Human pegivirus viremia in HCV/HIV co-infected patients: Direct acting antivirals exert anti-pegivirus effects.

BACKGROUND: Human pegivirus (HPgV) is a single-stranded RNA virus​ that is closely related to hepatitis C virus (HCV)​. HPgV has also been shown to infect patients with human immunodeficiency virus (HIV). The mechanisms and disease outcomes of HPgV infections are largely unknown, although it has been implicated in both cancer and neurological diseases. There are no established therapies for HPgV. OBJECTIVES: To estimate the prevalence of HPgV in a cohort of HCV/HIV co-infected patients undergoing treatment for HCV with direct acting antivirals (DAA) and investigate the effect of DAA therapy on HPgV infection. STUDY DESIGN: RNA was extracted from plasma samples collected at time points before, during, and after DAA. HPgV RNA abundance was quantified by droplet digital PCR assays targeting the NS5A and 5'UTR domains and confirmed by RT-qPCR. Clinical, demographic and treatment data were analysed. RESULTS: HPgV RNA was detected and quantified in 26 of 100 patients' plasma (26%) before starting DAA. Patients with detectable HPgV were more likely to be male, had higher peak HIV plasma levels, and a history of injection drug use. Patients receiving sofosbuvir/ledipasvir (n = 9) displayed significantly lower HPgV levels at time of DAA completion and had lower post-DAA HPgV rebound​ levels compared to patients receiving sofosbuvir/velpatasvir (n = 11) although both regimens significantly reduced viremia directly following DAA completion. Sustained suppression of HPgV was â€‹also observed among patients (n = 2) receiving pegylated-interferon. CONCLUSIONS: HPgV RNA ​was frequently detected in HCV/HIV co-infected patients and ​was​ supressed by DAA and pegylated interferon therapies with sofosbuvir-ledipasvir showing greatest antiviral activity. These findings suggest potential treatment strategies for HPgV infections​.

Acceptability of anal cancer screening tests for women living with HIV in the EVVA study.

Background: Anal cancer is potentially preventable through screening. For screening to be implemented, the screening procedures must be acceptable to the affected population. The objective of the present study was to measure the acceptability of currently available anal cancer screening tests in a population of women living with hiv who had experienced the tests. Methods: The evva study ("Evaluation of Human Immunodeficiency Virus, Human Papillomavirus, and Anal Intraepithelial Neoplasia in Women") is a prospective cohort study of adult women living with hiv in Montreal, Quebec. Participants were screened with cervical or anal hpv testing and cervical or anal cytology every 6 months for 2 years. High-resolution anoscopy (hra) and digital anal rectal examination (dare) were also performed systematically, with biopsies, at baseline and at 2 years. An acceptability questionnaire was administered at the final visit or at study withdrawal. Results: Of 124 women who completed the acceptability questionnaire, most considered screening "an absolute necessity" in routine care for all women living with hiv [77%; 95% confidence interval (ci): 69% to 84%]. Yearly anal cytology or anal hpv testing was considered very acceptable by 81% (95% ci: 73% to 88%); hra every 2 years was considered very acceptable by 84% (95% ci: 77% to 90%); and yearly dare was considered very acceptable by 87% (95% ci: 79% to 92%). Acceptability increased to more than 95% with a longer proposed time interval. Pain was the main reason for lower acceptability. Conclusions: Most participating women considered anal cancer screening necessary and very acceptable. Longer screening intervals and adequate pain management could further increase the acceptability of repeated screening.

"Another thing to live for": Supporting HCV treatment and cure among Indigenous people impacted by substance use in Canadian cities.

