Mortality In HIV Patients Research Articles

Adrenal Insufficiency: A Forgotten Diagnosis in HIV/AIDS Patients in Developing Countries.

Adrenal insufficiency (AI) is one of the most common endocrine disease in patients with HIV/AIDS, leading to high morbidity and mortality in HIV patients who become critically ill. Various etiologies are associated with the condition, including cytomegalovirus (CMV), Mycobacterium tuberculosis, lymphoma, Kaposi's sarcoma, and drugs such as rifampin, among others. HIV patients with advanced disease develop relative cortisol deficiency largely due to the reduction of cortisol reserve, which predisposes patients to adrenal crisis in periods of stress or critical illness. The prevalence of AI in HIV/AIDS patients during HAART era is higher in developing than developed countries, probably due to limited access to both diagnosis and adequate treatments which increases the risk of opportunistic infections. The clinical features of functional adrenal insufficiency in HIV/AIDS patients can be masked by various infectious, noninfectious, and iatrogenic causes, which reduce clinical recognition of the condition. Development of simple screening algorithms may help clinicians reach the diagnosis when approaching these patients. In many low-income countries, most HIV patients are diagnosed with advanced disease; thus, further research is necessary to elucidate the prevalence of adrenal insufficiency in HIV/AIDS patients and the condition's impact on mortality in this population.

Factors associated with mortality in HIV patients failing antiretroviral therapy, in Salvador, Brazil

Highly active antiretroviral therapy (HAART) has significantly improved survival of people living with HIV/Aids (PLWHA). However, poor treatment adherence to HAART and other problems, still cause therapy failure and contribute to increased morbidity and mortality of PLWHA. In this retrospective cohort study (2013–2015), we sought to evaluate the factors associated with mortality of PLWHA failing HAART in 2013, who were receiving care at a reference center for sexually transmitted diseases (STD) and HIV/AIDS. A total of 165 individuals over 18 years of age who were failing antiretroviral therapy were evaluated. In two-year follow-up, 19 (11.5%) deaths were documented. There were a significant association between mortality and report of illicit drug use (53%, p < 0.01), being attended by a larger number of medical professionals (6.3 ± 3.2, p = 0.02), use of firstline non-nucleoside reverse transcriptase inhibitor (74%, p = 0.01), and history of interrupting HAART ≥3 months (90%), p = 0.02). Patients who died had a significantly higher viral load (mean 49,192.4 ± 35,783.6 copies/mL) than survivors (26,389.2 ± 27,416 copies/mm3, p < 0.01), lower mean CD4 cell counts (127.8 ± 145.6 cells/mm3 vs. 303.3 ± 202.4 cells/mm3, p < 0.01), and higher frequency of previous virologic failure (89% vs. 74.7%, p < 0.01). Our results reinforce the importance of early detection and prevention of virologic failure, to reduce the mortality associated with this event.

A superiority of viral load over CD4 cell count when predicting mortality in HIV patients on therapy

BackgroundCD4 cell count has been identified to be an essential component in monitoring HIV treatment outcome. However, CD4 cell count monitoring sometimes fails to predict virological failure resulting in unnecessary switch of treatment lines which causes drug resistance and limitations of treatment options. This study assesses the use of both viral load (HIV RNA) and CD4 cell count in the monitoring of HIV/AIDS progression.MethodsTime-homogeneous Markov models were fitted, one on CD4 cell count monitoring and the other on HIV RNA monitoring. Effects of covariates; gender, age, CD4 baseline, HIV RNA baseline and adherence to treatment were assessed for each of the fitted models. Assessment of the fitted models was done using prevalence plots and the likelihood ratio tests. The analysis was done using the “msm” package in R.ResultsResults from the analysis show that viral load monitoring predicts deaths of HIV/AIDS patients better than CD4 cell count monitoring. Assessment of the fitted models shows that viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count.ConclusionFrom this study one can conclude that although patients take more time to achieve a normal CD4 cell count and less time to achieve an undetectable viral load, once the CD4 cell count is normal, mortality risks are reduced. Therefore, both viral load monitoring and CD4 count monitoring can be used to provide useful information which can be used to improve life expectance of patients living with HIV. However, viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count and hence viral load is deemed superior.

