutrients and fiber (seafood, plant protein, greens, and beans) in PLWH. Additionally, higher levels of 3-methylhistidine and PC metabolites, biomarkers associated with higher meat intake, were associated with higher liver fibrosis scores. These relationships confirm similar findings in the literature. Higher meat and lower vegetable intake are known risk factors for liver disease. These findings may provide the basis for larger studies and potential targets for dietary intervention in this population. Funding Sources National Institute on Drug Abuse and National Institute on Minority Health and Health Disparities.

Analysis of the CCR2-64I (rs1799864) genetic polymorphism distribution and its effect on the risk of HIV-1 infection and immunovirological outcomes in Moroccan ART-treated individuals

BackgroundSeveral studies have reported that the CCR2-64I genetic polymorphism influences the rate of markers of HIV-1 disease progression (HIV-1 viral loads and CD4+ T cell counts). However, the association between this mutation and HIV-1 infection among antiretroviral therapy (ART)-treated HIV-1 seropositive patients is controversial. In Morocco, no data is available regarding this polymorphism. ObjectivesIn the present case-control study, we aimed to investigate the frequency of the CCR2-64I genetic polymorphism and to evaluate the association of this mutant allele with susceptibility to HIV-1 infection and immunovirological outcomes in Morocco. MethodsWe recruited 100 HIV-1 seropositive patients (cases) undergoing antiretroviral therapy (ART) and 200 HIV-1 seronegative individuals from Mohammed V Military Training Hospital in Rabat. Genotyping of the CCR2-64I polymorphism was performed using Polymerase Chain Reaction (PCR) assay and automated DNA sequencing. The comparison between variables was performed using χ2-test, Fisher's exact test, or Mann–Whitney U test, as appropriate. Factors associated with immunovirological outcomes were assessed using logistic regression analysis. ResultsThe frequencies of CCR2-64V/CCR2-64V, CCR2-64V/CCR2-64I and CCR2-64I/CCR2-64I genotypes were 67, 30 and 3%, respectively among HIV-1 infected patients (cases), compared to 73, 24.50, and 2.50%, respectively, among HIV-1 uninfected individuals (controls). We didn't observe any statistically significant difference in the genotype distribution between cases and control groups. Additionally, the multivariate logistic regression analysis didn't reveal a significant association between the CCR2-64I polymorphism and the immunovirological outcomes after one year of ART (p> 0.05). ConclusionWe are the first to report the frequency of CCR2-64I polymorphism and its association with HIV-1 infection in Moroccan individuals. Our findings suggest that the CCR2-64I allele may not influence the susceptibility to HIV-1 infection, as was previously reported in other populations. Besides, we hypothesize that this mutation, independently of classical risk factors, may not impact the virological outcomes and immunological recovery among HIV-1 infected patients under treatment. Nevertheless, this result required confirmation by further large scale and extended follow-up studies, considering the low frequency of the CCR2-64I/CCR2-64I homozygous genotype in our population.

Effect of Withania somnifer on CD38 expression on CD8+ T lymphocytes among patients of HIV infection

CD38 on CD8 + T cells is considered a reliable marker of HIV disease progression. Withania somnifer, a traditional ayurvedic medicine, has Th1 immunomodulatory properties. PBMCs from 38 HIV patients were exposed to Withania somnifer root extract at standardized concentration. An overall decline in the percentage of CD38 expressing CD8 + T lymphocytes was observed, though the statistical significance was varied with different categories of HIV patients. Withania somnifer could have promising impact on HIV disease and therefore warrants a further study on larger parameters.

Investigation of CCR5-Δ32 (rs333) genetic polymorphism frequency and its relationship with HIV-1 susceptibility and disease progression: A Moroccan case-control study

