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Background Understanding care patterns of persons living with HIV prior to diagnosis can inform prevention opportunities, earlier diagnosis, and engagement strategies. We examined healthcare utilization among HIV-positive individuals and compared them to HIV-negative controls. Methods Data were from a retrospective cohort from Manitoba, Canada. Participants included individuals living with HIV presenting to care between 2007 and 2011, and HIV-negative controls, matched (1:5) by age, sex, and region. Data from population-based administrative databases included physician visits, hospitalizations, drug dispensation, and chlamydia and gonorrhea testing. Diagnoses associated with physician visits were classified according to International Classification of Diseases chapters. Conditional logistic regression models were used to compare cases/controls, with adjusted odds ratios (AORs) and their 95% confidence intervals (95% CI) reported. Results A total of 193 cases and 965 controls were included. Physician visits and hospitalizations were higher for cases, compared to controls. In the 2 years prior to case date, cases were more likely to be diagnosed with “blood disorders” (AOR: 4.2, 95% CI: 2.0–9.0), be treated for mood disorders (AOR: 2.4, 95% CI: 1.6–3.4), and to have 1+ visits to a hospital (AOR: 2.2, 95% CI: 1.4–3.6). Conclusion Opportunities exist for prevention, screening, and earlier diagnosis. There is a need for better integration of healthcare services with public health.

Background and Objective We describe the development of the first HIV care cascade for Manitoba, Canada, detailing steps taken to establish indicator definitions for each cascade step, and derive a full complement of local estimates. Methods Manitoba is a Canadian Prairie Province with disproportionately high annual HIV incidence. In 2013, a clinical cohort of people living with HIV was established within the primary HIV care program in Manitoba. Using cohort data from 2017, we describe the creation of a set of indicator definitions and calculate estimates for each cascade step to create the first Manitoban cascade model. Results Of the 703 cohort participants categorized as alive and diagnosed, 638 (90.8%) were in care, 606 (86.2%) retained in care, 573 (81.5%) on treatment, and 523 (74.4%) virologically suppressed. The greatest point of leakage occurred between the first and second steps; 9.3% of those alive and diagnosed in 2017 were not in care in the same calendar year. Conclusion This is the first comprehensive examination of HIV clinical epidemiology in Manitoba using a cascade framework, with the potential inform programming to improve service coverage within Manitoba and significantly contribute to evidence informing provincial policies to support these efforts.

PurposeThe LHIV-Manitoba cohort was developed as a way to provide a comprehensive source of HIV-related health information in the central Canadian Prairie province of Manitoba. The cohort will provide important information as we aim to better understand local HIV epidemiology and address key knowledge and practice gaps in HIV prevention, treatment and care programming in the province.ParticipantsIn total, 890 individuals, aged 18 or older and living or receiving HIV care in Manitoba are enrolled in the cohort. A complete clinical dataset exists for 725 participants, which includes variables on sociodemographic characteristics, comorbidities and co-infections, self-reported HIV exposure categories and HIV clinical indicators. A limited clinical dataset exists for an additional 165 individuals who were enrolled posthumously. 97.5% of cohort participants’ clinical records are linked to provincial administrative health datasets.Findings to dateThe average age of cohort participants is 49.7 years. Approximately three-quarters of participants are male, 42% self-identified as white and 42% as Indigenous. The majority of participants (64%) reported condomless vaginal sex as a risk exposure for HIV. Nearly one-fifth (18%) of participants have an active hepatitis C virus infection and the cohort’s median CD4 count increased from 316 cells/mm3 to 518 cells/mm3 between time of entry into care and end of the first quarter in 2019.Future plansThe LHIV-Manitoba cohort is an open cohort, and as such, participant enrolment, data collection and analyses will be continually ongoing. Future analyses will focus on the impact of provincial drug plans on clinical outcomes, determinants of mortality among cohort participants and deriving estimates for a local HIV care cascade.