BACKGROUND: Colonization and colonial systems have led to the overrepresentation of Indigenous people impacted by substance use and HCV infection in Canada. It is critical to ensure Indigenous people's equitable access to new direct acting antiviral HCV treatments (DAAs). Identifying culturally-safe, healing-centered approaches that support the wellbeing of Indigenous people living with HCV is an essential step toward this goal. We listened to the stories and perspectives of HCV-affected Indigenous people and HCV treatment providers with the aim of providing pragmatic recommendations for decolonizing HCV care. METHODS: Forty-five semi-structured interviews were carried out with Indigenous participants affected by HCV from the Cedar Project (n = 20, British Columbia (BC)) and the Canadian Coinfection Cohort (n = 25, BC; Ontario (ON); Saskatchewan (SK)). In addition, 10 HCV treatment providers were interviewed (n = 4 BC, n = 4 ON, n = 2 SK). Interpretive description identified themes to inform clinical approaches and public health HCV care. Themes and related recommendations were validated by Indigenous health experts and Indigenous participants prior to coding and re-contextualization. RESULTS: Taken together, participants' stories and perceptions were interpreted to coalesce into three overarching and interdependent themes representing their recommendations. First: treatment providers must understand and accept colonization as a determinant of health and wellness among HCV-affected Indigenous people, including ongoing cycles of child apprehension and discrimination within the healthcare system. Second: consistently safe attitudes and actions create trust within HCV treatment provider-patient relationships and open opportunities for engagement into care. Third: treatment providers who identify, build, and strengthen circles of care will have greater success engaging HCV-affected Indigenous people who have used drugs into care. CONCLUSION: There are several pragmatic ways to integrate Truth and Reconciliation as well as Indigenous concepts of whole-person wellness into the HCV cascade of care. By doing so, HCV treatment providers have an opportunity to create greater equity and support long-term wellness of Indigenous patients.

Prevalence and predictors of airflow obstruction in an HIV tertiary care clinic in Montreal, Canada: a cross-sectional study.

OBJECTIVES: The reported prevalence of chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWHIV) varies widely. Our objective was to estimate the prevalence of airflow obstruction and COPD in unselected PLWHIV and identify characteristics that increase the risk of nonreversible airflow obstruction in order to guide case finding strategies for COPD. METHODS: All adults attending the Chronic Viral Illness Service were invited to participate in the study, regardless of smoking status or history of known COPD/asthma. Individuals underwent spirometric testing both before and after use of a salbutamol bronchodilator. Airflow obstruction was defined as forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) < 0.7 post-bronchodilation, whereas COPD was defined as FEV1 /FVC < 0.7 post-bronchodilation and Medical Research Council (MRC) score > 2. Multivariate logistic regression was used to evaluate risk factors associated with airflow obstruction, reported as adjusted odds ratios (aORs). RESULTS: Five hundred and three participants successfully completed spirometry testing. The median (Q1; Q3) age was 52 (44; 58) years. The median (Q1; Q3) CD4 count was 598 (438; 784) cells/µL and the median (Q1; Q3) nadir CD4 count was 224 (121; 351) cells/µL. There were 119 (24%) current smokers and 145 (29%) former smokers. Among those screened, 54 (11%) had airflow obstruction whereas three (1%) of the participants had COPD. Factors that were associated with airflow obstruction included a history of smoking [aOR 2.2; 95% confidence interval (CI) 1.1; 4.7], older age (aOR 1.6; 95% CI 1.2; 2.2), and lower CD4 count (aOR 0.8; 95% CI 0.7; 1.0). CONCLUSIONS: Airflow obstruction was relatively uncommon. Our findings suggest that PLWHIV who are ≥50 years old, smokers and those with nadir CD4 counts ≤ 200 cells/µL could be targeted to undergo spirometry to diagnose chronic airflow obstruction.

Food insecurity may lead to incomplete HIV viral suppression and less immune reconstitution among HIV/hepatitis C virus-coinfected people.

