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IntroductionDespite the availability of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), 21 793 people were newly diagnosed with HIV in Europe in 2019. The Concerted action on seroconversion to AIDS and death in Europe study aims to understand current drivers of the HIV epidemic; factors associated with access to, and uptake of prevention methods and ART initiation; and the experiences, needs and outcomes of people with recently acquired HIV.Methods and analysisThis longitudinal observational study is recruiting participants aged ≥16 years with documented laboratory evidence of HIV seroconversion from clinics in Canada and six European countries. We will analyse data from medical records, self-administered questionnaires, semistructured interviews and participatory photography. We will assess temporal trends in transmitted drug resistance and viral subtype and examine outcomes following early ART initiation. We will investigate patient-reported outcomes, well-being, and experiences of, knowledge of, and attitudes to HIV preventions, including PrEP. We will analyse qualitative data thematically and triangulate quantitative and qualitative findings. As patient public involvement is central to this work, we have convened a community advisory board (CAB) comprising people living with HIV.Ethics and disseminationAll respective research ethics committees have approval for data to contribute to international collaborations. Written informed consent is required to take part. A dissemination strategy will be developed in collaboration with CAB and the scientific committee. It will include peer-reviewed publications, conference presentations and accessible summaries of findings on the study’s website, social media and via community organisations.

The effectiveness of antiretroviral therapy and its increasing availability globally means that millions of people living with HIV now have a much longer life expectancy. However, people living with HIV have disproportionately high incidence of major comorbidities and reduced health-related quality of life. Health systems must respond to this situation by pioneering care and service delivery models that promote wellness rather than mere survival. In this Series paper, we review evidence about the emerging challenges of the care of people with HIV beyond viral suppression and identify four priority areas for action: integrating HIV services and non-HIV services, reducing HIV-related discrimination in health-care settings, identifying indicators to monitor health systems' progress toward new goals, and catalysing new forms of civil society engagement in the more broadly focused HIV response that is now needed worldwide. Furthermore, in the context of an increasing burden of chronic diseases, we must consider the shift that is underway in the HIV field in relation to burgeoning policy and programmatic efforts to promote healthy ageing.

Scientific medical conferences have proliferated in recent years but little data are available to assess their effectiveness in achieving their commonly stated aims “to educate, advance science, and establish evidence-based policy”. The recent expansion of what has been labeled ‘predatory academia’ has heightened concerns about the quality of both published and conference “science”. A journal’s impact factor (JIF) became one accepted metric for the quality of publication science, but no such indicator exists for medical scientific conferences, such as a conference impact factor (CIF). To explore the feasibility of implementing a CIF metric for such conferences, we tested a tool that establishes a ranking system to help both attendees and funders identify quality. Using abstracts presented from 2013 to 2016 at an annual meeting (International Workshop on HIV/Hepatitis Observational Databases), we determined how many were subsequently published in peer-reviewed journals. We then calculated a CIF by dividing the number of peer reviewed published papers by the number of abstracts presented at each conference, then multiplied it by the median value of JIF of the publishing journals. For evaluating the quality of a scientific conference, the use of a CIF which, although limited in scope, can act as a tool for attendees and funders to prioritize their time and resources.

BACKGROUND: For people living with HIV, major guidelines in high-income countries recommend testing for transmitted drug resistance (TDR) to guide the choice of first-line antiretroviral therapy (ART). However, individuals who fail a first-line regimen can now be switched to one of several effective regimens. Therefore, the virological and clinical benefit of TDR testing needs to be evaluated. METHODS: We included individuals from the HIV-CAUSAL Collaboration who enrolled

