CD4(+) T follicular helper and IgA(+) B cell numbers in gut biopsies from HIV-infected subjects on antiretroviral therapy are similar to HIV-uninfected individuals

BACKGROUND: Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4(+) T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4(+) subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV(+) subjects on suppressive ART compared to HIV-negative controls (HNC). METHODS: Twenty-three HIV(+) subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM(+) epithelial cells, were accurately enumerated by flow cytometry, using counting beads. RESULTS: No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4(+) T cell count/10(6) epithelial cells was 2.4-fold lower in HIV(+) subjects versus HNC (19,679 versus 47,504 cells; p = 0.02). Similarly, median LC CD4(+) T cell counts were reduced in HIV(+) subjects (8,358 versus 18,577; p = 0.03) but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA(+) B cell counts at either site between HIV(+) subjects and HNC. Further analysis showed no difference in CD4(+), Tfh, or IgA(+) B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4(+) T cells, including CCR5(+) cells, CD127(+) long-term memory cells, CD103(+) tissue-resident cells, or CD161(+) cells (surrogate marker for Th17), but there was a slight increase in the proportion of T regulatory cells. CONCLUSION: While there were lower absolute CD4(+) counts in the TI and LC in HIV(+) subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA(+) B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.John Zaunders, Mark Danta, Michelle Bailey, Gerald Mak, Katherine Marks, Nabila Seddiki, Yin Xu, David J. Templeton, David A. Cooper, Mark A. Boyd, Anthony D. Kelleher and Kersten K. Koelsc

Cost-effectiveness of adult circumcision in a resource-rich setting for HIV prevention among men who have sex with men

Background.&nbsp; We examined the effects and cost‐effectiveness of 4 strategies of circumcision in a resource‐rich setting (Australia) in a population of men who have sex with men (MSM).Method.&nbsp; We created a dynamic mathematical transmission model and performed an economic analysis to estimate the costs, outcomes, and cost‐effectiveness of different strategies, compared with those of the status quo. Strategies included circumcision of all MSM at age 18 years, circumcision of all MSM aged 35&ndash;44 years, circumcision of all insertive MSM aged 18 years, and circumcision of all MSM aged 18 years . All costs are reported in US dollars, with a cost‐effectiveness threshold of 42,000 per quality‐adjusted life‐year.Results.  We find that 2%–5% of human immunodeficiency virus (HIV) infections would be averted per year, with initial costs ranging from 3.6 million to $95.1 million, depending on the strategy. The number of circumcisions needed to prevent 1 HIV infection would range from 118 through 338. Circumcision of predominately insertive MSM would save$21.7 million over 25 years with a $62.2 million investment. Strategies to circumcise 100% of all MSM and to circumcise MSM aged 35&ndash;44 years would be cost‐effective; the latter would require a smaller investment. The least cost‐effective approach is circumcision of young MSM close to their sexual debut. Results are very sensitive to assumptions about the cost of circumcision, the efficacy of circumcision, sexual preferences, and behavioral disinhibition.Conclusions.&nbsp; Circumcision of adult MSM may be cost‐effective in this resource‐rich setting. However, the intervention costs are high relative to the costs spent on other HIV prevention programs.<br /

Uptake of hepatitis C specialist services and treatment following diagnosis by dried blood spot in Scotland

Background: Dried blood spot (DBS) testing for hepatitis C (HCV) was introduced to Scotland in 2009. This minimally invasive specimen provides an alternative to venipuncture and can overcome barriers to testing in people who inject drugs (PWID). Objectives: The objective of this study was to determine rates and predictors of: exposure to HCV, attendance at specialist clinics and anti-viral treatment initiation among the DBS tested population in Scotland. Study design: DBS testing records were deterministically linked to the Scottish HCV Clinical database prior to logistic regression analysis. Results: In the first two years of usage in Scotland, 1322 individuals were tested by DBS of which 476 were found to have an active HCV infection. Linkage analysis showed that 32% had attended a specialist clinic within 12 months of their specimen collection date and 18% had begun anti-viral therapy within 18 months of their specimen collection date. A significantly reduced likelihood of attendance at a specialist clinic was evident amongst younger individuals (&#60;35 years), those of unknown ethnic origin and those not reporting injecting drug use as a risk factor. Conclusion: We conclude that DBS testing in non-clinical settings has the potential to increase diagnosis and, with sufficient support, treatment of HCV infection among PWID

Using population attributable risk to choose HIV prevention strategies in men who have sex with men

