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Abstract Background Anemia is common and associated with increased morbidity among people with HIV (PWH). Classification of anemia using the mean corpuscular volume (MCV) can help investigate the underlying causative factors of anemia. We characterize anemia using MCV among PWH receiving antiretroviral therapy (ART), and identify the risk factors for normocytic, macrocytic, and microcytic anemias. Methods Including PWH with anemia (hemoglobin measure 100 fL) or microcytic (

Abstract People with HIV (PWH) are at increased risk of COVID-19 infection. Both Canadian (NACI) and US (CDC) guidelines recommend that all PWH receive at least 2 doses of COVID-19 vaccine, and a booster. We examined vaccination uptake among PWH in Southern Alberta, Canada. Among adult PWH, we evaluated COVID-19 vaccination uptake between December 2020 and August 2022. Poisson regression models with robust variance (approximating log binomial models) estimated crude and adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for receiving (1) any vs. no vaccine, and (2) primary series with booster (≥ 3 vaccines) versus primary series without booster. Among 1885 PWH, 10% received no COVID-19 vaccinations, 37% 200 copies/mL), and using illegal substances. Factors associated with decreased booster uptake included being younger, Black (vs. White) ethnicity, substance use, lower educational attainment, and having an unsuppressed HIV viral load. COVID-19 booster uptake among PWH does not meet vaccine guidelines, and receipt of vaccines is unevenly distributed. Booster uptake is lowest among young females and marginalized individuals. Focused outreach is necessary to close this gap.

BackgroundEstimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030.Methods and findingsUsing the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts.ConclusionsThe PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

Background People with HIV (PWH) are at an increased risk of cardiovascular disease (CVD) with an unknown added impact of hepatitis C virus (HCV) coinfection. We aimed to identify whether HCV coinfection increases the risk of type 1 myocardial infarction (T1MI) and if the risk differs by age. Methods and Results We used data from NA‐ACCORD (North American AIDS Cohort Collaboration on Research and Design) from January 1, 2000, to December 31, 2017, PWH (aged 40–79 years) who had initiated antiretroviral therapy. The primary outcome was an adjudicated T1MI event. Those who started direct‐acting HCV antivirals were censored at the time of initiation. Crude incidence rates per 1000 person‐years were calculated for T1MI by calendar time. Discrete time‐to‐event analyses with complementary log–log models were used to estimate adjusted hazard ratios and 95% CIs for T1MI among those with and without HCV. Among 23 361 PWH, 4677 (20%) had HCV. There were 89 (1.9%) T1MIs among PWH with HCV and 314 (1.7%) among PWH without HCV. HCV was not associated with increased T1MI risk in PWH (adjusted hazard ratio, 0.98 [95% CI, 0.74–1.30]). However, the risk of T1MI increased with age and was amplified in those with HCV (adjusted hazard ratio per 10‐year increase in age, 1.85 [95% CI, 1.38–2.48]) compared with those without HCV (adjusted hazard ratio per 10‐year increase in age,1.30 [95% CI, 1.13–1.50]; P

