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The Novel Effects of a Hydrolyzed Polysaccharide Dietary Supplement on Immune, Hepatic, and Renal Function in Adults with HIV in a Randomized, Double-Blind, Placebo-Control Trial.
Lewis, JE, Atlas Bsn, SE, Abbas, MH, Rasul, A, Farooqi, A, Lantigua, LA, Michaud, F, Goldberg, S, Lages, LC, Higuera, OL, et al
Journal of dietary supplements. 2020;(4):429-441
Abstract
The primary objective of the study was to evaluate the effects of a hydrolyzed polysaccharide, rice bran arabinoxylan compound (RBAC), on immune, hepatic, and renal function in HIV + individuals. A 6-month randomized double-blind placebo-controlled trial was utilized to conduct the intervention. Forty-seven HIV + individuals on stable antiretroviral therapy were enrolled and randomly assigned to one of the 2 study conditions (n = 22 RBAC and n = 25 placebo) and consumed 3 gram/day of either compound for 6 months. Participants were assessed at baseline and 3 and 6 months follow-up for CD4+ and CD8+, liver enzymes, and kidney function. No side effects were reported, and liver and kidney markers remained nearly completely within normal limits. The percentage change in CD4+ was similar for the placebo (+2.2%) and RBAC (+3.1%) groups at 6 months follow-up. The percentage change in CD8+ count significantly decreased from baseline to 6 months in the RBAC group (-5.2%), whereas it increased in the placebo group (+57.8%; p = 0.04). The CD4+/CD8+ ratio improved clinically in the RBAC group from 0.95 (SD = 0.62) at baseline to 1.07 (SD = 0.11) at 6 months, whereas it declined in the placebo group from 0.96 (SD = 0.80) at baseline to 0.72 (SD = 0.59) at 6 months. Our results showed a statistically significant decrease in CD8+ count and a clinically significant increase in CD4+/CD8+ ratio for the RBAC group compared to the placebo group. Thus, the results of this study suggest that the immunomodulatory and antisenescent activities of RBAC are promising for the HIV population.
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The impact of integrase inhibitor-based regimens on markers of inflammation among HIV naïve patients.
Quiros-Roldan, E, Castelli, F, Bonito, A, Vezzoli, M, Calza, S, Biasiotto, G, Zanella, I, ,
Cytokine. 2020;:154884
Abstract
The use of combination anti-retroviral therapy (cART) correlates with longer and healthier life and with nearly normal life expectancy in people living with HIV. However, cART does not completely restore health. Chronic immune activation and inflammation persist in treated patients and have been described as predictors for clinical events and mortality in HIV-infected patients. Limited information is available on the impact of the various cART regimens on inflammation/immunoactivation. The aim of this work was to explore the impact of elvitegravir, dolutegravir, raltegravir (integrase strand transfer inhibitors, INSTIs) and atazanavir (protease inhibitor, PI) on several soluble markers of immune activation and inflammation during the first year of effective combination anti-retroviral therapy (cART). We conducted an observational retrospective cohort study in HIV-infected cART-naïve patients who initiated an INSTI or atazanavir regimen between March 2015 and February 2016 and a serum sample was available at baseline, 6 and 12 months after initiation. We compared the trend of D-Dimer, TNF- α, IL-2, IL-6, IL-7, IL-10, CCL4/MIP1-β, CCL5/RANTES, s-CD14, s-CD163, hs-CRP levels among the 4 arms of treatment. Percentage of variation from baseline was also measured for all markers. A total of 36 patients were included. We observed heterogeneous modifications in inflammation markers among arms. In particular, we noted that EVG have significant negative effect on s-CD14, hs-CRP, IL-6 and D-Dimer in respect to other INSTIs and this different effect occurs mainly during the first 6 months of cART. IL-7 values increased in the three arms with INSTIs (significantly only in EGV, 159.8%, p = 0.0003) and decreased significantly in patients on PI (-48.96%; p = 0.04) over the period. In conclusion, our results provide further data on changes of inflammatory marker levels, especially for the new INSTIs. Our data show that among INSTIs, EVG seems to have a worse impact on inflammation.