Factors Associated with Early Mortality in HIV Patients that Presented for Care in a Tertiary Health Facility in Northeastern Nigeria

Factors Associated with Early Mortality in HIV Patients that Presented for Care in a Tertiary Health Facility in Northeastern Nigeria

Characteristics and Outcomes of Acinetobacter baumannii Infections in Patients with HIV: A Matched Case-Control Study

Acinetobacter baumannii (AB) infection is an increasing global threaten to hospitalized patients, especially those with impaired immune function. Still, few studies addressed the disease burdens and outcomes of AB infection in HIV patients. We aimed to describe characteristics and outcomes of AB infections in patients with HIV, measure the impact of AB infection on 28-day mortality in HIV patients, as well as assess the predictors of 28-day survival among HIV patients with AB pneumonia. A retrospective study with HIV/AB co-infected patients was conducted at Shanghai Public Health Clinical Center (SPHCC), China. Patients with AB pneumonia were further analyzed for predictors of mortality, as well as an additional 1:1 case-control study to determine the fatality of AB pneumonia compared with pneumonia of other pathogens. We found the incidence of AB infection was 17.4 cases per 100 person-years among all hospitalized HIV patients. Hospital mortality rate was 37.5% (21/56). There was a higher 28-day mortality rate in HIV patients with pneumonia due to AB than other pathogens (34% vs 16%, P = 0.03). APACHE II score was independently associated with 28-day survival by multivariate logistic regression (P = 0.031). Our findings indicate that AB infection is incident and can be fatal in HIV seropositive population. AB infection is an independent risk factor of mortality in patients with HIV and pneumonia. A lower APACHE II score on admission predicts a higher 28-day survival rate among HIV/AB co-infected patients.

PULMONARY COINFECTION BY Pneumocystis jiroveci, Cryptococcus neoformans AND CYTOMEGALOVIRUS IN HIV PATIENT WITHOUT ANTIRETROVIRAL TREATMENT

Pulmonary diseases are among the main causes of morbidity and mortality in HIV patients. Here, we present the fatal case of a 30 year-old AIDS patient, who did not undergo antiretroviral treatment, presenting pulmonary coinfection by Pneumocystis jiroveci, Cryptococcus neoformans and Cytomegalovirus diagnosed in the postmortem histological examination. Concurrent pulmonary infection by these three agents is not common and, to date, apparently had not been reported in the literature.

Current characteristics of tuberculosis and human immunodeficiency virus co-infection in a cohort of hospitalized patients in Medellín, Colombia

Tuberculosis (TB) is an important cause of morbidity and mortality in HIV patients. It is unknown if the advent of molecular diagnostic methods and a greater availability of antiretroviral therapy (ART) in our country have changed some characteristics of the TB/HIV co-infection. To describe the epidemiology, clinical features, diagnosis, resistance patterns, tuberculosis drug effects and mortality in co-infected patients. Retrospective study based on the review of medical records of hospitalized co-infected adults in a university hospital in Medellín, Colombia. A total of 178 patients was included in the study. TB and HIV diagnosis was simultaneous in 49.4%. In the moment of TB diagnosis, the median CD4 count was 61 cells/μL (27-145). Pulmonary tuberculosis (PTB) occurred in 28% of patients, extrapulmonary (EPTB) in 23%, and mixed TB in 48.9%. The main EPTB affectations were lymphatic (55.4%), gastrointestinal (35.9%), and of the central nervous system (18.7%). Ziehl-Neelsen stain was positive in 137 patients (77%), mycobacterium culture in 121 (68%), and TB-PCR, in 85 of those patients in whom the test was done. Rifampicin resistance was detected in six cases (4.9%). Transaminases (ALT) increased in half of the patients during TB treatment, but only 10% met liver-toxicity criteria. In-hospital mortality was 11.3%. The single risk factor associated with mortality was CD4 count <50/μL (RR=3.9; 95% CI: 1.36-11.37; p=0.01). When it occurs as an opportunistic infection, TB usually leads to the diagnosis of advanced HIV disease. If used appropriately, TB diagnosis in these patients can be done by conventional methods. It is always necessary to monitor liver function during TB treatment and to rule out drug resistance.

