by
Lesley S. Park;
Janet P. Tate;
Keith Sigel;
David Rimland;
Kristina Crothers;
Cynthia Gibert;
Maria C. Rodriguez-Barradas;
Matthew Bidwell Goetz;
Roger J. Bedimo;
Sheldon T. Brown;
Amy C. Justice;
Robert Dubrow
Objective: Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era.
Design: Prospective cohort study.
Methods: We followed 44 787 HIV+ and 96 852 demographically matched uninfected persons during 1997–2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with incidence rate and IRR period trend P values for cancer groupings and specific cancer types.
Results: We observed 3714 incident cancer diagnoses in HIV+ and 5760 in uninfected persons. The HIV+ all-cancer crude incidence rate increased between 1997–2000 and 2009–2012 (P trend = 0.0019). However, after standardization, we observed highly significant HIV+ incidence rate declines for all cancer (25% decline; P trend <0.0001), AIDS-defining cancers (55% decline; P trend <0.0001), nonAIDS-defining cancers (NADC; 15% decline; P trend = 0.0003), and nonvirus-related NADC (20% decline; P trend <0.0001); significant IRR declines for all cancer (from 2.0 to 1.6; P trend <0.0001), AIDS-defining cancers (from 19 to 5.5; P trend <0.0001), and nonvirus-related NADC (from 1.4 to 1.2; P trend = 0.049); and borderline significant IRR declines for NADC (from 1.6 to 1.4; P trend = 0.078) and virus-related NADC (from 4.9 to 3.5; P trend = 0.071).
Conclusion: Improved HIV care resulting in improved immune function most likely contributed to the HIV+ incidence rate and the IRR declines. Further promotion of early and sustained ART, improved ART regimens, reduction of traditional cancer risk factor (e.g. smoking) prevalence, and evidence-based screening could contribute to future cancer incidence declines among HIV+ persons.
HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3-11.5). In analyses restricted to prostate cancer patients, HIVpositive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.
Background:Foreign-born, HIV-infected persons are at risk for sub-clinical parasitic infections acquired in their countries of origin. The long-term consequences of co-infections can be severe, yet few data exist on parasitic infection prevalence in this population.Methodology/Principal Findings:This cross-sectional study evaluated 128 foreign-born persons at one HIV clinic. We performed stool studies and serologic testing for strongyloidiasis, schistosomiasis, filarial infection, and Chagas disease based on the patient's country of birth. Eosinophilia and symptoms were examined as predictors of helminthic infection. Of the 128 participants, 86 (67%) were male, and the median age was 40 years; 70 were Mexican/Latin American, 40 African, and 18 from other countries or regions. Strongyloides stercoralis antibodies were detected in 33/128 (26%) individuals. Of the 52 persons from schistosomiasis-endemic countries, 15 (29%) had antibodies to schistosome antigens; 7 (47%) had antibodies to S. haematobium, 5 (33%) to S. mansoni, and 3 (20%) to both species. Stool ova and parasite studies detected helminths in 5/85 (6%) persons. None of the patients tested had evidence of Chagas disease (n = 77) or filarial infection (n = 52). Eosinophilia >400 cells/mm3 was associated with a positive schistosome antibody test (OR 4.5, 95% CI 1.1-19.0). The only symptom significantly associated with strongyloidiasis was weight loss (OR 3.1, 95% CI 1.4-7.2).Conclusions/Significance:Given the high prevalence of certain helminths and the potential lack of suggestive symptoms and signs, selected screening for strongyloidiasis and schistosomiasis or use of empiric antiparasitic therapy may be appropriate among foreign-born, HIV-infected patients. Identifying and treating helminth infections could prevent long-term complications.