Background Scabies is an extremely fastidious infestation caused by the Sarcoptes scabiei mite. It causes a persistent itch that can disrupt a person’s mental health, sleep, and overall quality of life. In endemic areas, treatment by targeting symptomatic individuals and their contacts is often unsuccessful due to an asymptomatic period and high rates of re-infection. To overcome this, Mass Drug Administration (MDA) is often used to treat the whole community, irrespective of whether individuals presently have scabies. This review summarises the evidence for the effectiveness of MDA in treating scabies. Methods An exhaustive literature review was conducted on MEDLINE, EMBASE, Web of Science and Scopus. All peer-reviewed articles published in English January 1990 to March 2020 were eligible and only if the studies were primary and interventional. Furthermore, the intervention had to be a pharmacological MDA method involving human subjects. Results TWELVE articles that qualified for inclusion were identified. MDA for scabies significantly reduced its prevalence in communities at follow up. Some of the drivers of success were communities with low levels of migration, an uptake of MDA of > 85%, the use of oral Ivermectin therapy, the treatment of children and pregnant women within the treated population, and repeated treatment for participants diagnosed with scabies at baseline. Conclusions The average absolute reduction in prevalence of scabies was 22.0% and the relative reduction average was 73.4%. These results suggest MDA is effective in treating scabies in the endemic community. Further evidence is needed surrounding MDA use in urban areas with increased levels of migration. Importantly, MDA should not substitute the tackling of socioeconomic factors which contribute to endemic disease such as good sanitation and hygiene.

Evaluate long-term rates of virological failure and treatment interruption for people living with HIV (PLWHIV) with viral suppression on first-line efavirenz+tenofovir disoproxil fumarate+emtricitabine/lamivudine (EFV+TDF+FTC/3TC), and compare these according to patient characteristics.Methods:PLWHIV enrolled in the Collaboration of Observational HIV Epidemiological Research Europe cohort collaboration, who started first-line EFV+TDF+FTC/3TC at age at least 16 years and had viral suppression (

Background The rate of transmitted drug resistance (TDR) may increase with wider use of antiretroviral therapy and can contribute to therapeutic failure. We analysed time trends in TDR among HIV seroconverters. Methods Using CASCADE data of individuals with well estimated dates of HIV seroconversion, we examined HIV nucleotide sequences collected prior to antiretroviral therapy use from 1996-2012. All samples were taken within 12 months of testing HIV positive. Using logistic regression, we examined the association between TDR and year of seroconversion, adjusting for confounders. Results Of 4717 individuals seroconverting between 1996 and 2012, median (IQR) age at seroconversion was 33 (27, 39) years. The majority (3839; 92%) were male, mainly exposed through MSM (3767; 80%), and infected with subtype B (3464; 73%). Overall, 515 (11%) individuals had at least one drug resistance-related mutation; 280 individuals with nucleoside reverse transcriptase, 185 with nonnucleoside reverse transcriptase, and 144 with protease inhibitor mutations. Estimated TDR prevalence was 19.4% (8.2, 36.0) in 1996, significantly decreasing to 8.5% (5.9, 11.9) in 2012 [odds ratio (OR; 95% confidence interval (CI)) = 0.92 (0.90, 0.95) per year increase]. Individuals exposed through sex between men and women were significantly less likely to have been infected with a drug-resistant strain [OR (95% CI) = 0.59 (0.41, 0.87) compared with MSM], and there was marginal evidence that sampling during acute infection was associated with higher odds of resistance [OR (95% CI) = 1.20 (0.97, 1.7), P = 0.093] compared with later sampling. Conclusion TDR has decreased over calendar time although a significant proportion of new infections still carry resistance-related mutations.

The continuum of HIV care is a simple conceptual framework for monitoring HIV programmes, comprising a series of stages that people living with HIV (PLHIV) pass through to access antiretroviral treatment (ART) and achieve viral suppression [1,2]. Individual benefits of suppression include reduced risk of morbidity and mortality. At the population level, viral suppression reduces the risk of onward transmission and enables epidemic containment [3]. Transmission risk may be further reduced by lowering the number of undiagnosed PLHIV [4,5]. Complete continua are, therefore, constructed beginning with the total number of PLHIV in a given population and ending with the number virally suppressed. Intervening stages have included the numbers diagnosed, linked to HIV care, retained in care, eligible for ART, on ART and adhering to ART. Although people can move between stages, the continuum is typically conceptualized as a ‘snapshot’ at one time-point. As the Joint United Nations Programme on HIV and AIDS (UNAIDS) announced the target of reaching ‘90-90-90’ by 2020, which envisions 90% of PLHIV diagnosed, 90% of those diagnosed on ART and 90% of those on ART virally suppressed [6], interest in constructing HIV care continua to inform national programmes and policies has grown [7–11]. However, there has been limited consistency in the methods used to construct these measures and the stages presented in publications. Key stages are often missing or continua entirely absent for many countries, including in Europe, particularly the Eastern region [7,8,11–15]. Drawing from a review of recent literature and expert opinion, we highlight the methodological inconsistencies, the challenges associated with constructing each stage and recommend a standardized way forward for monitoring the continuum of HIV care in Europe.