OBJECTIVES: The aim of this study was to determine the impact of food insecurity (FI) on HIV viral load and CD4 count among people coinfected with HIV and hepatitis C virus (HCV). METHODS: This study was conducted using data from the Food Security & HIV-HCV Sub-Study of the Canadian Co-Infection Cohort study. FI was measured using the adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food security, moderate food insecurity and severe food insecurity. The association between FI, HIV viral load, and CD4 count was assessed using a stabilized inverse probability weighted marginal structural model. RESULTS: A total of 725 HIV/HCV-coinfected people with 1973 person-visits over 3 years of follow-up contributed to this study. At baseline, 23% of participants experienced moderate food insecurity and 34% experienced severe food insecurity. The proportion of people with undetectable HIV viral load was 75% and the median CD4 count was 460 [interquartile range (IQR): 300-665] cells/µL. People experiencing severe food insecurity had 1.47 times [95% confidence interval (CI): 1.14, 1.88] the risk of having detectable HIV viral load and a 0.91-fold (95% CI: 0.84, 0.98) increase in CD4 count compared with people who were food secure. CONCLUSIONS: These findings provide evidence of the negative impact of food insecurity on HIV viral load and CD4 count among HIV/HCV-coinfected people.

A tale of two countries: all-cause mortality among people living with HIV and receiving combination antiretroviral therapy in the UK and Canada.

OBJECTIVES: We sought to compare all-cause mortality of people living with HIV and accessing care in Canada and the UK. METHODS: Individuals from the Canadian Observational Cohort (CANOC) collaboration and UK Collaborative HIV Cohort (UK CHIC) study who were aged ≥ 18 years, had initiated antiretroviral therapy (ART) for the first time between 2000 and 2012 and who had acquired HIV through sexual transmission were included in the analysis. Cox regression was used to investigate the difference in mortality risk between the two cohort collaborations, accounting for loss to follow-up as a competing risk. RESULTS: A total of 19 960 participants were included in the analysis (CANOC, 4137; UK CHIC, 15 823). CANOC participants were more likely to be older [median age 39 years (interquartile range (IQR): 33, 46 years) vs. 36 years (IQR: 31, 43 years) for UK CHIC participants], to be male (86 vs. 73%, respectively), and to report men who have sex with men (MSM) sexual transmission risk (72 vs. 56%, respectively) (all P < 0.001). Overall, 762 deaths occurred during 98 798 person-years (PY) of follow-up, giving a crude mortality rate of 7.7 per 1000 PY [95% confidence interval (CI): 7.1, 8.3 per 1000 PY]. The crude mortality rates were 8.6 (95% CI: 7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study participants, respectively. No statistically significant difference in mortality risk was observed between the cohort collaborations in Cox regression accounting for loss to follow-up as a competing risk (adjusted hazard ratio 0.86; 95% CI: 0.72-1.03). CONCLUSIONS: Despite differences in national HIV care provision and treatment guidelines, mortality risk did not differ between CANOC and UK CHIC study participants who acquired HIV through sexual transmission.

Quality of initial HIV care in Canada: extension of a composite programmatic assessment tool for HIV therapy.

OBJECTIVES: To document the quality of initial HIV care in Canada using the Programmatic Compliance Score (PCS), to explore the association of the PCS with mortality, and to identify factors associated with higher quality of care. METHODS: We analysed data from the Canadian Observational Cohort Collaboration (CANOC), a multisite Canadian cohort of HIV-positive adults initiating combination antiretroviral therapy (ART) from 2000 to 2011. PCS indicators of noncompliance with HIV treatment guidelines include: fewer than three CD4 count tests in the first year of ART; fewer than three viral load tests in the first year of ART; no drug resistance testing before initiation; baseline CD4 count < 200 cells/mm3 ; starting a nonrecommended ART regimen; and not achieving viral suppression within 6 months of initiation. Indicators are summed for a score from 0 to 6; higher scores indicate poorer care. Cox regression was used to assess the association between PCS and mortality and ordinal logistic regression was used to explore factors associated with higher quality of care. RESULTS: Of the 7460 participants (18% female), the median score was 1.0 (Q1-Q3 1.0-2.0); 21% scored 0 and 8% scored ≥ 4. In multivariable analysis, compared with a score of 0, poorer PCS was associated with mortality for scores > 1 [score = 2: adjusted hazard ratio (AHR) 1.64; 95% confidence interval (CI) 1.13-2.36; score = 3: AHR 2.02; 95% CI 1.38-2.97; score ≥ 4: AHR 2.14; 95% CI 1.43-3.21], after adjustments for age, sex, province, ART start year, hepatitis C virus (HCV) coinfection, and baseline viral load. Women, individuals with HCV coinfection, younger people, and individuals starting ART earlier (2000-2003) had poorer scores. CONCLUSIONS: Our findings further validate the PCS as a predictor of all-cause mortality. Disparities identified suggest that further efforts are needed to ensure that care is equitably accessible.