Feasibility and Efficacy of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for HIV-Associated Lymphoma: A Single-Institution Experience

BackgroundHIV-associated lymphomas (HAL) remain an important cause of morbidity and mortality in HIV patients, especially in the setting of treatment-refractory disease. Hematopoietic cell transplantation (HCT) is considered a curative option for patients with refractory HAL. Patients and MethodsWe report the efficacy of autologous HCT in 20 patients with HAL [non-Hodgkin lymphoma = 14 (70%), Hodgkin lymphoma = 6 (30%)]. At the time of transplantation, the median peripheral blood CD4+ count was 226 cells/μL. HIV virus load was undetectable in 14 (70%) of 20 patients. ResultsThe median follow-up of surviving patients was 47 months (range, 20-119 months). The median time to neutrophil engraftment was 11 days. The median progression-free survival and median overall survival have not been reached. At 4 years after transplantation, progression-free survival and overall survival were 65% and 70%, respectively. Six patients died from disease relapse or progression (n = 5) and infection (n = 1). Nonrelapse mortality was 0 and 5% at 100 days and 4 years after transplantation, respectively. ConclusionAutologous HCT is an effective therapy for refractory/relapsed HAL with manageable toxicity, similar to non-HIV patients.

Fulminant Hepatitis Following Ritonavir-Nevirapine-Efavirenz Regimen in a Female HIV Patient in Pointe-Noire in 2016

Current antiretroviral therapy has reduced morbidity and mortality of HIV patients. However, their induced hepatotoxicity constitutes a risk. In this issue, we report a clinical case of fulminant hepatitis, observed in the HIV unit of the hepatogastroenterology department of the General hospital of Loandjili in Pointe-Noire. The patient is a 36-year-old female HIV treated with triple-dug combination antiretroviral therapies (ART) including one antiprotease (ritonavir) and two non-nucleoside reverse transcriptase inhibitors (nevirapine and efavirenz). He developed fulminant hepatitis five years after treatment initiation. He succumbed to the side effects. Although antiretroviral combination therapies are the standard of care for HIV infection, increased vigilance is warranted to early identify this side effect and adjust treatment in order to prevent fatal consequences.

Evaluation of adverse drug reaction reports in adult patients on antiretroviral therepy in Ahmadu Bello University Teaching hospital Zaria-Nigeria

Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV patients. In Nigeria, there are over 400,000 patients on ART in over 200 secondary and tertiary hospitals. However, data on adverse drug reactions (ADRs) due to ARTs are limited. The aim of this study was to evaluate ADRs reports in adult patients on ART in Ahmadu Bello University Teaching Hospital Zaria (ABUTH). The study was a retrospective cross-sectional study on randomly selected adult patients on ART with ADR reports in Nasara Clinic of ABUTH, between January, 2012 and December, 2013. Medical records and ADR reports of the patients were reviewed and fitted into a structured questionnaire. Data were analyzed using SPSS Version 20.0. The study reviewed the records of 302 patients on ART as per the sample size out of a total of 1405 patients in the register within the study period. Of the 302 patients, 109 (36.1%) were reported to have at least one form of ADR, majority of whom were females 65 (59.6%). The most common ADRs were cough (34%), skin rash (44%), headache (20%) and diarrhea (10%), with few cases of anemia (5.5%), lipodostrophy (3.6%) and neuropathy (1.8%). 55% and 98% had concomitant disease and medications respectively. The actions taken to manage the ADR were; specific treatment of the ADR (69.7%), change of ARV regimen (22%) and few cases of hospitalization (6.4%). In conclusion, the study revealed the occurrence of ADRs in adult patients on ART in ABUTH. These reactions occurred within few months of medication, and were found to be related to age, social factor, ART regimen, gender, as well as other concomitant diseases and medications. Close monitoring is required to prevent severe ADR and improve adherence. Keywords : Antiretroviral therapy, adverse drug reaction, cough, retrospective

Incomplete viral suppression and mortality in HIV patients after antiretroviral therapy initiation.