HIV-1 infection is characterized by loss of CD4 T cells, leading to immunodeficiency. Initiation of antiretroviral therapy (ART) results in suppression of the viral load and increased CD4 counts. Both viral and host factors determine CD4 cell responses to ART with approximately 15–30% of individuals having suboptimal increase of CD4 T cell count, most commonly due to lack of compliance to ART. A smaller fraction of patients will have immune reconstitution failure and suboptimal CD4 increase despite suppression of HIV replication, and these individuals are at risk for adverse health outcomes. We sought to characterize the factors associated with decreased immunological response among Manitoba’s HIV patient population.This retrospective case-control study included HIV patients with immune reconstitution failure despite suppression of HIV replication by ART. The immune reconstitution failure was defined by CD4 cell count increase from baseline of less than 100 CD4 cells/mm3 or lack of increase to above 200 CD4 cells/mm3 within one year of viral load suppression. Age and nadir CD4 cell counts are known risk factors associated with immune reconstitution failure. We chose controls (Patients with immune reconstitution success) of similar age and CD4 nadir cell with cases (Patients with immune reconstitution failure). We explored the potential effects of gender, HLA type, presence of co-infection, ethnicity, ART type, and rate of pre-treatment CD4 decline among cases and controls. Of more than 550 patients followed by our HIV clinic, 42 individuals met our definition of immune reconstitution failure and they were assigned to the cases group. 31 patients, comprising a range of ages and CD4 nadirs similar to those of the cases, were assigned to the control group. Our primary analysis was a regression model, predicting post-ART change in CD4 over time.After controlling for age and nadir CD4 cell counts, the only potential predictor that appears consistently associated with the rate of post-ART rise in CD4 over time in our cohort, regardless of the other variables that we have controlled for, is the rate of decline in CD4 pre-ART initiation.Several factors have been variably correlated with immune reconstitution failure of CD4 T cell count. Age and low CD4 nadir are factors previously shown to correlate with immune reconstitution failure; and we have controlled for them in our study. Another possible predictor is the rate of decline in CD4 pre-ART, which can serve as an additional marker of reconstitution failure and necessitate prioritizing individuals to ART initiation or identification of a subset of individuals that may be targeted for future adjunct strategies to improve immune recovery. Keywords: HIV, CD4, Immune reconstitution, Virologic suppression

Tularemia is a zoonotic disease caused by the gram-negative coccobacillus Francisella tularensis, a Biosafety Level 3 pathogen and potential agent of bioterrorism. We describe 2 cases of perigenital ulcer disease caused by Francisella tularensis subspecies holarctica in Manitoba, Canada. These cases caused inadvertent exposure among laboratory personnel.

Central nervous system (CNS) infections (e.g., brain abscess, meningitis) caused by members of the Bacillus cereus group are rare, but the associated crude mortality is significant. The optimal antimicrobial regimen for patients with these infections remains poorly defined. This report describes a case of multiple brain abscesses in an immunocompromised patient caused by a member of the B. cereus group. The patient was successfully treated with a combination of high-dose ciprofloxacin and vancomycin, providing evidence for the clinical utility of this therapeutic regimen.

Lung infection in human immunodeficiency virus (HIV)-positive individuals remains an important cause of morbidity and mortality, even in the current antiretroviral therapy era. Pneumonia is the most common cause of admission in HIV-positive individuals in our centre as reported in a previously published study. The objective of this retrospective observational study was to further characterize these admissions, with respect to index of disease severity at presentation, organisms identified, and investigations pursued including bronchoalveolar lavage (BAL). There were 123 unique patients accounting for a total of 209 admissions from 2005 to 2015. An organism was isolated in only 33% of all admissions (68/209). The most common organism was Pneumocystis jirovecii with a frequency of 29% of all admissions. Eighty-seven percent of presentations were mild, and 13% were moderate by CURB-65 criteria. A total of 39 BALs were performed, of which 27 yielded an organism (69%). Considering the burden of disease, low diagnostic yield of the current diagnostic strategy and increased morbidity and mortality caused by pneumonia in HIV-positive individuals, further methods are needed to more accurately target therapy. The preponderance of mild disease in this study suggests that better diagnostic tests may identify individuals that can be candidates for outpatient therapy.

The nature of the HIV epidemic in the United States and Canada has changed with a shift toward rural areas. Socioeconomic factors, geography, cultural context, and evolving epidemics of injection drug use are coalescing to move the epidemic into locations where populations are dispersed and health care resources are limited. Rural–urban differences along the care continuum demonstrate the implications of this sociogeographic shift. Greater attention is needed to build a more comprehensive understanding of the rural HIV epidemic in the United States and Canada, including research efforts, innovative approaches to care delivery, and greater community engagement in prevention and care.

