Factors influencing initial implementation of an online community-based exercise intervention with adults living with HIV: a systems approach.

Introduction: Online community-based exercise (CBE) is a digital health intervention and rehabilitation strategy that promotes health among people living with HIV. Our aim was to describe the factors influencing initial implementation of a pilot online CBE intervention with adults living with HIV using a systems approach, as recommended by implementation science specialists. Methods: We piloted the implementation of a 6-month online CBE intervention and 6-month independent exercise follow up, in partnership with the YMCA in Toronto, Canada. We recruited adults living with HIV who identified themselves as safe to engage in exercise. The intervention phase included personalized exercise sessions online with a personal trainer; exercise equipment; access to online exercise classes; and a wireless physical activity monitor. Two researchers documented implementation factors articulated by participants and the implementation team during early implementation, defined as recruitment, screening, equipment distribution, technology orientation, and baseline assessments. Data sources included communication with participants; daily team communication; weekly team discussions; and in-person meetings. We documented implementation factors in meeting minutes, recruitment screening notes, and email communication; and analyzed the data using a qualitative descriptive approach using a systems engineering method called Cognitive Work Analysis. Results: Thirty-three adults living with HIV enrolled in the study (n = 33; median age: 52 years; cis-men: 22, cis-women: 10, non-binary: 1). Fifty-five factors influencing implementation, spanned five layers: (i) Natural, including weather and the COVID-19 virus; (ii) Societal, including COVID-19 impacts (e.g. public transit health risks impacting equipment pick-ups); (iii) Organizational, including information dissemination (e.g. tech support) and logistics (e.g. scheduling); (iv) Personal, including physical setting (e.g. space) and digital setting (e.g. device access); and (v) Human, including health (e.g. episodic illness) and disposition (e.g. motivation). The implementation team experienced heightened needs to respond rapidly; sustain engagement; and provide training and support. Additional organizational factors included a committed fitness training and research team with skills spanning administration and logistics, participant engagement, technology training, physical therapy, and research ethics. Conclusion: Fifty-five factors spanning multiple layers illustrate the complexities of online CBE with adults living with HIV. Initial implementation required a dedicated, rehabilitation-centred, multi-skilled, multi-stakeholder team to address a diverse set of factors.

Risk assessment of trace metals in Solanum lycopersicum L. (tomato) grown under wastewater irrigation conditions.

Heavy metal contamination of food crop plants is viewed as a global issue. Heavy metals like cadmium (Cd), copper (Cu), lead (Pb), chromium (Cr), zinc (Zn), nickel (Ni), arsenic (As), cobalt (Co), and mercury (Hg) are poisonous. Depending on their concentration and capacity for bioaccumulation, they can provide a range of health risks.This research sought to investigate the effects of toxic metals (TMs) on the growth characteristics of produced tomatoes grown under wastewater irrigation. Additionally, it looked into the potential repercussions of both domestic and foreign individuals consuming this plant. In south Cairo, Egypt, two study locations were looked into: a control site in Abu Ragwan, which received water from tributaries of the Nile River, and a contaminated site in El-Shobak El-Sharky, which had raw industrial wastewater. The nutrients of soil and tomato plants (N, P, and K) decreased (P < 0.01), while TMs increased (P < 0.001) significantly as a result of using wastewater for irrigation. Except for Cu, all examined TM accumulating in tomato plants' roots as opposed to shoots had a bioaccumulation factor (BF) > 1. However, the tomato plant's shoot had solely undergone Pb and Ni translocation and storage, with a translocation factor (TF) > 1. A significant amount of Fe (5000.1 mg kg-1), Pb (360.7 mg kg-1), and Mn (356.3 mg kg-1) were present in the edible fruits. The ingestion of contaminated crops increases the daily intake rate of metals (DIR). The values of the high hazard quotient (HQ) were obtained (2073.8 and 2558.9 for Pb, 574.0 and 708.3 for Cd, and 41.1 and 50.7 for Fe for adults and children, respectively). Therefore, tomato plants grown in soils irrigated with untreated wastewater may offer a greater danger to human health, indicating that they should not be grown as a crop for human consumption.