To determine whether there is a threshold of detectable HIV RNA under 1000 copies/ml after antiretroviral therapy initiation associated with 10-year all-cause mortality. This study included nearly 8000 patients from a US-based multicenter clinical cohort who started antiretroviral therapy between 1 January 1998 and 31 December 2013. Viral load was assessed 6 months after initiation of therapy. Patients were followed from 6 months after therapy initiation (between 1 July 1998 and 30 June 2014) until death, and data were administratively censored after 10 years or on 31 December 2014. We used nonparametric multiple imputation to account for left-censored viral load measurements, Cox proportional hazards models to estimate all-cause mortality hazard ratios, Nelson-Aalen cumulative hazard estimates to construct risk curves, and inverse probability of exposure weights to standardize estimated hazard ratios and risk curves to the total study population. Plots of standardized hazard ratio estimates and 95% confidence intervals indicated there was no demonstrable viral load threshold between 30 and 500 copies/ml associated with a marked increase in 10-year mortality. The standardized 10-year risk of mortality among patients with viral loads between 400 and 999 copies/ml 6 months after starting treatment was comparable with the risk of mortality among patients with viral loads between 1000 and 4 million copies/ml (20 vs. 23%). Incomplete suppression of plasma HIV RNA 6 months after starting therapy is associated with substantial 10-year all-cause mortality risk, highlighting the importance of rapid viral load suppression after therapy initiation.

Green synthesis of silver nanoparticles using Alysicarpus monilifer leaf extract and its antibacterial activity against MRSA and CoNS isolates in HIV patients

AbstractThe emergence of multi‐drug‐resistant microorganisms in hospital environments is a global public health problem and threat to everyone, especially HIV‐infected patients. Methicillin‐resistant Staphylococcus aureus (MRSA) and coagulase‐negative Staphylococci (CoNS) are the major causative agents associated with morbidity and mortality in HIV patients. Therefore, control of MRSA and CoNS‐related infections in HIV patients is a worldwide concern. To investigate novel, potent, and cost‐effective therapeutic approaches, the current study reports a simple and rapid synthesis of silver nanoparticles (AgNPs) using aqueous leaf extract of Alysicarpus monilifer and its antibacterial efficacy against multi‐drug‐resistant MRSA and CoNS isolates from HIV patients. The green‐synthesized AgNPs were characterized using ultraviolet‐visible spectroscopy, transmission electron microscopy, energy dispersive X‐ray analysis, selected area electron diffraction pattern, X‐ray diffraction patterns, and Fourier transform infrared spectroscopy. Stable, well‐defined AgNPs, mostly spherical in shape with mean size of 15 ± 2 nm, were obtained within an hour. Moreover, green synthesized AgNPs revealed significant dose‐dependent antibacterial action against MRSA and CoNS isolates. This study concludes that biogenic AgNPs have demonstrated to be potent antibacterial agents in comparison with conventional antibiotics.

Abstract P323: Cardiac Rehabilitation is Associated With Decreased Mortality in HIV Patients With Cardiovascular Disease

Background: Human immunodeficiency virus (HIV+) patients are at high risk for cardiovascular disease (CVD). While cardiac rehabilitation (CR) reduces mortality in uninfected (HIV-) patients with CVD, there are no specific data on CR use in CVD patients with HIV. Methods: We analyzed data on 7650 veterans (28.4% HIV+) eligible for CR from the Veterans Aging Cohort Study, an observational cohort of HIV+ and HIV- veterans. CR eligibility was defined as a hospitalization for acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, or cardiac valve surgery from 2003-2012, identified using ICD9 and CPT codes. CR use was ascertained from VA and non-VA facilities within one year of discharge from the index CVD hospitalization using CPT codes. We evaluated the association between CR and mortality after adjusting for age, eligibility diagnosis, race, sex, and comorbidities using Cox proportional hazard models. Results: CR use was low in HIV+ and HIV- veterans (9.1% vs. 9.6%, respectively, p=0.06). Among the 7650 CR eligible veterans, there were 2211 deaths over 25,715 person-years of follow-up. Mortality rates were higher among those who did not receive CR, regardless of HIV status (Figure). In adjusted models stratified by HIV status, CR was associated with a significant reduction in mortality for HIV+ (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.26-0.59) and HIV- veterans (HR 0.52, 95% CI 0.42-0.65). Among those receiving CR, HIV was not associated with an increased risk of mortality (Figure) even after adjusting for confounders (HR 1.01, 95% CI 0.63-1.61). Conclusions: CR utilization in both HIV+ and HIV- veterans is low. Participation in CR programs is associated with a significant reduction in mortality, regardless of HIV status. When CR is utilized, however, the risk of mortality is the same for HIV+ and HIV- veterans. CR may be particularly important for reducing mortality in HIV+ patients with CVD.

