Homelessness as a structural barrier to effective antiretroviral therapy among HIV-seropositive illicit drug users in a Canadian setting

Despite the advent of effective antiretroviral therapy (ART), HIV-seropositive injection drug users (IDU) continue to suffer from elevated levels of morbidity and mortality. Evidence is needed to identify social- and structural-level barriers to effective ART. We investigated the impact of homelessness on plasma HIV RNA response among illicit drug users initiating ART in a setting with free and universal access to HIV care. We accessed data from a long-running prospective cohort of community-recruited IDU linked to comprehensive HIV clinical monitoring and ART dispensation records. Using Cox proportional hazards with recurrent events modeling, we estimated the independent effect of homelessness on time to plasma HIV viral load suppression. Between May 1996 and September 2009, 247 antiretroviral na?ve individuals initiated ART and contributed 1755 person-years of follow-up. Among these individuals, the incidence density of plasma HIV RNA suppression less than 500 copies/mm(3) was 56.7 (95% confidence interval [CI]: 46.9-66.0) per 100 person-years. In unadjusted analyses, homelessness was strongly associated with lower rates suppression (hazard ratio = 0.56, 95% CI: 0.40-0.78, p = 0.001), however, after adjustment for adherence this association was no longer significant (adjusted hazard ratio = 0.79, 95% CI: 0.56-1.11, p = 0.177). Homelessness poses a significant structural barrier to effective HIV treatment. However, since this relationship appears to be mediated by lower levels of ART adherence, interventions to improve adherence among members of this vulnerable population are needed.     

Monoclonal antibodies recognizing epitopes on the extracellular face and intracellular N-terminus of the human erythrocyte anion transporter (band 3) and their application to the analysis of South East Asian ovalocytes

This report describes the production and characterization of 13 rodent monoclonal antibodies to the human erythrocyte anion transport protein AE1 (syn. band 3). Eleven antibodies (4 murine and 7 rat) recognize epitopes dependent on the integrity of the third extracellular loop of the protein. Two antibodies (1 murine and 1 rat) recognize epitopes on the N-terminal cytoplasmic domain. Quantitative binding studies using radioiodinated IgG and Fab fragments of antibodies to extracellular epitopes on AE1 ranged from 77,000 to 313,000 (IgG) and from 241,000 to 772,000 (Fab) molecules bound at saturation. The results indicate that the epitopes recognized by different antibodies vary in their accessibility and suggest that there is heterogeneity in the organization of individual AE1 molecules in the red blood cell membrane. Quantitative binding studies on South East Asian ovalocytes using several antibodies to AE1 and an anti-Wrb show a marked reduction in the number of antibody molecules bound at saturation. These results are consistent with the existence of highly cooperative interactions between transmembrane domains of AE1 in normal erythrocytes and the disruption of these interactions in the variant AE1 found in South East Asian ovalocytes.     

Socioeconomic status,access to triple therapy,and survival from HIV-disease since 1996

BACKGROUND: In the era before highly active antiretroviral therapy (HAART), socioeconomic status was associated with survival from HIV disease. We have explored socioeconomic status, access to triple therapy (HAART), and mortality in the context of a universal healthcare system. METHODS: We evaluated 1408 individuals who initiated double or triple therapy between 1 August 1996 and 31 December 1999, and were followed until 31 March 2000. Cumulative HIV-related mortality rates were estimated using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: In the overall Cox model, we found that adherence [risk ratio (RR) 0.83; per 10% increase], CD4 cell count (RR 1.53; per 100 cell decrease), and lower socioeconomic status (RR 2.19; high versus low), were associated with HIV-related mortality. However, socioeconomic status was not significant among patients prescribed triple therapy in a stratified analysis, or in a sub-analysis restricted to patients prescribed HAART in the initial regimen. When we investigated if inequitable access to HAART by socio-economic status could explain the discrepancy, we found that persons in the lower socio-economic strata were less likely to be prescribed triple therapy even after adjustment for clinical characteristics. CONCLUSION: In a universal healthcare system, socioeconomic status was strongly associated with HIV-related mortality. When we investigated possible explanations for this association, we found that individuals of lower socioeconomic status were less likely to receive triple therapy after adjustment for clinical characteristics. Our findings highlight the need for the monitoring of therapeutic guidelines to ensure equitable access, as treatment strategies are updated.     

Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection

Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge.     

Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Complexities of Short-Term Mobility for Sex Work and Migration among Sex Workers: Violence and Sexual Risks,Barriers to Care,and Enhanced Social and Economic Opportunities

Despite research on the health and safety of mobile and migrant populations in the formal and informal sectors globally, limited information is available regarding the working conditions, health, and safety of sex workers who engage in short-term mobility and migration. The objective of this study was to longitudinally examine work environment, health, and safety experiences linked to short-term mobility/migration (i.e., worked or lived in another city, province, or country) among sex workers in Vancouver, Canada, over a 2.5-year study period (2010–2012). We examined longitudinal correlates of short-term mobility/migration (i.e., worked or lived in another city, province, or country over the 3-year follow-up period) among 646 street and off-street sex workers in a longitudinal community-based study (AESHA). Of 646 sex workers, 10.84 % (n = 70) worked or lived in another city, province, or country during the study. In a multivariate generalized estimating equations (GEE) model, short-term mobility/migration was independently correlated with older age (adjusted odds ratio (AOR) 0.95, 95 % confidence interval (CI) 0.92–0.98), soliciting clients in indoor (in-call) establishments (AOR 2.25, 95 % CI 1.27–3.96), intimate partner condom refusal (AOR 3.00, 1.02–8.84), and barriers to health care (AOR 1.77, 95 % CI 1.08–2.89). In a second multivariate GEE model, short-term mobility for sex work (i.e., worked in another city, province, or country) was correlated with client physical/sexual violence (AOR 1.92, 95 % CI 1.02–3.61). In this study, mobile/migrant sex workers were more likely to be younger, work in indoor sex work establishments, and earn higher income, suggesting that short-term mobility for sex work and migration increase social and economic opportunities. However, mobility and migration also correlated with reduced control over sexual negotiation with intimate partners and reduced health care access, and mobility for sex work was associated with enhanced workplace sexual/physical violence, suggesting that mobility/migration may confer risks through less control over work environment and isolation from health services. Structural and community-led interventions, including policy support to allow for more formal organizing of sex work collectives and access to workplace safety standards, remain critical to supporting health, safety, and access to care for mobile and migrant sex workers.