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Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: A systematic review and meta-analysis.
Abate, BB, Aragie, TG, Tesfaw, G
PloS one. 2020;(9):e0238403
Abstract
BACKGROUND Malnutrition on the background of HIV (Human Immunodeficiency Virus) infection is a complex medical condition that carries significant morbidity and mortality for affected children, with greater mortality from SAM (Severe Acute Malnutrition) among HIV-positive children than their HIV-negative peers. HIV-induced immune impairment heightened risk of opportunistic infection and can worsen nutritional status of children. HIV infection often leads to nutritional deficiencies through decreased food intake, mal-absorption and increased utilization and excretion of nutrients, which in turn can hasten death. OBJECTIVE The aim of this systematic review and meta-analysis was to assess the magnitude of underweight, wasting and stunting among HIV positive children in East Africa. METHODS The authors systematically reviewed and meta-analyzed studies that assessed the prevalence of underweight, wasting and stunting among HIV positive children in East Africa from PubMed, Cochrane Library, Google Scholar, and Gray Literatures using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. The last search date was December 30/2019. The data was extracted in excel sheet considering country, study design, year of publication, prevalence reported. Then the authors transformed the data to STATA 14 for analysis. Heterogeneity across the studies was assessed by the Q and the I2 test. A weighted inverse variance random-effects model was used to estimate the magnitude of underweight, wasting and stunting. The subgroup analysis was done by country, year of publication, and study design. To examine publication bias, a funnel plot and Egger's regression test were used. RESULTS For the analysis a total of 22 studies with 22074 patients were used. The pooled prevalence of under-weight, wasting, and stunting among HIV positive children in East Africa was found to be 41.63% (95%CI; 35.69-47.57; I2 = 98.7%; p<0.001), 24.65% (95%CI; 18.34-30.95; I2 = 99.2%; p<0.001), and 49.68% (95%CI; 42.59-56.77; I2 = 99.0%; p<0.001) respectively. The prevalence of under-weight among HIV positive children was found to be 49.67% in Ethiopia followed by 42.00 in Rwanda. It was high among cohort studies (44.87%). Based on the year of publication, the prevalence of under-weight among HIV positive children was found to be 40.88% from studies conducted from January 2008-December 2014, while it was 43.68% from studies conducted from 2015-2019. The prevalence of wasting among HIV positive children was found to be 29.7% in Tanzania followed by 24.94% in Ethiopia. Based on the study design, the prevalence of wasting among HIV positive children was found to be high in cohort studies (31.15%). The prevalence of stunting among HIV positive children was found to be 51.63% in Ethiopia, followed by 48.21% in Uganda. CONCLUSIONS The results presented above provide evidence of a higher prevalence of under nutrition among HIV positive children in East Africa. Despite the country level variations of child under nutrition in East Africa, still it is high in all aspects compared to the studies from other parts of Africa. It is recommended that further systematic review and meta-analysis need to be conducted on magnitude of malnutrition among HIV positive children in Sub-Saharan Africa as a whole.
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Real word outcomes associated with use of raltegravir in older people living with HIV: results from the 60 months follow-up of the RAL-age cohort.
Santinelli, L, Ceccarelli, G, Borrazzo, C, Celani, L, Pavone, P, Innocenti, GP, Spagnolello, O, Fimiani, C, Ceci, F, Di Sora, F, et al
Expert review of anti-infective therapy. 2020;(5):485-492
Abstract
Objective: In people living with HIV (PLWH), antiretroviral treatments have increased the median life expectancy. Raltegravir (RAL) represents a long-term safe regimen used both in the first-line antiretroviral treatments and in the optimization strategies. Aim of the study was to evaluate the real-life efficacy, tolerability, and safety of the long-term RAL use in a multicenter cohort of elderly PLWH.Methods: A 60-month follow-up observational study was carried out in the RAL-AGE Cohort including aged PLWH (≥60 years old) treated with RAL-based regimens (n = 96). The control group was a cohort of PLWH aged less than 60 years (n = 50).Results: RAL treated aged HIV population experiences an increase of CD4+ cells and a stable control of viral load at 60 months of follow-up. A significant improvement in lipid metabolism profile, a decrease of platelet count and a reduction in cardiovascular risk levels were observed in the older population. Immune activation markers expressed on CD4+ T cells decreased compared to baseline, but this difference was greater in the control group.Conclusion: A 60-month treatment with RAL-containing regimens is safe and highly effective in the older PLWH and these data give new insights on the elderly population.Clinical trial registration: NCT02765776 and NCT03579485.