Fibroblast growth factor 23: associations with antiretroviral therapy in patients co-infected with HIV and hepatitis C.

OBJECTIVES: Fibroblast growth factor 23 (FGF23) has been associated with cardiovascular mortality. We estimate associations between the level of plasma FGF23 and exposure to abacavir (ABC) and to other components of antiretroviral therapy in patients co-infected with HIV and hepatitis C. METHODS: Both intact and c-terminal FGF23 were measured in plasma using commercial assays for a sub-cohort of 295 patients selected at random from the 1150 patients enrolled in the Canadian Co-infection Cohort. The multiplicative effects of antiretroviral drug exposures and covariates on median FGF23 were then estimated using a hierarchical Bayesian model. RESULTS: The median level of intact FGF23 was independent of either past or recent exposure to abacavir, with multiplicative ratios of 1.00 and 1.07, 95% credible intervals 0.90-1.12 and 0.94-1.23, respectively. Median intact FGF23 tended to increase with past use of both nonnucleoside reverse-transcriptase inhibitors and protease inhibitors, but tended to decrease with recent use of either tenofovir, efavirenz or lopinavir. There were no obvious associations between the median level of c-terminal FGF23 and individual drugs or drug classes. Age, female gender, smoking and the aspartate aminotransferase to platelet ratio index were all associated with a higher median c-terminal FGF23 but not with a higher median intact FGF23. CONCLUSIONS: The level of FGF23 in plasma was independent of exposure to ABC. Lower levels of intact FGF23 with recent use of tenofovir, efavirenz or lopinavir may reflect their adverse effects on bone and vitamin D metabolism relative to other drugs in their respective drug classes.

Opioid use and risk of liver fibrosis in HIV/hepatitis C virus-coinfected patients in Canada.

OBJECTIVES: Opioid use and opioid-related mortality have increased dramatically since the 1990s in North America. The effect of opioids on the liver is incompletely understood. Some studies have suggested that opioids cause liver damage and others have failed to show any harm. HIV/hepatitis C virus (HCV)-coinfected persons may be particularly vulnerable to factors increasing liver fibrosis. We aimed to describe opioid use in an HIV/HCV-coinfected population in Canada and to estimate the association between opioid use and liver fibrosis. METHODS: We conducted a cross-sectional descriptive analysis of the Canadian Co-infection Cohort Study data to characterize opioid use. We then conducted a longitudinal analysis to assess the average change in aspartate aminotransferase-to-platelet ratio index (APRI) score associated with opioid use using a generalized estimating equation with linear regression. We assessed the progression to significant liver fibrosis (APRI ≥ 1.5) associated with opioid use with pooled logistic regression. RESULTS: In the 6 months preceding cohort entry, 32% of the participants had received an opioid prescription, 28% had used opioids illicitly and 18% had both received a prescription and used opioids illicitly. Neither prescribed nor illicit opioid use was associated with a change in the median APRI score [exp(ß) 0.99 (95% confidence interval (CI) 0.82, 1.12) and exp(ß) 0.95 (95% CI 0.81, 1.10), respectively] or with faster progression to liver fibrosis [hazard odds ratio (HOR) 1.20 (95% CI 0.73, 1.67) and HOR 1.09 (95% CI 0.63, 1.55), respectively]. CONCLUSIONS: Although opioids were commonly used both legally and illegally in our cohort, we were unable to demonstrate a negative impact on liver fibrosis progression.

HIV virological rebounds but not blips predict liver fibrosis progression in antiretroviral-treated HIV/hepatitis C virus-coinfected patients.