<p>Abstract</p> <p>Background</p> <p>In Australia, HIV is concentrated in men who have sex with men (MSM) and rates have increased steadily over the past ten years. Health promotion strategies should ideally be informed by an understanding of both the prevalence of the factors being modified, as well as the size of the risk that they confer. We undertook an analysis of the potential population impact and cost saving that would likely result from modifying key HIV risk factors among men who have sex with men (MSM) in Sydney, Australia.</p> <p>Methods</p> <p>Proportional hazard analyses were used to examine the association between sexual behaviours in the last six months and sexually transmissible infections on HIV incidence in a cohort of 1426 HIV-negative MSM who were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007. We then estimated the proportion of HIV infections that would be prevented if specific factors were no longer present in the population, using a population attributable risk (PAR) method which controls for confounding among factors. We also calculated the average lifetime healthcare costs incurred by the HIV infections associated with specific factors by estimating costs associated with clinical care and treatment following infection and discounting at 3% (1% and 5% sensitivity) to present value.</p> <p>Results</p> <p>Unprotected anal intercourse (UAI) with a known HIV-positive partner was reported by 5% of men, the hazard ratio (HR) was 16.1 (95%CI:6.4-40.5), the PAR was 34% (95%CI:24-44%) and the average lifetime HIV-related healthcare costs attributable to UAI with HIV-positive partners were $AUD102 million (uncertainty range:$93-114 m). UAI with unknown HIV status partners was reported by 25% of men, the HR was 4.4 (95%CI:1.8-11.2), the PAR was 33% (95%CI:26-42%) and the lifetime incurred costs were $AUD99 million. Anal warts prevalence was 4$AUD39 million.</p> <p>Conclusions</p> <p>Our analysis has found that although UAI with an HIV-positive sexual partner is a relatively low-prevalence behaviour (reported by 5% of men), if this behaviour was not present in the population, the number of infections would be reduced by one third. No other single behaviour or sexually transmissible infections contributes to a greater proportion of infections and HIV-related healthcare costs.</p

Compositional Analysis of Lignocellulosic Feedstocks. 2. Method Uncertainties

The most common procedures for characterizing the chemical components of lignocellulosic feedstocks use a two-stage sulfuric acid hydrolysis to fractionate biomass for gravimetric and instrumental analyses. The uncertainty (i.e., dispersion of values from repeated measurement) in the primary data is of general interest to those with technical or financial interests in biomass conversion technology. The composition of a homogenized corn stover feedstock (154 replicate samples in 13 batches, by 7 analysts in 2 laboratories) was measured along with a National Institute of Standards and Technology (NIST) reference sugar cane bagasse, as a control, using this laboratory's suite of laboratory analytical procedures (LAPs). The uncertainty was evaluated by the statistical analysis of these data and is reported as the standard deviation of each component measurement. Censored and uncensored versions of these data sets are reported, as evidence was found for intermittent instrumental and equipment problems. The censored data are believed to represent the “best case” results of these analyses, whereas the uncensored data show how small method changes can strongly affect the uncertainties of these empirical methods. Relative standard deviations (RSD) of 1−3% are reported for glucan, xylan, lignin, extractives, and total component closure with the other minor components showing 4−10% RSD. The standard deviations seen with the corn stover and NIST bagasse materials were similar, which suggests that the uncertainties reported here are due more to the analytical method used than to the specific feedstock type being analyzed

Physical function limitation among gay and bisexual men aged ≥55years with and without HIV: findings from the Australian Positive and Peers Longevity Evaluation Study (APPLES)

Background. As people living with HIV now have a life expectancy approaching that of the general population, clinical care focuses increasingly on the management and prevention of comorbidities and conditions associated with aging. We aimed to assess the prevalence of physical function (PF) limitation among gay and bisexual men (GBM) and determine whether HIV is associated with severe PF limitation in this population. Methods. We analysed cross-sectional data from GBM aged ≥55 years in the Australian Positive and Peers Longevity Evaluation Study who completed a self-administered survey on health and lifestyle factors. PF was measured using the Medical Outcomes Study–Physical Functioning scale. Factors associated with severe PF limitation were assessed using logistic regression. Results. The survey was completed by 381 men: 186 without HIV and 195 with HIV. Median age was 64.3 years for GBM without HIV and 62.1 years for GBM with HIV. Compared with men without HIV, those with HIV had higher proportions of severe (13.3% vs 8.1%) and moderate-to-severe (26.7% vs 24.2%) PF limitation. Severe PF limitation commonly involved difficulty with vigorous activity (95% with severe PF limitation described being limited a lot), climbing several flights of stairs (68.4% limited a lot), bending, kneeling or stooping (60.5% limited a lot), and walking 1 km (55.0% limited a lot). In a model adjusted for age, body mass index, typical duration of physical activity, psychological distress, and number of comorbidities, we found a significant association between HIV and severe PF limitation (adjusted odds ratio 3.3 vs not having HIV, 95% confidence interval 1.3–8.7). Conclusions. The biological mechanisms underlying this association require further investigation, particularly given the growing age of the HIV population and inevitable increase in the burden of PF limitation