Summary Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3–6 months (when below the threshold) or every 9–12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86–1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95–1·22) for threshold 200 and 1·03 (0·96–1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17–3·43) for threshold 200 and 1·24 (0·89–1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (−25·5 to 26·3) cells per μL for threshold 200 and −3·5 (−16·0 to 8·9) cells per μL for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies. Funding National Institutes of Health.

Summary Background Standard approaches to estimation of losses in the HIV cascade of care are typically cross-sectional and do not include the population stages before linkage to clinical care. We used indiviual-level longitudinal cascade data, transition by transition, including population stages, both to identify the health-system losses in the cascade and to show the differences in inference between standard methods and the longitudinal approach. Methods We used non-parametric survival analysis to estimate a longitudinal HIV care cascade for a large population of people with HIV residing in rural KwaZulu-Natal, South Africa. We linked data from a longitudinal population health surveillance (which is maintained by the Africa Health Research Institute) with patient records from the local public-sector HIV treatment programme (contained in an electronic clinical HIV treatment and care database, ARTemis). We followed up all people who had been newly detected as having HIV between Jan 1, 2006, and Dec 31, 2011, across six cascade stages: three population stages (first positive HIV test, HIV status knowledge, and linkage to care) and three clinical stages (eligibility for antiretroviral therapy [ART], initiation of ART, and therapeutic response). We compared our estimates to cross-sectional cascades in the same population. We estimated the cumulative incidence of reaching a particular cascade stage at a specific time with Kaplan-Meier survival analysis. Findings Our population consisted of 5205 individuals with HIV who were followed up for 24 031 person-years. We recorded 598 deaths. 4539 individuals gained knowledge of their positive HIV status, 2818 were linked to care, 2151 became eligible for ART, 1839 began ART, and 1456 had successful responses to therapy. We used Kaplan-Meier survival analysis to adjust for censorship due to the end of data collection, and found that 8 years after testing positive in the population health surveillance, 16% had died. Among living patients, 82% knew their HIV status, 45% were linked to care, 39% were eligible for ART, 35% initiated ART, and 33% had reached therapeutic response. Median times to transition for these cascade stages were 52 months, 52 months, 20 months, 3 months, and 9 months, respectively. Compared with the population stages in the cascade, the transitions across the clinical stages were fast. Over calendar time, rates of linkage to care have decreased and patients presenting for the first time for care were, on average, healthier. Interpretation HIV programmes should focus on linkage to care as the most important bottleneck in the cascade. Cascade estimation should be longitudinal rather than cross-sectional and start with the population stages preceding clinical care. Funding Wellcome Trust, PEPFAR.

Socioeconomic inequality challenges population-level implementation of health interventions. We investigated differences by educational level in clinical, virological, and immunological responses to combined antiretroviral treatment (cART) in HIV-positive men and women in Collaboration of Observational HIV Epidemiological Research in Europe, a European collaboration.Data were pooled from 15 cohorts in eight countries of patients initiating cART in 1996-2013 with data on educational level categorized in UNESCO/ISCED classifications. Kaplan-Meier curves, Cox and piecewise linear mixed models were used.Of 24 069 HIV-positive patients, 9% had not completed primary education, 32% had completed primary, 44% secondary, and 15% tertiary education. Overall, 21% were women, who were overrepresented in lower educational strata. During 132 507 person-years of follow-up, 1081 individuals died; cumulative mortality decreased with higher educational level (P 0.001). Over 122 765 person-years, new AIDS events or death occurred in 2598 individuals; differences by education were more marked than for death alone (P 0.001). Virological response was achieved by 67% of patients without completed basic education, 85% with completed primary education, 82% with secondary, and 87% with tertiary (P 0.001). Patients with higher education had higher CD4 cell count at cART initiation and at each time after cART but rate of CD4 cell count recovery did not differ. Differences in mortality and clinical responses were similar for men and women and were not entirely explained by delayed HIV diagnosis and late cART initiation.HIV-positive patients with lower educational level had worse responses to cART and survival in European countries with universal healthcare. To maximize the population impact of cART, Europe needs to decrease the socioeconomic divide.

