RESUMEN
El objetivo del estudio fue describir los niveles de resistencia transmitida de VIH-1 en adultos atendidos en Unidades de Atención Integral de Guatemala. El estudio incluyó registros de 185 pacientes adultos VIH-1 positivo, de reciente diagnóstico sin antecedente de uso de TAR, de noviembre del 2019 a noviembre del 2020. El análisis se realizó en el software DeepChek® v2.0, para la clasificación de la resistencia se siguió el algoritmo de Stanford HIVdb (v9.4 - 07/12/2022). Se encontró 18.4% (IC 95% 13.1 - 24.7%) de resistencia general a alguna familia de ARVs. Se evidenció 15.1% (IC 95% 10.3 - 21.1%) de resistencia individual a la familia de INNTR afectando principalmente a NVP y EFV; 2.2% (IC 95% 0.6 - 5.4%) de resistencia a INTR, mayormente a FTC/3TC; y 2.7% (IC 95% 0.9 - 6.2%) de resistencia intermedia y baja los IP NFV y LPV/r. Tres casos presentaron resistencia múltiple a los INTR + INNTR. Las mutaciones más frecuentemente encontradas fueron K103N (41.2%), M184V/I (8.8%) y M46I (5.9%). La elevada resistencia transmitida del VIH-1 en pacientes atendidos en distintas Unidades de Atención Integral del VIH, demuestra la importancia de analizar periódicamente la tendencia de la resistencia en personas que no han estado expuestas a ARVs, lo cual a su vez es un marcador indirecto de presencia de resistencia adquirida en el país, datos que evidencian la necesidad de acciones e intervenciones prontas y efectivas dado su impacto en la salud pública.
The objective of this study was to describe the levels of transmitted HIV-1 resistance in patients with a recent HIV diagnosis before starting ART, treated in Comprehensive Care Units in Guatemala during the years 2019 and 2020. The study included records of 185 HIV-positive adult patients, recently diagnosed with HIV without a history of ART use. The analysis was carried out in the DeepChek® v2.0 software, the Stanford HIVdb algorithm (v9.4 - 07/12/2022) was followed to classify resistance. 18.4% (95% CI 13.1 - 24.7%) of general resistance to some family of ARVs was found. There was evidence of 15.1% (95% CI 10.3 - 21.1%) of individual resistance to the NNRTI family, mainly affecting NVP and EFV; 2.2% (95% CI 0.6 - 5.4%) resistance to INTR, mostly to FTC/3TC; and 2.7% (95% CI 0.9 - 6.2%) of intermediate and low resistance IP NFV and LPV/r. Three cases presented multiple resistance to NRTIs + NNRTIs. The most frequently found mutations were K103N (41.2%), M184V/I (8.8%) and M46I (5.9%). The high transmitted resistance of HIV-1 in patients treated in different Comprehensive HIV Care Units demonstrates the importance of periodically analyzing the trend of resistance in people who have not been exposed to ARVs, which in turn is an indirect marker. of the presence of acquired resistance in the country, data that demonstrate the need for prompt and effective actions and interventions given its impact on public health.
