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Background: In 2007–2012 the Mexican government launched the National HIV program and there was a major change in HIV policies implemented in 2013–2018, when efforts focused on prevention, increase in early diagnosis and timely treatment. Still, late HIV diagnosis is a major concern in Mexico due to its association with the development of AIDS development and mortality. Thus, the objectives of this study were to identify the determinants of late HIV diagnosis (i.e. CD4 count less than 200 cells/mm3) in Mexico from 2008 to 2017 and to evaluate the impact of the 2013–2017 National HIV program. Methods: Using patient level data from the SALVAR database, which includes 64% of the population receiving HIV care in Mexico, an adjusted logistic model was conducted. Main study outcomes were HIV late diagnosis which was defined as CD4 count less than 200 cells/mm3 at diagnosis. Results: The study included 106,830 individuals newly diagnosed with HIV and treated in Mexican public health facilities between 2008 and 2017 (mean age: 33 years old, 80% male). HIV late diagnosis decreased from 45 to 43% (P < 0.001) between 2008 and 2012 and 2013–2017 (i.e. before and after the implementation of the 2013–2017 policy). Multivariable logistic regressions indicated that being diagnosed between 2013 and 2017 (odds ratio [OR] = 0.96 [95% Confidence interval [CI] [0.93, 0.98]) or in health facilities specialized in HIV care (OR = 0.64 [95% CI 0.60, 0.69]) was associated with early diagnosis. Being male, older than 29 years old, diagnosed in Central East, the South region of Mexico or in high-marginalized locality increased the odds of a late diagnosis. Conclusions: The results of this study indicate that the 2013–2017 National HIV program in Mexico has been marginally successful in decreasing the proportion of individuals with late HIV diagnosis in Mexico. We identified several predictors of late diagnosis which could help establishing health policies. The main determinants for late diagnosis were being male, older than 29 years old, and being diagnosed in a Hospital or National Institute. [ABSTRACT FROM AUTHOR]

Evaluates couples discordant in their HIV-1 infection status for the presence of protective factors. Infectivity of phytohemagglutinin-stimulated CD4 blasts; Risk factors for HIV infection in seronegative subjects; Lysis of infected CD4 cells and B cell lines by autologous cytotoxic T lymphocytes.

Background: Knowledge of HIV drug resistance informs the choice of regimens and ensures that the most efficacious options are selected. In January 2014, a policy change to routine resistance testing was implemented in Ontario, Canada. The objective of this study was to investigate the policy change impact of routine resistance testing in people with HIV in Ontario, Canada since January 2014. Methods: We used data on people with HIV living in Ontario from administrative databases of the Institute for Clinical Evaluative Sciences (ICES) and Public Health Ontario (PHO), and ran ordinary least squares (OLS) models of interrupted time series to measure the levels and trends of 2-year mortality, 2-year hospitalizations and 2-year emergency department visits before (2005–2013) and after the policy change (2014–2017). Outcomes were collected in biannual periods, generating 18 periods before the intervention and 8 periods after. We included a control series of people who did not receive a resistance test within 3 months of HIV diagnosis. Results: Data included 12,996 people with HIV, of which 8881 (68.3%) were diagnosed between 2005 and 2013, and 4115 (31.7%) were diagnosed between 2014 and 2017. Policy change to routine resistance testing within 3 months of HIV diagnosis led to a decreasing trend in 2-year mortality of 0.8% every six months compared to the control group. No significant differences in hospitalizations or emergency department visits were noted. Interpretation: The policy of routine resistance testing within three months of diagnosis is beneficial at the population level. [ABSTRACT FROM AUTHOR]

