Strongyloides hyperinfection in an HIV-positive kidney transplant recipient: a case report.

BACKGROUND: Strongyloidiasis is caused by the helminth Strongyloides stercoralis and is well-recognised amongst transplant recipients. Serious complications, including Strongyloides hyperinfection which is a syndrome of accelerated autoinfection, or disseminated disease, can occur post-transplantation, resulting in significant morbidity and mortality. Here we present the first published case we are aware of, describing post-transplant Strongyloides hyperinfection in an HIV-positive kidney transplant patient. We discuss the diagnostic challenges and the role of pre-transplant screening. CASE PRESENTATION: A 58-year-old African-American male, originally from the Caribbean, received a deceased donor kidney transplant for presumed focal segmental glomerulosclerosis. He was known to be HIV-positive, with a stable CD4 count, and an undetectable viral load. Five months post-transplant, he developed gastrointestinal symptoms and weight loss. He had a normal eosinophil count (0.1-0.2 × 109/L), negative serum cytomegalovirus DNA, and negative blood and stool cultures. His Strongyloides serology remained negative throughout. A diagnosis of Strongyloides hyperinfection was made by the histological examination of his duodenum and lung, which identified the parasites. He completed his course of treatment with Ivermectin but exhibited profound deconditioning and required a period of total parenteral nutrition. He was subsequently discharged after a prolonged hospital admission of 54 days. CONCLUSIONS: This case highlights the challenges in diagnosing Strongyloides infection and the need to maintain a high index of clinical suspicion. Non-invasive techniques for the diagnosis of Strongyloides may be insufficient. Routine pre-transplant serological strongyloidiasis screening is now performed at our centre.

Monocyte-macrophage activation is associated with nonalcoholic fatty liver disease and liver fibrosis in HIV monoinfection independently of the gut microbiome and bacterial translocation.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and the development of fibrosis in this population. OBJECTIVES: The aim of this study was to investigate the association of bacterial translocation, adipose tissue dysfunction, monocyte activation and gut dysbiosis in patients with HIV monoinfection and NAFLD. METHODS: Cases with biopsy-proven NAFLD and HIV monoinfection were age and sex-matched to HIV-positive and HIV-negative controls. Markers of bacterial translocation [lipopolysaccharide-binding protein (LBP), bacterial DNA and lipopolysaccharide (LPS)], adipose tissue dysfunction (leptin, adiponectin) and monocyte activation (sCD14 and sCD163) were measured by ELISA. Hepatic patterns of macrophage activation were explored with immunohistochemistry. 16 s rRNA sequencing was performed with stool. RESULTS: Thirty-three cases were included (≥F2 fibrosis n = 16), matched to HIV-positive (n = 29) and HIV-negative (n = 17) controls. Cases with NAFLD were more obese (BMI 31.0 ±â€Š4.4 vs. 24.1 ±â€Š2.8 kg/m, P < 0.001) and had significantly increased levels of sCD14, sCD163 and higher leptin to adiponectin ratio vs. HIV-positive controls. Cases with ≥F2 verses < F2 fibrosis had increased sCD14 (1.4 ±â€Š0.4 vs. 1.1 ±â€Š0.3 µg/ml, P = 0.023) and sCD163 (1.0 ±â€Š0.3 vs. 0.8 ±â€Š0.3 µg/ml, P = 0.060), which correlated with waist circumference (sCD14 P = 0.022, sCD163 P = 0.011). Immunohistochemistry showed increased hepatic portal macrophage clusters in patients with fibrosis. No markers of bacterial translocation or changes to the microbiome were associated with NAFLD or fibrosis. CONCLUSION: NAFLD fibrosis stage in HIV monoinfected patients is associated with monocyte activation in the context of obesity, which may be independent of bacterial translocation and gut microbiome.

Serum creatinine and estimated glomerular filtration rates in HIV positive and negative adults in Ethiopia.

