Browsing by Author "Gill, M. J"

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    Increasing incidence of syphilis among patients engaged in HIV care in Alberta, Canada: a retrospective clinic-based cohort study
    (2018-03-13) Lang, Raynell; Read, Ron; Krentz, Hartmut B; Ramazani, Soheil; Peng, Mingkai; Gratrix, Jennifer; Gill, M. J
    Abstract Background Syphilis is a global health concern disproportionately affecting HIV-infected populations. In Alberta, Canada, the incidence of syphilis in the general population has recently doubled with 25% of these infections occurring in HIV-infected patients. The Southern Alberta HIV Clinic (SAC) and Calgary STI Program (CSTI) analyzed the epidemiologic characteristics of incident syphilis infections in our well-defined, HIV-infected population over 11 years. Methods Since 2006, as routine practice of both the Southern Alberta Clinic (SAC) and Calgary STI Programs (CSTI), syphilis screening has accompanied HIV viral load measures every four months. All records of patients who, while in HIV care, either converted from being syphilis seronegative to a confirmed seropositive or were re-infected as evidenced by a four-fold increase in rapid plasma reagin (RPR) after past successful treatment, were reviewed. Results Incident syphilis was identified 249 times in 194 HIV-infected individuals. There were 36 individuals with repeated infections (28.5% of episodes). Following a prior decline in annual incident syphilis rates, the rates have tripled from 8.08/1000 patient-years (95% confidence interval (CI): 4.14–14.75) in 2011, to 27.04 per 1000 person-years (95% CI: 19.45–36.76) in 2016. Half of the syphilis episodes were asymptomatic. Patients diagnosed with syphilis were twice as likely not to be taking ART and had a higher likelihood of having plasma HIV RNA viral loads > 1000 copies/mL (19%). Incident syphilis was seen predominantly in Caucasians (72%, P < 0.001), males (94%, P < 0.001) and men who have sex with men (MSM) as their HIV risk activity (75%, P < 0.001). Conclusions We have highlighted the importance of a regular syphilis screening program in HIV-infected individuals demonstrated by increasing rates of incident syphilis in our region. Targeted preventative strategies should be directed towards HIV-infected populations identified at highest risk, including; MSM, prior alcohol abuse, prior recreational drug use and those with prior syphilis diagnoses.
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    Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain
    (2017-10-16) Asahchop, Eugene L; Meziane, Oussama; Mamik, Manmeet K; Chan, Wing F; Branton, William G; Resch, Lothar; Gill, M. J; Haddad, Elie; Guimond, Jean V; Wainberg, Mark A; Baker, Glen B; Cohen, Eric A; Power, Christopher
    Abstract Background In patients with HIV/AIDS receiving antiretroviral therapy (ART), HIV-1 persistence in brain tissue is a vital and unanswered question. HIV-1 infects and replicates in resident microglia and trafficking macrophages within the brain although the impact of individual ART drugs on viral infection within these brain myeloid cells is unknown. Herein, the effects of contemporary ART drugs were investigated using in vitro and in vivo models of HIV-1 brain infection. Results The EC50 values for specific ART drugs in HIV-infected human microglia were significantly higher compared to bone marrow-derived macrophages and peripheral blood mononuclear cells. Intracellular ART drug concentrations in microglia were significantly lower than in human lymphocytes. In vivo brain concentrations of ART drugs in mice were 10 to 100-fold less in brain tissues compared with plasma and liver levels. In brain tissues from untreated HIV-infected BLT mice, HIV-encoded RNA, DNA and p24 were present in human leukocytes while ART eradicated viral RNA and DNA in both brain and plasma. Interruption of ART resulted in detectable viral RNA and DNA and increased human CD68 expression in brains of HIV-infected BLT mice. In aviremic HIV/AIDS patients receiving effective ART, brain tissues that were collected within hours of last ART dosing showed HIV-encoded RNA and DNA with associated neuroinflammatory responses. Conclusions ART drugs show variable concentrations and efficacies in brain myeloid cells and tissues in drug-specific manner. Despite low drug concentrations in brain, experimental ART suppressed HIV-1 infection in brain although HIV/AIDS patients receiving effective ART had detectable HIV-1 in brain. These findings suggest that viral suppression in brain is feasible but new approaches to enhancing ART efficacy and concentrations in brain are required for sustained HIV-1 eradication from brain.
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    Schistosoma and Strongyloides screening in migrants initiating HIV Care in Canada: a cross sectional study
    (2020-01-28) McLellan, Jessica; Gill, M. J; Vaughan, Stephen; Meatherall, Bonnie
    Abstract Background Following migration from Schistosoma and Strongyloides endemic to non-endemic regions, people remain at high risk for adverse sequelae from these chronic infections. HIV co-infected persons are particularly vulnerable to the serious and potentially fatal consequences of untreated helminth infection. While general screening guidelines exist for parasitic infection screening in immigrant populations, they remain silent on HIV positive populations. This study assessed the seroprevalence, epidemiology and laboratory characteristics of these two parasitic infections in a non-endemic setting in an immigrant/refugee HIV positive community. Methods Between February 2015 and 2018 individuals born outside of Canada receiving care at the centralized HIV clinic serving southern Alberta, Canada were screened by serology and direct stool analysis for schistosomiasis and strongyloidiasis. Canadian born persons with travel-based exposure risk factors were also screened. Epidemiologic and laboratory values were analyzed using bivariate logistic regression. We assessed the screening utility of serology, direct stool analysis, eosinophilia and hematuria. Results 253 HIV positive participants were screened. The prevalence of positive serology for Schistosoma and Strongyloides was 19.9 and 4.4%, respectively. Age between 40 and 50 years (OR 2.50, 95% CI 1.13–5.50), refugee status (3.55, 1.72–7.33), country of origin within Africa (6.15, 2.44–18.60), eosinophilia (3.56, 1.25–10.16) and CD4 count < 200 cells/mm3 (2.46, 1.02–5.92) were associated with positive Schistosoma serology. Eosinophilia (11.31, 2.03–58.94) was associated with positive Strongyloides serology. No Schistosoma or Strongyloides parasites were identified by direct stool microscopy. Eosinophilia had poor sensitivity for identification of positive serology. Hematuria was not associated with positive Schistosoma serology. Conclusion Positive Schistosoma and Strongyloides serology was common in this migrant HIV positive population receiving HIV care in Southern Alberta. This supports the value of routine parasitic screening as part of standard HIV care in non-endemic areas. Given the high morbidity and mortality in this relatively immunosuppressed population, especially for Strongyloides infection, screening should include both serologic and direct parasitological tests. Eosinophilia and hematuria should not be used for Schistosoma and Strongyloides serologic screening in HIV positive migrants in non-endemic settings.