To describe the 12-month evolution of lipid profile in HIV-infected virologically suppressed patients substituting tenofovir for stavudine.
'Recover' was a prospective, multicenter, switch study ...conducted at 120 HIV units across Spain designed to identify single nucleoside analogue substitution due to adverse events in real practice. Tenofovir substituted stavudine in 873 adult patients. No other substitutions were allowed. This lipid sub-study included 352 randomly recruited patients with complete follow-up and lipid parameters.
Changes in fasting levels of total cholesterol (TC), high and low-density lipoprotein cholesterol (HDL-C and LDL-C), and triglycerides (TG) at 48 weeks, and their cardiovascular risk (CVR) translation.
At 48 weeks, there was a sustained reduction in median TC (-17.5 mg/dl; P < 0.001), LDL-C (-8.1 mg/dl; P < 0.001), and TG (-35 mg/dl; P < 0.001). HDL-C remained roughly unchanged (-0.8 mg/dl). Patients with baseline hyperlipidaemia showed greater reductions in LDL-C (-29 mg/dl; P < 0.001) and TG (-76 mg/dl; P < 0.001). The greatest TG reduction was observed in patients with severe hyper-TG (-266 mg/dl; P < 0.001). The estimated 10-year CVR decreased in all patients (P < 0.001), and to a higher extent in patients with baseline hyperlipidaemia. There was a trend towards reduction according to the use of lipid-lowering agents (11.6% to 9,9%; P = non-significant).
The substitution of tenofovir for stavudine causes a sustained improvement of dyslipidaemia. The reduction, although modest, is robust and sustained over time, and significantly reduces the CVR. This switch strategy is safe and contributes to an improvement in the lipid profile, especially TG, in HAART-treated patients.
Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a ...combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives. We present the reasons and criteria for switching ART in patients with an undetectable PVL and in those who present virological failure, in which case salvage ART should include 3 (or at least 2) drugs that are fully active against HIV. We also update the criteria for ART in specific situations (acute infection, HIV-2 infection, pregnancy) and comorbidities (tuberculosis or other opportunistic infections, kidney disease, liver disease and cancer).
Extensively pretreated subjects with virological failure (VF) may receive salvage regimens containing NRTIs with only residual or no activity. Once virological suppression is achieved, their ...contribution remains elusive.
This was a multicentre, randomized, prospective study. Subjects with at least one prior VF, HIV-1 RNA <50 copies/mL for ≥6 months and receiving a regimen with at least two active drugs (one of them a boosted PI) were randomized 1:1 to stop (experimental arm) or maintain (control arm) NRTIs. EudraCT: 2012-000198-21.
Ninety subjects were randomized (experimental, n = 45; and control, n = 45). The mean age was 50 years, 80% were male, the mean CD4+ cell count was 542 cells/mm(3) and the median number of prior VFs was 3. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine-associated mutations was 3 (IQR: 0-4). In the experimental arm, thirty-two (71%) subjects removed one NRTI and 13 (29%) subjects removed two. Twenty-two of 45 (49%) discontinued tenofovir disoproxil fumarate. Forty-one of 45 (91.1%, experimental arm) and 44 of 45 (97.8%, control arm) had HIV-1 RNA <50 copies/mL at 48 weeks (difference: -6.7%; 95% CI: -17.4, 4.1). In a post-hoc analysis allowing NRTI reintroduction, efficacy rates were 95.6% and 97.8%, respectively (difference: -2.2%; 95% CI: -7.2, 2.7). Rates of discontinuation at 48 weeks were 2% in both arms. One subject developed a late VF with resistance selection.
In patients receiving a successful multidrug salvage regimen with at least two active drugs (one a boosted PI), the withdrawal of inactive NRTIs was safe, rates of VF were low and drug resistance was uncommon at 48 weeks in this small study. This strategy could potentially prevent long-term toxicities, reduce the number of drugs and reduce costs if non-inferiority was met in a fully powered trial.
Abstract
Background
Adherence to antiretroviral therapy (ART) to treat HIV remains a critical global health challenge given its relationship with individual health outcomes and population-level ...transmission. Given barriers associated with oral ART adherence, and considerations of patients’ preferences, long-acting injectable (LA) ART (cabotegravir + rilpivirine) is under development and has been shown to be non-inferior to daily oral ART in Phase III trials. While most of the trial participants have been men, as LA ART gets closer to becoming available for routine clinical use, it is critical to understand how this option is perceived by women.
Methods
We conducted in-depth interviews with 67 individuals, 53 people living with HIV (PLHIV) and 14 healthcare providers, in 11 sites in the United States and Spain participating in Phase III LA ART trials (ATLAS, ATLAS 2-M and FLAIR). Twenty percent (10/53) of trial participants interviewed were women. Interviews explored patient and provider perspectives and experiences with LA ART, and appropriate candidates and recommendations to support use. Interviews were audio-recorded, transcribed and coded using thematic content analysis.
Results
Overall, several salient themes emerged regarding participant’s generally positive experiences transitioning from daily oral ART to injectable ART including: the importance of the clinical efficacy of LA ART, the ability to learn to manage injection side-effects over time, and the “freedom” reportedly afforded by LA ART logistically and psychosocially. Women interviewed shared many of the aforementioned positive perceptions of LA ART but also had some unique perspectives. Female participants discussed how LA ART was easier to integrate into their daily lives including managing their multiple roles and responsibilities, which often involved working full-time and taking care of themselves as well as their family and children.