Introduction Despite the life-prolonging effects of Highly Active Antiretroviral Therapy (HAART), persons with HIV are still prone to higher rates of non-AIDS related morbidity (such as heart, kidney, and liver disease) than the general public. This is likely due to chronic immune activation and inflammation that persists in HIV-positive persons despite virological suppression. What remains undetermined, however, is whether a link exists between chronic inflammation/immune activation and suboptimal immune recovery on HAART. The hypothesis of the present study is that higher levels of systemic subclinical inflammation and immune activation are linked with suboptimal immune recovery on HAART. Methods Fifteen eligible patients from the Manitoba HIV program were enrolled and followed for up to two years; blood samples were drawn at 4 timepoints each, and concentrations of 21 proinflammatory markers were measured. Patients were grouped according to CD4:CD8 recovery at viral suppression, and the inflammatory profiles of the two groups were compared. Results and conclusions APRIL and BAFF are higher in those with poor recovery at the point of viral suppression, but were also higher in this group at the onset of therapy and through the three additional follow-up visits. TNF-R1, CD163, and Osteopontin, were also in higher concentrations at the outset of therapy and beyond. These five molecules could thus see potential use in the future as biomarkers of likely poor immune recovery. Future work should focus on replicating these findings with larger cohorts.

Background In the development of administrative data case-definitions for HIV, it is important to understand the contribution of each data source to prevalence estimates, especially as it pertains to generalizability of methods. Methods HIV case-definitions were constructed from four population-based databases available in Manitoba: physician claims, hospital discharge, pharmaceutical dispensations, and provincial laboratory tests. Performance was assessed using sensitivity, specificity, positive/negative predictive value (PPV & NPV), and Youden’s index (YI). Cases identified by HIV case-definitions, and those reported to public health surveillance were compared using annualized incidence. The distribution of those flagged as HIV-positive was compared by database. Results The best performing case-definition (YI 0.71) was two or more HIV diagnoses in two years in physician claims, or in hospital discharge abstracts; or 14 or more HAART dispensations in two years; or one positive HIV laboratory. Sensitivity, specificity, PPV and NPV was 82.3% (95%CI: 79.1%-85.5%), 86.8% (95%CI: 84.9%-88.7%), 74.1% (95%CI: 70.6%-77.6%), 91.4% (95%CI: 89.8%-93.1%), respectively. Annualized incidence (2009–2015) calculated from this case-definition was 7.4/100,000 persons (95%CI: 6.8–8.1)]; annualized incidence calculated from surveillance data was 7.7/100,000 persons (95%CI: 7.1–8.3). Approximately 76% of cases would have been flagged through a positive laboratory; 43% through pharmaceutical claims; 34% through physician claims; and 11% through hospital abstracts. 95% of cases would have been flagged through the combination of laboratory and pharmaceutical databases. Only 4% of cases were flagged in all four data sources. Conclusion Although the combination of four databases produced the most complete prevalence snapshot, laboratory data was the most important contributor. The combination of laboratory and pharmaceutical databases would have identified the predominant majority of cases in our sample. Findings can be used to inform the construction of administrative data cohorts where the availability of population-based data sources may be more limited. Disclosure No significant relationships.

Understanding patterns of serological testing for hepatitis B & C, and syphilis among HIV-positive individuals, prior to HIV diagnosis, can inform HIV diagnosis, engagement and prevention strategies. This was a population-based, retrospective analysis of prior serological testing among HIV-positive individuals in Manitoba, Canada. HIV cases were age-, sex- and region-matched to HIV-negative controls at a 1:5 ratio. Conditional logistic regression was used to examine previous serological tests and HIV status. Odds ratios (ORs) and their 95% confidence intervals (95% CI) were reported. A total of 193 cases and 965 controls were included. In the 5 years prior to diagnosis, 50% of cases had at least one test, compared to 26% of controls. Compared to those who did not have serological testing in the 5 years prior to HIV infection, those who had one serological test were at twice the odds of being HIV positive (OR: 1.9, 95% CI: 1.2-2.9), while those with 2 or more tests were at even higher odds (OR: 5.5, 95%CI: 3.7-8.4). HIV cases had higher serological testing rates. Interactions between public health and other healthcare providers should be strengthened.

