RESUMO
To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Espanha/epidemiologia , Filogenia , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Integrases/genética , Integrases/uso terapêutico , Mutação , Farmacorresistência Viral/genética , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , PrevalênciaRESUMO
BACKGROUND: To study whether the association between the CD4/CD8 ratio variation over time and the development of clinical outcomes vary in late presenters (CD4 count < 350/µL or AIDS event at enrolment) or advanced presenters (CD4 count < 200/µL or AIDS event at enrolment). METHODS: We included ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) enrolled between January 2004 up to November 2018 and with at least 6 months of follow-up. We used extended Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between CD4/CD8 ratio over time and a composite endpoint of the occurrence of the first AIDS event, first serious non-AIDS event or overall mortality occurring from 6 months after enrolment. HRs in non-late, late and advanced presenters were obtained by including an interaction term between late presentation status and CD4/CD8 ratio over time. RESULTS: Of 10,018 participants, 55.6% were late presenters and 26.5% were advanced presenters. Compared with CD4/CD8 ratio > 0.4, CD4/CD8 ratio ≤ 0.4 over time was associated with an increased risk of experiencing the composite endpoint in non-late (HR 1.90; 95%CI 1.48, 2.43), late (HR 1.94; 1.46, 2.57) and advanced presenters (HR 1.72; 1.26, 2.34). Similarly, CD4/CD8 ratio ≤ 0.4 over time was associated with a higher risk of developing an AIDS event (HR 3.31; 2.23, 4.93 in non-late; HR 2.75; 1.78, 4.27 in late and HR 2.25; 1.34, 3.76 in advanced presenters) or serious non-AIDS event (HR 1.39; 0.96, 2.02 in non-late, HR 1.62; 1.10, 2.40 in late and HR 1.49; 0.97, 2.29 in advanced presenters) as well as with a higher risk of overall mortality (HR 1.49; 0.92, 2.41 in non-late, HR 1.80; 1.04, 3.11 in late and HR 1.61; 0.92, 2.83 in advanced presenters) compared to CD4/CD8 > 0.4, regardless of the late presentation status. CONCLUSIONS: A low CD4/CD8 measured over time is associated with increased risk of morbidity and mortality in people living with HIV independently of their late presentation status. These data support the prognostic role of CD4/CD8 over time and can help defining a subgroup of patients who need closer monitoring to avoid comorbidities.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Estudos de Coortes , Infecções por HIV/epidemiologia , Humanos , MorbidadeRESUMO
PURPOSE: To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture. METHODS: Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. PRIMARY OUTCOME: early-PJI after HHA. RESULTS: Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33-3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15-7.10]). CONCLUSIONS: Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47.
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Artroplastia de Quadril/efeitos adversos , Bacteriúria/microbiologia , Artropatias/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções Assintomáticas/terapia , Bacteriúria/tratamento farmacológico , Bacteriúria/etiologia , Feminino , Fosfomicina/uso terapêutico , Humanos , Artropatias/tratamento farmacológico , Artropatias/etiologia , Masculino , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/etiologia , Trometamina/uso terapêuticoRESUMO
BACKGROUND: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). METHODS: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. RESULTS: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. CONCLUSIONS: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women.
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Depressão , Infecções por HIV , Ansiedade/epidemiologia , Transtornos de Ansiedade , Depressão/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Menopausa , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: We report the results of the reverse transcriptase (RT)/protease (PR) transmitted drug resistance (TDR) prevalence study in 2018, focusing on doravirine resistance-associated mutations and the differences observed when Stanford or French National Agency for AIDS Research (ANRS)/Spanish Network of AIDS Research (RIS)/IAS-USA resistance interpretation algorithms are used to describe clinically relevant resistance. METHODS: We used the WHO 2009 list to investigate the prevalence of NNRTI, NRTI and PI TDR, in treatment-naive HIV-1-infected patients, adding mutations E138A/G/K/Q/R, V106I, V108I, V179L, G190Q, H221Y, F227C/L/V, M230IDR, L234I, P236L and Y318F in RT. The prevalence of doravirine resistance-associated mutations, as described by Soulie et al. in 2019, was evaluated. Clinically relevant TDR was investigated using the latest versions of ANRS, RIS, IAS-USA and Stanford algorithms. RESULTS: NNRTI mutations were detected in 82 of 606 (13.5%) patients. We found 18 patients (3.0%) with NRTI mutations and 5 patients (0.8%) with PI mutations. We detected 11 patients harbouring doravirine resistance-associated mutations (prevalence of 1.8%). Furthermore, we observed important differences in clinically relevant resistance to doravirine when ANRS/RIS (0.7%), IAS-USA (0.5%) or Stanford algorithms (5.0%) were used. V106I, which was detected in 3.8% of the patients, was the main mutation driving these differences. V106I detection was not associated with any of the clinical, demographic or virological characteristics of the patients. CONCLUSIONS: The prevalence of NRTI and PI TDR remains constant in Spain. Doravirine TDR is very infrequent by RIS/ANRS/IAS-USA algorithms, in contrast with results using the Stanford algorithm. Further genotype-phenotype studies are necessary to elucidate the role of V106I in doravirine resistance.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Algoritmos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Mutação , Prevalência , Piridonas , Espanha , TriazóisRESUMO
PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.