Background: People aging with HIV are at risk for loneliness, with stigmatization and economic marginalization added to the health challenges arising from chronic infection. This study provides evidence for the extent, contributors, and consequences of loneliness in people living with HIV, focusing on brain health and quality of life. Setting: Cross-sectional data from 856 middle-aged and older adults living with HIV recruited from 5 urban specialty clinics in Canada were drawn from the inaugural visit of the Positive Brain Health Now cohort study. Methods: Participants completed an extensive assessment of biopsychosocial variables. The prevalence, severity, and quality of life impact of self-reported loneliness were described. Clinical and environmental factors hypothesized as contributing to loneliness, and the consequences of loneliness on health and function were identified using logistic, ordinal, and linear regression. Results: Eighteen percent reported being "quite often" and 46% "sometimes" lonely. Those with more loneliness were younger, less mobile, suffered more financial hardship, and were more likely to use opioids. HIV symptoms, pain, fatigue, low motivation, stigma, and unemployment were related to loneliness. Loneliness increased the odds of cognitive impairment, low mood, stress, and poor physical health. Those who were "quite often" lonely were over 4 times more likely to report poor or very poor quality of life than those who were "almost never" lonely. Conclusion: Loneliness is common in middle-aged and older people living with HIV in Canada. Many of the associated factors are modifiable, offering novel targets for improving brain health, general health, and quality of life in HIV. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) vaccines have promising safety and immunogenicity data in women living with HIV (WLWH). However, it is critical to understand the residual burden of oncogenic HPV within WLWH to inform postvaccination cervical screening needs. We assessed rates of persistent infection with nonquadrivalent HPV (qHPV) oncogenic types in a cohort of qHPV-vaccinated WLWH. Setting: Multicentre, longitudinal cohort across Canada. Methods: WLWH were scheduled to receive 3 doses of qHPV vaccine. Participants provided health data and HPV DNA samples. Persistent cases of HPV were defined as new HPV in samples from ≥2 consecutive visits or as HPV present in the last sample. HPV31/ 33/35/39/45/51/52/56/58/59/68/82 were considered to have oncogenic potential. Median follow-up time was 4 years after initial vaccine dose. Results: A total of 284 participants were eligible for this analysis with 1205 person-years (PY) of follow-up (≥1 dose of vaccine, ≥1 HPV DNA result after vaccination). The highest incidence of persistent infection was with HPV51 (1.38/100 PY), followed by HPV52 (1.18/100 PY), and HPV39 (1.06/100 PY). The incidence of persistent infection with pooled HPV types added in the nonavalent vaccine (HPV31/33/45/52/58) was lower than the incidence of persistent oncogenic HPV types not contained within available vaccines (HPV35/39/51/56/59/68) (2.4/100 PY versus 3.6/100 PY, respectively). Conclusions: qHPV-vaccinated WLWH continue to face a burden of persistent oncogenic HPV infection. Although the nonavalent vaccine could alleviate some of this burden, 2 of the top 3 persistent oncogenic HPVs in this cohort are not contained within any available vaccine. This highlights the need for ongoing cervical screening in HPV-vaccinated WLWH. [ABSTRACT FROM AUTHOR]

Background: Ethnic differences have the potential to confound associations between HIV-1 subtype and immunologic progression. We compared declines in CD4 cell counts during untreated infection for the most prevalent HIV-1 subtypes, focusing on distinguishing between the effects of viral subtype and ethnicity. Methods: We combined data from 4 European and 6 Canadian cohorts, selecting adults in the stable chronic phase of untreated HIV infection. We estimated the change in square root CD4 cell count over time for subtypes and ethnicities using mixed models, adjusting for covariates selected for their potential effect on initial CD4 cell count or its decline. Results: Data from 9772 patients were analyzed, contributing 79 175 measurements of CD4 cell count and 24 157 person-years of follow-up. Overall, there were no appreciable differences in CD4 cell count decline for viral subtypes A, CRF01_AE, CRF02_AG, C and G compared with viral subtype B; whereas the decline in CD4 cell count in patients of African ancestry was considerably slower than in patients of other ethnicity. When ethnic groups were studied separately, there was evidence for slower declines in CD4 cell count in viral subtypes C, and possibly A and G, compared with viral subtype B in patients of African ancestry but not among patients of other ethnicities, suggesting an interaction between subtype and ethnicity. Interpretation: Ethnicity is a major determinant of CD4 cell count decline; viral subtype differences may have existed but were small compared with the effect of ethnicity and were most apparent in patients of African ancestry. In developing countries, slower CD4 cell count declines among individuals of African descent may translate to a longer asymptomatic phase and increase the opportunity for HIV transmission. [ABSTRACT FROM AUTHOR]

Despite the use of antivirals to treat patients with severe influenza, questions remain with respect to effects and safety. Although a recent systematic review has provided some indication of benefit, the analysis is limited by the quality of the available evidence from randomized controlled trials. To supplement the existing information, the authors conducted a systematic review of observational studies of antiviral treatment for influenza. This report summarises the findings of that review. Similar to the randomised trials, the confidence in the estimates of the effects for decision-making is low to very low primarily due to the risk of selection and publication bias in the observational studies. From these observational studies, the summary estimates suggest that oseltamivir may reduce mortality, hospitalisation and duration of symptoms compared with no treatment. Inhaled zanamivir may also reduce symptom duration and hospitalisations, but patients may experience more complications compared with no treatment. Earlier treatment with antivirals is generally associated with better outcomes than later treatment. Further high-quality evidence is needed to inform treatment guidelines because of the overall low to very low quality of evidence. [ABSTRACT FROM AUTHOR]

