Suchergebnisse

IntroductionWhile HIV/AIDS remains an important cause of death among people who inject drugs (PWID), the potential mortality burden attributable to hepatitis C virus (HCV) infection among this population is of increasing concern. Therefore, we sought to identify trends in and predictors of liver‐related mortality among PWID.MethodsData were derived from prospective cohorts of PWID in Vancouver, Canada, between 1996 and 2011. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. Multivariate Cox proportional hazards regression was used to examine the relationship between HCV infection and time to liver‐related death. A sub‐analysis examined the effect of HIV/HCV co‐infection.Results and discussionIn total, 2,279 PWID participated in this study, with 1,921 (84.3%) having seroconverted to anti‐HCV prior to baseline assessments and 124 (5.4%) during follow‐up. The liver‐related mortality rate was 2.1 (95% confidence interval [CI]: 1.5–3.0) deaths per 1,000 person‐years and was stable over time. In multivariate analyses, HCV seropositivity was not significantly associated with liver‐related mortality (adjusted relative hazard [ARH]: 0.45; 95% CI: 0.15–1.37), but HIV seropositivity was (ARH: 2.67; 95% CI: 1.27–5.63). In sub‐analysis, HIV/HCV co‐infection had a 2.53 (95% CI: 1.18–5.46) times hazard of liver‐related death compared with HCV mono‐infection.ConclusionsIn this study, HCV seropositivity did not predict liver‐related mortality while HIV seropositivity did. The findings highlight the critical role of HIV mono‐ and co‐infection rather than HCV infection in contributing to liver‐related mortality among PWID in this setting.

IntroductionIn many resource‐limited settings, combination antiretroviral therapy (cART) failure is diagnosed clinically or immunologically. As such, there is a high likelihood that patients may stay on a virologically failing regimen for a substantial period of time. Here, we compared the long‐term impact of initiating non‐nucleoside reverse transcriptase inhibitor (NNRTI)‐ versus boosted protease inhibitor (bPI)‐based cART in British Columbia (BC), Canada.MethodsWe followed prospectively 3925 ART‐naïve patients who started NNRTIs (N=1963, 50%) or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six months, we assessed whether patients virologically failed therapy (a plasma viral load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time of failure ≤500 versus >500 copies/mL. We then followed these patients for another six months and calculated their probability of achieving subsequent viral suppression (pVL <50 copies/mL twice consecutively) and of developing drug resistance. These probabilities were adjusted for fixed and time‐varying factors, including cART adherence.ResultsAt six months, virologic failure rates were 9.5 and 14.3 cases per 100 person‐months for NNRTI and bPI initiators, respectively. NNRTI initiators who failed with a pVL ≤500 copies/mL had a 16% higher probability of achieving subsequent suppression at 12 months than bPI initiators (0.81 (25th–75th percentile 0.75–0.83) vs. 0.72 (0.61–0.75)). However, if failing NNRTI initiators had a pVL >500 copies/mL, they had a 20% lower probability of suppressing at 12 months than pVL‐matched bPI initiators (0.37 (0.29–0.45) vs. 0.46 (0.38–0.54)). In terms of evolving HIV drug resistance, those who failed on NNRTI performed worse than bPI in all scenarios, especially if they failed with a viral load >500 copies/mL.ConclusionsOur results show that patients who virologically failed at six months on NNRTI and continued on the same regimen had a lower probability of subsequently achieving viral suppression and a higher chance of evolving HIV drug resistance. These results suggest that improving access to regular virologic monitoring is critically important, especially if NNRTI‐based cART is to remain a preferred choice for first‐line therapy in resource‐limited settings.

IntroductionDespite the tremendous improvements in survival, some groups of people living with HIV (PLHIV) continue to have lower survival rates than the overall HIV‐positive population. Here, we characterize the evolving pattern of mortality among PLHIV in British Columbia since the beginning of the expansion of antiretroviral treatment in 2003.MethodsThis retrospective cohort study included 3653 individuals ≥20 years old, who enrolled on treatment between January 1, 2003, and December 31, 2012, and were followed until December 31, 2013. All‐cause mortality rates and standardized mortality ratios (SMRs) were calculated to compare mortality outcomes of PLHIV to the general population. Abridged life tables were constructed to estimate the life expectancy at age 20 years for PLHIV.ResultsThe overall crude mortality rate was 28.57 per 1000 person‐years, the SMR was 3.22 and the life expectancy was 34.53 years. Interestingly, if we considered only individuals alive after the first year, the life expectancy increased to 48.70 years (41% increase). The SMRs for males and females decreased over time. Although females had higher SMRs in 2003 to 2008, this difference no longer existed in 2009 to 2011. There were also important differences in mortality outcomes for different clinical and demographical characteristics.ConclusionsMortality outcomes of PLHIV who initiated antiretroviral treatment have dramatically improved over the last decade. However, there is still room for improvement and multilateral efforts should continue to promote early, sustained engagement of PLHIV on treatment so that the impact of treatment can be fully realized.