O objetivo deste estudo foi descrever os níveis de resistência transmitida ao HIV-1 em adultos tratados em Unidades de Cuidados Integrais na Guatemala. O estudo incluiu prontuários de 185 pacientes adultos HIV-1 positivos, recentemente diagnosticados sem histórico de uso de TARV, no período de novembro de 2019 a novembro de 2020. A análise foi realizada no software DeepChek® v2.0, para classificação da resistência, O algoritmo Stanford HIVdb (v9.4 - 07/12/2022) foi seguido. Foi encontrada 18.4% (IC 95% 13.1 - 24.7%) de resistência geral a alguma família de ARVs. Houve evidência de 15.1% (IC 95% 10.3 - 21.1%) de resistência individual à família de NNRTI, afetando principalmente NVP e EFV; 2.2% (IC 95% 0.6 - 5.4%) resistência ao INTR, principalmente ao FTC/3TC; e 2.7% (IC 95% 0.9 - 6.2%) de resistência intermediária e baixa ao IP NFV e LPV/r. Três casos apresentaram resistência múltipla a NRTIs + NNRTIs. As mutações mais frequentemente encontradas foram K103N (41.2%), M184V/I (8.8%) e M46I (5.9%). A elevada resistência transmitida do HIV-1 em pacientes atendidos em diferentes Unidades de Cuidados Integrados ao HIV demonstra a importância de analisar periodicamente a tendência de resistência em pessoas que não foram expostas aos ARVs, o que por sua vez é um marcador indireto da presença de ARVs adquiridos. resistência no país, dados que demonstram a necessidade de ações e intervenções rápidas e eficazes dado o seu impacto na saúde pública.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Adulto Joven , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Farmacorresistencia Viral/efectos de los fármacos , Infecciones por VIH/genética , Vigilancia de la Población , Estudios Transversales , VIH-1/genética , Inhibidores de la Proteasa del VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Inhibidores de la Transcriptasa Inversa/farmacología , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral/genética , Guatemala/epidemiología , MutaciónRESUMEN
BACKGROUND: Two-Drug Regimens (2DR) have proven effective in clinical trials but real-world data, especially in resource-limited settings, is limited. OBJECTIVES: To evaluate viral suppression of lamivudine-based 2DR, with dolutegravir or ritonavir-boosted protease inhibitor (lopinavir/r, atazanavir/r or darunavir/r), among all cases regardless of selection criteria. PATIENTS AND METHODS: A retrospective study, conducted in an HIV clinic in the metropolitan area of São Paulo, Brazil. Per-protocol failure was defined as viremia above 200 copies/mL at outcome. Intention-To-Treat-Exposed (ITT-E) failure was considered for those who initiated 2DR but subsequently had either (i) Delay over 30 days in Antiretroviral Treatment (ART) dispensation, (ii) ART changed or (iii) Viremia > 200 copies/mL in the last observation using 2DR. RESULTS: Out of 278 patients initiating 2DR, 99.6% had viremia below 200 copies/mL at last observation, 97.8% below 50 copies/mL. Lamivudine resistance, either documented (M184V) or presumed (viremia > 200 copies/mL over a month using 3TC) was present in 11% of cases that showed lower suppression rates (97%), but with no significant hazard ratio to fail per ITT-E (1.24, p = 0.78). Decreased kidney function, present in 18 cases, showed of 4.69 hazard ratio (p = 0.02) per ITT-E for failure (3/18). As per protocol analysis, three failures occurred, none with renal dysfunction. CONCLUSIONS: The 2DR is feasible, with robust suppression rates, even when 3TC resistance or renal dysfunction is present, and close monitoring of these cases may guarantee long-term suppression.
Asunto(s)
Fármacos Anti-VIH , Antiinfecciosos , Infecciones por VIH , Inhibidores de la Proteasa del VIH , Enfermedades Renales , Humanos , Lamivudine/uso terapéutico , Lamivudine/farmacología , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Viremia/tratamiento farmacológico , Brasil , Inhibidores de la Proteasa del VIH/uso terapéutico , Quimioterapia Combinada , Antiinfecciosos/farmacología , Enfermedades Renales/tratamiento farmacológico , Carga ViralRESUMEN