Accumulation and translocation of eight trace metals by the different tissues of Abelmoschus esculentus Moench. irrigated with untreated wastewater.

Due to water scarcity, the use of wastewater to irrigate crops is on the rise all over the world, including in Egypt (particularly untreated wastewater). The purpose of this study is to see if irrigation with untreated industrial wastewater in natural fields can cause Abelmoschus esculentus Moench. (okra plant) to accumulate and translocate eight trace metals (lead: Pb, cadmium: Cd, chromium: Cr, copper: Cu, iron: Fe, manganese: Mn, nickel: Ni, and zinc: Zn) in its different tissues. It was extended to look at the effects of wastewater irrigation on the farmed okra plants' growth characteristics, nutrients, colors, and organic content. Two studied sites at South of Cairo have been investigated: the first site (29°42'31.17" N and 31°15'11.56" E) represented by five cultivated fields irrigated with Nile water (control) and the second site (29°42'37.87" N and 31°17'14.53" E) fields irrigated with effluent received untreated industrial wastewater. Three composite soil and irrigated water samples were collected from each site. Because of wastewater irrigation, soil and plant nutrients (nitrogen, potassium, and phosphorus) decreased significantly (at P < 0.01), whereas trace metals increased significantly (at P < 0.01 and P < 0.05) for soil and plant samples irrigated with untreated wastewater. Due to irrigation with untreated wastewater, there was also a significant decrease in okra growth metrics (at P < 0.05) and leaves photosynthetic pigments: chlorophyll a and b, and carotenoids (at P < 0.01 and P < 0.05). In the plant's fruits (edible section) watered with wastewater, iron was the most abundant metal. Besides, Cd, Cu, Fe, Mn, Ni, and Zn concentrations were also in the phytotoxic range (42.57, 140.67, 2756.67, 1293.33, 1326.67, and 877.83 mg kg-1, respectively). All trace elements examined accumulate in the roots of wastewater irrigated okra (Bioaccumulation factor > 1). Okra plants, on the other hand, did not have an accumulated trace metals strategy in their shoots since the translocation factor was less than one. Because of substantial trace metal accumulation in their edible sections, the scientists advised against eating okra plants grown in fields watered with untreated wastewater.

Immunological and virological response to initial antiretroviral therapy among older people living with HIV in the Canadian Observational Cohort (CANOC).

OBJECTIVES: The aim of this study was to assess the adequacy of immunological recovery and virological suppression in response to antiretroviral therapy (ART) in the growing population of older people living with HIV (PLWH), as treatment regimens become more effective and tolerable. METHODS: An interprovincial Canadian cohort of treatment-naïve PLWH who initiated ART after 1 January 2000 was used and age assessed in decades. Longitudinal absolute CD4 count response to treatment was modelled using generalized estimating equations. Cumulative incidence functions and proportional hazards models with a competing risk of death were used to estimate time to: (1) CD4 ≥ 200 cells/µL, (2) CD4 ≥ 500 cells/µL, (3) virological suppression (≤ 50 copies/mL), and (4) virological failure (> 200 copies/mL). RESULTS: In all, 12 489 individuals starting ART between 2000 and 2016 with one or more post-treatment CD4 count or viral load were included in the analysis. Age > 60 years was associated with lower absolute CD4 recovery (adjusted ß = -31 cells/µL) compared with age ≤ 30 years when pre-treatment CD4 count and other covariates were accounted for. Older age groups were less likely to achieve a CD4 ≥ 500 cells/µL, with the greatest effect in the > 60 group [adjusted hazard ratio (aHR) = 0.69, 95% confidence interval (CI): 0.57-0.84 vs. age ≤ 30). Older age groups were more likely to achieve viral suppression (age > 60, aHR = 1.20, 95% CI: 1.05-1.37) and less likely to have virological failure (age > 60, aHR = 0.46, 95% CI: 0.3-0.71) compared with those aged ≤ 30 years. CONCLUSIONS: Older adults have robust virological responses to ART; however, individuals over the age 60 are more likely to experience blunted CD4 recovery.