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate in simple terms the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of HCV-infected individuals to diagnosis, treatment and cure. The value of reporting would be enhanced if reporting entities utilized a standardized approach for generating their CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and ensuring the accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets

Table S1. HIV-1 subtype distribution by cohort country and risk group. (DOCX 25 kb)

CASCADE and EuroCoord acknowledgements, and list of ethics committees. (DOCX 20 kb)

Table S2. Bootstrap support values of MTCs identified with ML phylogenies. (DOCX 22 kb)

The HIV‐CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems; International audience; Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.

Supplemental Digital Content is Available in the Text., Background: Total CD4+ T-cell counts predict HIV disease progression but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite antiretroviral therapy (ART), recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals. Methods: CD4+ count and CD4/CD8 ratio were analyzed using data from 2 cohorts: SPARTAC trial and the UK HIV Seroconverters Cohort where primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models, we examined the effect of CD4/CD8 ratio at seroconversion on disease progression (CD4 1.0). Findings: Of 573 seroconverters, 482 (84%) had abnormal CD4/CD8 ratios at HIV seroconversion. Individuals with higher CD4/CD8 ratio at seroconversion were significantly less likely to reach the disease progression endpoint [adjusted hazard ratio (aHR) (95% CI) = 0.52 (0.32 to 0.82), P = 0.005]. The longer the interval between seroconversion and ART initiation [HR (95% CI) = 0.98 per month increase (0.97, 0.99), P < 0.001], the less likely the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) = 2.47 (1.67 to 3.67), P < 0.001] than those initiating later. Interpretation: Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.

WOS: 000379080900004, PubMed ID: 26492497, ObjectivesThe objective of the 1st European AIDS Clinical Society meeting on Standard of Care in Europe was to raise awareness of the European scenario and come to an agreement on actions that could be taken in the future. MethodsData-driven presentations were given on specific topics followed by interactive panel discussions. ResultsIn Eastern European countries, the epidemic is largely driven by injecting drug use, in contrast with Western Europe where the infection mainly occurs through heterosexual contact. A high proportion of people living with HIV remain unaware of their infection. Substantial differences exist in Eastern Europe and Central Asia with respect to treatment coverage, regimen availability and continuity of drug supply. In 2012, tuberculosis case notification rates were 5-10 times higher in Eastern Europe compared with Western Europe, with an alarming proportion of newly diagnosed multi-drug-resistant cases. Hepatitis C is widespread in selected geographical areas and risk groups. ConclusionsThe key conclusion from the meeting was that a high-priority group of actions could be identified, including: increasing HIV awareness and testing, improving training for health care providers, ensuring equitable patient access to treatments and diagnostics for HIV and comorbidities, and implementing best practices in infection control and treatment of HIV-infected patients coinfected with tuberculosis and hepatitis C virus, for whom direct acting antiviral treatment. should be considered., Medical Research CouncilMedical Research Council UK (MRC) [MC_UU_12023/15]