BACKGROUND: Glomerular filtration rate estimating equations using serum creatinine are not validated in most African settings. We compared serum creatinine and estimated glomerular filtration rate (eGFR) in HIV positive and negative adults and assessed the performance of eGFR equations ((Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) compared to 24-hour creatinine clearance in HIV positive adults. METHODS: Data were collected on demographic, anthropometric, body composition, clinical parameters and serum creatinine in HIV positive and negative adults. 24-hour urine was collected from some of the HIV positive adults who volunteered. Bias was calculated as mean difference between 24-hr creatinine clearance and eGFR (eGFR- 24 hour creatinine clearance) and the accuracy of each eGFR equation was calculated as the percentage of estimates within 30% of creatinine clearance. RESULTS: A total of 340 HIV positive and 100 HIV negative adults were included in this study. Creatinine clearance was determined for 46 of HIV positive adults. Serum creatinine increased with increasing age, weight, height, body surface area, fat free mass and grip strength in both HIV positive and negative adults (P<0.05). No difference was observed in eGFR between HIV positive and HIV negative adults. For all eGFR equations, the correlation between eGFR and 24-hr creatinine clearance was 0.45-0.53 and the accuracy within 30% of 24-hr creatinine clearance was 24-46%. Removing ethnic coefficient reduced the bias and improved accuracy of the CKD-EPI and the MDRD estimates. CONCLUSION: Ethiopian HIV positive adults in the present study had good kidney function at the initiation of antiretroviral treatment. However, all eGFR equations overestimated 24-hr creatinine clearance in the study population. Creatinine based eGFR equations that accounts for low muscle mass and body surface area are needed.

Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial.

BACKGROUND: Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals. METHODS: We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per µL, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per µL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5 years. We analysed data on an intention-to-treat basis, and planned separate analyses in smokers and non-smokers because of the known effects of smoking on FEV1 decline. The substudy was registered at ClinicalTrials.gov number NCT01797367. FINDINGS: Between March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age 36 years (IQR 30-44), CD4 T-cell count 648 per µL (583-767), and HIV plasma viral load 4·2 log10 copies per mL (3·5-4·7). 29% were female and 28% were current smokers. Median follow-up time was 2·0 years (IQR 1·9-3·0). We noted no differences in FEV1 slopes between the immediate and deferred ART groups either in smokers (difference of -3·3 mL/year, 95% CI -38·8 to 32·2; p=0·86) or in non-smokers (difference of -5·6 mL/year, -29·4 to 18·3; p=0·65) or in pooled analyses adjusted for smoking status at each study visit (difference of -5·2 mL/year, -25·1 to 14·6; p=0·61). INTERPRETATION: The timing of ART initiation has no major short-term effect on rate of lung function decline in HIV-positive individuals who are naive to ART, with CD4 T-cell counts of more than 500 per µL. In light of updated WHO recommendations that all HIV-positive individuals should be treated with ART, regardless of their CD4 T-cell count, our results suggest an absence of significant pulmonary harm with such an approach. FUNDING: US National Heart Lung and Blood Institute, US National Institute of Allergy and Infectious Diseases, Division of AIDS, Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), Australian National Health and Medical Research Council, Danish National Research Foundation, European AIDS Treatment Network, German Ministry of Education and Research, UK Medical Research Council and National Institute for Health Research, and US Veterans Health Administration Office of Research and Development.

The prevalence of malaria among HIV seropositive individuals and the impact of the co- infection on their hemoglobin levels.

BACKGROUND: Malaria and HIV/AIDS are the two most common infections in sub-Sahara Africa. There are hypotheses and study reports on the possible association between these two infections, hence the prevalence and outcome of their co-infection in an endemic population will be important in defining healthcare strategies. A cross sectional study was carried out at the Holy Family Hospital in Techiman, Ghana, between November 2011 and January 2012, to determine the prevalence of malaria among HIV sero-positive patients and its impact on hemoglobin levels. METHOD: A total of 400 HIV sero-positive participants (292 females and 108 males) aged between 1 and 73 years were randomly sampled for the study. A questionnaire was administered and 2 ml of venous blood samples were drawn for malaria parasites detection, CD4 count and haemoglobin level estimations. RESULTS: Malaria parasites were detected in 47 (11.75%) of the participants. There was no statistically significant difference between the malaria prevalence rate of females (12.1%) and males (10.2%) P = 0.6047. An overall anaemia prevalence of 67% was observed. Among participants with malaria the anaemia prevalence was 93.6%. The CD4 cell count of all the participants ranged between 3 and 1604 cells/µl with a mean of 386.2 (±274.3) cells/µl. Participants with malaria had CD4 cell count ranged 3 and 512 Cells/µl with the mean being 186.33 (±133.49) Cells/µl. Out of 377 participants (all above 15 years) interviewed on knowledge of malaria transmission and prevention, 87.0% had knowledge on transmission but only 8.5% use in bed nets. CONCLUSION: It was revealed that almost all the patients with malaria infection were anemic.