The high prevalence of substance use among HIV-infected individuals creates numerous challenges to patient care. This study was undertaken in order to understand the impact of substance use on care outcomes for HIV-infected individuals in Manitoba. Clinical records of 564 HIV-infected individuals in care at Health Sciences Centre in Winnipeg, Manitoba were reviewed. Clinical data were extracted from patient charts for substance users (illicit substance users, alcohol abusers and chronic users of opioids or benzodiazepines) and non-users. Substance users and non-users were analysed using chi-square analysis and logistic regression models to compare basic socio-demographic and clinic variables. Chi-square and analysis of variance were used to compare a subset of substance users based on similar socio-demographic and clinical characteristics. Among HIV-infected individuals in Manitoba, 38% were substance users with over-representation by Aboriginals, females, young adults and residents of Winnipeg's core areas. Opioids and benzodiazepines were the most commonly used substances with the majority of substance users having used multiple classes of substances in their lifetime. Substance users were more likely than non-users to have missed clinic appointments. Among substance users, missed appointments were more common among those who self-identified as Aboriginal, female, young adults, residents of Winnipeg's core areas, heterosexuals and those who had abused alcohol or cocaine/crack. Aboriginal substance users were also less likely to achieve viral load suppression compared to non-Aboriginal substance users. With the high prevalence of substance use among HIV-infected individuals in Manitoba, it is important to identify at-risk individuals in order to implement appropriate care strategies and improve treatment adherence and health outcomes.

Transmitted by the bite of female sandflies, leishmaniasis is a protozoal infection. Visceral leishmaniasis, which is usually transmitted by Leishmania donovani and Leishmania infantum, occurs when the reticuloendothelial system is affected, and is more severe in HIV-infected patients because it increases HIV viral replication, as described in this case report. The authors also describe gastrointestinal complications that occurred in both this case and in other visceral leishmaniasis cases from the literature., The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm3, despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

Point-of-care (POC) HIV testing has been shown to be an acceptable method for increasing HIV testing uptake. To date, no studies have examined the use of POC testing for routine HIV screening on the medicine inpatient unit. A prospective cross-sectional study was conducted over a three-month period in July, August, and October 2016 to evaluate the prevalence of undiagnosed HIV and the attitudes towards routine POC HIV testing. Patients admitted directly to medicine inpatient teaching units at a tertiary hospital in Winnipeg, Canada, were approached for participation. The POC HIV test was administered at the bedside. Reactive and indeterminate tests were confirmed with standard serological HIV testing. Participants were given a questionnaire regarding their attitudes towards POC testing on the unit. Although no cases of previously undiagnosed HIV were identified during the study period, only 35% of participants were found to have ever had HIV testing previously. The majority of participants were satisfied with the POC testing experience and would choose to have the POC testing again. Overall, the low rate of outpatient testing highlights the need for routine HIV testing on an inpatient basis.

Summary: Immune Reconstitution Syndrome (IRIS) has been associated with a variety of infections in patients with human immunodeficiency virus (HIV). However, we are reporting the first case of IRIS secondary to Rhodococcus equi (R. equi) in a patient with HIV.We report the case of a 48-year-old male found to have HIV infection in the setting of Burkitt's lymphoma. While on anti-retroviral therapy and chemotherapy, he had developed IRIS secondary to R. equi that manifested as a cavitating pneumonia. This report outlines the successful management of the R. equi infection with the use of a combination of antibiotics, radiographic follow up and suppressive antibiotic while on chemotherapy. Keywords: Human immunodeficiency virus, Rhodococcus equi, Burkitt's lymphoma, Cavitating pneumonia

BACKGROUND: HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers. METHODS: Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses. RESULTS: HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control. CONCLUSIONS: Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.