BackgroundHost genetic factors are involved in resistance/susceptibility to HIV-1 infection and progression. The most relevant genetic variant of the gene encoding HIV-1 major co- receptor, CCR5-Δ32, has a protective effect against HIV-1 infection, and the prevalence of this mutation varies by ethnicity. In Morocco, only limited information is available concerning this protective allele. ObjectivesThe aim of this case-control study was to investigate the frequency of CCR5-Δ32 among HIV-1 infected and uninfected individuals in Morocco and to assess the association between this protective allele and HIV-1 susceptibility and disease progression. Patients and methodsA total of 148 HIV-1 seropositive (cases) and 342 healthy Moroccan individuals (controls) were recruited from Mohammed V Military Training Hospital in Rabat. The CCR5-Δ32 variant was analysed by Polymerase Chain Reaction (PCR) assay. Comparison of Genotype and allele frequencies between cases and controls was performed using the χ 2 test and the Fisher exact test. Association between CCR5-Δ32 polymorphism and HIV-1 disease progression was assessed using ANOVA test. Results7 of 148 (4.73%) HIV-1 seropositive (cases group) were heterozygous for the CCR5-Δ32 allele compared to 6 of 342 (1.75%) HIV-1 seronegative individuals (controls group). None of the analysed individuals had CCR5-Δ32 homozygous genotype. No statistical significant association was found in the genotype distribution between cases and controls. Also, we didn't observe any significant association between CCR5-Δ32 polymorphism and the markers of HIV-1 disease progression (HIV-1 viral load or CD4 cell counts) (p > 0.05). ConclusionThe present results are the first findings on the association of CCR5-Δ32 variant allele with HIV-1 susceptibility and the markers of HIV-1 disease progression among Moroccan HIV-1 seropositive patients. These results suggest that CCR5-Δ32 mutation may not affect HIV-1 susceptibility in heterozygous individuals. Given the low frequency of the Δ32 mutated allele in our population, further studies are needed to confirm our results and evaluate the relationship between CCR5-Δ32 polymorphism and HIV-1 disease progression in Morocco.

The association between cigarette smoking, virologic suppression, and CD4+ lymphocyte count in HIV-Infected Russian women

ABSTRACTCigarette smoking among people living with HIV/AIDS is associated with significant morbidity and mortality, but findings regarding the association between cigarette smoking and HIV viral load and CD4+ lymphocyte counts have been inconsistent. This study characterized the prevalence of cigarette smoking among HIV-infected Russian women and examined the association between smoking frequency and quantity and HIV viral load and CD4+ lymphocyte counts. HIV-infected Russian women (N = 250; M age = 30.0) in St. Petersburg, Russia, completed an audio computer-assisted self-interview survey assessing cigarette use, antiretroviral medication adherence, and provided blood samples assayed for HIV viral load and CD4+ lymphocyte counts. The majority (60.4%) reported cigarette smoking in the past month; 49.0% of recent smokers were classified as moderate or heavy smokers, defined as smoking ≥10 cigarettes daily. Viral load status did not differ between infrequent smokers and regular smokers. However, moderate/heavy smokers (relative to light smokers) were more likely to have a detectable viral load (AOR = 2.3, 95% CI: 1.1, 5.1). There were no significant differences in CD4+ lymphocyte counts by smoking frequency or quantity of cigarettes smoked. Results highlight the need for additional research to examine the association between cigarette smoking and virologic suppression and markers of HIV disease progression. Adverse health consequences of cigarette smoking coupled with a potential link between heavy smoking and poor virologic suppression highlight the need for assessment of cigarette use and provision of evidence-based smoking-cessation interventions within HIV medical care.

Plasma IP-10 Concentrations Correlate Positively with Viraemia and Inversely with CD4 Counts in Untreated HIV Infection.

Background:Chronic immune activation is a feature of HIV infection associated with accelerated HIV disease progression. There is conflicting data on the association of biomarkers of immune activation with traditional markers of HIV disease progression; CD4 counts and viral load (VL).Objective:The study aimed to determine the association of biomarkers of immune activation; interferon (IFN)-γ-induced protein 10 (IP-10) and soluble cluster of differentiation 14 (sCD14) in chronic HIV infection with traditional markers of HIV disease progression.Methods:We collected demographic data, enumerated CD4 counts and quantified VL in 183 antiretroviral therapy (ART)-naive adults with chronic HIV infection. Plasma concentrations of IP-10 and sCD14 were quantified in the ART-naive adults with chronic HIV infection and 75 HIV-uninfected controls.Results:IP-10 concentrations were significantly higher in the HIV-infected group (median; 257.40pg/ml, IQR; 174.08-376.32) than in the HIV-uninfected (median; 86.19pg/ml, IQR; 67.70-116.39) (P<0.001). Similarly, sCD14 concentrations were significantly higher in the HIV-infected (median; 1.45µg/ml, IQR; 1.02-2.16) group than in the controls (median; 0.89µ/ml, IQR; 0.74-1.18) (P<0.001). High log10 IP-10 concentrations were positively correlated with high log10 viral loads (Spearman’s correlation coefficient [R]=0.21, P=0.003) and inversely correlated with low CD4 counts (R= -0.19, P=0.011). In contrast, log10 sCD14 was not significantly associated with either log10 viral loads (R=0.03, P=0.707) nor CD4 count (R=-0.04, P=0.568).Conclusion:We conclude that plasma sCD14 and IP-10 were elevated in the HIV-infected patients compared to HIV-uninfected individuals possibly due to on-going immune activation. In addition, plasma high concentrations of IP-10 but not sCD14 concentrations are associated with high VL and low CD4 count.