Heavy metals uptake by the global economic crop (Pisum sativum L.) grown in contaminated soils and its associated health risks.

The aim of the present investigation was to determine the concentration of heavy metals in the different organs of Pisum sativum L. (garden pea) grown in contaminated soils in comparison to nonpolluted soils in the South Cairo and Giza provinces, Egypt, and their effect on consumers' health. To collect soil and plant samples from two nonpolluted and two polluted farms, five quadrats, each of 1 m2, were collected per each farm and used for growth measurement and chemical analysis. The daily intake of metals (DIM) and its associated health risks (health risk index (HRI) were also assessed. The investigated heavy metals were cadmium (Cd), arsenic (As), chromium (Cr), copper (Cu), nickel (Ni), iron (Fe), manganese (Mn), zinc (Zn), silver (Ag), cobalt (Co) and vanadium (V). Significant differences in soil heavy metals, except As, between nonpolluted and polluted sites were recorded. Fresh and dry phytomass, photosynthetic pigments, fruit production, and organic and inorganic nutrients were reduced in the polluted sites, where there was a high concentration of heavy metals in the fruit. The bioaccumulation factor for all studied heavy metals exceeded 1 in the polluted sites and only Pb, Cu and Mn exceeded 1 in the nonpolluted sites. Except for Fe, the DIM of the studied heavy metals in both sites did not exceed 1 in either children or adults. However, the HRI of Pb, Cd, Fe, and Mn in the polluted plants and Pb in the nonpolluted ones exceeded 1, indicating significant potential health risks to consumers. The authors recommend not to eat garden peas grown in the polluted sites, and farmers should carefully grow heavy metals non-accumulating food crops or non-edible plants for other purposes such as animal forages.

Breastfeeding by Women Living With Human Immunodeficiency Virus in a Resource-Rich Setting: A Case Series of Maternal and Infant Management and Outcomes.

The reduction in human immunodeficiency virus (HIV) transmission through breastmilk with maternal combination antiretroviral therapy (cART) has led many pregnant women living with HIV and healthcare providers to question exclusive formula feeding in resource-rich settings. Here, we describe cART prophylaxis in 3 breastfed infants whose mothers had sustained virologic suppression; all 3 of these infants remained uninfected.

Hazards assessment of the intake of trace metals by common mallow (Malva parviflora K.) growing in polluted soils.

Human risks increase by consuming plants growing in trace/heavy metals contaminated soil irrigated with polluted water. The present study aims to assess the ability of common mallow to accumulate trace/heavy metals from polluted soils at South Greater Cairo, Egypt; and their hazardous effects on consumer's health. Five quadrats were used to collect soil and plant samples from three sites of un-polluted and polluted fields for chemical analysis and measurement of growth variables, as well as for assessing the daily intake of metals (DIM) and hazard quotient (HQ). Irrigation water analysis showed elevated concentrations of the investigated metals and mineral salts in the polluted area compared with the un-polluted one. Plant samples showed reduction in their growth parameters; as well as pigments and nutrient content in the metal-contaminated soil. In addition, Pb, Cd, Cu, Ni, Fe, Mn, Zn, and Co concentrations in the shoots and roots of plants grown in polluted fields were higher compared with plants grown in un-polluted site. The bioaccumulation and translocation factors of most investigated metals indicated the great ability of common mallow to accumulate such metals, which would increase the human intake of metals in their daily diets compared to their reference values (RfD). The hazard quotient (HQ) of Pb, Cr, Fe, Mn and Zn for children and Pb, Cd, Fe and Mn for adults was >1, indicating health hazards for the consumers of common mallow cultivated in the polluted area.

Loneliness and perceived social support in pregnancy and early postpartum of mothers living with HIV in Ontario, Canada.

