Publications

BACKGROUND

The median age of the single adult homeless population is 50 and rising. Although the prevalence of substance use decreases as individuals age, older adults now have a higher prevalence of substance use than older adults did 10 years ago. Homeless individuals have a higher prevalence of substance use disorders than the general population. However, little is known about substance use in older homeless adults.

METHODS

The objective of the study was to examine prevalence of and factors associated with substance use in a population-based sample (N = 350) of homeless individuals aged 50 and older in Oakland, California. Dependent variables included moderate or greater severity illicit drug symptoms (Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) score >3) and moderate or greater alcohol symptoms (Alcohol Use Disorders Identification Test (AUDIT) score >7). Independent variables included demographics, mental health problems, and negative life course events such as physical and sexual abuse, school expulsion, and onset of homelessness.

RESULTS

Almost two thirds of participants, 64.6%, had moderate or greater severity symptoms for at least 1 illicit drug; 25.8% had moderate or greater severity alcohol symptoms. History of psychiatric hospitalization was associated with moderate or greater illicit drug symptoms (adjusted odds ratio [AOR] = 1.9, 1.0-3.6). The presence of major depressive symptoms was associated with moderate or greater severity alcohol symptoms (AOR = 1.8, 1.1-3.0).

CONCLUSIONS

In this sample of older homeless adults, substance use is common. There is a need for substance use treatment programs, integrated with mental health services, which are targeted towards the needs of older homeless adults.

For the 2016 end-of-the-year editorial, the PLOS Medicine editors asked 7 global health leaders to discuss developments relevant to the equitable provision of medical care to all populations. The result is a collection of expert views on ethical trial design, research during outbreaks, high-burden infectious diseases, diversity in research and protection of migrants.

OBJECTIVE

Synonymous substitutions K65K/K66K in HIV-1 reverse transcriptase alleviate fitness and fidelity defects in HIV-1 molecular clones harboring thymidine analogue mutations (TAMs); however, their potential for transmission and persistence is unknown. Here, we investigated the temporal appearance of K65K/K66K relative to TAMs in a HIV-1 cohort, their prevalence over time, and their impact on viral fitness in the context of patient-derived reverse transcriptase sequences.

METHODS

Retrospective analyses of the temporal appearance and longitudinal prevalence of synonymous substitutions and drug resistance mutations were performed using the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program (DTP) database. Plasma-derived HIV-1 from the DTP was used to generate infectious molecular clones. Growth competition assays were performed to determine viral fitness.

RESULTS

The prevalence of K65K/K66K in drug-naïve individuals tripled from 11% in 1997 to 37% in 2014 (P < 0.0001, n = 5221), with K66K mainly accounting for the increase. These mutations emerged in drug-treated individuals without TAMs in 14% of the cohort and conferred a fitness advantage in the context of patient-derived multidrug-resistant (MDR) virus in the absence of drug.

CONCLUSION

The appearance of K65K/K66K in drug-treated individuals was largely independent of TAMs, suggesting alternative factors are likely associated with their emergence. The increasing K65K/K66K prevalence to over a third of treatment-naïve individuals in the mostly subtype B DTP cohort and their ability to confer a fitness advantage to multidrug-resistant virus might explain the transmission and persistence of virus harbouring K65K/K66K in untreated individuals, and highlights their role in adaptive HIV-1 evolution.

OBJECTIVE

We sought to measure retention in care and identify predictors of nonretention among patients receiving antiretroviral therapy (ART) with streamlined delivery during the first year of the ongoing Sustainable East Africa Research on Community Health (SEARCH) 'test-and-treat' trial (NCT 01864603) in rural Uganda and Kenya.

DESIGN

Prospective cohort of patients in the intervention arm of the SEARCH study.

METHODS

We measured retention in care at 12 months among HIV-infected adults who linked to care and were offered ART regardless of CD4 cell count, following community-wide HIV-testing. Kaplan-Meier estimates and Cox proportional hazards modeling were used to calculate the probability of retention at 1 year and identify predictors of nonretention.

RESULTS

Among 5683 adults (age ≥15) who linked to care, 95.5% [95% confidence interval (CI): 92.9-98.1%] were retained in care at 12 months. The overall probability of retention at 1 year was 89.3% (95% CI: 87.6-90.7%) among patients newly linking to care and 96.4% (95% CI: 95.8-97.0%) among patients previously in care. Younger age and pre-ART CD4 cell count below country treatment initiation guidelines were predictors of nonretention among all patients. Among those newly linking, taking more than 30 days to link to care after HIV diagnosis was additionally associated with nonretention at 1 year. HIV viral load suppression at 12 months was observed in 4227 of 4736 (89%) of patients retained with valid viral load results.

CONCLUSION

High retention in care and viral suppression after 1 year were achieved in a streamlined HIV care delivery system in the context of a universal test-and-treat intervention.

OBJECTIVE

Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group.

DESIGN

A cross-sectional study in Zimbabwe of HIV-infected children aged 6-16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area.

METHODS

Standardized questionnaire, spirometry, incremental shuttle walk testing, CD4 cell count, HIV viral load and sputum culture for tuberculosis were performed.

RESULTS

A total of 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (interquartile range 2.8-7.5) and 6.1 (interquartile range 3.6-8.4) years, respectively. Median CD4 cell count was 726 cells/μl, and 79% had HIV viral load less than 400 copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children [n = 1 (0.7%)], but common in HIV-infected participants [51 (25%)], especially cough [30 (15%)] and dyspnoea [30 (15%)]. HIV-infected participants were more commonly previously treated for tuberculosis [76 (38%) vs 1 (0.7%), P < 0.001], had lower exercise capacity (mean incremental shuttle walk testing distance 771 vs 889 m, respectively, P < 0.001) and more frequently abnormal spirometry [43 (24.3%) vs 15 (11.5%), P = 0.003] compared with HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (P = 0.025). No participant tested positive for Mycobacterium tuberculosis.

CONCLUSION

In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required.

A major genomic alteration in prostate cancer (PCa) is frequent loss of chromosome (chr) 8p with a common region of loss of heterozygosity (LOH) at chr8p22 locus. Genomic studies implicate this locus in the initiation of clinically significant PCa and with progression to metastatic disease. However, the genes within this region have not been fully characterized to date. Here we demonstrate for the first time that a microRNA component of this region-miR-383-is frequently downregulated in prostate cancer, has a critical role in determining tumor-initiating potential and is involved in prostate cancer metastasis via direct regulation of CD44, a ubiquitous marker of PCa tumor-initiating cells (TICs)/stem cells. Expression analyses of miR-383 in PCa clinical tissues established that low miR-383 expression is associated with poor prognosis. Functional data suggest that miR-383 regulates PCa tumor-initiating/stem-like cells via CD44 regulation. Ectopic expression of miR-383 inhibited tumor-initiating capacity of CD44+ PCa cells. Also, 'anti-metastatic' effects of ectopic miR-383 expression were observed in a PCa experimental metastasis model. In view of our results, we propose that frequent loss of miR-383 at chr8p22 region leads to tumor initiation and prostate cancer metastasis. Thus, we have identified a novel finding that associates a long observed genomic alteration to PCa stemness and metastasis. Our data suggest that restoration of miR-383 expression may be an effective therapeutic modality against PCa. Importantly, we identified miR-383 as a novel PCa tissue diagnostic biomarker with a potential that outperforms that of serum PSA.