IntroductionHIV‐1 plasma viral load during treatment can be highly variable. Thus, there is the need to find a measure of cumulative viremia that can be used to assess both the short‐ and long‐term efficacy of highly active antiretroviral therapy (HAART). Here, we validate a measure of cumulative viremia to evaluate HAART efficacy.MethodsWe accessed HAART efficacy using data from a randomized clinical trial conducted in Mexico. We compared the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, against the cumulative plasma viral load, estimated as the area under the plasma viral load curve (AUVLC). High AUVLC indicates high cumulative viremia.Results and discussionThere was a strong and significant association between the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, with individuals suppressed having significant lower cumulative viremia. The median area was 7513 (25th–75th percentile [Q1–Q3] 6634−8180) if viral load <50 copies/mL and 7679 (Q1–Q3 6899−9373) if viral load ≥50 copies/mL (p‐value 0.0284). When the analysis was stratified by study arm, individuals on efavirenz had lower cumulative viremia than those on boosted lopinavir.ConclusionsOur findings suggest that cumulative viremia should be explored further as a tool to simultaneously evaluate the individual and public health efficacy of HAART. This is particularly relevant to the implementation and evaluation of the Treatment 2.0 strategy recently proposed by UNAIDS and the WHO, as a means to maximize the individual and public health benefit of HAART.

IntroductionAwareness and knowledge of treatment as prevention (TasP) was assessed among HIV‐positive and HIV‐negative gay, bisexual and other men who have sex with men (GBMSM) in Vancouver, Canada.MethodsBaseline cross‐sectional survey data were analyzed for GBMSM enrolled, via respondent‐driven sampling (RDS), in the Momentum Health Study. TasP awareness was defined as ever versus never heard of the term "TasP." Multivariable logistic regression identified covariates of TasP awareness. Among those aware of TasP, men's level of knowledge of TasP was explored through an examination of self‐perceived knowledge levels, risk perceptions and short‐answer definitions of TasP which were coded as "complete" if three TasP‐related components were identified (i.e. HIV treatment, viral suppression and prevention of transmission). Information source was also assessed. Analyses were stratified by HIV status and RDS adjusted.ResultsOf 719 participants, 23% were HIV‐positive, 68% Caucasian and median age was 33 (Interquartile range (IQR) 26,47). Overall, 46% heard of TasP with differences by HIV status [69% HIV‐positive vs. 41% HIV‐negative GBMSM (p<0.0001)]. In adjusted models: HIV‐positive GBMSM were more likely to have heard of TasP if they were Canadian born, unemployed, not using party drugs and had higher CD4 counts; HIV‐negative GBMSM were more likely to have heard of TasP if they were Caucasian (vs. Aboriginal), students, had higher education, a regular partner and multiple sexual partners. Among those aware of TasP 91% of HIV‐positive and 69% of HIV‐negative GBMSM (p<0.0001) felt they knew "a lot" or "a bit in general" about TasP; 64 and 41% (p=0.002) felt HIV treatment made the risk of transmission "a lot lower"; and 21 and 13% (p<0.0001) demonstrated "complete" TasP definitions. The leading information source was doctors (44%) for HIV‐positive GBMSM and community agencies (38%) for HIV‐negative GBMSM, followed by gay media for both populations (34%).ConclusionsNearly half of GBMSM in this study reported having heard of TasP, yet only 14% demonstrated complete understanding of the concept. Variations in TasP awareness and knowledge by HIV status, and key socio‐demographic, behavioural and clinical factors, highlight a need for health communication strategies relevant to diverse communities of GBMSM in order to advance overall TasP health literacy.

IntroductionCombination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment.MethodsParticipants from the Canadian Observational Cohort (CANOC), a multi‐site cohort of HIV‐positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm3 or an AIDS‐defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression.ResultsIn total, 8942 participants (18% female) of median age 40 years (Q1–Q3 33–47) were included. The median baseline CD4 count increased from 190 cells/mm3 (Q1–Q3 80–320) in 2000 to 360 cells/mm3 (Q1–Q3 220–490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm3 or AIDS‐defining illness. Late initiation was more common among women, non‐MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub‐analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm3), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation.ConclusionsThis analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.

AbstractIntroductionGlobally, prosecutions for non‐disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence.DiscussionTwenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV‐negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant.ConclusionsThe application of up‐to‐date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.

INTRODUCTION: Globally, prosecutions for non-disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence. DISCUSSION: Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV-negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant. CONCLUSIONS: The application of up-to-date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.