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Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors.
De Francesco, D, Sabin, CA, Reiss, P, Kootstra, NA
Frontiers in immunology. 2020;:581616
Abstract
MOTIVATION People with HIV on successful antiretroviral therapy show signs of premature aging and are reported to have higher rates of age-associated comorbidities. HIV-associated immune dysfunction and inflammation have been suggested to contribute to this age advancement and increased risk of comorbidities. METHOD Partial least squares regression (PLSR) was used to explore associations between biological age advancement and immunological changes in the T cell and monocyte compartment in people with HIV (n=40), comparable HIV-negative individuals (n=40) participating in the Comorbidity in Relation to AIDS (COBRA) cohort, and blood donors (n=35). RESULTS We observed that age advancement in all three groups combined was associated with a monocyte immune phenotypic profile related to inflammation and a T cell immune phenotypic associated with immune senescence and chronic antigen exposure. Interestingly, a unique monocyte and T cell immune phenotypic profile predictive for age advancement was found within each group. An inflammatory monocyte immune phenotypic profile associated with age advancement in HIV-negative individuals, while the monocyte profile in blood donors and people with HIV was more reflective of loss of function. The T cell immune phenotypic profile in blood donors was related to loss of T cell function, whereas the same set of markers were related to chronic antigen stimulation and immune senescence in HIV-negative individuals. In people with HIV, age advancement was related to changes in the CD4+ T cell compartment and more reflective of immune recovery after cART treatment. IMPACT The identified monocyte and T cell immune phenotypic profiles that were associated with age advancement, were strongly related to inflammation, chronic antigen exposure and immune senescence. While the monocyte and T cell immune phenotypic profile within the HIV-negative individuals reflected those observed in the combined three groups, a distinct profile related to immune dysfunction, was observed within blood donors and people with HIV. These data suggest that varying exposures to lifestyle and infection-related factors may be associated with specific changes in the innate and adaptive immune system, that all contribute to age advancement.
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Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives.
Achilles, SL, Meyn, LA, Mhlanga, FG, Matubu, AT, Stoner, KA, Beamer, MA, Chirenje, ZM, Hillier, SL
American journal of reproductive immunology (New York, N.Y. : 1989). 2020;(3):e13287
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PROBLEM Contraceptive hormones are systemically active, potent, and likely to invoke biological responses other than known fertility regulation impacts. We hypothesized that initiation of depot medroxyprogesterone acetate (DMPA) would increase genital HIV-target-cells and soluble immune mediators compared with baseline and initiation of other contraceptive methods. METHOD OF STUDY We collected cervical cytobrushes and cervicovaginal fluid from healthy Zimbabwean women aged 18-34 to assess immune cell populations, cytokines, and innate anti-HIV activity at baseline and after 30, 90, and 180 days use of DMPA (n = 38), norethisterone enanthate (n = 41), medroxyprogesterone acetate/estradiol cypionate (n = 36), levonorgestrel implant (n = 43), etonogestrel implant (n = 47), or copper intrauterine device (Cu-IUD) (n = 45). Cells were quantified by flow cytometry, cytokines were detected by multiplex assays, and innate anti-HIV activity was assessed by in vitro HIV challenge. RESULTS Compared to baseline, the number of cervical HIV target cells (#CD4 cells P < .04 and #CD11c cells P < .04), the concentration of the inflammatory cytokine IL-1β (P < .01), and the innate in vitro anti-HIV activity (P < .001) significantly decreased following DMPA initiation. In Cu-IUD users, genital HIV target cells increased (#CD4 cells P < .001, #CD4CCR5 cells P = .02, #CD4CD69 cells P < .001, #CD8CD69 P = .01, and #CD11c cells P = .003) at day 30 and resolved by day 180. IFN-γ (P < .001), IL-1β (P < .001), IL-6 (P < .001), IL-8 (P < .001), IL-10 (P < .01), and RANTES (P < .001) were also significantly increased at day 30. Minimal alterations were observed following initiation of subdermal implantable contraceptives. CONCLUSIONS This head-to-head study compared six contraceptives and found increased HIV target cells and cervical inflammation temporally associated with Cu-IUD initiation. Use of hormonal contraception, including DMPA, did not increase cervical HIV target cells or inflammation. Clinical Trial Number: NCT02038335.