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Desprescrições , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Infecções por HIV/tratamento farmacológico , Prescrição Inadequada/prevenção & controle , Medicamentos sob Prescrição/uso terapêutico , Interações Medicamentosas , Humanos , Expectativa de VidaRESUMO
BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART. OBJECTIVES: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain. METHODS: During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used. RESULTS: Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/lamivudine was 1.7%, 1.9% and 0.7%, respectively. CONCLUSIONS: Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.
Assuntos
Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Inibidores de Integrase de HIV/farmacologia , Adulto , Idoso , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Vigilância em Saúde Pública , Espanha/epidemiologiaRESUMO
HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1 infection with a longitudinal retrospective study design. Gag-specific T-cell responses were assessed by in vitro intracellular polycytokine production quantified by flow cytometry. Viral diversity determinations and sequence dating were performed in proviral DNA by PCR amplification at limiting dilution of env and gag genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity, and high proinflammatory cytokine levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r = -0.8; P = 0.02). RANTES was a potential biomarker of transient control. This study identified virological and immunological factors, including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in better clinical management of these individuals and in the development of future curative approaches.IMPORTANCE There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so-called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work, we found differences in virological and immune factors, including soluble inflammatory biomarkers, between subjects with persistent control of viral replication and EC that will lose virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose natural control of viral replication and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV infection.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Inflamação/imunologia , Leucócitos Mononucleares/imunologia , Replicação Viral , Adulto , Linfócitos T CD4-Positivos/virologia , Citocinas/metabolismo , Feminino , Infecções por HIV/virologia , Humanos , Inflamação/virologia , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga ViralRESUMO
Background: Concerns have been voiced over the capacity of deintensification strategies to preserve neurocognitive function and prevent neurocognitive impairment. Methods: We present the 96 week results of a neurocognitive substudy nested within the SALT clinical trial: a randomized, open-label, non-inferiority trial that compares whether atazanavir/ritonavir + lamivudine is non-inferior to atazanavir/ritonavir + two NRTIs in HIV-suppressed patients on stable triple therapy. A global deficit score (GDS) for five neurocognitive tasks was used to assess neurocognitive function. Changes in neurocognitive function (GDS value) were determined at weeks 48 and 96. The effect of atazanavir/ritonavir + lamivudine, adjusted for significant confounders, on the change in neurocognitive function was determined using analysis of covariance (ANCOVA) at week 96. Results: The per-protocol analysis included 92 participants (47 atazanavir/ritonavir + lamivudine and 45 atazanavir/ritonavir + two NRTIs). All baseline characteristics were comparable in both groups. At weeks 48 and 96, changes in GDS [week 48, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to 0.0), P = 0.39; week 96, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to -0.1); P = 0.471] were similar. This absence of differences was also observed in all cognitive tasks. Atazanavir/ritonavir + lamivudine did not impact the change in neurocognitive function at week 96; the adjusted effect of atazanavir/ritonavir + lamivudine on GDS change, considering atazanavir/ritonavir + two NRTIs as a reference, was 0.01 (95% CI -0.18 to 0.21) (P = 0.90). Conclusions: Neurocognitive function remained stable after 96 weeks, both in the atazanavir/ritonavir + lamivudine and in the atazanavir/ritonavir + two NRTIs arms, provided HIV remained suppressed.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Sulfato de Atazanavir/efeitos adversos , Infecções por HIV/tratamento farmacológico , Lamivudina/efeitos adversos , Transtornos Neurocognitivos/epidemiologia , Ritonavir/efeitos adversos , Adulto , Fármacos Anti-HIV/administração & dosagem , Sulfato de Atazanavir/administração & dosagem , Feminino , Infecções por HIV/complicações , Humanos , Lamivudina/administração & dosagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/induzido quimicamente , Ritonavir/administração & dosagemRESUMO