OBJECTIVES: Antiretroviral interruption is associated with liver fibrosis progression in HIV/hepatitis C virus (HCV) coinfection. It is not known what level of HIV viraemia affects fibrosis progression. METHODS: We evaluated 288 HIV/HCV-coinfected cohort participants with undetectable HIV RNA (<50 HIV-1 RNA copies/mL) on two consecutive visits while on combination antiretroviral therapy (cART) without fibrosis [aspartate aminotransferase to platelet ratio index (APRI) <1.5], end-stage liver disease or HCV therapy. An HIV blip was defined as a viral load of ≥ 50 and <1000 copies/mL, preceded and followed by undetectable values. HIV rebound was defined as: (i) HIV RNA ≥ 50 copies/mL on two consecutive visits, or (ii) a single HIV RNA measurement ≥ 1000 copies/mL. Multivariate discrete-time proportional hazards models were used to assess the effect of different viraemia levels on liver fibrosis progression (APRI ≥ 1.5). RESULTS: The mean age of the patients was 45 years, 74% were male, 81% reported a history of injecting drug use, 51% currently used alcohol and the median baseline CD4 count was 440 [interquartile range (IQR) 298, 609] cells/µL. Fifty-seven (20%) participants [12.4/100 person-years (PY); 95% confidence interval (CI) 9.2-15.7/100 PY] progressed to an APRI ≥ 1.5 over a mean 1.1 (IQR 0.6, 2.0) years of follow-up time at risk. Virological rebound [hazard ratio (HR) 2.3; 95% CI 1.1, 4.7] but not blips (HR 0.5; 95% CI 0.2, 1.1) predicted progression to APRI ≥ 1.5. Each additional 1 log10 copies/mL HIV RNA exposure (cumulative) was associated with a 20% increase in the risk of fibrosis progression (HR 1.2; 95% CI 1.0-1.3). CONCLUSIONS: Liver fibrosis progression was associated with HIV rebound, but not blips, and with increasing cumulative exposure to HIV RNA, highlighting the importance of achieving and maintaining HIV suppression in the setting of HIV/HCV coinfection.

Predictors of unstructured antiretroviral treatment interruption and resumption among HIV-positive individuals in Canada.

OBJECTIVES: Sustained optimal use of combination antiretroviral therapy (cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption (TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort (CANOC) collaboration. METHODS: cART-naïve individuals ≥ 18 years of age who initiated cART between 2000 and 2011 were included in the study. We defined TIs as ≥ 90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. RESULTS: A total of 7633 participants were eligible for inclusion in the study, of whom 1860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women [adjusted hazard ratio (aHR) 1.59; 95% confidence interval (CI) 1.33-1.92], younger individuals (aHR 1.27; 95% CI 1.15-1.37 per decade increase), earlier treatment initiators (CD4 count ≥ 350 vs. <200 cells/µL: aHR 1.46; 95% CI 1.17-1.81), Aboriginal participants (aHR 1.67; 95% CI 1.27-2.20), injecting drug users (aHR 1.43; 95% CI 1.09-1.89) and users of zidovudine vs. tenofovir in the initial cART regimen (aHR 2.47; 95% CI 1.92-3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count <200 cells/µL at cART initiation. CONCLUSIONS: Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART.

HIV/hepatitis C virus coinfection management: changing guidelines and changing paradigms.

OBJECTIVES: The aim of the study was to consider the impact of new direct-acting antiviral (DAA) regimens on hepatitis C virus (HCV) treatment in HIV/HCV coinfection. METHODS: Current coinfection guidelines were reviewed and the impact of recent DAA publications evaluating HIV-coinfected individuals was considered. RESULTS: Current coinfection guidelines recommend HIV antiretroviral therapy initiation prior to HCV antiviral therapy. New all-oral, combination antiviral therapy composed of one or more DAAs with or without ribavirin will change this paradigm. As these regimens are better tolerated, it will be possible to offer nearly all HCV-infected patients antiviral therapy, including those with HIV infection. All-oral regimens may impact the incidence of HCV infection by providing a treatment option that can be safely and broadly utilized in high-risk populations with the benefits of curing individual patients and addressing broader public health concerns related to HCV. CONCLUSIONS: HCV infection treatment should no longer be a secondary consideration restricted to the minority of HIV/HCV-coinfected patients.