The numbers and demographics of HIV-positive patients in care between 2003 and 2007 in the prairie provinces were examined.Estimates of HIV-positive patients presenting to care between 2003 and 2007 were obtained from four clinic registries in Manitoba, Saskatchewan and southern Alberta. Detailed data were collected from clinical records of new patients in 2007.By the end of December 2007, 2263 HIV-positive persons were in care in Manitoba, Saskatchewan and southern Alberta. Males and females accounted for 1674 (74.0%) and 589 of the cases, respectively. Overall, there was a 12% increase per year in new HIV cases to care between 2003 and 2007 (P=0.026), with the rate of increase for males being 60% higher than for females over this time period (P=0.002). In 2007, there were 222 new HIV cases to care (37.4% female). Heterosexual contact was the most common HIV risk, but diversity was seen across sites with frequent injection drug use and men who have sex with men risk in Saskatchewan and southern Alberta, respectively. The Aboriginal population remains heavily over-represented, with approximately 36.0% of new cases being Aboriginal. Late presentation was common across all care sites, with 35.1% of cases presenting with CD4 counts of less than 200 cells/mm(3).Heterosexual risk is the most common risk reported for HIV acquisition, but injection drug use risk remains significant in Saskatchewan. Aboriginals are over-represented at all sites, and in Saskatchewan accounted for the majority of new cases seen. In contrast to national trends, numbers of new and late diagnoses are increasing in the praire provinces, and this has significant treatment implications and potential public health consequences. Further efforts need to be made to facilitate earlier testing and linkage to care.The numbers and demographics of HIV-positive patients in care between 2003 and 2007 in the prairie provinces were examined.Estimates of HIV-positive patients presenting to care between 2003 and 2007 were obtained from four clinic registries in Manitoba, Saskatchewan and southern Alberta. Detailed data were collected from clinical records of new patients in 2007.By the end of December 2007, 2263 HIV-positive persons were in care in Manitoba, Saskatchewan and southern Alberta. Males and females accounted for 1674 (74.0%) and 589 of the cases, respectively. Overall, there was a 12% increase per year in new HIV cases to care between 2003 and 2007 (P=0.026), with the rate of increase for males being 60% higher than for females over this time period (P=0.002). In 2007, there were 222 new HIV cases to care (37.4% female). Heterosexual contact was the most common HIV risk, but diversity was seen across sites with frequent injection drug use and men who have sex with men risk in Saskatchewan and southern Alberta, respectively. The Aboriginal population remains heavily over-represented, with approximately 36.0% of new cases being Aboriginal. Late presentation was common across all care sites, with 35.1% of cases presenting with CD4 counts of less than 200 cells/mmHeterosexual risk is the most common risk reported for HIV acquisition, but injection drug use risk remains significant in Saskatchewan. Aboriginals are over-represented at all sites, and in Saskatchewan accounted for the majority of new cases seen. In contrast to national trends, numbers of new and late diagnoses are increasing in the praire provinces, and this has significant treatment implications and potential public health consequences. Further efforts need to be made to facilitate earlier testing and linkage to care.Les chercheurs ont examiné le nombre et la démographie des patients positifs au VIH soignés entre 2003 et 2007 dans les provinces des Prairies.Les chercheurs ont pu évaluer le nombre de patients positifs au VIH qui ont consulté pour la première fois entre 2003 et 2007 d’après quatre registres cliniques du Manitoba, de la Saskatchewan et du sud de l’Alberta. Ils ont également recueilli les données détaillées des dossiers cliniques de nouveaux patients en 2007.À la fin de décembre 2007, 2 263 personnes positives au VIH étaient soignées au Manitoba, en Saskatchewan et dans le sud de l’Alberta. Les hommes et les femmes représentaient 1 674 (74,0 %) et 589 cas, respectivement. Dans l’ensemble, on a constaté une augmentation annuelle de 12 % des nouveaux cas de VIH soignés entre 2003 et 2007 (P=0,026), le taux d’augmentation pour les hommes étant 60 % plus élevé que pour les femmes (P=0,002). En 2007, on a recensé 222 nouveaux cas de VIH soignés (37,4 % de femmes). Le contact hétérosexuel représentait le principal risque de VIH, mais on remarquait une diversité selon les lieux, le risque posé par la consommation fréquente de drogues par injection et par les relations sexuelles entre hommes étant observé en Saskatchewan et au sud de l’Alberta, respectivement. La population autochtone demeure lourdement surreprésentée, puisqu’environ 36,0 % des nouveaux cas étaient d’origine autochtone. Une présentation tardive était fréquente partout, la numération de CDLes contacts hétérosexuels constituent le principal risque déclaré d’acquisition du VIH, mais la consommation de drogues par injection demeure importante en Saskatchewan. Les Autochtones sont surreprésentés partout, et en Saskatchewan, ils représentent la majorité des nouveaux cas observés. Contrairement aux tendances nationales, le nombre de nouveaux diagnostics et de diagnostics tardifs augmente dans les provinces des Prairies, ce qui a des répercussions thérapeutiques importantes et des conséquences potentielles en matière de santé publique. Il faut faire davantage d’efforts pour favoriser la tenue de tests et des mises en relation plus rapides vers les soins.