BACKGROUND: The mitochondrial DNA (mtDNA) seems to influence in a large number of diseases, including HIV infection. Moreover, there is a substantial inter-individual variability in the CD4+ recovery in HIV-infected patients on combination antiretroviral therapy (cART). Our study aimed to analyze the association between mtDNA haplogroups and CD4+ recovery in HIV-infected patients on cART. METHODS: This is a retrospective study of 324 naïve cART patients with CD4+ < 200 cells/mm3, who were followed-up during 24 months after initiating cART. All patients had undetectable HIV viral load during the follow-up. Besides, we included 141 healthy controls. MtDNA genotyping was performed by using Sequenom's MassARRAY platform. The primary outcome variable was the slope of CD4+ recovery. Patients were stratified into two groups by the median slope value of CD4+ (9.65 CD4+ cells/mm3/month). Logistic regression analyses were performed to calculate the odds of CD4+ recovery according to mtDNA haplogroups. RESULTS: Our study included European HIV-infected patients within the N macro-cluster. The baseline values of CD4+ T-cells were similar between groups of patients stratified by the P50th of the slope of CD4+ T-cells recovery. Patients in the low CD4+ T-cells recovery group were older (p = 0.001), but this variable was included in the multivariate models. When we analyzed the frequencies of mtDNA haplogroups, no significant differences between HIV-infected individuals and healthy controls were found. We did not find any significant association between mtDNA haplogroups and the slope of CD4+ T-cells recovery by linear regression analysis. However, Patients carrying haplogroup H had a higher odds of having a better CD4+ recovery (> 9.65 CD4+ cells/mm3/month) than patients without haplogroup H (p = 0.032). The adjusted logistic regression showed that patients carrying haplogroup H had a higher likelihood of achieving a CD4+ recovery > 9.65 CD4+ cells/mm3/month [adjusted odds ratio (aOR) = 1.75 (95% CI = 1.04; 2.95); p = 0.035]. CONCLUSIONS: European mitochondrial haplogroup H was associated with the improved CD4+ recovery in HIV-infected patients starting cART with CD4+ < 200 cells/mm3.
Assuntos
Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/genética , Infecções por HIV/imunologia , Haplótipos/genética , Mitocôndrias/genética , Adulto , Estudos de Casos e Controles , DNA Mitocondrial/genética , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , MasculinoRESUMO
BACKGROUND.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using ß-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with ß-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of ß-lactams are confirmed and maybe also a potential benefit from adding rifampin.
Assuntos
Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/terapia , Infecções Relacionadas à Prótese/terapia , Infecções Estreptocócicas/terapia , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Artrite Infecciosa/microbiologia , Artrite Infecciosa/mortalidade , Biofilmes/efeitos dos fármacos , Desbridamento , Feminino , Humanos , Internacionalidade , Masculino , Prognóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/mortalidade , Estudos Retrospectivos , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Terapia de Salvação , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus agalactiae/isolamento & purificação , Falha de Tratamento , beta-Lactamas/administração & dosagem , beta-Lactamas/uso terapêuticoRESUMO
INTRODUCTION: GESIDA and the AIDS National Plan panel of experts suggest preferred (PR), alternative (AR), and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for the year 2016. The objective of this study is to evaluate the costs and the efficacy of initiating treatment with these regimens. METHODS: Economic assessment of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48 in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2016. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable, and least favourable. RESULTS: In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,894 Euros for TDF/FTC+RAL (PR). The efficacy varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/efficacy, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR), and RAL+DRV/r (OR), respectively. CONCLUSION: Despite the overall most efficient regimen being 3TC+LPV/r (OR), among the PR and AR, the most efficient regimen was ABC/3TC/DTG (PR). Among the AR regimes, the most efficient was TDF/FTC/RPV.