Cathepsin B and cystatin B in HIV-seropositive women are associated with infection and HIV-1-associated neurocognitive disorders.

OBJECTIVE: HIV-1-associated neurocognitive disorders (HAND) is triggered by immune activation of brain cells and remain prevalent during progressive viral infection despite antiretroviral therapy. Cathepsins and cystatins are lysosomal proteins secreted by macrophages and microglia, and may play important roles in neuroregulatory responses. Our laboratory has shown increased secretion and neurotoxicity of cathepsin B from in-vitro HIV-infected monocyte-derived macrophages, and increased expression in postmortem brain tissue with HIV encephalitis and HAND. We hypothesized that cystatin B and cathepsin B could represent potential biomarkers for HAND. METHODS: Monocytes, plasma, and cerebrospinal fluid (CSF) from retrospective samples from 63 HIV-seropositive Hispanic women were selected for this study. These were stratified as 27 normal, 14 asymptomatic, and 22 HIV dementia, and as 14 progressors and 17 nonprogressors. Samples were evaluated for cystatins B and C and cathepsin B expression and activity. RESULTS: Increased cathepsin B and cystatins B and C were found in plasma of HIV-seropositive women. Higher intracellular expression of cathepsin B and cystatin B were found in monocytes from women with HIV-associated dementia (P < 0.05). Significant increase in cystatin B concentration in CSF was found in women with dementia compared with HIV-seropositive asymptomatic women. CONCLUSION: These results demonstrate that dysregulation of cystatin B-cathepsin B system is operative in HIV-associated neurocognitive impairment and suggests that intracellular expression of cystatin B and cathepsin B in monocytes could be potential candidate biomarkers for HIV dementia, whereas increased cathepsin B and cystatins B and C in plasma are potential candidate markers of chronic HIV-1 activation.

Polyneuropathy induced by HIV disease and antiretroviral therapy.

OBJECTIVE: To investigate the underlying mechanisms of polyneuropathy induced by HIV infection or antiretroviral drugs. METHODS: We tested 100 HIV patients (59 with AIDS). Ninety-three patients received antiretroviral drugs. Forty-four were treated with neurotoxic compounds (ddI, ddC, d4T). Nerve conduction velocities and the sympathetic skin response (SSR) in palms and soles were measured in all patients. In skin biopsies (ankle and thigh), the intraepidermal nerve fiber density (IENFD) and the number of epidermal fibers without contact to the basal membrane (fragments) were quantified using PGP9.5 staining. RESULTS: Severity of the disease (CD4 +count) correlated to conduction velocities of peroneal (p < 0.01, Spearmans rank correlation), sural (p < 0.01) and median nerves (p < 0.05/p < 0.001, sensory/motor). In contrast, the duration of neurotoxic treatment did not impair conduction velocities (p > 0.3) but correlated to reduced IENFD in the ankle (r = -0.24, p < 0.05). Despite their reduced IENFD, patients with long neurotoxic treatment had a high number of fragments irrespective of their CD4 +count. CONCLUSIONS: Neurotoxic treatment appears to primarily impair thin fiber conduction, whereas HIV neuropathy is linked to large fiber impairment and reduction of fragments of nerve fibers. SIGNIFICANCE: These findings emphasize the differential pattern of polyneuropathy in HIV patients caused by the infection or induced by antiretroviral treatment.

Endothelial dysfunction in HIV infection--the role of circulating endothelial cells, microparticles, endothelial progenitor cells and macrophages.