Although the concept of the HIV treatment cascade has reached nearly ubiquitous acceptance in international HIV policy and research, methods for estimating it vary drastically. These variations become increasingly important as the focus of the HIV response shifts from emergency response to long-term outcomes and financial and organizational sustainability. We review the history of the cascade and the current literature and develop the first comprehensive typology of cascade scope and methods.We define the cascade scope in terms of both breadth (range from first to final event) and depth (given breadth, number of cascade stages that analyzed). We distinguish cascade measurement according to four dimensions: denominator-denominator linkage (data used for cascade construction are linked at the individual level across stages); denominator-numerator linkage (data are linked at the individual level within each stage); single vs. multiple populations from which data sources are drawn; and longitudinal vs. cross-sectional design.Everything else equal, we would prefer broader and deeper cascades, denominator-denominator linkage, denominator-numerator linkage, single population, and longitudinal data over their respective alternatives. Increased investments in population-based cohorts and data linkage are required to complement clinical cohorts for 'broad' longitudinal cascade analyses.

INTRODUCTION: There are few data on the frequency of virological remission in African individuals after treatment with antiretroviral therapy (ART) in primary HIV infection (PHI). METHODS: We studied participants (n = 82) from South Africa and Uganda in Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion, the first trial of treatment interruption in African individuals with PHI randomized to deferred ART or 48 weeks of immediate ART. All were female and infected with non-B HIV subtypes, mainly C. We measured HIV DNA in CD4+ T cells, CD4+ cell count, plasma viral load (pVL), cell-associated HIV RNA and T-cell activation and exhaustion. We explored associations with clinical progression and time to pVL rebound after treatment interruption (n = 22). Data were compared with non-African Short Pulse Antiretroviral Treatment at HIV-1 Seroconversion participants. RESULTS: Pretherapy pVL and integrated HIV DNA were lower in Africans compared with non-Africans (median 4.16 vs. 4.72 log10 copies/ml and 3.07 vs. 3.61 log10 copies/million CD4+ T cells, respectively; P

Objectives In persons with hepatitis C virus (HCV) infection, HIV coinfection leads to faster progression to advanced liver disease. The aim of our study was to estimate diagnosed HIV prevalence among people with evidence of current HCV infection (polymerase chain reaction positive) and examine predictors of coinfection. Methods Adults (≥ 15 years old) with a current HCV infection reported to the Public Health England (PHE) sentinel surveillance of blood-borne viruses were linked to the PHE national HIV database using a deterministic methodology. Descriptive and multivariate analyses were conducted. Results Between 2008 and 2014, 5.0% (999/20 088) of adults with a current HCV infection were diagnosed with HIV coinfection. The majority acquired HIV through sex between men (441; 64.9%), followed by injecting drug use (153; 22.5%) and heterosexual contact (84; 12.4%). Of persons who were coinfected, 65.5% had been diagnosed with HIV infection > 6 months before their HCV diagnosis, 41.4% of whom had a negative anti-HCV test between their HIV and HCV diagnoses. In a multivariable model among persons with current HCV infection, an HIV diagnosis was more likely among men [adjusted odds ratio (aOR) 3.29; 95% confidence interval (CI) 2.60-4.16] and persons of black ethnicity (aOR 3.19; 95% CI 1.36-7.46), and less likely among older adults (aOR 0.85 per 10-year increase; 95% CI 0.79-0.92) and persons of Asian ethnicity (aOR 0.59; 95% CI 0.41-0.86). Conclusions Our results indicate that the majority of diagnosed HIV and current HCV coinfections are among men who have sex with men. Safer sex campaigns should include awareness of transmission of HCV among MSM living with HIV.

We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/μl and initiation with CD4 cell count less than 350 cells/μl.Cohort study based on routinely collected data from the HIV-CAUSAL collaboration.For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics.In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/μl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/μl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/μl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2).Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.