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Fármacos Anti-HIV/economia , Fármacos Anti-HIV/uso terapêutico , Análise Custo-Benefício , Infecções por HIV/tratamento farmacológico , Infecções por HIV/economia , Humanos , Guias de Prática Clínica como Assunto , EspanhaRESUMO
Post-exposure prophylaxis (PEP) can be a secondary measure to prevent infection by human immunodeficiency virus (HIV) when primary prevention has failed. PEP is advised for people with sporadic and exceptional risk exposure to HIV. This consensus document about occupational and non-occupational PEP recommendations aims to be a technical document for healthcare professionals. Its main objective is to facilitate the appropriate use of PEP. To this end, some recommendations have been established to assess the risk of transmission in different types of exposure, situations where PEP should be recommended, special circumstances to take into account, antiretroviral (ARV) guidelines including start and end of the treatment, early monitoring of tolerance and adherence to the treatment, subsequent monitoring of people exposed, independently of having received PEP or not, and need of psychological support. This document is intended for all professionals who work in clinical practice in the field of HIV infection.
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Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Hepatite C/tratamento farmacológico , Profilaxia Pós-Exposição , Adulto , Fármacos Anti-HIV/uso terapêutico , Antivirais/uso terapêutico , Criança , Consenso , Humanos , Exposição Ocupacional/prevenção & controle , Guias de Prática Clínica como AssuntoRESUMO
Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.
Assuntos
Infecções por HIV/complicações , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Terapia Antirretroviral de Alta Atividade , Infecções Bacterianas/tratamento farmacológico , Coinfecção , Humanos , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/prevenção & controle , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/prevenção & controle , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Infecções Oportunistas/etiologia , Doenças Parasitárias/tratamento farmacológico , Doenças Parasitárias/prevenção & controle , Viroses/tratamento farmacológico , Viroses/prevenção & controleRESUMO
Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.
Assuntos
Infecções por HIV/complicações , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Coinfecção/tratamento farmacológico , Coinfecção/prevenção & controle , Humanos , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/prevenção & controle , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Doenças Parasitárias/tratamento farmacológico , Doenças Parasitárias/prevenção & controle , Viroses/tratamento farmacológico , Viroses/prevenção & controleRESUMO
OBJECTIVES: The objective of this study was to evaluate the incidence, prevalence and clinical consequences of virological failure (VF) to raltegravir-based regimens in Spain. METHODS: A multicentre, retrospective, observational study was performed in 10 tertiary hospitals (January 2006 to June 2013). The study included HIV-1-infected patients with loss of virological suppression (LVS; two consecutive HIV-1 RNA ≥50 copies/mL) while receiving raltegravir. VF and low-level viraemia (LLV) were defined as two consecutive HIV-1 RNA ≥200 copies/mL and 50 to <200 copies/mL, respectively. Integrase strand-transfer inhibitor resistance was investigated at LVS. During the 48 weeks following LVS, recorded data included clinical characteristics, treatment discontinuations, AIDS-associated events and deaths. Effectiveness of therapy following LVS was evaluated by ITT and PP. Multivariate regression was used to assess predictors of efficacy. RESULTS: Of the 15â009 HIV-infected patients in participating centres, 2782 (18.5%) had received raltegravir-based regimens. Of those, 192 (6.9%), 125 (4.5%) and 67 (2.4%) experienced LVS, VF and LLV, respectively. The incidence of VF was 1.8 (95% CI, 1.5-2.1) per 100 patients/year. The prevalence of VF was 4.5% (95% CI, 3.8%-5.3%). Integrase-associated mutations were found in 78.8% of patients with integrase genotyping results available. High-level resistance to dolutegravir was not observed. Salvage therapy failed in 34.1% of patients; progression to AIDS/death occurred in 8.3% during the first year following LVS. The latter was associated with intravenous drug use, time on raltegravir and lower CD4+ count nadir in patients who started raltegravir-based treatments as salvage regimens. CONCLUSIONS: VF with raltegravir is infrequent, but often associated with major clinical complications in treatment-experienced patients.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Raltegravir Potássico/uso terapêutico , Carga Viral , Farmacorresistência Viral , Genótipo , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Incidência , Prevalência , Estudos Retrospectivos , Espanha , Centros de Atenção Terciária , Falha de TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Cardiovascular disease is a major concern in HIV-infected patients. Lifetime risk estimations use the risk of developing it over the course of remaining lifetime, and are useful in communicating this risk to young patients. We aim to describe the prevalence of cardiovascular risk factors among a representative sample of HIV-infected subjects under antiretroviral therapy in Spain, and to estimate their lifetime risk of cardiovascular disease. METHODS: Cross-sectional survey about cardiovascular risk factors in 10 HIV units across Spain. Lifetime risk assessed according to Barry was classified in two major categories: low and high lifetime risk. RESULTS: We included 895 subjects, 72% men, median age 45.7âyears; median CD4 lymphocyte count 598âcells/µl, median time since HIV diagnosis 11âyears, median time on antiretroviral treatment 6.3âyears, 87% had undetectable HIV viral load. Tobacco smoking was the most frequent risk factor (54%), followed by dyslipidemia (48.6%) and hypertension (38.6%). Estimated 10-year coronary risk (Framingham/Regicor Risk Score) risk was low ( < 5%) in 78% of the patients, and intermediate (5-10%) in 20%. Lifetime risk estimation showed a high risk profile for 71.4% of the population studied, which was associated with increasing age, prolonged antiretroviral therapy and patient's place of origin. CONCLUSIONS: Modifiable cardiovascular risk factors in this population are very common. There are significant disparities between the low 10-year risk estimated with the Framingham/Regicor score and the higher lifetime risk in HIV patients on antiretroviral therapy. A more aggressive management of modifiable cardiovascular risk factors in these patients seems advisable.