Background: Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations. Methods: HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for Cmin and Cmax were drawn weekly for 3 weeks. The ratio of each individual's median Cmin and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed Cmin and Cmax ratios. Results: Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral Cmin and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher Cmin. No significant correlates for Cmax were found. Conclusions: Compared to historical control data, Cmin in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral Cmin ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to examine the relationship between the Medical Outcomes Study-HIV Health Survey (MOS-HIV) and the SF-12v2 to determine if the latter is adequate to assess the health-related quality of life (HRQoL) of men and women living with HIV/AIDS. 112 men and women living with HIV/AIDS who access care at a tertiary HIV clinic in Hamilton, Ontario were included in this cross-sectional analysis. Correlation coefficients of the MOS-HIV physical and mental health summary scores (PHS and MHS) and the SF-12v2 physical and mental component summary scales (PCS and MCS) were calculated along with common sub-domains of the measures including physical functioning (PF), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF) and mental health (MH) to explore the relationship between these two HRQoL measures. The sub-domains role physical (RP) and role emotional (RE) of the SF-12v2 were compared separately to the sub-domain role functioning (RF) of the MOS-HIV. Weighted kappa scores were calculated to determine agreement beyond chance between the MOS-HIV and SF-12v2 in assigning a HRQoL state (i.e. low, moderate, good, very good). Results: The MOS-HIV had mean PHS and MHS summary scores of 47.3 (SD = 11.5) and 49.2 (SD = 10.7) respectively. The mean SF-12v2 PCS and MCS scores were 47.7 (SD = 11.0) and 44.0 (SD = 10.4). The MOS-HIV and SF-12v2 physical and mental health summary scores were positively correlated (r = 0.84, p < 0.001 and r = 0.76, p < 0.001). All common sub-domains were significantly correlated at p values from < 0.001 to 0.034. Substantial agreement was observed in assigning a HRQoL state (Physical: κ = 0.788, SE = 0.095; Mental: κ = 0.707, SE = 0.095). Conclusions: This analysis validates the SF-12v2 for measuring HRQoL in adult men and women living with HIV/AIDS. [ABSTRACT FROM AUTHOR]

Background: Smoking prevalence in human immunodeficiency virus (HIV) positive subjects is about three times of that in the general population. However, whether the extremely high smoking prevalence in HIV-positive subjects affects their lung function is unclear, particularly whether smoking decreases lung function more in HIV-positive subjects, compared to the general population. We conducted this study to determine the association between smoking and lung function, respiratory symptoms and diseases amongst HIV-positive subjects. Results: Of 120 enrolled HIV-positive subjects, 119 had an acceptable spirogram. Ninety-four (79%) subjects were men, and 96 (81%) were white. Mean (standard deviation [SD]) age was 43.4 (8.4) years. Mean (SD) of forced expiratory volume in one second (FEV1) percent of age, gender, race and height predicted value (%FEV1) was 93.1% (15.7%). Seventy-five (63%) subjects had smoked 24.0 (18.0) pack-years. For every ten pack-years of smoking increment, %FEV1 decreased by 2.1% (95% confidence interval [CI]: -3.6%, -0.6%), after controlling for gender, race and restrictive lung function (R2 = 0.210). The loss of %FEV1 in our subjects was comparable to the general population. Compared to non-smokers, current smokers had higher odds of cough, sputum or breathlessness, after adjusting for highly active anti-retroviral therapy (HAART) use, odds ratio OR = 4.9 (95% CI: 2.0, 11.8). However respiratory symptom presence was similar between non-smokers and former smokers, OR = 1.0 (95% CI: 0.3, 2.8). All four cases of COPD (chronic obstructive pulmonary disease) had smoked. Four of ten cases of restrictive lung disease had smoked (p = 0.170), and three of five asthmatic subjects had smoked (p = 1.000). Conclusions: Cumulative cigarette consumption was associated with worse lung function; however the loss of % FEV1 did not accelerate in HIV-positive population compared to the general population. Current smokers had higher odds of respiratory symptoms than non-smokers, while former smokers had the same odds of respiratory symptoms as non-smokers. Cigarette consumption was likely associated with more COPD cases in HIV-positive population; however more participants and longer follow up would be needed to estimate the effect of smoking on COPD development. Effective smoking cessation strategies are required for HIV-positive subjects. [ABSTRACT FROM AUTHOR]