Summary: Background: An obesity epidemic has been documented among adult Latinos/as in Latin America and the United States (US); however, little is known about obesity among Latinos/as with HIV (PWH). Moreover, Latinos/as PWH in the US may have different weight trajectories than those in Latin America due to the cultural and environmental contexts. We assessed weight and body mass index (BMI) trajectories among PWH initiating antiretroviral therapy (ART) across 5 countries in Latin America and the Caribbean and the US. Methods: ART-naïve PWH ≥18 years old, enrolled in Brazil, Honduras, Mexico, Peru, and Haiti (sites within CCASAnet) and the US (NA-ACCORD) starting ART between 2000 and 2017, with at least one weight measured after ART initiation were included. Participants were classified according to site/ethnicity as: Latinos/as in US, non-Latinos/as in US, Haitians, and Latinos/as in Latin America. Generalized least squares models were used to assess trends in weight and BMI. Models estimating probabilities of becoming overweight/obese (BMI ≥25 kg/m²) and of becoming obese (BMI ≥30 kg/m²) post ART initiation for males and females were fit using generalized estimating equations with a logit link and an independence working correlation structure. Findings: Among 59,207 PWH, 9% were Latinos/as from Latin America, 9% Latinos/as from the US, 68% non-Latinos/as from the US and 14% were Haitian. At ART initiation, 29% were overweight and 14% were obese. Post-ART weight and BMI increases were steeper for Latinos/as in Latin America compared with other sites/ethnicities; however, BMI at 3-years post ART remained lower compared to Latinos/as and non-Latinos/as in the US. Among females, at 3-years post ART initiation the greatest adjusted probability of obesity was found among non-Latinas in the US (15·2%) and lowest among Latinas in Latin America (8·6%). Among males, while starting with a lower BMI, Latinos in Latin America had the greatest adjusted probability of becoming overweight or obese 3-years post-ART initiation. Interpretation: In the Americas, PWH gain substantial weight after ART initiation. Despite environmental and cultural differences, PWH in Latin America, Haiti and Latinos and non-Latinos in the US share similar BMI trajectories on ART and high probabilities of becoming overweight and obese over time. Multicohort studies are needed to better understand the burden of other metabolic syndrome components in PWH across different countries.

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

BackgroundAlthough micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH).MethodsThis study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/μL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/μL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months.ResultsOf 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/μL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/μL and -79.763 cells/μL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/μL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed.ConclusionsIn ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation.Clinical trial registrationClinicalTrials.gov Identifier: NCT00798772.

ABSTRACT HIV infection persists in different tissue reservoirs among people with HIV (PWH) despite effective antiretroviral therapy (ART). In the brain, lentiviruses replicate principally in microglia and trafficking macrophages. The impact of ART on this viral reservoir is unknown. We investigated the activity of contemporary ART in various models of lentivirus brain infection. HIV-1 RNA and total and integrated DNA were detected in cerebral cortex from all PWH (n = 15), regardless of ART duration or concurrent plasma viral quantity and, interestingly, integrated proviral DNA levels in brain were significantly higher in the aviremic ART-treated group (P

The COVID-19 pandemic has illustrated the importance of infection tracking. The role of asymptomatic, undiagnosed individuals in driving infections within this pandemic has become increasingly evident. Modern phylogenetic tools that take into account asymptomatic or undiagnosed individuals can help guide public health responses. We finetuned established phylogenetic pipelines using published SARS-CoV-2 genomic data to examine reasonable estimate transmission networks with the inference of unsampled infection sources. The system utilised Bayesian phylogenetics and TransPhylo to capture the evolutionary and infection dynamics of SARS-CoV-2. Our analyses gave insight into the transmissions within a population including unsampled sources of infection and the results aligned with epidemiological observations. We were able to observe the effects of preventive measures in Canada's "Atlantic bubble" and in populations such as New York State. The tools also inferred the cross-species disease transmission of SARS-CoV-2 transmission from humans to lions and tigers in New York City's Bronx Zoo. These phylogenetic tools offer a powerful approach in response to both the COVID-19 and other emerging infectious disease outbreaks.

Background: Staphylococcal blood stream infections (SBSI) are a significant cause of morbidity and mortality, however there is little data on such infections in persons with HIV (PWH) in the combination antiretroviral therapy era, particularly when divided by species; methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative Staphylococcus (CoNS). Methods: Using linked longitudinal clinical and microbiologic databases, all cases of SBSI in PWH accessing care at Southern Alberta Clinic were identified and demographic features and outcomes characterized. We compared participants with SBSI to those with no SBSI and determined the 1-year all-cause mortality following SBSI and longitudinally over the study period. Findings: From 2000 to 2018, 130 SBSI occurred in 95 PWH over 21,526 patient-years follow-up. MSSA caused 38.4%, MRSA 26.1% and CoNS 35.3% of SBSI. Highest risks for SSBI were in Hepatitis C coinfection, low CD4 nadir, Indigenous/Metis ethnicity and in persons who use injection drugs (PWID). During follow-up, 423 deaths occurred in all PWH. Mortality rates for PWH with SBSI was 74.9/1000 patient-years (95% CI 59.2–94.9) compared with no SBSI 16.0/1000 patient-years (95% CI 14.4–17.7). The mortality Hazard Ratio was 2.61(95% CI 1.95–3.49, P=

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

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.