The HIV Mothering Study (n = 72) was a prospective, observational, cohort study exploring psychosocial experiences and needs of WLWHIV in pregnancy and postpartum. We performed quantitative analysis of determinants of loneliness (UCLA Loneliness Scale) and lower perceived social support (SS) (Medical Outcomes Study-Social Support Survey). The hypothesized determinants included: age, years with HIV, racism (Everyday Discrimination Scale), depression (Edinburgh Postnatal Depression Scale [EPDS]), nadir CD4 (<200 cells/µL), tertiary vs. community HIV care, and marital status. The median age was 33 (IQR = 30-37); 65.3% were African/Caribbean/Black. Multivariable analyses revealed associations between marital status and perceived social support (ß = -16.48, p < 0.0001), and this association was also seen with change over time (p = 0.02). Variables associated with SS that did not change over time were: income, EDS racism, EPDS score. Significant associations with loneliness were seen with the same variables associated with SS. Variables associated with loneliness that also changed over time were: EDS Racism (ß = 0.22, p = 0.0005, and over time p = 0.003), and EPDS score (ß = 0.74, p < 0.0001), and over time (p = 0.0211). Variables associated with loneliness but that did not change over time were: marital status and income. This analysis provides clinicians with prenatal risk factors which may be associated with increase loneliness and lower SS during pregnancy and postpartum: marital status, income, racism and depression.

Lost but not forgotten: A population-based study of mortality and care trajectories among people living with HIV who are lost to follow-up in Ontario, Canada.

OBJECTIVES: Selection as a consequence of volunteer participation in, and loss to follow-up from, cohort studies may bias estimates of mortality and other health outcomes. To quantify this potential, we estimated mortality and health service use among people living with HIV (PLWH) who were lost to cohort follow-up (LTCFU) from a volunteer clinical HIV-infected cohort, and compared these to mortality and health service use in active cohort participants and non-cohort-participants living with HIV in Ontario, Canada. METHODS: We analysed population-based provincial health databases from 1995 to 2014, identifying PLWH ≥ 18 years old; these included data from participants in the Ontario HIV Treatment Network Cohort Study (OCS), a volunteer, multi-site clinical HIV-infected cohort. We calculated all-cause mortality, hospitalization and emergency department (ED) visit rates per 100 person-years (PY) and estimated hazard ratios (HRs) of mortality, adjusting for age, sex, income, rurality, and immigration status. RESULTS: Among 23 043 PLWH, 5568 were OCS participants. Compared with nonparticipants, participants were younger and less likely to be female, to be an immigrant and to reside in a major urban centre, and had lower comorbidity. Mortality among active participants, participants LTCFU and nonparticipants was 2.52, 3.30 and 2.20 per 100 PY, respectively. After adjustment for covariates, mortality risk was elevated among participants LTCFU compared with active participants (HR 2.26; 95% confidence interval 1.91, 2.68). Age-adjusted hospitalization rates and ED visit rates were highest among participants LTCFU. CONCLUSIONS: Mortality risk and use of health care resources were lower among active cohort participants. Our findings may inform health outcome estimates based on volunteer cohorts, as well as quantitative bias adjustment to correct for such biases.

Late diagnosis, delayed presentation and late presentation among persons enrolled in a clinical HIV cohort in Ontario, Canada (1999-2013).

OBJECTIVES: Timely HIV diagnosis and presentation to medical care are important for treatment and prevention. Our objective was to measure late diagnosis, delayed presentation and late presentation among individuals in the Ontario HIV Treatment Network Cohort Study (OCS) who were newly diagnosed in Ontario. METHODS: The OCS is a multi-site clinical cohort study of people living with HIV in Ontario, Canada. We measured prevalence of late diagnosis [CD4 count < 350 cells/µL or an AIDS-defining condition (ADC) within 3 months of HIV diagnosis], delayed presentation (≥ 3 months from HIV diagnosis to presentation to care), and late presentation (CD4 count < 350 cells/µL or ADC within 3 months of presentation). We identified characteristics associated with these outcomes and explored their overlap. RESULTS: A total of 1819 OCS participants were newly diagnosed in Ontario from 1999 to 2013. Late diagnosis (53.0%) and presentation (54.0%) were common, and a quarter (23.1%) of participants were delayed presenters. In multivariable models, the participants of delayed presentation decreased over calendar time, but that of late diagnosis/presentation did not. Late diagnosis contributed to the majority (> 87%) of late presentation, and the prevalence of delayed presentation was similar among those diagnosed late versus early (13.4 versus 13.4%, respectively; P = 0.99). Characteristics associated with higher odds of late diagnosis/presentation in multivariable analyses included older age at diagnosis/presentation; African, Caribbean and Black race/ethnicity; Indigenous race/ethnicity; female sex; and being a male who did not report sex with men. There were lower odds of late diagnosis/presentation among participants who had ever injected drugs. In contrast, delayed presentation risk factors included younger age at diagnosis and having ever injected drugs. CONCLUSIONS: Late presentation is common in Ontario, as it is in other high-income countries. Our findings suggest that efforts to reduce late presentation should focus on facilitating earlier diagnosis for the populations identified in this analysis.