Endothelial dysfunction has emerged as one of the major mechanisms involved in the increased cardiovascular disease risk seen in the HIV population. Endothelial progenitor cells, circulating endothelial cells, endothelial microparticles, and platelet microparticles are all now considered as biomarkers of cardiovascular disease risk in otherwise healthy individuals. Preliminary evidence suggests that these biomarkers may similarly predict cardiovascular disease risk in HIV-infected patients, helping to assist in preventive and therapeutic decision making. This review updates the current knowledge and the most recent advances in the pathophysiology of cells and particles involved in atherosclerosis in the HIV setting. The potential usefulness of measuring cardiovascular disease risk biomarkers in HIV-infected individuals to prevent future cardiovascular events is further discussed.

Fractures after antiretroviral initiation.

BACKGROUND: Bone mineral density declines by 2-6% within 1-2 years after initiation of antiretroviral therapy (ART); however, it is uncertain whether this results in an immediate or cumulative increase in fracture rates. METHODS: We evaluated the incidence and predictors of fracture in 4640 HIV-positive participants from 26 randomized ART studies followed in the AIDS Clinical Trials Group (ACTG) Longitudinal-Linked Randomized Trial study for a median of 5 years. Fragility and nonfragility fractures were recorded prospectively at semiannual visits. Incidence was calculated as fractures/total person-years. Cox proportional hazards models evaluated effects of traditional fracture risks, HIV disease characteristics, and ART exposure on fracture incidence. RESULTS: Median (interquartile range) age was 39 (33, 45) years; 83% were men, 48% white, and median nadir CD4 cell count was 187 (65, 308) cells/µl. Overall, 116 fractures were reported in 106 participants with median time-to-first fracture of 2.3 years. Fracture incidence was 0.40 of 100 person-years among all participants and 0.38 of 100 person-years among 3398 participants who were ART naive at enrollment into ACTG parent studies. Among ART-naive participants, fracture rates were higher within the first 2 years after ART initiation (0.53/100 person-years) than subsequent years (0.30/100 person-years). In a multivariate analysis of ART-naive participants, increased hazard of fracture was associated with current smoking and glucocorticoid use but not with exposure to specific antiretrovirals. CONCLUSION: Fracture rates were higher within the first 2 years after ART initiation, relative to subsequent years. However, continuation of ART was not associated with increasing fracture rates in these relatively young HIV-positive individuals.

Impact of protective killer inhibitory receptor/human leukocyte antigen genotypes on natural killer cell and T-cell function in HIV-1-infected controllers.

OBJECTIVE: Both protective T-cell genotypes and natural killer (NK) cell genotypes have been associated with delayed progression to AIDS and shown to be co-inherited in HIV-1-infected individuals who limit viral replication in absence of antiretroviral therapy ('controllers'). However, a comparative analysis of the genotype and function of the innate and adaptive immune compartments in HIV-1-infected controller individuals has been understudied to date. DESIGN: Here, we simultaneously tested NK and T-cell function in controllers to investigate the mechanism(s) that might account for host immune control over viral replication. METHODS: We measured CD8 T-cell responses against HIV-1 utilizing overlapping 15-mer peptides spanning the HIV-1 consensus clade B Gag protein and tested NK cell degranulation and cytokine secretion against tumor target cells following interferon-α (IFNα) stimulation. RESULTS: Among a cohort of 37 controllers, the presence of protective major histocompatibility complex class I human leukocyte antigen (HLA) alleles (such as HLA-B*57) was not correlated with HIV-specific CD8 responses. In contrast, the inheritance of a protective killer inhibitory receptor KIR3DL1*h/*y receptor genotype along with the corresponding HLA-Bw4*80I ligand was associated with significantly heightened target cell-induced NK degranulation and cytokine secretion following IFNα stimulation (P = 0.0201, n = 13). Interestingly, we observed a significant inverse association between the IFNα stimulated NK response to K562 cells and the HIV-specific CD8 T-cell response to Gag among elite controllers (rho = -0.8321, P = 0.0010, n = 12). CONCLUSION: Together, these results suggest that heightened NK responses can be evidenced independently of HIV-specific T-cell responses in HIV-1-infected elite controllers.