Modern computational methods using patient Human Immunodeficiency Virus type 1 (HIV-1) genetic sequences can model population-wide viral transmission dynamics. Accurate transmission inferences can play a critical role in the characterization of high-risk transmission clusters important for enhanced epidemiological control. We evaluated a phylogenetics-based analysis pipeline to infer person-to-person (P2P) infection dates and transmission relationships using 139 patient HIV-1 polymerase Sanger sequences curated by the Southern Alberta HIV Clinic. Parameter combinations tailored to HIV-1 transmissions were tuned with respect to inference accuracy. Inference accuracy was assessed using clinically confirmed P2P transmission patient data. The most accurate parameter settings correctly inferred 48.56% of the P2P relationships (95% confidence interval 63.89−33.33%), slightly lower than next-generation-sequencing methods. The infection date was correctly inferred 43.02% (95% confidence interval 49.89−35.63%). Several novel unsuspected transmission clusters of up to twelve patients were identified. An accuracy trade-off between inferring transmission relationships and infection dates was observed. Using clinically confirmed P2P transmission data as benchmark, our phylogenetic methods identified sufficient P2P transmission relationships using readily available low-resolution Sanger sequences. These approaches may give valuable information about HIV infection dynamics within a population and may be easily deployed to guide public health interventions, without a need for next generation sequencing technology.

Liver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV) co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis.A case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119). HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679) were eligible. A random subcohort (n = 236) was selected from those eligible. Pro-fibrogenic markers and Interferon Lambda (IFNL) rs8099917 genotype were measured from first available sample in all fibrosis cases (APRI ≥ 1.5 during follow-up) and the subcohort. We used Cox proportional hazards and compared Model 1 (selected clinical predictors only) to Model 2 (Model 1 plus selected markers) for predicting 3-year risk of liver fibrosis using weighted Harrell's C and Net Reclassification Improvement indices.113 individuals developed significant liver fibrosis over 1300 person-years (8.63 per 100 person-years 95% CI: 7.08, 10.60). Model 1 (age, sex, current alcohol use, HIV RNA, baseline APRI, HCV genotype) was nested in model 2, which also included IFNL genotype and IL-8, sICAM-1, RANTES, hsCRP, and sCD14. The C indexes (95% CI) for model 1 vs. model 2 were 0.720 (0.649, 0.791) and 0.756 (0.688, 0.825), respectively. Model 2 classified risk more appropriately (overall net reclassification improvement, p

BACKGROUND: HIV-1 is a highly diverse virus; subtypes may exhibit differences in rates of transmission, disease progression, neurotoxicity, antiretroviral treatment failure profiles and accuracy of viral load measurements. To date, the HIV epidemic in Canada and the rest of the developed world has been largely due to subtype B; however, shifts in subtype epidemiology could have significant implications.