BACKGROUND The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor (NRTI) backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated four neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS 26,172 individuals initiated efavirenz, 5,858 initiated atazanavir, 8,479 initiated lopinavir, and 4,799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% CIs) were 1.72 (1.00, 2.96) for atazanavir, 2.21 (1.38, 3.54) for lopinavir, and 1.41 (0.61, 3.24) for darunavir. The respective hazard ratios (95% CIs) for the combined endpoint were 1.18 (0.74, 1.88) for atazanavir, 1.61 (1.14, 2.27) for lopinavir, and 1.36 (0.74, 2.48) for darunavir. The results varied in subsets defined by calendar year, NRTI backbone, and age. CONCLUSION Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

International audience; BACKGROUND: Achieving the UNAIDS 90-90-90 target by 2020 is expected to end the HIV epidemic by 2030. We report on progress in the WHO European Region in meeting this target.METHODS: The European Centre for Disease Prevention and Control (ECDC) sent questionnaires to 55 countries in 2016. We report estimates for 4 stages of the continuum of HIV care (living with HIV, diagnosed, treated, and virally suppressed), corresponding to the Joint United Nations Programme on HIV and AIDS (UNAIDS) target and explore differences by subregion and challenges with reporting data.FINDINGS: Forty-four countries provided data for ≥1 stage, and 29 for all 4 stages. Estimated HIV prevalence was 0.19% (range 0.02%-0.84%, n = 37 countries providing stage 1 data). The proportion diagnosed of people living with HIV ranged from 38% to 98% (n = 37 reporting number of people living with HIV and diagnosed). The proportion on ART of those diagnosed ranged from 27% to 96% (n = 40 reporting numbers diagnosed and treated), and viral suppression rates ranged from 32% to 97% (n = 31 providing numbers treated and virally suppressed). The overall continuum of care estimate for 29 countries with complete data was 81-84-88, which differed by subregion: 84-88-90, 84-69-62, and 57-45-57 for the western, central, and eastern subregions, respectively. Challenges in reporting data included absence of a single data source for all stages, shortage of expertise, and lack of financial and human resources.CONCLUSIONS: There is an urgent need to strengthen HIV testing programs throughout Europe, particularly in the eastern subregion, and to remove constraints hampering access to testing and care. Recent changes to treatment guidelines should help reduce the numbers diagnosed not treated.

Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration.

OBJECTIVE Interruption of antiretroviral therapy (ART) in chronic HIV disease is associated with increased mortality, predicted by elevations in interleukin-6 (IL-6) and D-dimer. The effect of ART interruption in primary HIV-1 infection on these biomarkers is unknown. METHODS Plasma samples from 200 HIV seroconverters enrolled in the Short Pulse Anti-Retroviral Therapy At HIV Seroconversion trial of deferred ART (standard of care) - 12 or 48 week ART (ART12 or ART48, respectively) - were analysed for IL-6 and D-dimer at weeks 0, 12, 16, 48, 52, 60 and 108 after randomization. Changes in log10 levels from weeks 0 to 12 were analysed using linear regression, as were changes from baseline to 4 weeks after stopping ART. Areas under the biomarker-time curves (AUC) to week 108 were adjusted for baseline values, and compared across all arms. RESULTS Median (inter-quartile range) baseline IL-6 and D-dimer were 1.45 (0.88, 2.41) pg/ml and 0.34 (0.20, 0.50) mg/l, respectively. At week 12, D-dimer levels were significantly lower among treated compared to untreated individuals (P

Objective: The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART). Design: Two observational studies: the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC). Methods: Combined data from UK CHIC and NSHPC were used to identify factors associated with LEE (grade 1-4) and severe LEE (grade 3-4). Women starting ART in 2000-2012 were included irrespective of pregnancy status. Cox proportional hazards were used to assess fixed and time-dependent covariates including pregnancy status, CD4 + cell count, drug regimen and hepatitis B virus/hepatitis C virus (HBV/HCV) coinfection. Results: One-quarter (25.7%, 982/3815) of women were pregnant during follow-up, 14.2% (n = 541) when starting ART. The rate of LEE was 14.5/100 person-years in and 6.0/100 person-years outside of pregnancy. The rate of severe LEE was 3.9/100 person-years in and 0.6/100 person-years outside of pregnancy. The risk of LEE and severe LEE was increased during pregnancy [LEE: adjusted hazard ratio (aHR) 1.66 (1.31-2.09); severe LEE: aHR 3.57 (2.30-5.54)], including in secondary analyses excluding 541 women pregnant when starting ART. Other factors associated with LEE and severe LEE included lower CD4 + cell count (