Qualidade do sono em portadores do vírus da imunodeficiência humana / Sleep quality in HIV-positive outpatients / Calidad del sueño en portadores del virus de la inmunodeficiencia humana

Este estudo teve por objetivo caracterizar a qualidade do sono de pessoas com o vírus da imunodeficiência humana (HIV) - AIDS - , com ou sem manifestações clínicas e sob tratamento ambulatorial. Para tal, foi realizada pesquisa descritiva e transversal. Os instrumentos utilizados foram: Questionário de Caracterização Sociodemográfica e Clínica; Índice de Qualidade de Sono de Pittsburgh (PSQI-BR). Participaram da pesquisa 122 pacientes (55,7% de homens e 44,3% de mulheres, com idade média de 42,3 (± 8,9 anos), dos quais 53,3% referiram apresentar sono de boa qualidade e 46,7%, sono de má qualidade. Dormiam, em média, 7,3 (± 1,8) horas, com latência de 23,2 (± 26,2) minutos e eficiência do sono de 87,8% (± 14,4). Observou-se associação significativa entre o sono de boa qualidade e os seguintes fatores: ter companheiro(a); apresentar carga viral indetectável; manter comportamento de risco. Recomenda-se que os profissionais de enfermagem incluam sistematicamente questões sobre o sono ao avaliarem o paciente com HIV/AIDS, detectando alterações precocemente e reunindo subsídios para o planejamento de intervenções.

The objective of this study was to characterize the sleep quality of Human Immuno-Deficiency Virus (HIV) seropositive outpatients with or without AIDS symptoms. This is a descriptive and cross-sectional study. Sociodemographic and clinical data were collected by means of a questionnaire, and sleep quality by means of the Pittsburgh Sleep Quality Index, Brazilian version. Participants were 122 subjects (55.7% male, 44.3% female; mean age 42.3 ± 8.9 years); 53.3% reported good sleep quality and 46.7% reported poor sleep quality. Subjects reported sleeping a mean of 7.3 (± 1.8) hours; sleep latency was 23.2 (± 26.2) minutes, and sleep efficiency, 87.8% (± 14.4). A significant association was found between good sleep quality and: having a partner; undetectable viral load; and maintenance of risk behavior. It is recommended that nursing professionals systematically include questions regarding sleep when evaluating patients with HIV/AIDS, so that changes are detected early and relevant background information is obtained in order to plan interventions.

Se objetivó caracterizar la calidad del sueño de portadores del virus de inmunodeficiencia humana (VIH), con o sin manifestaciones clínicas de SIDA y bajo tratamiento ambulatorio. Investigación descriptiva y transversal. Los instrumentos utilizados fueron: Cuestionario de Caracterización Sociodemográfica y Clínica; Índice de Calidad del Sueño de Pittsburgh (PSQI-BR). Participaron 122 pacientes (55,7% hombres, 44,3% mujeres, edad promedio 42,3±8,9 años), de los cuales 53,3% refirieron buena calidad de sueño y 46,7% mala calidad. Dormían en promedio 7,3 (±1,8) horas, con latencia de 23,2 (±26,2) minutos y eficiencia del sueño de 87,8% (±14,4). Se observó asociación significativa entre buena calidad de sueño y: tener compañero; carga viral indetectable; observar comportamientos de riesgo. Se recomienda que los profesionales de enfermería incluyan sistemáticamente preguntas sobre el sueño al evaluar al paciente con VIH/SIDA, detectando alteraciones precozmente y reuniendo elementos útiles para planificación de intervenciones.

Performance of creatinine and cystatin C GFR estimating equations in an HIV-positive population on antiretrovirals.

OBJECTIVE: To evaluate the performance of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C, and creatinine-cystatin C estimating equations in HIV-positive patients. METHODS: We evaluated the performance of the Modification of Diet in Renal Disease (MDRD) Study and CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012, and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate (GFR) estimating equations compared with GFR measured using plasma clearance of iohexol in 200 HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were standardized to certified reference materials. RESULTS: Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an undetectable HIV viral load. Mean (SD) measured GFR (mGFR) was 87 (26) mL/min per 1.73 m. All CKD-EPI equations performed better than the MDRD Study equation. All 3 CKD-EPI equations had similar bias and precision. The cystatin C equation was not more accurate than the creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the cystatin C equation, and there was a trend toward greater accuracy than the creatinine equation. Accuracy was equal or better in most subgroups with the combined equation compared to either alone. CONCLUSIONS: The CKD-EPI cystatin C equation does not seem to be more accurate than the CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-EPI creatinine equation for routine clinical care for use in North American populations with HIV. The use of both filtration markers together as a confirmatory test for decreased estimated GFR based on creatinine in individuals who are HIV-positive requires further study.

