A global action agenda for turning the tide on fatty liver disease.

BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

A global research priority agenda to advance public health responses to fatty liver disease.

BACKGROUND & AIMS: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. METHODS: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. RESULTS: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had <80% 'agree', with greater reliance on 'somewhat agree' to achieve >90% combined agreement. CONCLUSIONS: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat. IMPACT AND IMPLICATIONS: An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat.

Late diagnosis of HIV: An updated consensus definition.

INTRODUCTION: In recent years, HIV testing frequency has increased, resulting in more people being diagnosed during seroconversion with a temporarily low CD4 count. Using the current consensus definition of late HIV presentation ('presenting for care with a CD4 count < 350 cells/µL or an AIDS-defining event, regardless of CD4 count') these individuals would be incorrectly assigned as being diagnosed late. METHODS: In spring 2022, a European expert group convened to revise the current late HIV presentation consensus definition. A survey on data availability to apply this revised definition was sent to nominated European focal points responsible for HIV surveillance (n = 53). RESULTS: Experts agreed that the updated definition should refer to late HIV diagnosis rather than presentation and include the following addition: People with evidence of recent infection should be reclassified as 'not late', with evidence of recent infection considered hierarchically. The individual must have: (i) laboratory evidence of recent infection; (ii) a last negative HIV test within 12 months of diagnosis; or (iii) clinical evidence of acute infection. People with evidence of being previously diagnosed abroad should be excluded. A total of 18 countries responded to the survey; 83% reported capturing CD4 count and/or AIDS at diagnosis through national surveillance, 67% captured last negative test and/or previous HIV diagnosis, 61% captured seroconversion illness at diagnosis and 28% captured incident antibody results. CONCLUSIONS: Accurate data on late diagnosis are important to describe the effects of testing programmes. Reclassification of individuals with recent infection will help to better identify populations most at risk of poor HIV outcomes and areas for intervention.

Pre-exposure Prophylaxis Persistence Among Greek Sexual Minority Men: Results from PrEP for Greece (P4G) Study.

Nearly half the new HIV infections in Greece occur in sexual minority men, yet pre-exposure prophylaxis is not currently supported in the national HIV program. We examined factors associated with PrEP persistence among Greek SMM in PrEP for Greece, the first PrEP study in Greece. Participants (n = 100) were recruited from 2016 to 2018 through respondent-driven sampling among SMM in Athens, receiving supplies for daily PrEP at interval visits over 12-months. PrEP persistence, operationalized as Total PrEP Time, was high, 74% of participants achieving perfect persistence. Higher alcohol risk scores (OR 1.27, 95% CI 1.08-1.49) and adherence to HIV testing guidelines (OR 1.23, 95% CI 1.00-1.51) were associated with persistence. Housing impermanence (OR 0.14, 95% CI 0.04-0.48) and serostatus disclosure concerns (OR 0.77, 95% CI 0.60-0.97) were associated with limited PrEP persistence. While PrEP persistence among Greek SMM is high, socioeconomic factors and societal attitudes may challenge prevention efforts.

A Network Approach to Determine Optimization of PrEP Uptake in Athens, Greece.

Although the HIV epidemic in Athens, Greece has reemerged and spread in men who have sex with men (MSM), state-supported PrEP programs have not been instituted. A PrEP intervention was implemented building upon an existing network cohort of MSM (308 participants; 1212 network members). A PrEP intervention cohort of 106 participants was selected based upon sex behaviors. Individual, partner, and network characteristics were compared between the cohorts. The PrEP cohort members were more highly connected and in more influential positions in the network than their peers. Further, their sexual network connections' behaviors increased their vulnerability to HIV infection relative to the rest of the network's sex partners. This included greater stimulant use (24.2% vs 7.0%; χ2 = 28.2; p < 0.001), greater rates of at least weekly condomless sex (OR = 2.7; 95% CI 2.1-3.5; χ2 = 59.2; p < 0.001) and at least weekly use of drugs or alcohol during sex (OR = 3.4; 95% CI 2.6-4.3; χ2 = 89.7; p < 0.001). Finally the PrEP cohort's social networks showed similarly increased vulnerability to seroconversion, including greater rates of injection drug use (4.1% vs 0.5%; χ2 = 3.9; p = 0.04), greater stimulant use (33.6% vs 14.6%; χ2 = 16.9, p < 0.001), and higher rates of recent STIs (21.6% vs 13.1%; χ2 = 4.4; p = 0.04). Thus, this PrEP intervention engaged individuals in vulnerable positions with vulnerable connections within an MSM community.