BACKGROUND: We have previously shown that the initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here, we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation. METHODS: ART-naïve people with HIV were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal computed tomography scans from baseline and week 96 were reanalyzed for psoas density and area and correlations explored with inflammation [interleukin-6 (IL-6) and high-sensitivity C-reactive protein] and immune activation [soluble CD14 (sCD14), soluble CD163 (sCD163), and %CD38+HLADR+ on CD4+ or CD8+ T cells]. RESULTS: Two hundred twenty-two participants had available inflammation/immune activation markers and paired computed tomography scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = -0.26, P < 0.001) and sCD163 (r -0.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, high-sensitivity C-reactive protein, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T cells (r = -0.30-0.13; all P ≤ 0.05). From baseline to week 96, greater percent decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r = -0.14; P = 0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38+HLADR+ on CD8+ T cells (r = -0.15 to -0.18; all P < 0.04). CONCLUSIONS: Greater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Inflamación , Músculo Esquelético , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Sistema Inmunológico/efectos de los fármacos , Interleucina-6/sangre , Receptores de Lipopolisacáridos , Resultado del TratamientoRESUMEN
PURPOSE: To report a case involving a patient with presumed panretinal ritonavir-induced retinopathy. METHODS: A 52-year-old, HIV-positive patient, with no criteria for AIDS associated with the use of ritonavir for more than 10 years, underwent clinical examination, fundus photography, spectral domain optical coherence tomography, and fundus autofluorescence imaging. RESULTS: Fundus examination revealed areas of atrophy and hypertrophy in the retinal pigment epithelium throughout the retina. Laboratory tests for other diseases were all negative. CONCLUSION: HIV-positive patients undergoing ritonavir therapy should be carefully followed in the presence of low-acuity vision complaints and retinal changes.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , VIH , Enfermedades de la Retina/inducido químicamente , Epitelio Pigmentado de la Retina/patología , Ritonavir/efectos adversos , Agudeza Visual , Angiografía con Fluoresceína/métodos , Estudios de Seguimiento , Fondo de Ojo , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/diagnóstico , Ritonavir/uso terapéutico , Factores de Tiempo , Tomografía de Coherencia Óptica/métodosRESUMEN
OBJECTIVE: There are generic fixed-dose combinations (FDCs) of ritonavir-boosted darunavir (DRV/r) available in Argentina. Experiences with these FDCs in dual therapy remain limited in clinical practice. We aimed to describe clinical and virologic outcomes in patients exposed to FDC DRV/r + raltegravir (RAL) 400 mg every 12 h in a real-life setting. METHODS: Retrospective analysis of electronic medical records of HIV-infected patients under FDC DRV/r + RAL in an HIV clinic in Argentina (2014-2018). Individuals were classified as "switch group" (SG, undetectable viral load [VL] with any toxicity/comorbidity) and "virologic group· (VG, detectable viremia and infection by multidrug-resistant HIV). RESULTS: Of 7,380 patients on ART, 116 (1.5%) received FDC DRV/r + RAL, being 58% in SG. Sixty percent received DRV/r 800/100 mg dose (rest, 600/100 mg). The median (IQR) age and CD4+ T-cell count were: 52 (42-58) years, and 373 cell/µL (202-642). Ninety-eight percent were ART-experienced with a median of 3 (IQR 2-5) prior treatments. Main reasons for switch (SG) were renal (57%), cardiovascular (54%) and bone (14%) comorbidities. Median exposure to DRV/r + RAL was 18 months. Among patients in SG, 98% and 96% had undetectable VL at 6 and 12 months; in the VG, 89% and 87% had undetectable VL at 6 and 12 months. No patient required suspension due to toxicity/ intolerance. CONCLUSIONS: In this cohort of mostly experienced HIV-infected patients, FDC DRV/r + RAL was effective and safe. Such therapy may be considered an option for patients with comorbid conditions and/or with multidrug-resistant HIV.