People living with serious illness: stories of spirituality.

AIMS AND OBJECTIVES: To examine stories of spirituality in people living with serious illness. BACKGROUND: Although knowledge about the experience of people with various chronic illnesses is growing, there is little known about peoples' beliefs and perspectives relating to spirituality where there is a diagnosis of a serious chronic and life-limiting illness. DESIGN OF THE STUDY: A social constructionist approach to narrative inquiry was used. METHODS: In-depth narrative interviews were conducted on one occasion with 32 participants. This included 10 people with cancer, 14 people with end stage renal disease (ESRD) and eight people with HIV/AIDS. They ranged in age from 37-83 and included 18 men and 14 women. RESULTS: The themes were reflecting on spiritual religious and personal beliefs, crafting beliefs for their own lives, finding meaning and transcending beyond words. Participants melded various belief systems to fit their own lives. They also looked to find meaning in their illness experience and described what gave life meaning. For some aspects of these belief systems, participants could not or would not express themselves verbally, and it seemed that aspects of their experience were beyond language. CONCLUSIONS: The stories revealed considerable depth relating to perspectives on life, illness and existential questions, but many participants were not comfortable with the term 'spirituality'. RELEVANCE TO CLINICAL PRACTICE: Nurses must remain open to learning about belief systems of each individual in their care, regardless of that individual's declared religious affiliation or declaration of no religious affiliation, given that personal beliefs and practices do not always fit into specific categories.

Lessons learned from the first wave of aging with HIV.

In this perspective piece, the authors consider what has been learned and is being studied about aging with HIV in resource-rich settings. The authors argue that although there is much that will be different about aging with HIV in other parts of the globe, there are common themes and approaches to care. These include the observation that most patients have more than one health condition, and the need to assess individual risk, prioritize care, and consider the total burden of disease when considering further testing and treatment.

Immune reconstitution in HIV+ subjects on lopinavir/ritonavir-based HAART according to the severity of pre-therapy CD4+.

BACKGROUND: We aimed to assess the impact of TDF/FTC +LPV/r-based HAART on the quality of immune reconstitution and on microbial translocation (MT) in HIV-infected antiretroviral-na�ve late presenting patients. METHODS: 40 HIV+ antiretroviral-naive patients starting a first TDF/FTC+LPV/r HAART with CD4+≤350 cell/µL (20 "severe immune depression" patients -SID CD4+≤100/µL; 20 "moderate immune depression" patients -MID, CD4+ 200- 350/µL) were followed for 12 months (T12). CD38+CD8+, CD45R0+CD38+CD8+, CD95+CD4+/CD8+, CD127+CD4+/CD8+, pStat5 signalling (flow cytometry), plasma IL-7, sCD14 (ELISA), LPS (LAL) were tested at T0 and T12. RESULTS: By T12, both study groups displayed significant CD4+ increase and HIV-RNA reduction (p < .01). Despite similar CD38+CD8+ reduction in both SID (p=.039) and MID (p=.007), SID displayed a significant rise in CD45R0+CD38+CD8+ (p=.039). MID displayed significant increase of CD95+CD4+ (p=.002), with higher baseline and T12 levels (p=.024; p=.002), suggesting reduced commitment to apoptosis. At T12, different IL-7/IL-7R profile was shown according to pre-therapy immune depression. As compared to SID, MID increased circulating IL-7 (p=.049) displaying higher baseline and T12 CD127+CD4+ (p=.0001; p=.004) and CD127+CD8+ (p=.006; p=.009). By T12, only MID displayed significant reduction in LPS (p=.020) and sCD14 (p=.005). CONCLUSIONS: In antiretroviral-naive late presenters, we show different immune reconstitution quality and MT upon 12 months TDF/FTC+LPV/r-containing HAART according to the severity of pre-therapy immune depression. Despite equal T-cell activation decline, only MID patients tend to reduce pro-apoptotic T-lymphocytes, with a gain in circulating IL-7 and higher CD127+ central-memory T-cells, and a possible control over MT.