The Relationship Between Caffeine Intake and Immunological and Virological Markers of HIV Disease Progression in Miami Adult Studies on HIV Cohort.

Although there are many studies on adverse health effects of substance use and HIV disease progression, similar studies about caffeine consumption are few. In this study, we investigated the effects of caffeine on immunological and virological markers of HIV disease progression. A convenience sample of 130 clinically stable people living with HIV/AIDS on antiretroviral therapy (65 consuming ≤250 mg/day and 65 consuming >250 mg/day of caffeine) were recruited from the Miami Adult Studies on HIV (MASH) cohort. This study included a baseline and 3-month follow-up visit. Demographics, body composition measures, substance use, Modified Caffeine Consumption Questionnaire (MCCQ), and CD4 count and HIV viral load were obtained for all participants. Multivariable linear regression and Linear Mixed Models (LMMs) were used to understand the effect of caffeine consumption on CD4 count and HIV viral load. The mean age of the cohort was 47.9 ± 6.4 years, 60.8% were men and 75.4% were African Americans. All participants were on ART during both the visits. Mean caffeine intake at baseline was 337.6 ± 305.0 mg/day and did not change significantly at the 3-month follow-up visit. Multivariable linear regressions after adjustment for covariates showed significant association between caffeine consumption and higher CD4 count (β = 1.532, p = 0.049) and lower HIV viral load (β = -1.067, p = 0.048). LMM after adjustment for covariates showed that the relationship between caffeine and CD4 count (β = 1.720, p = 0.042) and HIV viral load (β = -1.389, p = 0.033) continued over time in a dose-response manner. Higher caffeine consumption was associated with higher CD4 cell counts and lower HIV viral loads indicating beneficial effects on HIV disease progression. Further studies examining biochemical effects of caffeine on CD4 cell counts and viral replication need to be done in the future.

Study of serum albumin as surrogate marker of immune suppression in patients living with HIV and AIDS

Background: HIV/AIDS being a life long illness requires regular monitoring. CD 4 + cell counts and HIV RNA levels have been widely accepted as the most reliable indicators of HIV disease progression but these tests are not readily available and costly too. This study examines that whether Serum albumin levels can be used as a surrogate marker for HIV disease monitoring as an alternate to CD 4 cell count and HIV viral load measurements in low resource set-up. Methods: This prospective observational study was conducted at a tertiary care hospital in Central India. We studied a total of 100 PLHIV (patients living with HIV and AIDS). Correlation of CD 4 count was done with serum albumin levels at baseline and at follow-up visits. Results: Several studies have suggested that albumin could serve as a useful marker of HIV disease progression in resource-limited settings. In the present study, the baseline and follow up values of albumin and CD 4 counts were obtained. It was found to have a strong positive correlation amongst them with low CD 4 cell counts being associated with lower serum albumin concentrations. Conclusions: The results of this study suggest that serum albumin levels have potential to be used as a surrogate low-cost prognostic marker for HIV disease monitoring in resource-limited settings where frequent estimation of CD 4 cell count and HIV viral load is not possible.

Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8+ T cells in HIV/TB co-infection

The role of T-cell immunosenescence and functional CD8+ T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8+ T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8+ T cells, besides diminished expression of CD127 (IL-7Rα) on CD57+CD4+ T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8+ T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8+ T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8+ T cells.