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Fármacos Anti-VIH , Infecciones por VIH , Inhibidores de la Proteasa del VIH , Fármacos Anti-VIH/uso terapéutico , Argentina/epidemiología , Darunavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Raltegravir Potásico/uso terapéutico , Estudios Retrospectivos , Ritonavir/uso terapéutico , Carga ViralRESUMEN
Even though darunavir/ritonavir (DRV/r) has high potency and a greater genetic barrier, there are few studies on the long-term effectiveness of DRV/r-based salvage therapy in people living with HIV (PLWH) in low and middle-income countries. This retrospective cohort study, from São Paulo, Brazil, included ART-experienced PLWH aged ≥18 years with virological failure (VF) who had started DRV/r plus an optimized background regimen (OBR) between 2008 and 2012. The proportion of patients with viral load (VL) <50 copies/mL, the improved mean CD4+ T cell count and the factors associated with VF during the 144-week follow-up were assessed. The study included 173 patients with the following characteristics [median (interquartile range)]: age 48 (42 -53) years; CD4+ T cell count, 229 (89 -376) cells/mm3; VL, 4.26 (3.70 -4.74) log10; 6 (4 -7) previous regimens; and 100 (38 -156) months of VF. After 144 weeks, 129 (75%) patients had VL< 50 copies/mL and a mean increase in the CD4+ T cell count of 190 cells/mm3. VL>100,000 copies/mL and poor adherence were associated with VF. DRV/r plus an OBR showed high long-term virological suppression and immunological recovery. VL>100,000 copies/mL and poor adherence were associated with VF at 144 weeks.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Darunavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Ritonavir/uso terapéutico , Terapia Recuperativa , Adulto , Fármacos Anti-VIH/uso terapéutico , Brasil , Recuento de Linfocito CD4 , Quimioterapia Combinada , Femenino , Sobrevivientes de VIH a Largo Plazo , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/genética , Estudios Retrospectivos , Resultado del Tratamiento , Carga ViralAsunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Neumonía Viral/mortalidad , Dexametasona/uso terapéutico , Infecciones por Coronavirus/mortalidad , Terapia por Inhalación de Oxígeno , Alta del Paciente , Plasma , Neumonía Viral/inmunología , Respiración Artificial , Dexametasona/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Mortalidad/tendencias , Inhibidores de la Proteasa del VIH/uso terapéutico , Corticoesteroides/uso terapéutico , Infecciones por Coronavirus/inmunología , Azitromicina/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Betacoronavirus/efectos de los fármacos , Reino UnidoRESUMEN
BACKGROUND: Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors. DESIGN: Plasma was obtained from 103 WLHIV with SPTD (≤35 weeks gestation) and 205 controls with term deliveries (TDs; ≥37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNFα, IFNγ, IL6, IL8, IL1ß, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Rα, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GROα, MMP9, IL10, TGFß, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors. RESULTS: Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Rα was associated with increased risk of SPTD. High sCD14, GCSF, PGF2α, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin D insufficiency was associated with higher inflammatory sCD14 and PGF2α, and lower anti-inflammatory 5-HEPE. CONCLUSIONS: The best plasma predictor of SPTD in WLHIV was sIL2Rα, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder.
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Infecciones por VIH/sangre , Inhibidores de la Proteasa del VIH/uso terapéutico , Complicaciones Infecciosas del Embarazo/sangre , Nacimiento Prematuro/etiología , Vitamina D/análogos & derivados , Biomarcadores/sangre , Eicosanoides/sangre , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Subunidad alfa del Receptor de Interleucina-2/sangre , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , ARN Viral/análisis , Vitamina D/sangreRESUMEN
OBJECTIVE: We aimed to assess the effectiveness of first-line antiretroviral therapy (ART) regimens in achieving viral suppression at 12 months, from 2014 to 2017 in Brazil. DESIGN: A retrospective cohort study utilizing programmatic data from the Brazilian HIV Program. METHODS: Adults (aged 15-80 years) who started ART from January 2014 to July 2017 and had a viral load 365 (±90) days after treatment initiation were included. Associations with achieving viral suppression (<50âcopies/ml) at 365 (±90) days were assessed using logistic regression. Our main study variable was ART regimen, and covariates included year of ART initiation, sex/exposure group, age, education, race, region, baseline CD4 and viral load counts, and adherence measured by pharmacy refill data. We performed both intent-to-treat and per-protocol analogous analyses. RESULTS: Out of 107â647 ART-naive patients, 71.5% initiated with tenofovir/lamivudine/efavirenz (TLE) and 10.5% with tenofovir/lamivudine/dolutegravir (TLD). Median age and CD4 cell counts were 34 [interquartile range (IQR) 26-46] and 379âcells/µl (IQR 190-568), respectively; 68.0% were men. Viral suppression by 12 months was 84.0% [95% confidence interval (95% CI) 83.7-84.2] with TLE and 90.5% (95% CI 90.0-91.0) with TLD, and below 80% for protease-inhibitor-based regimens. In the multivariable intent-to-treat-analogous analysis, controlling for cofactors related to viral suppression including adherence, the adjusted odds ratio (aOR) for TLD's viral suppression relative to TLE was 1.56 (95% CI 1.40-1.75). Findings were robust to secondary per-protocol analogous and sensitivity analysis. CONCLUSION: Our results showed the superiority of dolutegravir- over efavirenz- and protease-inhibitor-based regimens in suppressing viral replication in a real-word cohort of HIV-positive adults. This superiority was not driven by higher levels of adherence with dolutegravir-based regimens.