ABSTRACT Cryptococcus neoformans is a pathogenic yeast and a leading cause of life-threatening meningitis in AIDS patients. Natural killer (NK) cells are important immune effector cells that directly recognize and kill C. neoformans via a perforin-dependent cytotoxic mechanism. We previously showed that NK cells from HIV-infected patients have aberrant anticryptococcal killing and that interleukin-12 (IL-12) restores the activity at least partially through restoration of NKp30. However, the mechanisms causing this defect or how IL-12 restores the function was unknown. By examining the sequential steps in NK cell killing of Cryptococcus, we found that NK cells from HIV-infected patients had defective binding of NK cells to C. neoformans. Moreover, those NK cells that bound to C. neoformans failed to polarize perforin-containing granules to the microbial synapse compared to healthy controls, suggesting that binding was insufficient to restore a defect in perforin polarization. We also identified lower expression of intracellular perforin and defective perforin release from NK cells of HIV-infected patients in response to C. neoformans. Importantly, treatment of NK cells from HIV-infected patients with IL-12 reversed the multiple defects in binding, granule polarization, perforin content, and perforin release and restored anticryptococcal activity. Thus, there are multiple defects in the cytolytic machinery of NK cells from HIV-infected patients, which cumulatively result in defective NK cell anticryptococcal activity, and each of these defects can be reversed with IL-12. IMPORTANCE The mechanisms by which NK cells bind directly to pathogens and deploy their deadly cytolytic machinery during microbial host defense are only beginning to be elucidated. With the goal of understanding this process, we used NK cells from HIV-infected patients, which were known to have a defect in killing of Cryptococcus neoformans. Taking advantage of previous studies that had shown that IL-12 restored killing, we used the cytokine as a gain-of-function approach to define the relevance of multiple steps in the recognition and cytolytic pathway. We demonstrated that NK cells from HIV-infected patients failed to kill Cryptococcus due to defects in perforin expression, granule polarization, and release of perforin. Additionally, IL-12 restored recognition of C. neoformans through binding of the NK-activating receptor NKp30. These observations identify important mechanisms used by NK cells to kill microbes and determine that defects in NK cells from HIV-infected patients are reversible.

Introduction Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi‐country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. Methods Using data from the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2–7% of persons known to be living with HIV in these countries. Results Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm3. Haiti, Mexico, and several states had >85% retention in care; lower (50–74%) retention in care was observed in the US West, South, and Mid‐Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. Conclusions These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.

OBJECTIVE:We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. METHODS:A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. RESULTS:Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. CONCLUSIONS:The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the effectiveness and tolerability of dual therapy regimens, it remains unclear whether these potential benefits can be maintained long-term. Appropriately powered studies with longer follow-up periods are needed to more definitively assess potential toxicity reduction advantages with dual therapy.

BACKGROUND: The numbers and demographics of HIV-positive patients in care between 2003 and 2007 in the prairie provinces were examined.

High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count

IntroductionThe MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection.ObjectiveWe planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions.MethodsParticipants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS).ResultsPrior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%80% in 75% of participants.ConclusionMicronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects.Trial registrationClinicalTrials.gov NCT00798772.

Since 1999, Cryptococcus gattii has been identified as a primary pathogen on Vancouver Island in British Columbia, and it has resulted in infection of both people and animals living in that area. A previously healthy 45-year-old female resident of Alberta developed C gattii infection 11 months after travelling to an endemic region of Vancouver Island. A case of an immunocompetent patient, with an atypically long incubation time, who presented with subacute meningitis secondary to disseminated pulmonary cryptococcosis is presented. The present report highlights the need for clinical vigilance in treating patients presenting with atypical pulmonary infections or meningitis who have been holiday travellers to endemic areas of Vancouver Island.

OBJECTIVE: To determine the prevalence of exposure to cytomegalovirus (CMV), Toxoplasma gondii, syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV) in a large, well characterized, regional population presenting for human immunodeficency virus (HIV) care.

BackgroundCombination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada.MethodsParticipants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.ResultsThe crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000-2002 to 2006-2007. Men and women had comparable life expectancies in all periods except the last (2006-2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts ConclusionsA 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.

Human immunodeficiency virus type 1 (HIV-1) infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS). The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI) dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM) enrolled pre-HAART (Highly Active Antiretroviral Therapy). We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon) biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum) and somatostatin (duodenum and colon) immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis.