Hepatitis C virus infection, HIV and pain sensitivity in opioid-dependent patients

s / Drug and Alcohol Dependence 146 (2015) e2–e33 e7 did not see amain effect for HIV or an interaction effect. Additional analyses will examine the potential moderating role of markers of HIV disease progression. Financial support: K23 DA-028660, T32 AI-007392. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.699 Predictors of substance use outcomes in mentorship for addiction problems Kathlene Tracy1, Mark Burton1, Matthew Warren1, Deborah Guzman1, Marc Galanter1, Theresa Babuscio2, Charla Nich2 1 Psychiatry, New York University School of Medicine, New York, NY, United States 2 Psychiatry, Yale University School of Medicine, New Haven, CT, United States Aims: We conducted a Stage Ia pilot to develop a new intervention, Mentorship for Addiction Problems (MAP), for individuals with substance use disorders in community treatment programsby pilot/feasibility testing, manual writing, training program development, and adherence/competence measure construction. We examined intervention and participant predictors of substance use outcomes. Methods: TenMentors participated for 6months in a piloting of MAP until 30 Mentees received MAP for 12 weeks. Behavioral and biological measures were conducted at baseline, weekly, monthly, and termination.Aseriesofbivariate regressionswereconducted to determine whether any treatment process or participant variables were associated with substance use outcomes. Results: Intervention Predictors. Mentor group supervision attendance was predictive of Mentee percentage of days abstinent from drugs and alcohol for Mentee weeks in treatment, R2 = .790, F(1, 8) = 30.13, p 3months). The independent variablewas HCV status (uninfected controls; mono-infected HCV+; or co-infected HCV+/HIV+). Chisquare and Kruskal-Willis tests were conducted. Results: The sample included 77 opioid-dependent adults: 23 uninfected controls, 35 HCV+, and 19 HCV+/HIV+. Mean age was 44 (SD±9) years, 48% were female, 32% non-white. Median duration on OAT was 2 years (range 1 month to 10 years), the majority (83%) were treated with buprenorphine. No significant differences were detected across groups for both primary and secondary outcomes. Median cold pain tolerance was 22 (controls) vs. 30 (HCV+) vs. 19 (HCV+/HIV+) s, (p=0.63).No significant effectswere found for cold pain thresholds or wind-up ratio. Chronic pain appearedmore prevalent among HCV+ (82%) compared to HCV+/HIV+ participants (63%) and controls (65%), though differences were not statistically significant (p=0.21). Conclusions: Among opioid dependent adults treated with OAT, we did not detect an association between HCV infection and increased pain sensitivity. Chronic pain may be more common amongHCVmono-infected individuals, however thismerits further investigation. Financial support: This study is supported by NIH/NIDA grant K23DA027367. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.701 Who in the world buys ARVs on the black market? The impact of drug use and ARV diversion on adherence Kiyomi Tsuyuki, Hilary Surratt, Maria A. Levi Minzi, Catherine L. O’Grady Center for Applied Research on Substance Use and Health Disparities, Nova Southeastern University, Miami, FL, United States Aims: Anti-retroviral (ARV) adherence is the most important predictor of regimen success and HIV viral suppression. HIVpositive drug users are found to have less access to ARV treatment and to initiate treatment at more advanced stages of infection than non-drug users. Recent studies also identify ARV diversion as a factor that may affect ARV adherence in drug users. This study

A novel Acute Retroviral Syndrome Severity Score predicts the key surrogate markers for HIV-1 disease progression.

Objective: Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression. Methods: We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined “Acute Retroviral Syndrome Severity Score” (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4+ cell count, and log viral setpoint (sVL) (i.e. VL measured ≥90 days after infection or treatment interruption).ResultsMean ARSSS was 2.89. CD4+ cell count at baseline was negatively correlated with ARSSS (p = 0.03, n = 289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n = 290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4+cell count decline of 12/µl, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p = 0.029, n = 64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p = 0.28, n = 40).ConclusionThe ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.

Tuberculosis distorts the inhibitory impact of interleukin-10 in HIV infection.

