Publications

BACKGROUND

Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted.

METHODS

We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4 T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4 T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period.

RESULTS

All patients have been in continued remission for 4-6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir-related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT.

CONCLUSIONS

These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes.

Background

Human immunodeficiency virus (HIV) antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals receiving antiretroviral therapy (ART).

Methods

HIV antibody responses were measured over time in the presence or absence of suppressive ART and were compared to the HIV reservoir size and expression of antiviral restriction factors.

Results

Among untreated individuals, including both elite controllers (ie, persons with a viral load of ≤40 copies/mL) and noncontrollers, antibody parameters were stable over time and correlated with the individual viral load. Viral suppression with ART led to a progressive decline in antibody responses after treatment induction that persisted for 5-7 years. Higher levels of HIV antibodies during suppressive therapy were associated with later initiation of ART after infection, with higher DNA and cell-associated RNA levels, and with lower expression of multiple anti-HIV host restriction factors.

Discussion

These findings suggest that declining antibody levels during ART reflect lower levels of antigen production and/or viral replication in the persistent HIV reservoir. Results of relatively inexpensive and quantitative HIV antibody assays may be useful indirect markers that enable efficient monitoring of the viral reservoir and suppression during functional-cure interventions.

We examined risk factors for advanced hepatic fibrosis [fibrosis-4 (FIB)-4 >3.25] including both current alcohol use and a diagnosis of alcohol use disorder among HIV-infected patients. Of the 12,849 patients in our study, 2133 (17%) reported current hazardous drinking by AUDIT-C, 2321 (18%) had a diagnosis of alcohol use disorder, 2376 (18%) were co-infected with chronic hepatitis C virus (HCV); 596 (5%) had high FIB-4 scores >3.25 as did 364 (15%) of HIV/HCV coinfected patients. In multivariable analysis, HCV (adjusted odds ratio (aOR) 6.3, 95% confidence interval (CI) 5.2-7.5), chronic hepatitis B (aOR 2.0, 95% CI 1.5-2.8), diabetes (aOR 2.3, 95% CI 1.8-2.9), current CD4 <200 cells/mm (aOR 5.4, 95% CI 4.2-6.9) and HIV RNA >500 copies/mL (aOR 1.3, 95% CI 1.0-1.6) were significantly associated with advanced fibrosis. A diagnosis of an alcohol use disorder (aOR 1.9, 95% CI 1.6-2.3) rather than report of current hazardous alcohol use was associated with high FIB-4. However, among HIV/HCV coinfected patients, both current hazardous drinkers (aOR 1.6, 95% CI 1.1-2.4) and current non-drinkers (aOR 1.6, 95% CI 1.2-2.0) were more likely than non-hazardous drinkers to have high FIB-4, with the latter potentially reflecting the impact of sick abstainers. These findings highlight the importance of using a longitudinal measure of alcohol exposure when evaluating the impact of alcohol on liver disease and associated outcomes.

Hazardous alcohol use is associated with detrimental health outcomes among persons living with HIV (PLWH). We examined the prevalence and factors associated with hazardous alcohol use in the current era using several hazardous drinking definitions and binge drinking defined as ≥5 drinks for men versus ≥4 for women. We included 8567 PLWH from 7 U.S. sites from 2013 to 2015. Current hazardous alcohol use was reported by 27% and 34% reported binge drinking. In adjusted analyses, current and past cocaine/crack (odd ratio [OR] 4.1:3.3-5.1, p < 0.001 and OR 1.3:1.1-1.5, p < 0.001 respectively), marijuana (OR 2.5:2.2-2.9, p < 0.001 and OR 1.4:1.2-1.6, p < 0.001), and cigarette use (OR 1.4:1.2-1.6, p < 0.001 and OR 1.3:1.2-1.5, p < 0.001) were associated with increased hazardous alcohol use. The prevalence of hazardous alcohol use remains high in the current era, particularly among younger men. Routine screening and targeted interventions for hazardous alcohol use, potentially bundled with interventions for other drugs, remain a key aspect of HIV care.

In this issue, Ferguson and colleagues demonstrate that chronic kidney disease (CKD) screening in populations burdened with CKD may be cost effective. Whether we should screen for CKD, however, continues to be debated despite the availability of effective clinical strategies that mitigate the risks of CKD progression. This study highlights the need for pragmatic trials to test the effectiveness of early CKD detection combined with optimization of clinical management and calls for innovation to tackle CKD.

OBJECTIVE

The study aim was to examine the relationships of organizational safety practices with nurses' perceptions about job and risk and experiences of work-related injury and symptoms.

BACKGROUND

Nursing professions report high rates of work-related injuries. Organizational safety practices have been linked to workers' safety outcomes and perceptions about work.

METHODS

This study analyzed data from a random sample of 280 California RNs in a cross-sectional statewide survey. Data were collected by both postal and online surveys.

RESULTS

Higher perceptions of organizational safety practices (safety climate, ergonomic practices, people-oriented culture) were significantly associated with lower physical workload, lower job strain, higher job satisfaction, lower risk perception, and lower work-related injury and symptom experiences. Ergonomic practices and people-oriented culture were associated with less intention of leaving job.

CONCLUSIONS

Organizational safety practices may play a pivotal role in improving positive perceptions about jobs, reducing injury risks, and promoting nurse retention.

Objectives

Hammer drills are used extensively in commercial construction for drilling into concrete for tasks including rebar installation for structural upgrades and anchor bolt installation. This drilling task can expose workers to respirable silica dust and noise. The aim of this pilot study was to evaluate the effects of bit wear on respirable silica dust, noise, and drilling productivity.

Method

Test bits were worn to three states by drilling consecutive holes to different cumulative drilling depths: 0, 780, and 1560 cm. Each state of bit wear was evaluated by three trials (nine trials total). For each trial, an automated laboratory test bench system drilled 41 holes 1.3 cm diameter, and 10 cm deep into concrete block at a rate of one hole per minute using a commercially available hammer drill and masonry bits. During each trial, dust was continuously captured by two respirable and one inhalable sampling trains and noise was sampled with a noise dosimeter. The room was thoroughly cleaned between trials.

Results

When comparing results for the sharp (0 cm) versus dull bit (1560 cm), the mean respirable silica increased from 0.41 to 0.74 mg m-3 in sampler 1 (P = 0.012) and from 0.41 to 0.89 mg m-3 in sampler 2 (P = 0.024); levels above the NIOSH recommended exposure limit of 0.05 mg m-3. Likewise, mean noise levels increased from 112.8 to 114.4 dBA (P < 0.00001). Drilling productivity declined with increasing wear from 10.16 to 7.76 mm s-1 (P < 0.00001).

Discussion

Increasing bit wear was associated with increasing respirable silica dust and noise and reduced drilling productivity. The levels of dust and noise produced by these experimental conditions would require dust capture, hearing protection, and possibly respiratory protection. The findings support the adoption of a bit replacement program by construction contractors.