Clinical Perspectives of ERCC1 in Bladder Cancer.

ERCC1 is a key regulator of nucleotide excision repair (NER) pathway that repairs bulky DNA adducts, including intrastrand DNA adducts and interstrand crosslinks (ICLs). Overexpression of ERCC1 has been linked to increased DNA repair capacity and platinum resistance in solid tumors. Multiple single nucleotide polymorphisms (SNPs) have been detected in ERCC1 gene that may affect ERCC1 protein expression. Platinum-based treatment remains the cornerstone of urothelial cancer treatment. Given the expanding application of neoadjuvant and adjuvant chemotherapy in locally advanced bladder cancer, there is an emerging need for biomarkers that could distinguish potential responders to cisplatin treatment. Extensive research has been done regarding the prognostic and predictive role of ERCC1 gene expression and polymorphisms in bladder cancer. Moreover, novel compounds have been recently developed to target ERCC1 protein function in order to maximize sensitivity to cisplatin. We aim to review all the existing literature regarding the role of the ERCC1 gene in bladder cancer and address future perspectives for its clinical application.

HIV incidence among men who have sex with men at a community-based facility in Greece.

OBJECTIVE: Men who have sex with men (MSM) are disproportionately affected by HIV in Greece. However, research on HIV incidence in this group is lacking. This study aimed at estimating HIV incidence among MSM in Athens, Greece. METHODS: The analysis included routinely collected data between January 2013-June 2015 from adult MSM who visited a community-based facility (Ath Checkpoint) at least twice and were non-reactive to the rapid INSTITM HIV-1/HIV-2 assay at baseline. HIV conversion rates were calculated by dividing the number of clients who became reactive by the person-years of observation. All statistical analyses including Poisson regression models were conducted in STATA 14. RESULTS: A total of 1,243 MSM contributed 1,102.50 person-years (py). The overall (per 100 py) conversion rate was 3.99 (95% CI: 2.97-5.36). In multivariable analyses, age less than 30 years was associated with an increased risk of HIV conversion (rate ratio: 2.01; 95% CI: 1.08-3.76). CONCLUSIONS: This analysis shows high rates of HIV conversion among MSM who repeatedly visit a community-based testing site. Ath Checkpoint could contribute to HIV surveillance and identify a high-risk group that could benefit from essential health interventions.

Beyond viral suppression of HIV - the new quality of life frontier.

BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV-related discrimination. We propose adding a 'fourth 90' to the testing and treatment target: ensure that 90 % of people with viral load suppression have good health-related quality of life. The new target would expand the continuum-of-services paradigm beyond the existing endpoint of viral suppression. Good health-related quality of life for PLHIV entails attention to two domains: comorbidities and self-perceived quality of life. CONCLUSIONS: Health systems everywhere need to become more integrated and more people-centered to successfully meet the needs of virally suppressed PLHIV. By doing so, these systems can better meet the needs of all of their constituents - regardless of HIV status - in an era when many populations worldwide are living much longer with multiple comorbidities.

Treatment as prevention: arriving at community consensus.

At a satellite meeting preceding the 2013 Controlling the HIV Epidemic With Antiretrovirals evidence summit in London, England, a group of organizations and advocates discussed and formulated the final draft of a document, the Community Consensus Statement on the Use of Antiretroviral Therapy in Preventing HIV Transmission, that succinctly outlines a set of principles that should be followed in the provision of antiretroviral therapy to people with living with human immunodeficiency virus (HIV) for the purposes of preventing HIV, particularly as a public health measure. The satellite meeting's conclusions were subsequently outlined in a presentation and panel discussion at the evidence summit.

Steatotic liver disease and HIV: an agenda for 2030.