Asunto(s)
Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alquinos , Benzoxazinas/uso terapéutico , Brasil , Ciclopropanos , Femenino , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , Estudios Retrospectivos , Respuesta Virológica Sostenida , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
HIV aspartyl protease inhibitors are able to modulate multiple defense mechanisms. However, their influence on the immune response against Leishmania has rarely been investigated. The aim of our study was to investigate whether in vivo treatment with HIV aspartyl protease inhibitors is able to modulate the immune response during Leishmania infection. Using Leishmania (L.) amazonensis-infected mice, we analyzed the disease evolution and parasite load, immunophenotypic profiles of splenic T and B lymphocytes, numbers of lymphoid aggregates in the spleen, percentages of circulating atypical lymphocytes and reactive monocytes, and serum levels of cytokines and nitric oxide (NO) after 30â¯days of oral treatment with lopinavir/ritonavir (LPV/RTV) or atazanavir (ATV). We observed that LPV/RTV and ATV did not modify the disease evolution or parasite load. However, the antiretroviral treatment induced an increase in activated lymphocytes in the spleen and blood, as well as a decrease in CD69 expression in T and B lymphocytes in the spleen. The treatment also resulted in an increase in activated monocytes in the blood. In addition, antiretrovirals decreased levels of IL-17A and increased levels of NO in sera from Leishmania-infected mice. Thus, our results demonstrate for the first time that in vivo treatment with HIV aspartyl protease inhibitors modifies innate and adaptative immune responses during Leishmania infection and suggest that these drugs could change the clinical course of leishmaniasis in HIV infected-individuals.
Asunto(s)
Inhibidores de la Proteasa del VIH/farmacología , Inhibidores de la Proteasa del VIH/uso terapéutico , Leishmaniasis/tratamiento farmacológico , Animales , Sulfato de Atazanavir/farmacología , Sulfato de Atazanavir/uso terapéutico , Citocinas/sangre , Femenino , Leishmaniasis/sangre , Leishmaniasis/parasitología , Recuento de Leucocitos , Leucocitos/efectos de los fármacos , Lopinavir/farmacología , Lopinavir/uso terapéutico , Ratones Endogámicos BALB C , Óxido Nítrico/sangre , Ritonavir/farmacología , Ritonavir/uso terapéutico , Piel/efectos de los fármacos , Piel/parasitología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/parasitologíaRESUMEN
OBJECTIVES: The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. METHODS: 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). RESULTS: A total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4â¯+â¯T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy. CONCLUSIONS: Metabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART.