Human health risks from consuming cabbage (Brassica oleracea L. var. capitata) grown on wastewater irrigated soil.

The present study investigated the impact of cumulative irrigation with wastewater on the soil properties and, its health hazards on the consumers of cabbage plants at south Cairo Province, Egypt. Irrigation water, soil and cabbage plants were sample d from two polluted and other two unpolluted farms. The physicochemical properties of water and soil were analyzed and the growth parameters, as well as nutrients and heavy metals concentration in cabbage were investigated. In addition, the daily intake of metals (DIM) and health risk index (HRI) were estimated. Wastewater posed a decrease in the availability of N, P and K, but increases heavy metals in the soil solution. Cabbage stem and root lengths as well as the number of leaves and biomass were greatly reduced in the polluted farms. In addition, the photosynthetic pigments, carbohydrates and proteins were decreased under pollution stress. The concentration of most investigated metals in the leaves and roots were increased with translocation factor greater than one for Pb, Cd, As, Cr, Ni, Fe, and Co. The study revealed that the HRI exceeded one for Pb and Cd in polluted and unpolluted plants; and Fe in polluted ones. Irrigation with wastewater is not suitable for cabbage as it has health risks on humans due to accumulation of heavy metals. It worth noting that, the high ability of cabbage plants to accumulate Pb and Cd from both polluted and unpolluted soils should be taken into consideration when consuming this plant.

Bioaccumulation and rhizofiltration potential of Pistia stratiotes L. for mitigating water pollution in the Egyptian wetlands.

The bioaccumulation and rhizofiltration potential of P. stratiotes for heavy metals were investigated to mitigate water pollution in the Egyptian wetlands. Plant and water samples were collected monthly through nine quadrats equally distributed along three sites at Al-Sero drain in Giza Province. The annual mean of the shoot biomass was 10 times that of the root. The concentrations of shoot heavy metals fell in the order: Fe < Mn < Cr < Pb < Cu < Zn < Ni < Co < Cd, while that of the roots were: Fe < Mn < Cr < Pb < Zn < Ni < Co < Cu < Cd. The bio-concentration factor (BCF) of most investigated heavy metals, except Cr and Pb, was greater than 1000, while the translocation factor (TF) of most investigated metals, except Pb and Cu, did not exceed one. The rhizofiltration potential (RP) of heavy metals was higher than 1000 for Fe, and 100 for Cr, Pb and Cu. Significant positive correlations between Fe and Cu in water with those in plant roots and leaves, respectively were recorded, which, in addition to the high BCF and RP, indicate the potential use of P. stratiotes in mitigating these toxic metals.

Promoting high standards of care for women living with HIV: position statement from the Women Against Viruses in Europe Working Group.

OBJECTIVES: Gender-related factors can influence management decisions, treatment outcomes and the overall long-term wellbeing of people living with HIV (PLWH). The Women Against Viruses in Europe (WAVE) Working Group was established to promote the health and wellbeing of women living with HIV (WLWH). WAVE is part of the European AIDS Clinical Society (EACS) and organizes annual workshops to discuss different issues in the management of WLWH. METHODS: In 2016, 34 WAVE members including community representatives, HIV clinicians and researchers met to discuss standards of care for WLWH and to review current guidelines. Participants focused on three different themes: (1) access to and engagement and retention in care; (2) monitoring of women on antiretroviral therapy and management of comorbidities; and (3) review of EACS treatment guidelines. RESULTS: Five priority areas for optimizing the care of WLWH were identified: (1) psychosocial aspects of HIV diagnosis and care; (2) mental health and wellbeing; (3) pharmacokinetics, toxicity and tolerability of antiretroviral therapy; (4) coinfections and comorbidities; and (5) sexual and reproductive health. WAVE recommendations are provided for each of these areas, and gaps in knowledge and needs for changes in currently existing standards are discussed. CONCLUSIONS: This position statement provides an overview of the key recommendations to optimize the care of WLWH that emerged during the 2016 WAVE workshop.