Involvement of the pericardium in meningococcal disease is a well-recognized but rare complication. Isolated meningococcal pericarditis is defined as purulent pericarditis without clinical evidence of meningococcemia. Neisseria meningitidis serotypes C, B, and W135 have been previously described to cause pericarditis. This is the 1st case report of isolated meningococcal myopericarditis due to N. meningitidis serotype Y.

Regulatory T cells, a subset of CD4(+) T lymphocytes, play a pivotal role in the maintenance of the balance between the tissue-damaging and protective effects of the immune response. These cells have immunosuppressive function and have been intensely studied in the context of autoimmunity, cancer, allergies, asthma, and infectious diseases. Their role in chronic and persistent viral infections is well appreciated. In acute viral infections, the function of these cells is still unclear. The host and pathogen factors that control the generation and activity of regulatory T cells and the role of these cells in modulating expansion, contraction, and development of immune memory in acute respiratory virus infection need to be further elucidated.

Human immunodeficiency virus type 1 (HIV-1) infection is associated with variable rates of disease progression, influenced by the quality of CD8 T-lymphocyte response, which is determined by human leukocyte antigen (HLA) I alleles. Some individuals progress slowly and maintain viral control, while at the opposite end of the spectrum some individuals endure a faster progression with rapid CD4 decline. We sought to determine the role of HLA-B allele frequency on rapid HIV disease progression. It was hypothesized that rapid progression is associated with the presence of high allele frequency of HLA-B35 and HLA-B homozygocity.This retrospective cohort study was conducted in the Manitoba HIV Program, Health Sciences Centre, a tertiary care facility in Winnipeg, Manitoba, Canada. We defined a set of new criteria to describe a subset of individuals with the most rapid HIV disease progression, and collected demographic, clinical, laboratory (CD4 count, viral load) and HLA data on a subset of 20 individuals meeting these criteria.Among those individuals who display extreme rapid progression, an overrepresentation of Aboriginal ethnicities, high frequencies of HLA-B35 and significantly higher rates of HLA-B51, as well as a very high rate of homozygocity for HLA-B alleles, were observed.Individuals with the most rapid disease progression have higher rates of HLA-B homozygocity, HLA-B51 alleles and higher viral loads than those with normal progression rates. This group, at the extreme end of the spectrum of progression, should be targeted for early treatment.

Human leucocyte antigen (HLA) alleles influence the rate of CD4 decline among HIV-infected individuals. We investigated the association between HLA B35 and HLA B51 and the rate of CD4 decline and/or opportunistic infections, among 294 HIV-positive individuals from Manitoba, Canada. All individuals presenting with a CD4 count >200 cells μL(-1) , who had at least two CD4 counts, and no evidence of co-infection were included. Individuals bearing HLA B35 or HLA B51 were compared to controls. A multivariate model demonstrated that HLA B35 allele was associated with a hazard ratio of 2.05 (95% CI 1.31-3.18) for reaching AIDS and HLA B51 allele with HR of 2.03 (95% CI 1.18-3.49) for reaching the same end-point. High prevalence of HLA B35 was seen in the patient population receiving care in Manitoba. Our observations confirm the association of HLA B35 with rapid disease progression. We report, for the first time, faster CD4 decline among individuals with HLA B51 allele.

Educational interventions may prevent misuse of antimicrobials and reduce antimicrobial resistance, but effects may fade over time. We created the penicillin pyramid for first year medical students to remember these drugs. Eighteen months later, 68 % recalled the penicillin pyramid and 99 % recalled correct information about the penicillins and their antimicrobial spectrum.