Incomplete viral suppression and mortality in HIV patients after antiretroviral therapy initiation

Incomplete viral suppression and mortality in HIV patients after antiretroviral therapy initiation

Clinical Characteristics and Outcomes of HIV-Infected Patients with Non-AIDS Defining Cancers in a National Institute Cancer in Mexico

Background Non-AIDS Defining Cancers (NADCs) have been recognized as an increasing cause of morbidity and mortality in HIV patients, related mainly to co-infections and/or lifestyle risks. There is no data of NADCs prevalence in Mexico. We describe type of NADCS, clinical characteristics and outcomes of HIV-infected individuals with NADCs.Methods We conducted a retrospective study of 1126 patients attending the HIV/AIDS Clinic at Instituto Nacional de Cancerología in Mexico city (a tertiary care center for adult patients with cancer), since 1996 to December 2016, who had confirmed NADCs after HIV diagnosis. Demographic and clinical data were collected for all HIV patients with NADCs.ResultsOver 1126 HIV-positive individuals seen at the INCan, 139 (12.3%) patients developed a NADC, five patients developed two NADCs during their follow-up, 114 (82%) were male. The median age at diagnosis of NADCs was 42.4 ± 10.9 years, the median of CD4 was 354.4 cell/mm at that time of NADCs, 81 of them (56.3%) had a CD4 count >200 cell/mm3, 81 (56.3%) had undetectable HIV viral load. In males the distribution of NADCS was 36 (25%) Hodgkin’s lymphoma (HL), 16 (11.1%) anal cancer, 13 (9%) germinal tumors males, and two lung cancers, and in females: 11 (7.7%) vulvo-vaginal, seven (4.9%) breast cancer, four (2.8%) thyroid cancer and one case of Hodgkin’s lymphoma. The median of follow-up of NADCs was 2.5 (IQR 0.4,3.6) years. Nine patients died attributable to NADCs and 51 patients lost of follow-up.Conclusion HL was the most frequent NADC on men as it has been described in other reports, followed by anal cancer. In women vulvo-vaginal cancers were the most frequent. These three malignances are related with viral etiology. Lung cancer was uncommon, different from that described in the US population, smoking is less frequent in the HIV Mexican population. NADCS can occur at any stage of HIV infection, regardless of immune status.Disclosures All authors: No reported disclosures.

Survival Pattern and Its Determinants among Adult HIV-Infected Patients after Initiation of HAART in Dilla Hospital Ethiopia

Background: In resource poor countries like Ethiopia the survival of patients treated with ART depends on a variety of factors, which might vary greatly with economic, demographic, behavioral and health risk factors. However, factors affecting survival in Ethiopia are poorly understood. The aim of this study is to determine causes of mortality in adult HIVpositive patients receiving highly active anti-retroviral treatment (HAART) in Dilla referral Hospital. Methods: The medical records of 1391 ART patients who enrolled at Dilla Hospital between 2010 and 2014 were reviewed and sociodemographic, clinical, behavioral and immunological data were collected. Multivariable Cox proportional hazards regression model was used to measure risk of death and identify the independent predictors of mortality. Result: Out of 1391 cohorts of adults ART patients 1081 (77.7%) were alive and continued their treatment in the hospital, 128 (9.2%) were reported dead, 111 (8%) were transfer out, and 71 (5.1%) were lost follow up. The probability of remaining alive and on treatment after 60 months of follow up was 89.3% for TB/HIV patients and 91.1% for HIV only infected patients. HIV patients who developed TB had shorter survival time than not developed TB. Death occurred 26% and 52% in the first 3 and 12 months of ART initiation respectively. The overall incidence rate of mortality during ART treatment was 3.5 per 100 person year observations (PYO). In multivariate analysis low body weight BMI &lt;18.5 kg/m2 (HR 3.12, 95% CI 1.39-7.76, P&lt;0.0001), CD4 countless than 50 cells/mm3 (HR 4.55, 95% CI 1.19 – 8.44, p &lt;0.002), anemia, WHO clinical stage III and IV, drug addiction and presence of active TB infection were predictor of survival and statistically significant association with mortality in HIV patients under ART follow up. Conclusion: The presence of lower baseline CD4-cell, TB infection, WHO clinical stage III and IV, lower body weight, anemia, and drug addiction were factors associated with mortality among ART clients. Improving nutritional status, prevention and control of TB and other opportunistic infections were the recalled recommendations to decrease AIDSrelated morality. These determinants should be taken into account by health care providers to enhance better clinical outcomes of ART attendees.