by
Julie A. Womack;
Terrence E. Murphy;
Harini Bathulapalli;
Kathleen M. Akgun;
Cynthia Gibert;
Ken M. Kunisaki;
David Rimland;
Maria Rodriguez-Barradas;
H. Klar Yaggi;
Amy C. Justice;
Nancy S. Redeker
by
P. Todd Korthuis;
David A. Fiellin;
Kathleen A. McGinnis;
Melissa Skanderson;
Amy C. Justice;
Adam J. Gordon;
Donna Almario Doebler;
Steven M. Asch;
Lynn E. Fiellin;
Kendall Bryant;
Cynthia L. Gibert;
Stephen Crystal;
Matthew Bidwell Goetz;
David Rimland;
Maria C. Rodriguez-Barradas;
Kevin L. Kraemer
HIV-infected patients with substance use experience suboptimal health outcomes, possibly because of variations in care. OBJECTIVES: To assess the association between substance use and the quality of HIV care (QOC) received. RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: HIV-infected patients enrolled in the Veterans Aging Cohort Study. MEASURES: We collected self-report substance use data and abstracted 9 HIV quality indicators (QIs) from medical records. Independent variables were unhealthy alcohol use (AUDIT-C score ≥4) and illicit drug use (self-report of stimulants, opioids, or injection drug use in past year). Main outcome was the percentage of QIs received, if eligible. We estimated associations between substance use and QOC using multivariable linear regression. RESULTS: The majority of the 3410 patients were male (97.4%) and black (67.0%) with a mean age of 49.1 years (SD = 8.8). Overall, 25.8% reported unhealthy alcohol use, 22% illicit drug use, and participants received 81.5% (SD = 18.9) of QIs. The mean percentage of QIs received was lower for those with unhealthy alcohol use versus not (59.3% vs. 70.0%, P < 0.001) and those using illicit drugs vs. not (57.8% vs. 70.7%, P < 0.001). In multivariable models, unhealthy alcohol use (adjusted β-2.74; 95% confidence interval:-4.23 to-1.25) and illicit drug use (adjusted β-3.51; 95% CI:-4.99 to-2.02) remained inversely associated with the percentage of QIs received. CONCLUSIONS: Although the overall QOC for these HIV-infected Veteran patients was high, gaps persist for those with unhealthy alcohol and illicit drug use. Interventions that address substance use in HIV-infected patients may improve the QOC received.
The anaerobic gastrointestinal pathogen Clostridium difficile must form a metabolically dormant spore to survive in oxygenic environments and be transmitted from host to host. The regulatory factors by which C. difficile initiates and controls the early stages of sporulation in C. difficile are not highly conserved in other Clostridium or Bacillus species. Here, we investigated the role of two conserved oligopeptide permeases, Opp and App, in the regulation of sporulation in C. difficile. These permeases are known to positively affect sporulation in Bacillus species through the import of sporulation-specific quorum-sensing peptides. In contrast to other spore-forming bacteria, we discovered that inactivating these permeases in C. difficile resulted in the earlier expression of early sporulation genes and increased sporulation in vitro. Furthermore, disruption of opp and app resulted in greater virulence and increased the amounts of spores recovered from feces in the hamster model of C. difficile infection. Our data suggest that Opp and App indirectly inhibit sporulation, likely through the activities of the transcriptional regulator SinR and its inhibitor, SinI. Taken together, these results indicate that the Opp and App transporters serve a different function in controlling sporulation and virulence in C. difficile than in Bacillus subtilis and suggest that nutrient availability plays a significant role in pathogenesis and sporulation in vivo. This study suggests a link between the nutritional status of the environment and sporulation initiation in C. difficile.
Although patients with HIV infection are living decades longer than before with the advent of combination antiretroviral therapy, they have an increased rate of co-morbidities associated with chronic HIV, such as osteoporosis, cardiovascular disease, and immune dysfunction. Many of these complications are known to be affected by vitamin D status in the general population. Thus, the high rate of vitamin D deficiency among HIV-infected patients is alarming. Many observational and cohort studies have demonstrated that vitamin D deficiency is associated with these HIV-related complications, but randomized, placebo-controlled trials are limited. This paper reviews recent data on vitamin D deficiency in HIV infection.
Background: HIV-infected patients are at increased risk of cardiovascular disease (CVD). This study assessed long-term changes in carotid intima-media thickness (IMT) as a surrogate marker for CVD risk in HIV-infected children and young adults. Methods: This was a longitudinal, observational study comparing carotid IMT in HIV-infected subjects who were 2-21 years old to matched controls over 144 weeks. Results: A total of 34 HIV-infected subjects and 29 controls were included in the analyses. Among the HIV-infected group, median age was 10 years, 74% were black, and 65% were female. Overall, 91% were perinatally-infected with 82% on antiretroviral therapy and a median CD4 + T-cell count of 681 cells/mm3. At baseline, HIV-infected subjects had increased internal carotid artery (ICA) and common carotid artery (CCA) IMT (ICA, HIV-infected 0.90 mm versus controls 0.73 mm; P<0.01; CCA, HIV-infected 1.00 mm versus controls 0.90 mm; P=0.02). Relatively large changes in ICA and CCA IMT were seen from year to year in both groups. However, by week 144, there were no net changes in ICA or CCA IMT within the HIV-infected group. In the controls, CCA increased 0.1 mm and ICA increased 0.17 mm from baseline to week 144. ICA and CCA IMT were similar between groups by 144 weeks. Conclusions: Despite variations from year to year in carotid IMT in HIV-infected children and healthy controls, likely due to arterial growth and/or luminal diameter change, little or no net change occurred in carotid IMT over the entire 144-week study period. This suggests that only small net changes occur over time in HIV-infected children despite an increased long-term risk of CVD.
