Search

Purpose Comparison of anal pre-cancer screening strategies in men who have sex with men (MSM).Methods MSM in the Multicenter AIDS Cohort Study underwent repeated anal cytology (aCyt), oncogenic human papillomavirus (oncHPV) testing. A subset received High-Resolution Anoscopy (HRA). We evaluated three screening strategies for their ability to predict anal histological High-Grade Squamous Intraepithelial lesion (HSIL): single aCyt, sequential aCyt, and oncHPV co-testing. Multivariable logistic regression models evaluated risk of HSIL among participants undergoing HRA within 5 years of screening. Sensitivity and specificity were estimated among participants with HRA, and results corrected for verification bias using weighted generalized estimating equations.Results There were 1426 MSM with aCyt screening (48% people with HIV [PWH]) and 428 that underwent HRA. Median age was 57 years, 14% of PWH had CD4< 350 cells/mm3. HSIL probability was higher in MSM with one (39%, p< 0.01) or two abnormal aCyt results (46%, p< 0.01), versus those with normal aCyt (23–24%). Among men with abnormal aCyt, men with oncHPV+ had significantly higher risk than those who were oncHPV- (47% vs. 16%, p< 0.01). Specificity was modest with single aCyt+ (50%) but increased with sequential aCyt+ (79%) or oncHPV+ (67%). Sensitivity was high with single oncHPV+ (88%), moderate with single aCyt+ (66%) and oncHPV+ co-testing (61%), and low with sequential aCyt+ (39%). After correcting for potential verification bias, specificity increased and sensitivity decreased, but inferences were similar.Conclusion None of the screening strategies evaluated had both sufficient specificity and sensitivity to warrant routine widespread use.

Background: HIV-1 genotypic and phenotypic susceptibility testing (GPT) optimizes antiretroviral selection, but its effect on survival is unknown. Objective: To evaluate the association between GPT and survival. Design: Cohort study. Setting: 10 U.S. HIV clinics. Patients: 2699 HIV-infected patients eligible for GPT (plasma HIV RNA level >1000 copies/mL) seen from 1999 through 2005. Measurements: Demographic characteristics, clinical factors, GPT use, all-cause mortality, and crude and adjusted hazard ratios (HRs) for the association of GPT with survival. Results: Patients were followed for a median of 3.3 years; 915 (34%) had GPT. Patients who had GPT had lower mortality rates than those who did not (2.0 vs. 2.7 deaths per 100 person-years). In standard Cox models, GPT was associated with improved survival (adjusted HR, 0.69 [95% CI, 0.51 to 0.94]; P = 0.017) after controlling for demographic characteristics, [CD4.sup.+] cell count, HIV RNA level, and intensity of clinical follow-up. In subgroup analyses, GPT was associated with improved survival for the 2107 highly active antiretroviral therapy (HAART)-experienced patients (2.2 vs. 3.2 deaths per 100 person-years for patients who had GPT vs. those who did not have GPT; adjusted HR, 0.60 [CI, 0.43 to 0.82]; P = 0.002) and for the 921 triple antiretroviral class-experienced patients (2.1 vs. 3.1 deaths per 100 person-years; adjusted HR, 0.61 [CI 0.40 to 0.93]; P = 0.022). Marginal structural models supported associations between GPT and improved survival in the overall cohort (adjusted HR, 0.54; P = 0.001) and in the HAART-experienced group (adjusted HR, 0.56; P = 0.003). Limitations: Use of GPT was not randomized. Residual confounding may exist. Conclusion: Use of GPT was independently associated with improved survival among HAART-experienced patients. Primary Funding Source: Centers for Disease Control and Prevention.

Background: Optimal timing of antiretroviral therapy (ART) initiation for HIV-infected persons remains unclear. Objective: To assess survival benefit of initiating ART at different CD4+ cell counts. Design: Prospective observational study. Setting: U.S. clinics in the HIV Outpatient Study (HOPS). Patients: HIV-infected patients with CD4+ cell counts, plasma HIV RNA viral load, and ART use recorded from January 1994 through March 2002. Measurements: Before initiation of ART, patients were grouped by their CD4+ cell counts into three subgroups: 0.201 to 0.350 x 10(super 9) cells/L (n=399), 0.351 to 0.500 x 10(super 9) cells/L (n=327), and 0.501 to 0.750 x 10(super 9) cells/L (n=122). We compared mortality rates for each CD4+ subgroup among patients who initiated ART and patients who delayed ART until reaching a lower CD4+ subgroup. Results: Mortality rates for 340 patients who initiated ART and 59 who delayed ART in the CD4+ subgroup of 0.201 to 0.350 x 10(super 9) cells/L were 15.4 and 56.4 deaths per 1000 person-years, respectively (rate ratio, 0.27 [95% CI, 0.14 to 0.55]; P0.2). Patients in the 0.201 to 0.350 x 10(super 9) cells/L and 0.351 to 0.500 x 10(super 9) cells/L subgroups who initiated ART were more likely than those who delayed ART to achieve an undetectable HIV viral load (P=0.03 and 0.04, respectively). Conclusions: Among HIV-infected persons with CD4+ cell counts of 0.201 to 0.350 x 10(super 9) cells/L, initiating ART is associated with reduced mortality compared with delaying such therapy. Survival benefits of earlier ART initiation (at CD+ cell counts of 0.351 to 0.500 x 10(super 9) cells/L) are possible.