This study aimed to assess how Mycobacterium tuberculosis (MTB) coinfection alters the impact of interleukin-10 in chronic HIV infection. We assessed plasma cytokine levels (interleukin-10, interferon-γ, tumor necrosis factor-α, interleukin-2, interleukin-6 and interleukin-13) in 82 individuals presenting with HIV monoinfection, HIV-LTBI (latent MTB infection) coinfection or HIV-TB (active tuberculosis) coinfection. We also assessed the influence of MTB on the functional impact of interleukin-10 receptor alpha (interleukin-10Rα) blockade on HIV and MTB-specific CD4(+) T cells. Plasma cytokine levels were measured by high sensitivity Luminex. We used an ex-vivo interleukin-10Rα blockade assay to assess if functional enhancement of HIV and MTB-specific CD4(+) T cells was possible following a 48-h stimulation with HIV gag or pooled ESAT-6 (6 kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein) peptides. Cell supernatant was collected 48 h after stimulation and the cytokine profile was measured by Luminex. Plasma interleukin-10 levels were elevated in HIV-TB as compared with HIV monoinfection (P < 0.05) and HIV-LTBI (P < 0.05). Plasma interleukin-10 levels correlated to HIV viral load in HIV monoinfection (P = 0.016) and HIV-LTBI (P = 0.042), but not HIV-TB. Ex-vivo blockade of interleukin-10Rα significantly enhanced MTB and HIV-specific CD4(+) T-cell function in HIV-LTBI individuals but not in HIV-TB individuals. Tuberculosis disrupts the correlation between interleukin-10 and markers of HIV disease progression. In addition, HIV-TB is associated with a more inflammatory cytokine milieu compared with HIV monoinfection. Interestingly, interleukin-10Rα blockade can enhance both HIV and MTB-specific T-cell function in HIV-LTBI, but not in HIV-TB coinfection.

Protein intake is associated with HIV disease progression in HIV‐infected patients (810.9)

Background: This longitudinal study examines the effect of protein intake on markers of HIV disease progression.Methods: In a secondary analysis of data from 267 HIV+ patients on ART over a period of 6 months, we estimated protein intake from 24‐hour recalls and obtained CD4 cell counts and viral load from medical records. Multiple Linear Regressions and Mixed Models were used for over time analyses. Statistical significance was set at p&lt;0.05.Results: Participants mean age was 49±5 years, 62% were male and 71.3% were African Americans. Mean protein intake was 111±87 g/day (1.8 times the RDA for age and gender), mean CD4 cell count was 516.7±342 cells/μL and viral load 2.5±1.5 log10. Protein intake (g/day) was associated with decreased CD4 cell counts (β=‐0.68, p=0.05) and increased viral loads (β=51.27, p&lt;0.01) over time. This adverse relationship remained significant (β=44.4, p&lt;0.01), after adjusting for age and gender.Conclusion: The results suggest a detrimental relationship of excessive protein consumption with disease progression over time in HIV‐infected patients on ART.Grant Funding Source: NIDA

Role of metabolic syndrome and antiretroviral therapy in adiponectin levels and oxidative stress in HIV-1 infected patients

ObjectiveHIV-1 infection is accompanied by severe metabolic and immune dysfunction. The aim of this study was to evaluate the role of metabolic syndrome (MetS) and antiretroviral therapy (ART) utilization on the adiponectin levels and oxidative stress in patients infected with HIV-1. MethodsWe allocated 285 patients into four groups: group 1: patients without MetS who were not using ART; group 2: patients without MetS using ART; group 3: patients with MetS who were not using ART; and group 4: patients with MetS using ART. Biochemical, immunologic, and oxidative stress parameters were measured. ResultsGroup 4 exhibited higher lipoperoxides when compared with group 1 (P < 0.0001) and higher advanced oxidation protein products (AOPP) compared with group 2 or group 1 (P < 0.0001). Group 3 also presented higher AOPP than group 2 (P < 0.05). Group 4 showed lower adiponectin levels compared with groups 1 or 2 (P < 0.0001). Similarly, group 3 presented lower adiponectin levels compared with group 2 (P < 0.05) or group 1 (P < 0.0001). Multivariate analysis showed that both an increase in AOPP and a decrease in total radical-trapping antioxidant parameter/uric acid were independently associated with MetS in HIV-1 patients. Regarding immunologic markers of HIV-1 disease progression and viral replication, group 4 exhibited significantly higher CD45+, CD3+, and CD4+ T cells count compared with group 2 (P < 0.01). ConclusionHIV-1–infected patients with MetS exhibited hypoadiponectinemia and increased oxidative stress, and these findings were not influenced by ART use. The findings of the present study allow the suggestion that MetS and inflammation might be mainly responsible for the aforementioned features. More studies are needed to verify whether drugs or food, which yield increased adiponectinemia and decreased oxidative stress, could reduce cardiovascular risk in HIV-infected patients.