People living with HIV are particularly susceptible to developing metabolic disorders, including metabolic dysfunction-associated steatotic liver disease and other forms of SLD. However, people living with HIV have been historically excluded from clinical trials and large cohort studies of SLD. Therefore, our understanding of the risk factors and natural history of SLD in this population is poor. Moreover, relevant knowledge gaps on the epidemiology and barriers for adequate health care, such as stigma, hamper adequate responses to the ongoing HIV and SLD syndemic. This Viewpoint provides a comprehensive perspective on how to tackle SLD in people living with HIV by examining the role of social determinants of health in the development of liver disease and metabolic syndrome comorbidities among this population, emphasising the importance of prioritising SLD management, summarising the most urgent needs in the field, and offering recommendations for advancing research to fill key data gaps and protect liver health of people living with HIV.

Patients' satisfaction with sexual and reproductive health services delivered in HIV clinics across European regions.

BACKGROUND: Throughout Europe, differences in satisfaction with HIV-care of people living with HIV (PLHIV) persist, despite a tendency towards harmonisation of policy and management. METHODS: A European sample of 1,549 PLHIV responded to an anonymous questionnaire assessing demographic background, general health, mental health, sexual health, and HIV-service provision. We compared the results across 3 regions: Western, Southern and Central/Eastern Europe. RESULTS: PLHIV differed in several socio-demographic variables (gender, migrant status, sexual orientation, and financial situation) as well as specific psychosocial aspects (HIV-related discrimination, satisfaction with sexual and reproductive health (SRH) services in HIV-care settings, and complaints about service provision). Using multivariate analysis, a predictive model for satisfaction with SRH services in HIV clinics was developed, resulting into region of residence, and participants' satisfaction with their own health status as significant predictors. CONCLUSIONS: Better integration of SRH services in HIV-care should be encouraged. Service providers should be trained and encouraged to discuss SRH issues with their patients to create a supportive environment, free of discrimination. More time should be allocated to discuss SRH issues with individual patients.

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV.

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006-2007, 7.54 [6.59, 8.59] in 2020-2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63-3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.

Access of People Living with HIV to Testing Services in Greece: A Challenge for Equity in Care.

(1) Background: Access to laboratory testing services for HIV in Greece is persistently challenged and this impacts both the continuum of care and, potentially, equity in access. (2) Methods: A cross-sectional study with two parts (first part: HIV-positive people/PLWHIV; second part: HIV clinicians) was conducted in Greece to quantify challenges regarding access to laboratory testing for HIV. Data were collected through online surveys, during a one-month period, between 2019 and 2020. The total sample consisted of 153 PLWHIV and 26 HIV clinicians. (3) Results: Access to viral load testing varied significantly according to place of residence (p = 0.029) and year of diagnosis (p = 0.054). Patients diagnosed after 2015 reported worse access to viral load testing (72.7% vs. 85.9%). Over one third of respondents perceived viral load tests as being not at all accessible (11.4%) or somewhat accessible, only after facing multiple systemic obstacles (24.2%). Equally, most of HIV clinicians reported barriers or no access to baseline viral load testing (80%) and baseline genotype resistance tests (96%). (4) Conclusions: Access of people diagnosed with HIV to CD4 lymphocyte tests and genotype resistance screening is significantly challenged in Greece, especially after 2015. Addressing this challenge is critical in removing access barriers and achieving the UNAIDS 95-95-95 HIV elimination goals.

Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting.

BACKGROUND: Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure. METHODS: Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months. RESULTS: Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36-51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9-7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3-7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi's sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89-1.49], >6-12 months; 0.97 [95% CI, 0.71-1.32], >12-24 months; 0.84 [95% CI, 0.64-1.11], >24-36 months; 1.10 [95% CI, 0.82-1.47], >36 months; 0.90 [95% CI, 0.65-1.26] [P = .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P < .0001). CONCLUSIONS: Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding.

ERCC1 19007 Polymorphism in Greek Patients with Advanced Urothelial Cancer Treated with Platinum-Based Chemotherapy: Effect of the Changing Treatment Paradigm: A Cohort Study by the Hellenic GU Cancer Group.