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text

Many HIV patients with advanced disease may develop Pneumocystis carinii pneumonia (PCP) even though they are taking drugs to prevent this opportunistic infection. In a study of 2,842 HIV patients, 1,582 were given drugs to prevent PCP. A total of 153 new cases of PCP occurred in these patients, and 67% of the new infections occurred in patients receiving drugs to prevent PCP. Patients with CD4+ T cell counts below 50 who had a history of PCP were most likely to develop PCP.

Aspects of resistance to HIV treatment are presented from a panel of leading experts in virology and infectious diseases. A discussion is made concerning the correct sequencing of protease inhibitors in order to achieve the full benefits of the effectiveness and length of therapy.

The purpose of this study was to compare the risks of incident heart failure (HF) among a variety of chronic inflammatory diseases (CIDs) and to determine whether risks varied by severity of inflammation within each CID.

Supplemental Digital Content is available in the text.

Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes.

ObjectiveHIV-infected (HIV+) individuals may be at increased risk for sudden arrhythmic cardiac death. Some studies have reported an association between HIV infection and prolongation of the electrocardiographic QT interval, a measure of ventricular repolarisation, which could potentiate ventricular arrhythmias. We aimed to assess whether HIV+ men have longer QT intervals than HIV-uninfected (HIV−) men and to determine factors associated with QT duration.MethodsWe performed resting 12-lead ECGs in 774 HIV+ and 652 HIV− men in the Multicenter AIDS Cohort Study (MACS). We used multivariable linear and logistic regression analyses to assess associations between HIV serostatus and Framingham corrected QT interval (QTc), after accounting for potential confounders. We also determined associations among QTc interval and HIV-related factors in HIV+ men. In a subgroup of participants, levels of serum markers of inflammation were also assessed.ResultsAfter adjusting for demographics and risk factors, QTc was 4.0 ms longer in HIV+ than HIV− men (p<0.001). Use of antiretroviral therapy (ART), specific ART drug class use and other HIV-specific risk factors were not associated with longer QTc. Among the subgroup with inflammatory biomarker measurements, higher interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and B-cell activating factor levels were independently associated with longer QTc and their inclusion partially attenuated the HIV effect.ConclusionsHIV+ men had longer QTc, which was associated with higher levels of systemic inflammatory factors. This longer QTc may contribute to the increased risk for sudden arrhythmic cardiac death in some HIV+ individuals.

Supplemental Digital Content is available in the text

Background:The process of obtaining approval for hepatitis C virus (HCV) treatment may be time consuming and complicated due to prior authorizations and the need to appeal denials. Pharmacists are poised to play a critical role in the acquisition and management of oral direct acting antivirals (DAAs) for the treatment of HCV infection; however, the time expended in this activity requires assessment. Objective:The objective of this study was to assess time expenditures by pharmacists to acquire DAAs for HCV therapy. Methods:Patients were enrolled in the Northwestern University Viral Hepatitis Registry, a prospective, observational cohort of ambulatory, adult patients living with human immunodeficiency virus (HIV) coinfected with chronic hepatitis B and/or C virus, and recruited since 2013 from the Infectious Disease Center at Northwestern Memorial Hospital, Chicago, IL. Patients were included in the current study if they were referred to the pharmacist for HCV DAA acquisition, drug-drug interaction management, and adherence counseling between February 1, 2014, and April 30, 2015. Patient demographics, virus-specific characteristics, and time required to secure HCV DAA treatment, counsel patients, and follow-up therapy were collected. Results:Among 54 HIV/HCV coinfected patients referred for treatment, all eventually received approval for DAA therapy. However, 87% (n = 47) required prior authorization. Pharmacists dedicated 2.1 hours/patient (interquartile range 1.5-2.8 hours; range 0.75-6.5 hours) to manage DAA therapy. Conclusion:Successful acquisition of HCV DAA therapy relied heavily on pharmacist effort, reflecting the vital role that pharmacists play in this process. Dedicated resources for medication access should be considered to ensure timely DAA acquisition.