Background: Maraviroc is an allosteric, non-competitive blocker of CCR5, interfering with its ability to bind to the HIV GP120 and thus preventing HIV cell entry. CCR5 is involved in recruiting immune cells to sites of viral invasion in the respiratory tract. This postulated role of CCR5 led us to perform a meta-analysis of the largest clinical drug trials that evaluated CCR5 antagonists, as part of antiretroviral regimens, with focus on the occurrence of respiratory infections in general and viral infections in particular in CCR5 antagonist recipients. Data source and eligibility criteria: Clinical trials involving administration of Maraviroc to HIV infected individuals were reviewed with emphasis on reported respiratory infections. We included in the analysis those studies enrolling more than 100 participants in the maraviroc treatment arm. Results: We compared individuals treated with optimized background regimen plus placebo to those receiving the background regimen along with the CCR5 anatagonist maraviroc. We found in the clinical data significantly more respiratory infections in the CCR5 blocker treated arm than in the control arm. Limitations: The studies had limited microbiological analysis of respiratory infections and the categorization differs between the studies included. Conclusions: This observation suggests that the CCR5 blockade may lead to more infections caused by other viruses and respiratory pathogens in HIV infected patients and the incidence of such infections needs to be carefully assessed.

To the Editor—We read with interest the report by Suleiman et al [1] on the encouraging results of the VICTOR-E1 Phase 2 Trial, demonstrating vicriviroc's good and sustained antiretroviral and immunologic activity over 48 weeks in treatment-experienced HIV-infected individuals. These promising results need to be balanced with caution against the possibility that treatment could lead to more severe manifestations of other viral infections; this is due to the mechanism of action of vicriviroc and the significant role of CCR5 in the response to viral infections other than HIV. CCR5 is a chemokine receptor expressed on a variety of immune cells and is responsible for mediating leukocyte chemotaxis and homing to sites of infection. Until recently, understanding of the role of CCR5 was limited to its role in HIV cell entry and the protection from HIV afforded by its absence. More recent evidence is mounting to link CCR5 receptor deficiency (ie, the presence of the CCR5Δ32 allele) with an increased risk of symptomatic and fatal West Nile virus infection [2–4]. Additionally, a severe adverse reaction to the yellow fever virus vaccine in a CCR5Δ32 heterozygote and an association of the Δ32 mutation with severe tickborne encephalitis symptoms [5, 6] suggest a broader role for CCR5 in flaviviral infections. Several lines of evidence point to the CCR5Δ32 allele being important in determining disease severity of other viral infections, albeit in animal models. In a mouse model, challenge of CCR5-deficient animals with influenza virus was associated with impaired recruitment of CD8+ to the lungs, accompanied by an increased mortality rate [7, 8]. The vicriviroc treatment arms in the Suleiman et al study included 79 participants. Four deaths were reported in the study, including 2 subjects in the placebo group and 2 in the vicriviroc 20 mg treatment group; the latter 2 were attributed to bilateral atypical pneumonia and presumed disseminated tuberculosis, complicated by multiple organ failure. The concept of targeting a human receptor has numerous advantages but is also accompanied by concerns for untoward effects, especially when the receptor blocked is nonspecific for a given pathogen and has an important role in the general function of cellular immunity against other viruses. In the future, the encouraging results of this trial should be followed up by studying additional patients with specific attention to other viral infections and for a longer follow-up period.

Hemophagocytic syndrome (HPS) is a rare clinical presentation infrequently associated with lymphoproliferative disorders. We describe a 29-year-old male with aggressive HPS and T-cell lymphoma managed successfully with high-dose chemotherapy and autologous peripheral stem cell transplantation (APSCT), in remission at 41 months of follow-up. In reviewing the literature, this case illustrates the 2nd longest surviving individual post stem cell transplant for aggressive HPS.

Three cases of severe rash associated with the use of atazanavir are described. In all cases, the rash was maculopapular and pruritic. Rash onset occurred eight to 11 days after initiation of therapy, and resolved with atazanavir discontinuation. Clinicians prescribing atazanavir should be aware of this potential adverse effect.

Canadian data regarding the characteristics of HIV-positive patients admitted to hospital as well as the causes and patterns of admissions remain limited. Chart reviews were performed to ascertain admission diagnosis, co-morbidities and CD4 counts among this sub-population, which had an over-representation of Aboriginal persons. Infectious diseases, particularly pneumonia, represent the most common admission diagnosis for HIV-positive persons in Winnipeg. Further, individuals presenting to hospital often have very low CD4 counts, representing significant immune suppression. Earlier HIV diagnosis and treatment in an effort to delay the onset of advanced disease and hospitalization is needed.