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Review on the Alteration of Gut Microbiota: The Role of HIV Infection and Old Age.
Ashuro, AA, Lobie, TA, Ye, DQ, Leng, RX, Li, BZ, Pan, HF, Fan, YG
AIDS research and human retroviruses. 2020;(7):556-565
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Human immunodeficiency virus (HIV) infection results in gut microbiota alteration and this is associated with immune activation and chronic inflammation. The gastrointestinal tract is a primary site of viral replication and thus HIV-induced loss of T-helper (Th) cells in the gut causes impairments in intestinal barriers, resulting in disruptions in intestinal immunity and precipitating into gut dysbiosis. Here, we show that late HIV diagnosis can negatively affect the immunological, virological, and clinical prognosis of the patients with its higher implication at an older age. Further, the review indicates that antiretroviral therapy affects the gut microbiota. We discussed the use of probiotics and prebiotics that have been indicated to play a promising role in reversing gut microbiota alteration in HIV patients. Though there are several studies reported with regard to such alterations in gut microbiota regarding HIV infection, there is a need to provide comprehensive updates. It is, therefore, the objective of this review to present most recently available evidence on the alteration of gut microbiota among HIV patients.
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Brief Report: Dipyridamole Decreases Gut Mucosal Regulatory T-Cell Frequencies Among People With HIV on Antiretroviral Therapy.
Mallarino-Haeger, C, Abebe, KZ, Jackson, EK, Zyhowski, A, Klamar-Blain, C, Cyktor, JC, Comer, D, Brand, RM, Gillespie, DG, Holleran, K, et al
Journal of acquired immune deficiency syndromes (1999). 2020;(5):665-669
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BACKGROUND We had previously conducted a double-blind, randomized placebo-controlled, partial cross-over trial showing that 12 weeks of dipyridamole decreased CD8 T-cell activation among treated HIV(+) individuals by increasing extracellular adenosine levels. METHODS In this substudy, rectosigmoid biopsies were obtained from 18 participants (9 per arm), to determine whether 12 weeks of dipyridamole affects mucosal immune cells. Participants randomized to placebo were then switched to dipyridamole for 12 weeks while the treatment arm continued dipyridamole for another 12 weeks. We evaluated T-cell frequencies and plasma markers of microbial translocation and intestinal epithelial integrity. Linear regression models on log-transformed outcomes were used for the primary 12-week analysis. RESULTS Participants receiving dipyridamole had a median 70.2% decrease from baseline in regulatory T cells (P = 0.007) and an 11.3% increase in CD8 T cells (P = 0.05). There was a nonsignificant 10.80% decrease in plasma intestinal fatty acid binding protein levels in the dipyridamole arm compared with a 9.51% increase in the placebo arm. There were no significant differences in plasma levels of β-D-glucan. In pooled analyses, there continued to be a significant decrease in regulatory T cells (-44%; P = 0.004). There was also a trend for decreased CD4 and CD8 T-cell activation. CONCLUSION Increasing extracellular adenosine levels using dipyridamole in virally suppressed HIV (+) individuals on antiretroviral therapy can affect regulation of gut mucosal immunity.
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Early Progression and Immune Reconstitution Inflammatory Syndrome During Treatment of Mild-To-Moderate Kaposi Sarcoma in Sub-Saharan Africa and South America: Incidence, Long-Term Outcomes, and Effects of Early Chemotherapy.