Characteristics and determinants of T-cell phenotype normalization in HIV-1-infected individuals receiving long-term antiretroviral therapy.

OBJECTIVES: Although combination antiretroviral therapy (cART) can restore CD4 T-cell numbers in HIV infection, alterations in T-cell regulation and homeostasis persist. We assessed the incidence and predictors of reversing these alterations with cART. METHODS: ART-naïve adults (n = 4459) followed within the Canadian Observational Cohort and exhibiting an abnormal T-cell phenotype (TCP) prior to cART initiation were studied. Abnormal TCP was defined as having (1) a low CD4 T-cell count (< 532 cells/µL), (2) lost T-cell homeostasis (CD3 < 65% or > 85%) or (3) CD4:CD8 ratio dysregulation (ratio < 1.2). To thoroughly evaluate the TCP, CD4 and CD8 T-cell percentages and absolute counts were also analysed for a median duration of 3.14 years [interquartile range (IQR) 1.48-5.47 years]. Predictors of TCP normalization were assessed using adjusted Cox proportional hazards models. RESULTS: At baseline, 96% of pateints had CD4 depletion, 32% had lost homeostasis and 99% exhibited ratio dysregulation. With treatment, a third of patients had normalized CD4 T-cell counts, but only 85 individuals (2%) had normalized their TCP. In a multivariable model adjusted for age, measurement frequency and baseline regimen, higher baseline CD4 T-cell counts and time-dependent viral suppression independently predicted TCP normalization [hazard ratio (HR) for baseline CD4 T-cell count = 1.42 (1.31-1.54) per 100 cells/µL increase; P ≤ 0.0001; HR for time-dependent suppressed viral load = 3.69 (1.58-8.61); P-value ≤ 0.01]. CONCLUSIONS: Despite effective cART, complete TCP recovery occurred in very few individuals and was associated with baseline CD4 T-cell count and viral load suppression. HIV-induced alterations of the TCP are incompletely reversed by long-term ART.

HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality.

OBJECTIVES: Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV-coinfected Canadians. METHODS: HIV/HCV-coinfected patients were enrolled prospectively in a multicentre cohort from 16 centres across Canada between 2003 and 2010 and followed every 6 months. We determined rates of a first liver fibrosis or endstage liver disease (ESLD) event and all-cause mortality since cohort enrolment and calculated standardized mortality ratios compared with the general Canadian population. RESULTS: A total of 955 participants were enrolled in the study and followed for a median of 1.4 (interquartile range 0.5-2.3) years. Most were male (73%) with a median age of 44.5 years; 13% self-identified as aboriginal. There were high levels of current injecting drug and alcohol use and poverty. Observed event rates [per 100 person-years; 95% confidence interval (CI)] were: significant fibrosis (10.21; 8.49, 12.19), ESLD (3.16; 2.32, 4.20) and death (3.72; 2.86, 4.77). The overall standardized mortality ratio was 17.08 (95% CI 12.83, 21.34); 12.80 (95% CI 9.10, 16.50) for male patients and 28.74 (95% CI 14.66, 42.83) for female patients. The primary causes of death were ESLD (29%) and overdose (24%). CONCLUSIONS: We observed excessive morbidity and mortality in this HIV/HCV-coinfected population in care. Over 50% of observed deaths may have been preventable. Interventions aimed at improving social circumstances, reducing harm from drug and alcohol use and increasing the delivery of HCV treatment in particular will be necessary to reduce adverse health outcomes among HIV/HCV-coinfected persons.

Simultaneous triple point-of-care testing for HIV, syphilis and hepatitis B virus to prevent mother-to-child transmission in India.