Conclusion
Similar to all participants, female participants had generally positive views of LA ART. However, the gendered nature of their daily lives also led to some unique perspectives on why and how they were satisfied with LA ART that merits further exploration in future research.
Disclosures
All authors: No reported disclosures.
To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND).
We assembled a panel of experts ...appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS.
Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies.
Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective.
The life expectancy of HIV-infected individuals has dramatically improved with potent antiretroviral therapies. However, organ-specific toxicities of some antiretrovirals and persistent inflammation ...and immune activation due to residual virus replication account for a high burden of age-associated comorbidities in the HIV population.
The prevalence of overt cardiovascular, renal and bone diseases as well as their major risk factors were cross-sectionally examined during the year 2014 in the VACH cohort, a large nationwide population of HIV-infected individuals in Spain.
A total of 10,897 HIV-infected patients were examined. Seventy-one point four percent were male and the mean age was 48 years. Mean time since HIV diagnosis was 15.8 years and mean time on antiretroviral therapy was 13.1 years. The proportion of patients with undetectable viral load was 87.1%, whereas 65.7% had CD4 counts>500 cells/mm3. Overall, cardiovascular, renal and bone disease were recorded in 4.7%, 5.9% and 2.8%, respectively. The prevalence of major risk factors was as follows: smoking 51.3%, alcohol abuse 7.8%, overweight/obesity 42.2%, diabetes 19.9%, dyslipidaemia 72.6%, hypertension 25.6%, and osteoporosis 11.1%. In the subset of patients older than 55 years-old (18%), all figures for overt disease and their major risk factors were significantly greater.
Major age-related medical conditions and most of their risk factors are highly prevalent in HIV-infected individuals on long-term antiretroviral therapy in Spain. Preventive actions, including careful selection of antiretroviral agents, should be prioritized in the ageing HIV population.
La esperanza de vida de las personas infectadas por el VIH ha mejorado con la terapia antirretroviral. Sin embargo, la toxicidad de algunos antirretrovirales, la inflamación persistente y la activación inmune explican la alta carga de comorbilidades asociadas con el envejecimiento en la población con VIH.
La prevalencia de enfermedad cardiovascular, renal y ósea, así como sus principales factores de riesgo, se analizó en una cohorte de individuos infectados por el VIH en un estudio realizado en España durante el año 2014.
Se examinaron un total de 10.897 pacientes infectados por VIH. Varones el 74,1%, edad media 48 años. El tiempo medio transcurrido desde el diagnóstico del VIH fue de 15,8 años y el tiempo medio de tratamiento antirretroviral fue de 13,1 años. La proporción de pacientes con carga viral indetectable fue del 87,1%, mientras que el 65,7% tenían recuentos de CD4>500 células/mm3. La enfermedad cardiovascular, renal y ósea se encontró en el 4,7, 5,9 y 2,8%, respectivamente. La prevalencia de los principales factores de riesgo fue: fumar 51,3%, abuso de alcohol 7,8%, sobrepeso/obesidad 42,2%, diabetes 19,9%, dislipidemia 72,6%, hipertensión 25,6% y osteoporosis 11,1%. En el grupo de pacientes mayores de 55 años (18%), la prevalencia de comorbilidades y sus principales factores de riesgo fue significativamente mayor.
Las principales comorbilidades relacionadas con la edad y la mayoría de los factores de riesgo asociados son muy prevalentes en las personas infectadas por el VIH que reciben tratamiento antirretroviral en España. Las acciones preventivas, incluida la selección cuidadosa de agentes antirretrovirales, deben ser priorizadas en la población con VIH que está envejeciendo.
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 ...plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR 95% CI = 67.6 5.7-9,196.6) than for auto-Abs neutralizing IFN-ω only (OR 95% CI = 2.6 1.2-5.3). ORs were also higher for auto-Abs neutralizing high concentrations (OR 95% CI = 12.9 4.6-35.9) than for those neutralizing low concentrations (OR 95% CI = 5.5 3.1-9.6) of IFN-ω and/or IFN-α2.
This study focuses on actions at the political and administrative level in Spain in relation to the implementation of pre-exposure prophylaxis (PrEP). We analysed a whole range of different formal ...initiatives taken by the political and administrative actors involved. The information was obtained from official public data sources. As of February 2018, PrEP had not been implemented. The decision is dependent on both state and regional governments. The Ministry of Health and some Autonomous Regions are working on different interventions, but without providing an implementation timetable. The political parties have kept a very low profile in terms of initiatives related to the implementation of PrEP. From a legal point of view, proceedings are passing back and forth with the extension of the patent. The role of intergovernmental and interdepartmental institutions is very important for the implementation of PrEP in Spain.
Este estudio se ha centrado en las actuaciones a nivel político y administrativo que se han realizado en España en relación con la implementación de la profilaxis preexposición (PrEP) al VIH. Se ha analizado todo tipo de iniciativas formales por parte de los actores políticos y administrativos implicados. Las fuentes utilizadas son las fuentes oficiales públicas. Hasta febrero de 2018, la PrEP no ha sido implementada. La decisión depende de los niveles estatal y autonómico. El Ministerio de Sanidad y algunas Comunidades Autónomas trabajan en diversas intervenciones sin establecer un calendario de implementación. Los partidos políticos por su parte han promovido escasas iniciativas relacionadas con la implementación de la PrEP. En el terreno jurídico, se han producido vaivenes legales relacionados con la extensión de la patente. El papel de los órganos intergubernamentales e interdepartamentales es vital para la implementación de la PrEP.
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