Nyirenda, M, Ngongondo, M, Kang, M, Umbleja, T, Krown, SE, Godfrey, C, Samaneka, W, Mngqibisa, R, Hoagland, B, Mwelase, N, et al
Journal of acquired immune deficiency syndromes (1999). 2020;(4):422-429
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BACKGROUND Early progression of AIDS-associated Kaposi sarcoma (KS-PD) and immune reconstitution inflammatory syndrome (KS-IRIS) sometimes occur after the initiation of antiretroviral therapy (ART). METHODS Early KS-PD and KS-IRIS were assessed in the A5264/AMC-067 trial in which participants with mild-to-moderate AIDS-KS were randomized to initiate ART with either immediate or as-needed oral etoposide. Early KS-PD was defined as tumor progression within 12 weeks of ART initiation. When investigators had concern that early KS-PD was KS-IRIS, additional evaluations were performed. Suspected KS-IRIS was defined as early KS-PD accompanied by a CD4 count increase of ≥50 cells per cubic millimeter or plasma HIV-1 RNA decrease of ≥0.5 log10 copies/mL. Clinical outcome was a composite end point categorized as failure, stable, and response at 48 and 96 weeks compared with baseline. RESULTS Fifty of 190 participants had early KS-PD (27%): 28 had KS-IRIS and 22 were not evaluated for KS-IRIS. Early KS-PD and KS-IRIS incidences with immediate etoposide versus ART alone were 16% versus 39%, and 7% versus 21%, respectively. Week 48 clinical outcome was 45% failure, 18% stable, and 37% response for no early KS-PD; 82% failure, 2% stable, and 16% response for early KS-PD; and 88% failure, 0% stable, and 12% response for KS-IRIS. Cumulative incidence of KS tumor response by week 96 was 64% for no early KS-PD, 22% with early KS-PD, and 18% with KS-IRIS. CONCLUSIONS Early KS-PD, including suspected KS-IRIS, was common after starting ART for AIDS-KS and was associated with worse long-term clinical outcomes. Starting ART concurrently with etoposide reduced the incidence of both early KS-PD and KS-IRIS compared with ART alone.
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Impact of counseling in knowledge, attitude and practice and association of nutritional status with CD4 count and opportunistic infections of HIV patients of Udupi, India.
Pokharel, P, Shettigar, PG
Clinical nutrition ESPEN. 2019;:154-159
Abstract
BACKGROUND AND AIMS HIV infection and insufficient nutritional intake form a malicious cycle which leads to immunodeficiency and malnutrition. Thus, this research was done to see the effect of nutritional counseling on knowledge, attitude and practice (KAP) of HIV patients of Udupi district. Also, the rational evidence of association of nutritional status with CD4 counts and opportunistic infections combined are limited which led to design of this study. METHODS This interventional study was done in ART Centre, Udupi, India with a sample size of 66 with 33 each in experimental and control group (EG and CG). At first, the biochemical parameters, KAP, 3 day dietary intake and food group intake over Food Frequency Questionnaire (FFQ) were recorded. PG-SGA (Scored Patient-Generated Subjective Global Assessment) scoring was used to categorize patients' nutritional status. Individual nutritional counseling was provided to EG and change in KAP of EG and CG were recorded after 1 month. RESULTS Pre-KAP mean of EG was 151.56 which increased to 169.13 after intervention. The mean KAP score of EG was statistically different from CG after counseling, P < 0.001. Of the total, 15 (22.7%) patients were found to be malnourished. The dietary intake of nutrients and food group was significantly lower than RDA. Tukey HSD post hoc analysis showed significant statistical difference for the CD4 count between moderate and severe malnourished category with P = 0.017. Statistically significant nutrient intake differences were also observed between PGSGA groups while odds ratio showed no significant association. CONCLUSIONS Improvement in KAP and poor nutritional status indicates that individual Nutrition and Health Education Counseling be made an integral part in the management of HIV in Udupi. Also, the difference in CD4 count across two PG-SGA stages depicts an association between nutritional status and immune status of HIV patients.