An innovative simultaneous triple point-of-care (STPOC) screening strategy for syphilis, hepatitis B and HIV with Determine(®) tests was offered to pregnant women presenting for antenatal care and evaluated for feasibility and preference in rural India. Of 1066 participants approached, 1046 consented, of which 1002 (96.0%) completed the strategy. Only 9% reported any history of testing in their current pregnancy. With STPOC screening, 989 women (98.7%) tested negative and 13 had preliminary positive results for infection. The total time taken was 45 minutes per participant. Mothers and infants were provided prophylaxis/treatment for HIV, syphilis and hepatitis B, with interventions initiated within 3-5 days. STPOC was preferred by 99.3% (95%CI: 98.8-99.8%) of participants, facilitated early simultaneous screening for the three infections, timely initiation of prophylaxis/treatment and was feasible in this rural setting. These data suggest that multiplexed STPOC screening for syphilis, hepatitis B and HIV in pregnancy would be desirable for women in rural India.

Relationship of chronic hepatitis C infection to rates of AIDS-defining illnesses in a Canadian cohort of HIV seropositive individuals receiving highly active antiretroviral therapy.

BACKGROUND: The influence of chronic hepatitis C virus (HCV) infection on the risk, timing, and type of AIDS-defining illnesses (ADIs) is not well described. To this end, rates of ADIs were evaluated in a Canadian cohort of HIV seropositive individuals receiving highly active antiretroviral therapy (HAART). METHODS: ADIs were classified into 6 Centers for Disease Control and Prevention (CDC)-defined etiological subgroups: non-Hodgkin lymphoma, viral infection, bacterial infection, HIV-related disease, protozoal infection, and mycotic infection. Generalized estimating equation (GEE) Poisson regression models were used to estimate the effect of HCV on rates of ADIs after adjusting for covariates. RESULTS: Among 2,706 HAART recipients, 768 (28%) were HCV coinfected. Rates of all ADIs combined and of bacterial infection, HIV-related disease, and mycotic infection were increased in HCV-coinfected persons and among those with CD4 counts <200 cells/mm3 HCV was associated with an increased risk of ADIs (rate ratio [RR], 1.38; 95% CI, 1.01-1.88) and a 2-fold increased risk of mycotic infections (RR, 2.21; 95% CI, 1.35-3.62) in univariate analyses and after adjusting for age, baseline viral load, baseline CD4 count, and region of Canada. However, after further adjustment for HAART interruptions, HCV was no longer associated with an increased rate of ADIs overall (RR, 1.13; 95% CI, 0.80-1.59), but remained associated with an increased rate of mycotic infections (RR, 1.97, 95% CI, 1.08-3.61). CONCLUSION: Although HCV coin-fected individuals are at increased risk of developing ADIs overall, our analysis suggests that behavioral variables associated with HCV (including rates of retention on HAART), and not biological interactions with HCV itself, are primarily responsible.

Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort.

OBJECTIVE: The aim of the study was to evaluate time to virological suppression in a cohort of individuals who started highly active antiretroviral therapy (HAART), and to explore the factors associated with suppression. METHODS: Eligible participants were HIV-positive individuals from a multi-site Canadian cohort of antiretroviral-naïve patients initiating HAART on or after 1 January 2000. Viral load and CD4 measurements within 6 months prior to HAART initiation were assessed. Univariate and multivariate analyses were conducted using piecewise survival exponential models where time scale was divided into intervals (<10 months; ≥10 months). Virological suppression was defined as the time to the first of at least two consecutive viral load measurements <50 HIV-1 RNA copies/mL. RESULTS: A total of 3555 individuals were included in the study, of median age 40 years [interquartile range (IQR) 34-47 years]. Eighty per cent were male, 18% had a history of injecting drug use (IDU), and 13% presented with an AIDS-defining illness at baseline. The median time to suppression was 4.55 months (IQR 2.99-7.89 months). In multivariate analyses, older age, male sex, treatment in Ontario rather than British Columbia, non-IDU history, and having an AIDS diagnosis at baseline predicted increased likelihood of suppression. Patients with low baseline viral load were more likely to have suppression [4-5 log(10) copies/mL, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.18-1.38; <4 log(10) copies/mL, HR 1.49, 95% CI 1.32-1.68] than patients with baseline viral load ≥5 log(10) copies/mL; however, this effect ceased after 18 months of follow-up. Suppression was more likely with nonnucleoside reverse transcriptase inhibitors and ritonavir-boosted HAART. CONCLUSION: Identification of patients at risk for diminished likelihood of virological suppression will allow focusing of efforts and the utilization of resources to maximize the benefits of HAART.

