Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

HIV; Integrase strand transfer inhibitorsVIH; Inhibidores de transferencia de cadena de integrasaVIH; Inhibidors de transferència de cadena de la integrasaIntroduction: Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. Methods: Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. Results: Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/μL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. Discussion: Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.This study received funding from ViiV Healthcare and Fight Infections Foundation. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication

Joseph Roisman, Colby College

Interview to Joseph Roisman (Main Voices in Ancient Macedonian Studies)Entrevista a Joseph (Yossi) Roisma

Late presentation for HIV remains a major health issue in Spain: Results from a multicenter cohort study, 2004-2018.

With the purpose of reducing the well-known negative impact of late presentation (LP) on people living with HIV (PLWH), guidelines on early HIV diagnosis were published in 2014 in Spain, but since then no data on LP prevalence have been published. To estimate prevalence and risk factors of LP and to evaluate their impact on the development of clinical outcomes in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) during 2004-2018. CoRIS is an open prospective multicenter cohort of PLWH, adults, naive to ART at entry. LP was defined as HIV diagnosis with CD4 count ≤350 cells/μL or an AIDS defining event (ADE). Multivariable Poisson regression models were used to estimate both prevalence ratios (PR) for the association of potential risk factors with LP and Incidence rate ratios (IRRs) for its impact on the development of the composite endpoint (first ADE, first serious non-AIDS event [SNAE] or overall mortality). 14,876 individuals were included. Overall, LP prevalence in 2004-2018 was 44.6%. Risk factors for LP included older age, having been infected through injection drug use or heterosexual intercourse, low educational level and originating from non-European countries. LP was associated with an increased risk of the composite endpoint (IRR: 1.34; 95%CI 1.20, 1.50), ADE (1.39; 1.18, 1.64), SNAE (1.22; 1.01, 1.47) and mortality (1.71; 1.41, 2.08). LP remains a health problem in Spain, mainly among certain populations, and is associated with greater morbidity and mortality. Public policies should be implemented to expand screening and early diagnosis of HIV infection, for a focus on those at greatest risk of LP.RR received funds from Gilead for this work.The funders had no role in study design,data collection and analysis, decision to publish,or preparation of the manuscript.S

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PROSTR study

Introduction: Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients’ well-being, assessed by several validated measures. Methods: Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. Results: Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.59307.29 and 123 (98.4%) had viral load B50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (B50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21915.55) to week 4 (10.89912.36) & week 16 (10.81912.62), pB0.001. In all the patients, quality of life tools showed a significant benefit in wellbeing of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), pB0.001 and to week 16 (72.0%), pB0.001. Conclusions: Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response

Multi-Level Considerations for Optimal Implementation of Long-Acting Injectable Antiretroviral Therapy to Treat People Living with HIV: Perspectives of Health Care Providers Participating in Phase 3 Trials

BACKGROUND: Long-acting injectable antiretroviral therapy (LA ART) has been shown to be non-inferior to daily oral ART, with high patient satisfaction and preference to oral standard of care in research to date, and has recently been approved for use in the United States and Europe. This study examined the perspectives of health care providers participating in LA ART clinical trials on potential barriers and solutions to LA ART roll-out into real world settings. METHODS: This analysis draws on two data sources: (1) open-ended questions embedded in a structured online survey of 329 health care providers participating in the ATLAS-2 M trial across 13 countries; and (2) in-depth interviews with 14 providers participating in FLAIR/ ATLAS/ATLAS-2 M trials in the United States and Spain. Both assessments explored provider views and clinic dynamics related to the introduction of LA ART and were analyzed using thematic content analysis. The Consolidated Framework for Implementation Research (CFIR) was drawn on as the conceptual framework underpinning development of a model depicting study findings. RESULTS: Barriers and proposed solutions to LA ART implementation were identified at the individual, clinic and health system levels. Provider perceptions of patient level barriers included challenges with adhering to frequent injection appointments and injection tolerability. Proposed solutions included patient education, having designated staff for clinic visit retention, and clinic flexibility with appointment scheduling. The main provider concern was identifying appropriate candidates for LA ART; proposed solutions focused on patient provider communication and decision making. Clinic level barriers included the need for additional skilled individuals to administer injections, shifts in workflow as demand increases and the logistics of cold-chain storage. Proposed solutions included staff hiring and training, strategic planning around workflow and logistics, and the possibility of offering injections in other settings, including the home. Health system level barriers included cost and approvals from national regulatory bodies. Potential solutions included governments subsidizing treatment, ensuring cost is competitive with oral ART, and offering co-pay assistance. CONCLUSIONS: Results suggest the importance of multi-level support systems to optimize patient-provider communication and treatment decision-making; clinic staffing, workflow, logistics protocols and infrastructure; and cost-related factors within a given health system

Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

IntroductionSecond-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients. MethodsReal-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naive patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) & GE;200 copies/mL at 24 weeks or as a single determination of VL & GE;1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated. ResultsVirological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naive patients with CD4+ nadir <100 cells/& mu;L were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles. DiscussionWhereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available

Patient-Reported Outcomes in ATLAS and FLAIR Participants on Long-Acting Regimens of Cabotegravir and Rilpivirine Over 48 Weeks

The phase 3 ATLAS and FLAIR studies demonstrated that maintenance with Long-Acting (LA) intramuscular cabotegravir and rilpivirine is non-inferior in efficacy to current antiretroviral (CAR) oral therapy. Both studies utilized Patient-Reported Outcome instruments to measure treatment satisfaction (HIVTSQ) and acceptance (ACCEPT general domain), health status (SF-12), injection tolerability/acceptance (PIN), and treatment preference. In pooled analyses, LA-treated patients (n = 591) demonstrated greater mean improvements from baseline than the CAR group (n = 591) in treatment satisfaction (Week 44, + 3.9 vs. +0.5 HIVTSQs-points; p /= 97% of LA group participants with recorded data preferred LA treatment compared with prior oral therapy. These results further support the potential of a monthly injectable option for people living with HIV seeking an alternative to daily oral treatment

La situación político-administrativa en España de la Profilaxis Pre-Exposición al VIH

Antecedentes de la PrEP en España, contexto, metodología. Actividad institucional a nivel estatal: Ministerio de Sanidad, Servicios Sociales e Igualdad, cuestiones al Comité de Bioética, líneas de trabajo del MSSSI. Profilaxis. Comisión Interministerial de Precios de los Medicamentos (Reglamento interno), Comité asesor. Procedimiento de fijación de precio, criterios de evaluación para fijar el precio, procedimiento de actualización de la cartera de servicios comunes, estado de la tramitación. Actividad política a nivel estatal y autonómico. Breve referencia al Parlamento Europeo. La Patente y su ampliación. Conclusione

LipoDDx: a mobile application for identification of rare lipodystrophy syndromes

BACKGROUND: Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx(R). Our aim was to establish the effectiveness of LipoDDx(R). Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx(R). The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. RESULTS: LipoDDx(R) provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx(R) the success rate was 17 +/- 20%, while with LipoDDx(R) the success rate was 79 +/- 20% (p < 0.01). CONCLUSIONS: LipoDDx(R) is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value