Publications

BACKGROUND

Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.

METHODS

The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected"), 1-19, 20-399, 400-9999, and ≥ 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.

RESULTS

HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥ 10,000 copies/ml was associated with 89% higher IL-6 (p<0.001). This association was attenuated by ~50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA ≥ 10,000 copies/ml). Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation.

CONCLUSION

HIV RNA ≥ 10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years.

OBJECTIVE

Stem cell therapy for angiogenesis and vascular regeneration has been investigated using adult or embryonic stem cells. In the present study, we investigated the potential of endothelial cells (ECs) derived from human induced pluripotent stem cells (hiPSCs) to promote the perfusion of ischemic tissue in a murine model of peripheral arterial disease.

METHODS AND RESULTS

Endothelial differentiation was initiated by culturing hiPSCs for 14 days in differentiation media supplemented with BMP-4 and vascular endothelial growth factor. The hiPSC-ECs exhibited endothelial characteristics by forming capillary-like structures in matrigel and incorporating acetylated-LDL. They stained positively for EC markers such as KDR, CD31, CD144, and eNOS. In vitro exposure of hiPSC-ECs to hypoxia resulted in increased expression of various angiogenic related cytokines and growth factors. hiPSC-ECs were stably transduced with a double fusion construct encoded by the ubiquitin promoter, firefly luciferase for bioluminescence imaging and green fluorescence protein for fluorescent detection. The hiPSC-ECs (5×10(5)) were delivered by intramuscular injection into the ischemic hindlimb of SCID mice at day 0 and again on day 7 after femoral artery ligation (n=8). Bioluminescence imaging showed that hiPSC-ECs survived in the ischemic limb for at least 2 weeks. In addition, laser Doppler imaging showed that the ratio of blood perfusion was increased by hiPSC-EC treatment by comparison to the saline-treated group (0.58±0.12 versus 0.44±0.04; P=0.005). The total number of capillaries in the ischemic limb of mice receiving hiPSC-EC injections was greater than those in the saline-treated group (1284±155 versus 797±206 capillaries/mm(2)) (P<0.002).

CONCLUSION

This study is a first step toward development of a regenerative strategy for peripheral arterial disease based on the use of ECs derived from hiPSCs.

The future health costs associated with predicted climate change-related events such as hurricanes, heat waves, and floods are projected to be enormous. This article estimates the health costs associated with six climate change-related events that struck the United States between 2000 and 2009. The six case studies came from categories of climate change-related events projected to worsen with continued global warming-ozone pollution, heat waves, hurricanes, infectious disease outbreaks, river flooding, and wildfires. We estimate that the health costs exceeded $14 billion, with 95 percent due to the value of lives lost prematurely. Actual health care costs were an estimated $740 million. This reflects more than 760,000 encounters with the health care system. Our analysis provides scientists and policy makers with a methodology to use in estimating future health costs related to climate change and highlights the growing need for public health preparedness.

PURPOSE OF REVIEW

The purpose of this review is to highlight new findings published in 2010-2011 related to noninvasive fibrosis assessment in HIV/hepatitis C virus (HCV) co-infected patients. Overall, in 2010-2011, 15 studies were published, of which two were excluded because they were published in languages other than English.

RECENT FINDINGS

Eleven studies focused on serum marker panels. Studies sought to validate established panels in HIV/HCV co-infected patients often by comparing multiple serum marker panels in the same population; establish new marker panels using combinations of markers used in previously validated panels; and develop new marker panels using novel methodology. Overall, all panels performed within similar ranges of diagnostic accuracy as measured by the area under the receiver operating characteristic curve (AUROC) but the FibroMeter panel and its derivations achieved the highest performance. Four studies focused on transient elastography. Two studies confirmed its accuracy for identifying fibrosis and cirrhosis and two studies confirmed that misclassification rates are higher in the presence of elevated triglycerides and steatosis.

SUMMARY

Overall, performance of transient elastography appeared superior to the majority of serum marker panels for the detection of significant fibrosis and cirrhosis in HIV/HCV co-infected patients. Challenges of widespread application of transient elastography remain high misclassification in some subgroups, lack of standardized cut-points and lack of widespread availability. Panels that were newly developed in 2010-2011 specifically for HIV/HCV appeared to perform better than existing panels such as APRI and FIB-4; however, additional external validation will be needed to confirm their accuracy.

CONTEXT

No approved pharmacologic treatments for methamphetamine dependence exist. Methamphetamine use is associated with high morbidity and is a major cofactor in the human immunodeficiency virus epidemic among men who have sex with men (MSM).

OBJECTIVE

To determine whether mirtazapine would reduce methamphetamine use among MSM who are actively using methamphetamine.

DESIGN

Double-blind, randomized, controlled, 12-week trial of mirtazapine vs placebo conducted from September 5, 2007, to March 4, 2010.

SETTING

San Francisco Department of Public Health.

PARTICIPANTS

Participants were actively using, methamphetamine-dependent, sexually active MSM seen weekly for urine sample collection and substance use counseling.

INTERVENTIONS

Random assignment to daily oral mirtazapine (30 mg) or placebo; both arms included 30-minute weekly substance use counseling.

MAIN OUTCOME MEASURES

The primary study outcome was reduction in methamphetamine-positive urine test results. Secondary outcomes were study medication adherence (by self-report and medication event monitoring systems) and sexual risk behavior.

RESULTS

Sixty MSM were randomized, 85% of follow-up visits were completed, and 56 participants (93%) completed the final visit. In the primary intent-to-treat analysis, participants assigned to the mirtazapine group had fewer methamphetamine-positive urine test results compared with participants assigned to the placebo group (relative risk, 0.57; 95% CI, 0.35-0.93, P = .02). Urine positivity decreased from 67% (20 of 30 participants) to 63% (17 of 27) in the placebo arm and from 73% (22 of 30) to 44% (12 of 27) in the mirtazapine arm. The number needed to treat to achieve a negative weekly urine test result was 3.1. Adherence was 48.5% by medication event monitoring systems and 74.7% by self-report; adherence measures were not significantly different between arms (medication event monitoring systems, P = .82; self-report, P = .92). Most sexual risk behaviors decreased significantly more among participants taking mirtazapine compared with those taking placebo (number of male partners with whom methamphetamine was used, P = .009; number of male partners, P = .04; episodes of anal sex with serodiscordant partners, P = .003; episodes of unprotected anal sex with serodiscordant partners, P = .003; episodes of insertive anal sex with serodiscordant partners, P = .001). There were no serious adverse events related to study drug or significant differences in adverse events by arm (P ≥ .99).

CONCLUSION

The addition of mirtazapine to substance use counseling decreased methamphetamine use among active users and was associated with decreases in sexual risk despite low to moderate medication adherence. Trial Registration  clinicalTrials.gov Identifier NCT00497081.