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text

Background Chronic kidney disease (CKD) is common among HIV-infected individuals but serum creatinine is insensitive for detecting kidney damage at early stages. We hypothesized that HIV infection would be associated with elevations in subclinical markers of kidney injury and fibrosis in a contemporary cohort of men.Methods In this cross-sectional study, we measured urine levels of interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), pro-collagen type III N-terminal pro-peptide (PIIINP) and albumin-creatinine ratio (ACR) in 813 HIV-infected and 331 uninfected men enrolled in the Multi-center AIDS Cohort Study.Results Median eGFR was 95 ml/min/1.73 m2among African-Americans (n=376) and 87 ml/min/1.73 m2among Caucasians (n=768). Among HIV-infected men, the median CD4 lymphocyte count was 572 cells/mm3and 76% of men had undetectable HIV RNA levels. After multivariable adjustment for traditional CKD risk factors including eGFR, HIV infection was associated with 52% higher urine IL-18 (95% CI, 33%, 73%), 44% higher KIM-1 (27%, 64%), 30% higher PIIINP (15%, 47%) and 84% higher ACR (54%, 120%), with similar effect sizes among African-Americans and Caucasians (P>0.2 for tests of interaction by race). These associations remained statistically significant in analyses that excluded persons with detectable HIV RNA levels and in models that adjusted for cumulative exposure to tenofovir disoproxil fumarate.Conclusions Compared with uninfected men, HIV-infected men had more extensive glomerular and tubulointerstitial damage, as assessed by urine biomarkers. Future studies should evaluate whether combinations of biomarkers can be used to monitor stages of kidney injury and to predict CKD risk in HIV-infected individuals.

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text

Tenofovir disoproxil fumarate (TDF) can cause proximal tubular damage and chronic kidney disease in human immunodeficiency virus (HIV)-infected individuals. Urine α1-microglobulin (A1M), a low-molecular-weight protein indicative of proximal tubular dysfunction, may enable earlier detection of TDF-associated tubular toxicity.

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text

Background Generalized obesity has been associated with cognitive decline, a process potentially mediated by adipocytokines. The effects of regional adipose tissue (AT) on cognition, however, are not well understood. We explored cross-sectional relationships between regional AT, adipocytokines, inflammatory markers and neuropsychological (NP) test scores among HIV+ and HIV- men enrolled in the Multicenter AIDS Cohort Study.Methods Visceral, subcutaneous abdominal and subcutaneous thigh AT areas were quantified by computed tomography (CT). NP tests (Trail Making Test parts A and B, and Symbol-Digit Modalities) obtained within 2 years of CT screened for psychomotor speed and executive function. Adiponectin, leptin, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were measured.Results Of 509 HIV+ and 271 HIV- participants, HIV+ men (98% on antiretroviral therapy, 81% HIV-1 RNA<50 copies/ml) had lower median subcutaneous AT and adiponectin levels and higher hs-CRP levels, but visceral AT, body mass index, IL-6 and NP scores did not vary by HIV serostatus. In multivariable analysis, older age, = high school education and African American race, but not AT area or site, were associated with worse NP test scores among all participants. In HIV+ only, higher adiponectin and IL-6 were associated with worse cognitive function independent of AT area. No HIV-specific factors were associated with NP test scores.Conclusions Demographic factors were associated with NP test performance, but regional adiposity was not. In HIV+ only, higher adiponectin and IL-6 were associated with worse NP test scores, supporting a role for chronic inflammation and adipocytokine imbalance in neurocognitive decline in HIV+ persons.

Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and antiretroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine whether HIV infection is associated with greater epicardial fat and whether epicardial fat is associated with subclinical coronary atherosclerosis.

To examine whether altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.

Background Certain sociodemographic subgroups of HIV-infected patients may experience more chronic disease than others due to behavioural risk factors, advanced HIV disease or complications from extended use of combination antiretroviral therapy (cART), but recent comparative data are limited.Methods We studied HIV-infected adult patients in care during 2006–2010 who had been prescribed =6 months of cART. We analysed the prevalence of selected key chronic conditions and polymorbidity (having 2 or more out of 10 key conditions) by gender and race/ethnicity.Results Of the 3,166 HIV-infected patients (median age 47 years, CD4+T-cell count 496 cells/mm3, duration of cART use 6.8 years), 21% were female, 57% were non-Hispanic White and over half were current or former tobacco smokers. The five most frequent conditions among women (median age 45 years) were dyslipidaemia (67.3%), hypertension (57.4%), obesity (31.7%), viral hepatitis B or C coinfection (29.0%) and low high-density lipoprotein cholesterol (HDLc; 27.3%). The five most frequent conditions in men (median age 47 years) were dyslipidaemia (81.2%), hypertension (54.4%), low HDLc (41.1%), elevated triglycerides (32.3%) and elevated non-HDLc (26.8%). In multivariable analyses, Hispanic patients had higher prevalence of obesity and diabetes than White patients; Black patients had higher prevalence of obesity and hypertension but lower rates of lipid abnormalities. Of all patients, 73.7% of women and 66.8% of men had polymorbidity, with no evidence of disparities by race/ethnicity.Conclusions Among contemporary cART-treated HIV-infected adults, chronic conditions and polymorbidity were common, underscoring the importance of chronic disease prevention and management among ageing HIV-infected patients.