Elevated Biomarkers of Inflammation and Coagulation in Patients with HIV Are Associated with Higher Framingham and VACS Risk Index Scores.

BackgroundBiomarkers of inflammation and altered coagulation are of increasing interest as predictors of chronic disease and mortality in HIV patients, as well as the use of risk stratification scores such as the Framingham index and the Veterans Aging Cohort Study (VACS) score.MethodsDemographic and laboratory data for 252 HIV patients were assessed for their relationship with 5 biomarkers: hsCRP, D-dimer, Cystatin C, IL-6 and TNF-alpha. Analysis of variance was used to model the association between the number of elevated biomarkers patients had and their Framingham 10 year cardiovascular risk and VACS scores.Results87% of patients were male and 75.7% were virally suppressed (HIV RNA <48 copies/ml). The median and interquartile ranges for each biomarker were: hsCRP 1.65 ug/mL (0.73, 3.89), D-dimer 0.17 ug/mL (0.09, 0.31), Cystatin C 0.87 mg/L (0.78, 1.01), IL-6 2.13 pg/mL (1.3, 3.59), TNF-alpha 4.65 pg/mL (3.5, 5.97). 62.6% of patients had more than one biomarker >75th percentile, while 18.6% had three or more elevated biomarkers. Increased age, cigarette smoking, CD4 counts of <200 cells/mm3, Framingham scores and VACS scores were most strongly associated with elevations in biomarkers. When biomarkers were used to predict the Framingham and VACS scores, those with a higher number of elevated biomarkers had higher mean VACS scores, with a similar but less robust finding for Framingham scores.ConclusionsDespite viral suppression and immunological stability, biomarkers of inflammation and coagulation remain elevated in a significant number of patients with HIV and are associated with higher scores on risk stratification indices.

Lung Cancer in HIV Positive Patients, in the Era of Highly Active Antiretroviral Therapy

SESSION TITLE: Lung Cancer Posters SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: With the introduction of antiretroviral therapies (HAART) the causes of mortality in HIV patients (pts) have changed considerably. The incidence of lung cancer has risen dramatically in these pts, with lung cancer being a major contributor to mortality in HIV-positive pts. Our objective was to determine the characteristics of non-small cell lung cancer (NSCLC) in HIV-positive pts and compare them with HIV-negative NSCLC pts. METHODS: We reviewed the charts of 1440 HIV-positive pts that followed at our institution's infectious disease clinic from 2000 to 2010. Demographics, CD4 counts and NSCLC characteristics were studied. RESULTS: A total of 19 (1.34%) pts with NSCLC were identified; there were more females than males (68%vs 32%). Regarding HIV infection: median (M) age of HIV diagnosis was 43 years (22-66), the most common modes of infection were heterosexual contact (53%) and IV drug use (31%). M CD4 at diagnosis was 71 (12-800). 89.5% of pts had been in HAART therapy, but only 47% were compliant with the regimen. About co-infections: 47% had hepatitis C and 21% hepatitis B. 95% were current or former smokers. In regards to NSCLC, M age at diagnosis was 50 years (43-69), M CD4 count at cancer diagnosis was 252 (13-818), 79% of the pts were stage IV at diagnosis, 84% of the pts were symptomatic at diagnosis with almost half of these pts (47%) having a prior lung infection. Adenocarcinoma was the most prevalent histologic subtype followed by squamous cell. Following cancer diagnosis, only 32% of the pts received a combination of chemotherapy and HAART therapy. Compared with HIV-positive pts, the HIV-negative pts were older at diagnosis (M age 70 years), contained fewer smokers (55%), and had a greater frequency of squamous cell carcinomas (38% vs. 16%), with only 61%of the of pts presenting with stage IV NSCLC. CONCLUSIONS: We observed a higher incidence of NSCLC in HIV-positive young females. Most of the pts presented with advanced disease and almost half of these pts had a prior lung infection. Our HIV-positive pts were 20 years younger at the time of diagnosis compared with the national median age of NSCLC diagnosis (70 years). CLINICAL IMPLICATIONS: NSCLC HIV-positive pts tend to have a worse prognosis than the general population, management can be difficult as many pts present with advanced disease and co-infections. The risk of NSCLC based on gender differences, especially among HIV-positive females requires further investigation at this could impact cancer screening in the HIV-positive population. DISCLOSURE: The following authors have nothing to disclose: Narjust Duma, Jaimie Mittal, Sobia Nizami, Mohleen Kang, David Cennimo No Product/Research Disclosure Information