Health risk assessment and growth characteristics of wheat and maize crops irrigated with contaminated wastewater.

The present study evaluated the effect of untreated wastewater irrigation and its health risks in Triticum aestivum (wheat) and Zea mays (maize) cultivated at south Cairo, Egypt. Morphological measurements (stem and root lengths, number of leaves per plant, and dry weights of main organs) as well as soil, irrigation water, and plant analyses for nutrients and heavy metals were conducted in polluted and unpolluted sites. Wastewater irrigations leads to reduction in the morphological traits of the plants and reduced its vegetative biomass and yield production, with more negative impacts on maize than wheat. The concentrations of Pb, Cd, Cr, and Fe in roots and leaves of wheat were above the phytotoxic limits. Conversely, Pb, Cd, and Fe were significantly high and at phytotoxic concentrations in the leaves of maize at polluted site. The present study indicated that wheat plants tend to phytostabilize heavy metals in their roots, while maize accumulates it more in their leaves. Maize and wheat had toxic concentrations of Pb and Cd in their grains under wastewater irrigation. The health risk index showed values > 1 for Pb and Cd in polluted site for both crops, in addition to maize in unpolluted site. Consequently, this will have greatest potential to pose health risk to the consumers.

Out of focus: tailoring the cascade of care to the needs of women living with HIV.

Around half of the global adult HIV-positive population are women, yet historically women have been under-represented in clinical studies of antiretroviral therapy (ART) and there has been minimal exploration of gender-specific factors related to the response to and appropriateness of treatment choices in women living with HIV (WLWH). There are several key issues pertaining to the cascade of HIV care that make it important to differentiate WLWH from men living with HIV. Factors that are gender specific may impact on the status of WLWH, affecting access to diagnosis and treatment, optimal clinical management, ART outcomes, retention in care, and the overall long-term wellbeing of WLWH. In this review, we discuss the results of recently reported women-only clinical trials and highlight the key unmet needs of WLWH as they pertain to the cascade of HIV care across World Health Organization European Region countries. As significant knowledge gaps remain, the review identifies key areas where further research is required, in order to support improved management of WLWH and guide informed clinical decision-making, including addressing psychosocial factors as part of comprehensive care.

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.

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.

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.

A role for mucosal IL-22 production and Th22 cells in HIV-associated mucosal immunopathogenesis.

Interleukin-22 (IL-22) is a cytokine with epithelial reparative and regenerative properties that is produced by Th22 cells and by other immune cell subsets. Therefore, we explored the hypothesis that disruption of the gut barrier during HIV infection involves dysregulation of these cells in the gastrointestinal mucosa. Sigmoid IL-22-producing T cell and Th22 cells were dramatically depleted during chronic HIV infection, epithelial integrity was compromised, and microbial translocation was increased. These alterations were reversed after long-term antiretroviral therapy. While all mucosal IL-22-producing T-cell subsets were also depleted very early during HIV infection, at these early stages IL-22 production by non-T-cell populations (including NKp44+ cells) was increased and gut epithelial integrity was maintained. Circulating Th22 cells expressed a higher level of the HIV co-receptor/binding molecules CCR5 and α4ß7 than CD4+ T-cell subsets in HIV-uninfected participants, but this was not the case after HIV infection. Finally, recombinant IL-22 was protective against HIV and tumor necrosis factor-α-induced gut epithelial damage in a validated in vitro gut epithelial system. We conclude that reduced IL-22 production and Th22 depletion in the gut mucosa are important factors in HIV mucosal immunopathogenesis.