4.0 When to start

4.0 When to start

Impact of GB virus C viraemia on clinical outcome in HIV‐1‐infected patients: a 20‐year follow‐up study

The impact of coexisting GB virus C (GBV-C) infection on the clinical course of HIV infection remains controversial. Early data from HIV-1 infected patients attending the Hannover Medical School in 2001 suggested prognostic benefit in GBV-C viraemic patients. The aim of this study was to evaluate patterns in long-term mortality and morbidity outcomes in this cohort. The impact of the introduction of antiretroviral therapy (ART) on the perceived benefits of GBV-C viraemia was subsequently investigated. A retrospective follow-up analysis of data in this cohort was performed. GBV-C status (GBV-C RNA positive, antibodies against GBV-C envelope protein E2 or no evidence of GBV-C exposure) had been determined at enrolment, with several markers of HIV disease progression (such as viral load and CD4 cell count) being collated from 1993/1994, 2000 and 2012. These eras were chosen to reflect variations in treatment strategies within the cohort. In addition, mortality and HIV-related morbidity data were collated for all patients. Complete data were available for 156 of 197 patients (79%). In highly active antiretroviral therapy (HAART)-naïve patients, GBV-C RNA positivity conferred significant improvements in the course of HIV infection and mortality as well as lower rates of HIV-related diseases. E2 positivity alone conferred no significant advantage. With the advent of HAART, however, the benefits GBV-C RNA positivity disappeared. Although GBV-C coinfection appears to inherently improve morbidity and mortality in HIV-infected patients, modern HAART has eradicated these advantages. Evidence of synergy between GBV-C status and HAART response exists, with further studies examining the role of GBV-C in existing treatment de-escalation strategies being required.

Regulatory B cell frequency correlates with markers of HIV disease progression and attenuates anti-HIV CD8+ T cell function in vitro

HIV infection is associated with elevated expression of IL-10 and PD-L1, contributing to impairment of T cell effector functions. In autoimmunity, tumor immunology, and some viral infections, Bregs modulate T cell function via IL-10 production. In this study, we tested the hypothesis that during HIV infection, Bregs attenuate CD8(+) T cell effector function, contributing to immune dysfunction. We determined that in vitro, TLR2-, TLR9-, and CD40L-costimulated Bregs from HIV(-) individuals exhibited a high frequency of cells expressing IL-10 and PD-L1. Compared with Bregs from HIV(-) individuals, a significantly higher percentage of Bregs from HIV(+) individuals spontaneously expressed IL-10 (P=0.0218). After in vitro stimulation with HIV peptides, Breg-depleted PBMCs from HIV(+) individuals exhibited a heightened frequency of cytotoxic (CD107a(+); P=0.0171) and HIV-specific CD8(+) T cells compared with total PBMCs. Furthermore, Breg depletion led to enhanced proliferation of total CD8(+) and CD107a(+)CD8(+) T cells (P=0.0280, and P=0.0102, respectively). In addition, augmented CD8(+) T cell effector function in vitro was reflected in a 67% increased clearance of infected CD4(+) T cells. The observed Breg suppression of CD8(+) T cell proliferation was IL-10-dependent. In HIV(+) individuals, Breg frequency correlated positively with viral load (r=0.4324; P=0.0095), immune activation (r=0.5978; P=0.0005), and CD8(+) T cell exhaustion (CD8(+)PD-1(+); r=0.5893; P=0.0101). Finally, the frequency of PD-L1-expressing Bregs correlated positively with CD8(+)PD-1(+) T cells (r=0.4791; P=0.0443). Our data indicate that Bregs contribute to HIV-infection associated immune dysfunction by T cell impairment, via IL-10 and possibly PD-L1 expression.

Impact of age on markers of HIV-1 disease.

Aging is a complicated process characterized by a progressive loss of homeostasis, which results in an increased vulnerability to multiple diseases. HIV-1-infected patients demonstrate a premature aging phenotype and develop certain age-related diseases earlier in their lifespan than what is seen in the general population. Age-related comorbidities may include the development of bone disease, metabolic disorders, neurologic impairment and immunosenescence. Age also appears to have an effect on traditional markers of HIV-1 disease progression, including CD4+ T-cell count and viral load. These effects are not only a consequence of HIV-1 infection, but in many cases, are also linked to antiretroviral therapy. This review summarizes the complex interplay between HIV-1 infection and aging, and the impact that aging has on markers of HIV-1 disease.