Minimal impact of an iron-fortified lipid-based nutrient supplement on Hb and iron status: a randomised controlled trial in malnourished HIV-positive African adults starting antiretroviral therapy.

Anaemia, redistribution of Fe, malnutrition and heightened systemic inflammation during HIV infection confer an increased risk of morbidity and mortality in HIV patients. We analysed information on Fe status and inflammation from a randomised, double blind, controlled phase-III clinical trial in Lusaka, Zambia and Mwanza, Tanzania. Malnourished patients (n 1815) were recruited at referral to antiretroviral therapy (ART) into a two-stage nutritional rehabilitation programme, randomised to receive a lipid-based nutrient supplement with or without added micronutrients. Fe was included in the intervention arm during the second stage, given from 2 to 6 weeks post-ART. Hb, serum C-reactive protein (CRP), serum ferritin and soluble transferrin receptor (sTfR) were measured at recruitment and 6 weeks post-ART. Multivariable linear regression models were used to assess the impact of the intervention, and the effect of reducing inflammation from recruitment to week 6 on Hb and Fe status. There was no effect of the intervention on Hb, serum ferritin, sTfR or serum CRP. A one-log decrease of serum CRP from recruitment to week 6 was associated with a 1.81 g/l increase in Hb (95% CI 0.85, 2.76; P< 0.001), and a 0.11 log decrease in serum ferritin (95% CI - 0.22, 0.03; P= 0.012) from recruitment to week 6. There was no association between the change in serum CRP and the change in sTfR over the same time period (P= 0.78). In malnourished, HIV-infected adults receiving dietary Fe, a reduction in inflammation in the early ART treatment period appears to be a precondition for recovery from anaemia.

Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes is regulated by miRNA-181a.

BackgroundAlthough highly active antiretroviral therapy (HAART) has significantly reduced the morbidity and mortality in HIV patients, virus continues to reside in the central nervous system (CNS) reservoir. Hence, a complete eradication of virus remains a challenge. HIV productively infects microglia/macrophages, but astrocytes are generally restricted to HIV infection. The relative importance of the possible replication blocks in astrocytes, however, is yet to be delineated. A recently identified restriction factor, sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1), restricts HIV infection in resting CD4+T cells and in monocyte-derived dendritic cells. However, SAMHD1 expression and HIV-1 restriction activity regulation in the CNS cells are unknown. Though, certain miRNAs have been implicated in HIV restriction in resting CD4+T cells, their role in the CNS HIV restriction and their mode of action are not established. We hypothesized that varying SAMHD1 expression would lead to restricted HIV infection and host miRNAs would regulate SAMHD1 expression in astrocytes.ResultsWe found increased SAMHD1 expression and decreased miRNA expression (miR-181a and miR-155) in the astrocytes compared to microglia. We report for the first time that miR-155 and miR-181a regulated the SAMHD1 expression. Overexpression of these cellular miRNAs increased viral replication in the astrocytes, through SAMHD1 modulation. Reactivation of HIV replication was accompanied by decrease in SAMHD1 expression.ConclusionsHere, we provide a proof of concept that increased SAMHD1 in human astrocytes is in part responsible for the HIV restriction, silencing of which relieves this restriction. At this time, this concept is of theoretical nature. Further experiments are needed to confirm if HIV replication can be reactivated in the CNS reservoir.