Assuntos
Antirretrovirais/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Infecções por HIV/epidemiologia , Adulto , Idoso , Contagem de Linfócito CD4 , Doenças Cardiovasculares/complicações , Estudos Transversais , Dislipidemias , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Hipertensão , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Espanha/epidemiologia , Fumar TabacoRESUMO
In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Infecções Oportunistas Relacionadas com a AIDS , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Aleitamento Materno , Contagem de Linfócito CD4 , Comorbidade , Contraindicações , Farmacorresistência Viral , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , HIV-1/efeitos dos fármacos , HIV-2 , Humanos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Carga Viral , Viremia/tratamento farmacológicoRESUMO
OBJECTIVES: Ritonavir-boosted protease inhibitor monotherapy (PIMT) is a maintenance strategy that prevents nucleoside reverse transcriptase inhibitor toxicity and reduces costs. Some trials compare PIMT with combined antiretroviral therapy, but restricted selection criteria and low sample size hamper data extrapolation to routine practice. Here, we analyse the effectiveness and safety of PIMT in clinical practice. METHODS: This was a retrospective, observational, multicentre study. Adult HIV-1 patients receiving PIMT with darunavir or lopinavir were included. A Cox regression model identified independent predictors for virological failure (VF). RESULTS: A total of 664 patients (435 on darunavir/ritonavir and 229 on lopinavir/ritonavir) [74% male, median age of 54 years, one-third with previous protease inhibitor VF, CD4 nadir 189 cells/mm(3) and 42% coinfected with hepatitis C virus (HCV)] were analysed. After a median follow-up of 16 months, 78% of patients (95% CI 74%-81%) remained free from therapeutic failure (TF) (change between ritonavir-boosted PIs not considered failure). At 12 months, by intention-to-treat analysis (change between ritonavir-boosted PIs equals failure), 83% of patients were free from TF (87% darunavir/ritonavir versus 77% lopinavir/ritonavir, P = 0.001). Regarding VF, 88% of patients maintained viral suppression at 12 months (93% darunavir/ritonavir versus 88% lopinavir/ritonavir, P = not significant). CD4 nadir <200 cells/mm(3) [hazard ratio (HR) 1.58, 95% CI 1.01-2.49] and undetectable viral load prior to PIMT <24 months (HR 1.86, 95% CI 1.20-2.91) were independent predictors for VF. Prior protease inhibitor failure, HCV coinfection and the protease inhibitor/ritonavir used were not associated with PIMT outcome. A total of 158 patients stopped PIMT, 6% due to adverse events. Two patients developed encephalitis. CONCLUSIONS: PIMT effectiveness was consistent with data from clinical trials. Viral suppression duration prior to PIMT and CD4 cell count nadir were independent predictors for PIMT outcome.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Quimioterapia de Manutenção/métodos , Ritonavir/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Darunavir , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Inibidores da Protease de HIV/efeitos adversos , HIV-1/isolamento & purificação , Humanos , Lopinavir/efeitos adversos , Lopinavir/uso terapêutico , Quimioterapia de Manutenção/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Carga ViralRESUMO
The main objective in the management of HIV-infected pregnant women is prevention of mother-to-child transmission; therefore, it is essential to provide universal antiretroviral treatment, regardless of CD4 count. All pregnant women must receive adequate information and undergo HIV serology testing at the first visit. If the serological status is unknown at the time of delivery, or in the immediate postpartum, HIV serology testing has to be performed as soon as possible. In this document, recommendations are made regarding the health of the mother and from the perspective of minimizing mother-to-child transmission.