Background: Improvements in life expectancy and quality of life for HIV-positive women coupled with reduced vertical transmission will likely lead numerous HIV-positive women to consider becoming pregnant. In order to clarify the demand, and aid with appropriate health services planning for this population, our study aims to assess the fertility desires and intentions of HIV-positive women of reproductive age living in Ontario, Canada. Methodology/Principal Findings: A cross-sectional study with recruitment stratified to match the geographic distribution of HIV-positive women of reproductive age (18-52) living in Ontario was carried out. Women were recruited from 38 sites between October 2007 and April 2009 and invited to complete a 189-item self-administered survey entitled ''The HIV Pregnancy Planning Questionnaire'' designed to assess fertility desires, intentions and actions. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios of significant predictors of fertility intentions. The median age of the 490 participating HIV-positive women was 38 (IQR, 32-43) and 61%, 52%, 47% and 74% were born outside of Canada, living in Toronto, of African ethnicity and currently on antiretroviral therapy, respectively. Of total respondents, 69% (95% CI, 64%-73%) desired to give birth and 57% (95% CI, 53%-62%) intended to give birth in the future. In the multivariable model, the significant predictors of fertility intentions were: younger age (age,40) (p,0.0001), African ethnicity (p,0.0001), living in Toronto (p = 0.002), and a lower number of lifetime births (p = 0.02). Conclusions/Significance: The proportions of HIV-positive women of reproductive age living in Ontario desiring and intending pregnancy were higher than reported in earlier North American studies. Proportions were more similar to those reported from African populations. Healthcare providers and policy makers need to consider increasing services and support for pregnancy planning for HIV-positive women. This may be particularly significant in jurisdictions with high levels of African immigration. [ABSTRACT FROM AUTHOR]

Background. To date, no randomized trial to address the use of adjunctive rifampin in addition to metronidazole for the treatment of Clostridium difficile-associated diarrhea has been reported. Rifampin has excellent in vitro activity against C. difficile and penetrates into cellular materials where the organisms may persist. Methods. This was a prospective, randomized, single-blinded study of 39 patients that compared therapy with metronidazole alone versus therapy with metronidazole and rifampin for 10 days to treat laboratory-confirmed primary episode C. difficile-associated diarrhea. Twenty patients were randomly assigned to the metronidazole group, and 19 were randomly assigned to the metronidazole and rifampin group. Data were analyzed by intention-to-treat analysis using the 2-tailed Kaplan-Meier method and the log-rank test. Results. Adjunctive rifampin treatment for 10 days, compared with treatment with metronidazole alone for 10 days, was associated with a similar median time to symptom improvement (9.0 days vs. 6.5 days; P = .74), a similar median time to first relapse (26 days vs. 16 days; P = .23), a similar proportion of patients with relapse by study day 40 (42% vs. 38%; P = 1.0), and a similar proportion of patients experiencing nonfatal adverse events (37% vs. 40%; P = .55). There were a significantly higher number of deaths in the metronidazole and rifampin group, compared with the metronidazole group (6 of 19 patients vs. 1 of 20 patients; P = .04), but there were fewer laboratory-confirmed relapses by study day 40 (2 vs. 4; P = .66). Conclusions. We conclude that there is no role for routine rifampin as an adjunct to treatment with metronidazole for hospitalized patients with C. difficile-associated diarrhea. The cure rates for both treatment groups remain unacceptably low, and better treatments are urgently needed. [ABSTRACT FROM AUTHOR]

Reports that beta-chemokine RANTES production by T cells and CD8-mediated inhibition of human immunodeficiency virus gene expression before initiation of potent antiretroviral therapy predict sustained suppression of viral replication. Effect of the introduction of potent combinations of antiretroviral drugs or highly active antiretroviral therapy in the treatment of human immunodeficiency virus infection.

Background: Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) C(min) and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations.Methods: HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for C(min) and Cmax were drawn weekly for 3 weeks. The ratio of each individual's median C(min) and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed C(min) and Cmax ratios.Results: Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral C(min) and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher C(min). No significant correlates for Cmax were found.Conclusions: Compared to historical control data, C(min) in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral C(min) ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations.Trial Registration: NCT00433979. [ABSTRACT FROM AUTHOR]