We previously showed that ERCC1 19007 C>T polymorphism was associated with cancer-specific survival (CSS) after platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). We aimed to confirm this association in a different cohort of patients. Genotyping of the 19007C>T polymorphism was carried out by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) in 98 aUC patients, treated with platinum-based chemotherapy. Median age of the patients was 68.8, 13.3% of them were female, 90.8% had ECOG PS of 0 or 1, and 48% received cisplatin-based chemotherapy. In addition to chemotherapy, 32.7% of the patients received immunotherapy, and 19.4% vinflunine. Eighty-one patients (82.7%) were carriers of the 19007T polymorphic allele: 46 (46.9%) were heterozygotes, and 35 (35.7%) were homozygotes. The ERCC1 polymorphism was not associated with CSS, progression-free (PFS), or overall (OS) survival in the total population. Nevertheless, there was a significant interaction between the prognostic significance of ERCC1 polymorphism and the use of modern immunotherapy: the T allele was associated with worse outcome in patients who received chemotherapy only, while this association was lost in patients who received both chemotherapy and immune checkpoint inhibitors. Our study suggests that novel therapies may influence the significance of ERCC1 polymorphism in patients with aUC. Its determination may be useful in the changing treatment landscape of the disease.

Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV.

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field's longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.

Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium.

BACKGROUND: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. METHODS: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. RESULTS: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per µL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively). INTERPRETATION: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences.

The First Women Physicians in the History of Modern Greek Medicine: Maria Kalapothaki (1859-1941) and Aggeliki Panagiotatou (1878-1954)

In an era when medicine in Greece was dominated by men, at the end of the 19th and during the first decades of 20th century, two women, Maria Kalapothakes [in Greek: Μαρία Καλαποθάκη] (1859-1941) and Angélique Panayotatou [in Greek: Αγγελική Παναγιωτάτου] (1878-1954), managed to stand out and contribute to the evolution of medicine. Maria Kalapothakes received medical education in Paris and then she returned to Greece. Not only did she contribute to several fields of medicine, but also exercised charity and even undertook the task of treating war victims on many occasions. Angélique Panayotatou studied medicine at the University of Athens and then moved to Alexandria in Egypt, where she specialized in tropical medicine and also engaged in literature. Panayotatou became the first female professor of the Medical School of Athens and the first female member of the Academy of Athens. In recognition for their contributions, Kalapothakes and Panayotatou received medals and honors for both their scientific work and social engagement.

Patient-Reported Outcomes in First-Line Antiretroviral Therapy: Results From NEAT001/ANRS143 Trial Comparing Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine or Raltegravir.

BACKGROUND: There are few data comparing patient-reported outcomes (PROs) in randomized trials of initial antiretroviral therapy. We present results from a substudy of the NEAT001/ANRS143 trial. METHODS: The randomized trial compared first-line DRV/r 800/100 mg once daily plus RAL 400 mg twice daily and DRV/r plus TDF/FTC 245/200 mg once daily. Changes in PROs were assessed with 3 questionnaires: EuroQoL 5 domains (EQ-5D), Center for Epidemiologic Studies Depression (CES-D) scale, and HIV Treatment Satisfaction Questionnaire. Major depressive disorder (MDD) was defined as CES-D ≥ 16. General estimating equations were used to model change over 96 weeks in PROs from baseline. RESULTS: Of the 805 participants, 797 (99%) contributed to the substudy. Baseline PRO data were similar for the 2 randomized groups. Health status improved over time with a mean increase in EQ-5D visual analogue scale (VAS) of 8.0 by W96 [95% confidence interval (CI): 6.5 to 9.4; P < 0.001], and no statistically significant differences between groups (difference of 0.3 on VAS score (95% CI: -1.7 to 2.3); P = 0.7, global P value ≥0.05 for all domains over follow-up). There was no significant difference between groups on CES-D [difference of -0.1 (95% CI: -1.3 to 1.1); P = 0.9], or MDD during follow-up, adjusted for baseline MDD (odds ratio = 0.98, 95% CI: 0.82 to 1.18; P = 0.9). RAL + DRV/r group had lower level of convenience (P = 0.03) and fitted less well into patients' lifestyle (P = 0.007) than the TDF/FTC + DRV/r regimen, and was associated with lower treatment satisfaction [median score: 53 RAL + DRV/r vs 55 TDF/FTC + DRV/r (P = 0.001)]. CONCLUSION: PROs improved after starting antiretroviral therapy, with no statistically significant difference between groups. The lower satisfaction with RAL + DRV/r may be explained by twice-daily administration.