OBJECTIVE: To determine the incidence of human immunodeficiency virus (HIV) associated non-Hodgkin’s lymphoma (NHL) in a cohort of patients from a distinct geographic region (southern Alberta). The type and location of NHL as well as how it affected the survival of these patients was examined.

We describe the immediate- and longer-term direct medical costs of care for individuals diagnosed with HIV at CD4 counts 350/mm3 despite significantly their improved CD4 counts. The sustained high cost for late presenters has implications for recent recommendations for wider routine HIV testing and the earlier initiation of cART. Earlier diagnosis and treatment, while increasing the immediate expenditures within a population, may produce both direct and indirect cost savings in the longer term.

Pneumocystis jiroveci pneumonia uncommonly presents with pulmonary nodules and granulomatous inflammation. An unusual case of granulomatous P jiroveci pneumonia in an HIV patient with a CD4+ lymphocyte count of greater than 200 cells/mm3, occurring in the context of immune reconstitution with highly active antiretroviral therapy, is described. The case highlights the importance of establishing this diagnosis to institute appropriate therapy.

OBJECTIVES: We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). METHODS: Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997-2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (

Since the first report of human infection with Pneumocystis carinii in 1942, cases of pneumonia due to this opportunistic pathogen have become increasingly common. Animal studies and clinical observations show that a significant depletion or dysfunction of T helper lymphocytes predisposes to clinical disease. Individuals with damaged T helper cells secondary to malignancies (eg, Hodgkin’s lymphoma), drugs (eg, cyclosporine, steroids), or certain infections (eg, human immunodeficiency virus) are at particular risk. Serological studies suggest that disease is most often secondary to the reactivation of an asymptomatic infection, usually acquired during childhood. Increasing shortness of breath, a nonproductive cough and hypoxia often preceded by several weeks of lethargy, fever and weight loss are the classical features of P carinii pneumonia in acquired immune deficiency syndrome. Bronchoalveolar lavage is usually the optimal diagnostic test. Immunofluorescent staining on liquified sputum induced by nebulized saline appears to be a promising and noninvasive test. Early empiric therapy with trimethoprim-sulphamethoxazole (trimethoprim 5 mg-sulphamethoxazole 25 mg/kg/day every 6 h) or intravenous pentamidine (4 mg/kg/day) for 21 days is usually effective, but infection is not eradicated, and clinical disease is likely to recur. Prophylaxis using aerosolized pentamidine reduces the risk of pulmonary disease but can predispose to extrapulmonary infection. Improved in vitro and in vivo models of human pneumocystis infection would significantly increase understanding of the molecular biology of the organism, the pathogenesis of disease, and the optimal therapeutic regimens.

Efavirenz is a potent antiretroviral agent used in combination with other antiretroviral agents as part of highly active antiretroviral therapy. Efavirenz is generally well tolerated because the majority of its adverse effects are self-limiting, with central nervous symptoms and rash being the most frequent. In routine practice, the discontinuation rate of efavirenz due to adverse effects appears higher than that described in clinical trials. To minimize early treatment interruption and maximize the benefit of long term viral suppression that can be achieved with efavirenz therapy, health care providers and patients have identified that there is a need for information, education about and practical tools for the management of efavirenz-related side effects. To this end, a panel of experts in the care of HIV patients consisting of primary care physicians, infectious disease specialists, psychiatrists and pharmacists was convened. Through the evaluation of current literature and discussion among the group, the panel arrived at consensus recommendations. The present report outlines general management recommendations that apply to adverse effects related to efavirenz initiation, as well as specific management strategies for central nervous system symptoms such as agitation, sleep disturbances, dreams, dizziness, impaired concentration and depression. It is hoped that these practical recommendations will aid clinicians in minimizing and improving patient tolerance of side effects, thereby achieving improved adherence and patient outcomes.

Extraintestinal infections of Clostridium difficile are rare and often associated with underlying disorders. A case of empyema caused by aspiration of C difficile in a patient with carcinoid syndrome and C difficile colitis is described.