Validation of a simple model for predicting liver fibrosis in HIV/hepatitis C virus-coinfected patients.

OBJECTIVES: Recently, several models incorporating laboratory measurements have been validated for use as surrogate markers for liver fibrosis in hepatitis C virus (HCV) mono-infection, the simplest of these being the aspartate aminotransferase (AST) to platelet ratio index (APRI). We evaluated how well the APRI predicts significant hepatic fibrosis in patients with HIV/HCV coinfection. METHODS: Forty-six HIV/HCV-coinfected patients who underwent liver biopsy and had concomitant laboratory measurements (+/-3 months) were included in the study. Significant fibrosis was defined as F2-F4 using Batt and Ludwig scoring (=3 Ishak). APRI=[(AST/upper limit of normal)/platelet count (10(9)/L)] x 100. We used sas proc logistic (SAS Institute, Cary, NC) to calculate the area under the receiver operating curve (ROC) (AUC). Sensitivities, specificities, positive predictive value (PPV) and negative predictive value (NPV) were compared using cut-offs previously identified in the literature. RESULTS: Thirty-three of 46 patients (72%) had significant fibrosis on biopsy. For significant fibrosis, the area under the ROC for the APRI was 0.847+/-0.057. APRI scores >1.5 (the higher cut-off) were 100% specific and 52% sensitive; PPV was 100% and NPV 45%. Scores <0.5 (the lower cut-off) were 82% sensitive and 46% specific in ruling out significant fibrosis (PPV 79%; NPV 50%). CONCLUSIONS: A simple model incorporating readily available laboratory data is highly predictive of significant fibrosis in HIV/HCV coinfection and could serve as a biopsy-sparing measure, thus making treatment more accessible for this population.

CT angiography in complex upper extremity reconstruction.

Computed tomography angiography is a new technique that provides high-resolution, three-dimensional vascular imaging as well as excellent bone and soft tissue spatial relationships. The purpose of this study was to examine the use of computed tomography angiography in planning upper extremity reconstruction. Seventeen computed tomography angiograms were obtained in 14 patients over a 20-month period. All studies were obtained on an outpatient basis with contrast administered through a peripheral vein. All the studies demonstrated the pertinent anatomy and the intraoperative findings were as demonstrated in all cases. Information from two studies significantly altered pre-operative planning. The average charge for computed tomography angiography was 1,140 dollars, compared to 3,900 dollars for traditional angiography.

Flexor tendon wound healing in vitro: the effect of lactate on tendon cell proliferation and collagen production.

Flexor tendon repair in zone II is complicated by adhesions to the surrounding fibro-osseous sheath. Lactate is an early mediator of wound healing known to play an important role in stimulation of collagen production after cellular injury. Little attention has been paid to the role of lactate in flexor tendon wound healing. In this study tendon and tendon sheath were excised from rabbit forepaws. We examined proliferation of tendon sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes; collagen production by each of these 3 cell types; and effects of lactate on cell proliferation and collagen production. Three cell lines, tendon sheath, epitenon, and endotenon, were isolated and cultured. Tendon sheath fibroblasts showed the greatest proliferation. All 3 cell lines produced collagen I, II, and III. Lactate significantly increased collagen production by all 3 cell lines. We show that cells of the tendon sheath, epitenon, and endotenon produce collagen in vitro. Modulation of lactate levels may provide a means to modulate collagen production.