To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition.

ABSTRACTIt is uncertain which methods for the diagnosis of rectal gonococcal and chlamydial infection are optimal. This study evaluated the performance of culture and nucleic acid amplification tests (NAATs) for rectal chlamydial and gonococcal diagnosis. From July 2003 until February 2007, 441 rectal test sets were collected from individuals attending a sexually transmitted disease clinic and three HIV clinics who gave a history of anal intercourse or were women at high risk for Neisseria gonorrhoeaeor Chlamydia trachomatisinfections. Rectal swab specimens were tested using culture and commercial NAATs employing transcription-mediated amplification (TMA), strand displacement amplification (SDA), and PCR amplification. Test performance was evaluated using a rotating standard by which patients were classified as infected if either two or three comparator tests were positive. Test sensitivities for the detection of N. gonorrhoeaeranged from 66.7% to 71.9% for culture to 100% for TMA. Specificities were 99.7% to 100% for culture and greater than 95.5% for all three NAATs. Test sensitivities for C. trachomatisranged from 36.1% to 45.7% for culture and among NAATS from 91.4% to 95.8% for PCR to 100% for TMA. Specificities of the NAATs ranged from 95.6% to 98.5% (two-of-three standard) and from 88.8% to 91.8% (three-of-three standard). Over 60% and 80% of gonococcal and chlamydial infections, respectively, among men who have sex with men and over 20% of chlamydial infections in women would have been missed if the rectal site had not been tested. Currently available NAATs are more sensitive for the detection of chlamydial and gonococcal infection at the rectal site than is culture.

Background: There has been increasing concern that HIV-infected individuals may be more at risk for cardiovascular events in the highly-active antiretroviral therapy (HAART) era. This study examined the risk of thromboembolic events in HIV-infected and non-infected individuals and the effect of macrolide prophylaxis on those outcomes. Methods: A subcohort analysis was undertaken using data collected in the Multicenter AIDS Cohort Study to examine the relative risk of vascular events (myocardial infarction, unstable angina and ischaemic stroke). Cox proportional hazard model using age as the time scale with time varying cofactors obtained at each semi-annual visit were used to assess the independent effect of macrolide use. Results: Controlling for other significant effects including race and smoking, HIV-infection was not independently associated with vascular events. Increased risk was observed among those who used HAART (relative hazard 1.09, 95% confidence intervals 1.00?1.19 in multivariate model), antihypertensive treatment (1.81 [1.26?2.60]), lipid-lowering medication (1.65 [1.12?2.42]), and antibiotics (1.72 [1.25?2.36]). The protective association of macrolide use for a vascular event in the HAART era was also significant (0.10 [0.01?0.75]). Conclusions: Traditional risk factors are important in the pathogenesis of vascular events in HIV-infected individuals. Macrolide antibiotics may have a protective effect in the HIV-infected individuals in the HAART era.

Z-100 is an extract of the Mycobacterium tuberculosisstrain Aoyama B, which contains various polysaccharides. Aoyama B has previously been shown to induce a T helper 1-type cytokine response in various murine oncological models and has also demonstrated inhibitory activity against HIV-1 in vitro.This multicentre study primarily determined the safety of Z-100 in early HIV-1-infected patients who were treatment naive; were treatment experienced, but had elected to discontinue highly active antiretroviral therapy (HAART) 8 weeks or longer before the study; or were stable on their first or second HAART regimen for at least 12 weeks before the study. Thirty-two individuals participated in this study and self-injected either placebo, 20 µg or 40 µg Z-100 twice a week for 8 weeks. Z-100 was well tolerated and the safety profiles of the Z-100 treatment groups were not meaningfully different compared with the placebo group. Plasma levels of HIV-1 RNA were not statistically significantly different in any treatment group at the end of the treatment period. There were no statistically significant differences among the treatment groups in the change from baseline to week 8 for any of the biological endpoints including plasma levels of HIV-1 RNA; CD4+and CD8+T-cell counts; levels of macrophage inflammatory protein 1; soluble tumour necrosis factor receptor 1; C-reactive protein; interleukin-6; and granulocyte colony stimulating factor. Consequently, this trial demonstrates the safety of Z-100 in HIV-1 infected patients without evidence of any activity at the doses administered.