Relationship between total bilirubin and endothelial function, inflammation and oxidative stress in HIV-infected adults on stable antiretroviral therapy.

OBJECTIVES: Enhanced inflammation is evident in HIV infection, even with virological suppression. Outside HIV infection, studies show an independent association between higher total bilirubin and better endothelial function as well as a lower prevalence of coronary heart disease, possibly as a consequence of the anti-inflammatory and antioxidant effect of bilirubin. The aim of this study was to determine whether such an association exists in HIV-infected individuals. METHODS: A cross-sectional study was performed in HIV-1-infected adults on stable antiretroviral therapy (ART) to determine if a relationship exists between total bilirubin and endothelial function [flow-mediated dilation (FMD) of the brachial artery], inflammation [interleukin-6 (IL-6), soluble tumour necrosis factor receptors, C-reactive protein, and adhesion molecules], coagulation markers (fibrinogen and D-dimer) and oxidative stress (F (2) -isoprostanes). Endpoints were compared based on total bilirubin levels and atazanavir status using distributionally appropriate, two-sample tests. Correlation coefficients were determined between total bilirubin and endpoints. Linear regression was used to model the relationship between total bilirubin (and atazanavir status) and FMD. RESULTS: A total of 98 adults were included in the study. Total bilirubin was higher in the atazanavir group when compared to the non-atazanavir group [median (interquartile range) 1.8 (1.1-2.6) vs. 0.6 (0.4-1.4) mg/dL; P < 0.01] as were insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) and fibrinogen. Total bilirubin was positively correlated with fibrinogen and was not correlated with other outcomes. After adjustment, neither total bilirubin nor atazanavir status was associated with FMD. CONCLUSIONS: In virologically suppressed, HIV-infected adults on stable ART, neither total bilirubin nor atazanavir use was associated with improved endothelial function as measured using FMD, inflammation or oxidative stress as measured using biomarkers.

Relationship between inflammatory mediator patterns and anemia in HIV-1 positive and exposed children with Plasmodium falciparum malaria.

Anemia is the primary hematological manifestation of both Plasmodium falciparum malaria and HIV-1 in pediatric populations in sub-Saharan Africa. We have previously shown that HIV-1 positive and exposed children have greater risk of developing severe anemia (hemoglobin, Hb <6.0 g dL⁻¹) during acute malaria. However, enhanced severity of anemia was unrelated to either erythropoietic suppression or parasite-driven red blood cell hemolysis. To further explore mechanisms of anemia, circulating inflammatory mediators (IMs) were determined using a 25-plex bead array in P. falciparum-infected (Pf[+]) children (3-36 month, n = 194) stratified into three groups: HIV-1 negative (HIV-1[-]/Pf[+]); HIV-1 exposed (HIV-1[exp]/Pf[+]); and HIV-1 infected (HIV-1[+]/Pf[+]). IL-12, MIG/CXCL9, eotaxin/CCL11, and GM-CSF differed significantly and progressively increased across the groups (HIV-1[-]→HIV-1[exp]→HIV-1[+]). To further explore the relationship between the inflammatory milieu (i.e., cytokines, chemokines, and growth factors) and HIV-1 status, the large panel of IMs was reduced into discrete groups by principal component factor analysis. Of the six principal components that emerged, three components were significantly higher in the HIV-1 [+]/pf[+] and HIV[exp]/Pf[+] groups, demonstrating that inflammatory profiles differ according to HIV-1 status. Additional analyses exploring the relationship between the components and anemia revealed significant positive correlations between Hb and Component 3 (IL-1Ra, IL-7, IL-17, IFN-α, IFN-γ, MIG/CXCL9) in the HIV-1[-]/Pf[+] group, and Component 4 (IL-4, IL-5, IL-12, Eotaxin/CCL11) in HIV-1[+]/Pf[+] children. Further analyses of the HIV-1[+]/Pf[+] group revealed that IL-12 had the strongest association with anemia. Results presented here demonstrate that there are unique relationships between the inflammatory environment and anemia in HIV-1 positive and exposed children with malaria.