Objective. We sought to determine whether the bacterial burden in the nares, as determined by the cycle threshold (CT) value from real-time MRSA PCR, is predictive of environmental contamination with MRSA Methods. Patients identified as MRSA nasal carriers per hospital protocol were enrolled within 72 hours of room admission. Patients were excluded if (1) nasal mupirocin or chlorhexidine body wash was used within the past month or (2) an active MRSA infection was suspected. Four environmental sites, 6 body sites and a wound, if present, were cultured with premoistened swabs. All nasal swabs were submitted for both a quantitative culture and real-time PCR (Roche Lightcycler, Indianapolis, IN) Results. At study enrollment, 82 patients had a positive MRSA-PCR. A negative correlation of moderate strength was observed between the CT value and the number of MRSA colonies in the nares (r= −0.61; P<0.01). Current antibiotic use was associated with lower levels of MRSA nasal colonization (CT value, 30.2 vs 27.7; P < 0.01). Patients with concomitant environmental contamination had a higher median log MRSA nares count (3.9 vs 2.5, P = 0.01) and lower CT values (28.0 vs 30.2; P < 0.01). However, a ROC curve was unable to identify a threshold MRSA nares count that reliably excluded environmental contamination Conclusions. Patients with a higher burden of MRSA in their nares, based on the CT value, were more likely to contaminate their environment with MRSA. However, contamination of the environment cannot be predicted solely by the degree of MRSA nasal colonization.
Background: Current available malaria diagnostic methods each have some limitations to meet the need for real-time and large-scale screening of asymptomatic and low density malaria infection at community level. It was proposed that malaria parasite-specific low molecular-weight metabolites could be used as biomarkers for the development of a malaria diagnostic tool aimed to address this diagnostic challenge. In this study, high resolution metabolomics (HRM) was employed to identify malaria parasite-specific metabolites in Plasmodium falciparum in vitro culture samples. Methods: Supernatants were collected at 12 hours interval from 3% haematocrit in vitro 48-hour time-course asynchronized culture system of P. falciparum. Liquid chromatography coupled with high resolution mass spectrometry was applied to discover potential parasite-specific metabolites in the cell culture supernatant. A metabolome-wide association study was performed to extract metabolites using Manhattan plot with false discovery rate (FDR) and hierarchical cluster analysis. The significant metabolites based on FDR cutoff were annotated using Metlin database. Standard curves were created using corresponding chemical compounds to accurately quantify potential Plasmodium-specific metabolites in culture supernatants. Results: The number of significant metabolite features was 1025 in the supernatant of the Plasmodium infected culture based on Manhattan plot with FDR q=0.05. A two way hierarchical cluster analysis showed a clear segregation of the metabolic profile of parasite infected supernatant from non-infected supernatant at four time points during the 48 hour culture. Among the 1025 annotated metabolites, the intensities of four molecules were significantly increased with culture time suggesting a positive association between the quantity of these molecules and level of parasitaemia: i) 3-methylindole, a mosquito attractant, ii) succinylacetone, a haem biosynthesis inhibitor, iii) S-methyl-L-thiocitrulline, a nitric oxide synthase inhibitor, and iv) O-arachidonoyl glycidol, a fatty acid amide hydrolase inhibitor, The highest concentrations of 3-methylindole and succinylacetone were 178 ± 18.7 pmoles at 36 hours and 157±30.5 pmoles at 48 hours respectively in parasite infected supernatant. Conclusion: HRM with bioinformatics identified four potential parasite-specific metabolite biomarkers using in vitro culture supernatants. Further study in malaria infected human is needed to determine presence of the molecules and its relationship with parasite densities.