Antiretroviral treatment use, co-morbidities and clinical outcomes among Aboriginal participants in the Australian HIV Observational Database (AHOD)

Background: There are few data regarding clinical care and outcomes of Indigenous Australians living with HIV and it is unknown if these differ from non-Indigenous HIV-positive Australians. Methods: AHOD commenced enrolment in 1999 and is a prospective cohort of HIV-positive participants attending HIV outpatient services throughout Australia, of which 20 (74 %) sites report Indigenous status. Data were collected up until March 2013 and compared between Indigenous and non-Indigenous participants. Person-year methods were used to compare death rates, rates of loss to follow-up and rates of laboratory testing during follow-up between Indigenous and non-Indigenous participants. Factors associated with time to first combination antiretroviral therapy (cART) regimen change were assessed using Kaplan Meier and Cox Proportional hazards methods. Results: Forty-two of 2197 (1.9 %) participants were Indigenous. Follow-up amongst Indigenous and non-Indigenous participants was 332 & 16270 person-years, respectively. HIV virological suppression was achieved in similar proportions of Indigenous and non-Indigenous participants 2 years after initiation of cART (81.0 % vs 76.5 %, p = 0.635). Indigenous status was not independently associated with shorter time to change from first- to second-line cART (aHR 0.95, 95 % CI 0.51-1.76, p = 0.957). Compared with non-Indigenous participants, Indigenous participants had significantly less frequent laboratory monitoring of CD4 count (rate:2.76 tests/year vs 2.97 tests/year, p = 0.025) and HIV viral load (rate:2.53 tests/year vs 2.93 tests/year, p < 0.001), while testing rates for lipids and blood glucose were almost half that of non-indigenous participants (rate:0.43/year vs 0.71 tests/year, p < 0.001). Loss to follow-up (23.8 % vs 29.8 %, p = 0.496) and death (2.4 % vs 7.1 %, p = 0.361) occurred in similar proportions of indigenous and non-Indigenous participants, respectively, although causes of death in both groups were mostly non-HIV-related. Conclusions: As far as we are aware, these are the first data comparing clinical outcomes between Indigenous and non-Indigenous HIV-positive Australians. The forty-two Indigenous participants represent over 10 % of all Indigenous Australians ever diagnosed with HIV. Although outcomes were not significantly different, Indigenous patients had lower rates of laboratory testing for HIV and lipid/glucose parameters. Given the elevated risk of cardiovascular disease in the general Indigenous community, the additional risk factor of HIV infection warrants further focus on modifiable risk factors to maximise life expectancy in this population

Sharing a household with children and risk of COVID-19: a study of over 300 000 adults living in healthcare worker households in Scotland

Objective: Children are relatively protected from COVID-19, due to a range of potential mechanisms. We investigated if contact with children also affords adults a degree of protection from COVID-19. Design: Cohort study based on linked administrative data. Setting: Scotland. Study population: All National Health Service Scotland healthcare workers and their household contacts as of March 2020. Main exposure: Number of young children (0–11 years) living in the participant’s household. Main outcomes: COVID-19 requiring hospitalisation, and any COVID-19 (any positive test for SARS-CoV-2) in adults aged ≥18 years between 1 March and 12 October 2020. Results: 241 266, 41 198, 23 783 and 3850 adults shared a household with 0, 1, 2 and 3 or more young children, respectively. Over the study period, the risk of COVID-19 requiring hospitalisation was reduced progressively with increasing numbers of household children—fully adjusted HR (aHR) 0.93 per child (95% CI 0.79 to 1.10). The risk of any COVID-19 was similarly reduced, with the association being statistically significant (aHR per child 0.93; 95% CI 0.88 to 0.98). After schools reopened to all children in August 2020, no association was seen between exposure to young children and risk of any COVID-19 (aHR per child 1.03; 95% CI 0.92 to 1.14). Conclusion: Between March and October 2020, living with young children was associated with an attenuated risk of any COVID-19 and COVID-19 requiring hospitalisation among adults living in healthcare worker households. There was no evidence that living with young children increased adults’ risk of COVID-19, including during the period after schools reopened