Asunto(s)
Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Lopinavir/uso terapéutico , Plasma/efectos de los fármacos , Plasma/metabolismo , Ritonavir/uso terapéutico , Adulto , Anciano , Terapia Antirretroviral Altamente Activa/métodos , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Progresión de la Enfermedad , Quimioterapia Combinada/métodos , Femenino , VIH-1/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Medicina de Precisión/métodos , Curva ROC , Adulto JovenAsunto(s)
Humanos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Ritonavir/uso terapéutico , Darunavir/uso terapéutico , Brasil , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Estudios Prospectivos , Estudios de Seguimiento , Terapia Recuperativa , Recuento de Linfocito CD4Asunto(s)
Darunavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Ritonavir/uso terapéutico , Brasil , Recuento de Linfocito CD4 , Estudios de Seguimiento , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Estudios Prospectivos , Terapia RecuperativaRESUMEN
Abstract Introduction: The widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. Methods: Patients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal-Wallis and Chi-square tests. Results: Forty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1-30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. Conclusions: The high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are needed to inform the predictors of transmitted resistance and the antiretroviral therapy outcomes among these population.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , Inhibidores de la Proteasa del VIH/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral/genética , Brasil , Infecciones por VIH/genética , Infecciones por VIH/tratamiento farmacológico , Enfermedad Aguda , Genotipo , MutaciónRESUMEN
INTRODUCTION: The widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. METHODS: Patients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal-Wallis and Chi-square tests. RESULTS: Forty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1-30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. CONCLUSIONS: The high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are needed to inform the predictors of transmitted resistance and the antiretroviral therapy outcomes among these population.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , Mutación , Enfermedad Aguda , Adulto , Brasil , Farmacorresistencia Viral/genética , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1/genética , Humanos , MasculinoRESUMEN
Including antiretroviral drug switches as a measure of ART failure could be more suitable than conventional measures to evaluate health outcomes in "real-world" settings. This is part of a historical cohort of HIV-infected adults who initiated ART from 2001-2005, and were followed up for a maximum of five years in three HIV/AIDS centers in Belo Horizonte, Brazil. Follow-up information included data from 2001-2010. All patients switched from first-line ART were included. Second-line ART effectiveness was measured as the time-to-ART failure. Failure was defined simulating two scenarios: (1) Clinical, immunological and virological failure (scenario 1); and scenario 1 plus ART switches (scenario 2). Descriptive analysis, Kaplan-Meier curves, log-rank test, and Cox proportional hazards model were performed. We identified 119 eligible patients; most had protease inhibitor (PI)-based regimens prescribed as second-line. The incidence of failure was different for the two scenarios (29.4% vs. 54.6% for scenario 1 and 2, respectively; p < 0.001). The main identifiers of failure were increase in viral load (31.1%) for scenario 1 and ART switches (42.8%) for scenario 2. Median duration on second-line ART was 36.8 vs. 19.8 months for scenario 1 and 2, respectively. In the Cox analysis of scenario 2, increased risk was found for patients given PI-based second-line regimens (HR = 2.26; 95% CI: 1.09-3.17). There is a high incidence of ART failure associated with PI-based regimens when ART switches are considered as an indicator of failure. This demonstrates the impact of ART switches in representing lack of ART effectiveness.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Insuficiencia del Tratamiento , Carga Viral/efectos de los fármacos , Adulto , Antirretrovirales/uso terapéutico , Brasil , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
Intestinal microbiome changes that occur in HIV positive individuals on different antiretroviral therapy (ART) regimens are important to understand, as they are potentially linked with chronic inflammation and microbiome-linked comorbidities that occur at increased incidence in this population. We conducted a cross-sectional study comparing the fecal microbiomes of HIV-uninfected (HIV SN) to HIV-infected individuals on long-term ART (HIV+ LTART) from Mexico using 16S ribosomal RNA (16sRNA) targeted sequencing. These individuals were on two ART regimens based on either Non-Nucleoside Reverse Transcriptase Inhibitors (EFV) or ritonavir-boosted Protease Inhibitors (PI) with the same backbone of Nucleoside Reverse Transcriptase Inhibitors. Microbiome diversity was reduced in treated HIV infection compared to HIV SN (p < 0.05). Several operational taxonomic units (OTUs) related to the Ruminococcaceae family including Faecalibacterium prausnitzii were depleted in EFV and PI compared to HIV SN and negatively correlated with intestinal gut dysfunction as measured by the intestinal fatty binding protein (p < 0.05). This is the first report to address the fecal bacterial communities in HIV-infected individuals on two ARV regimens from Mexico.
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Fármacos Anti-VIH/farmacología , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Adulto , Anciano , Animales , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Biodiversidad , Recuento de Linfocito CD4 , Comorbilidad , Modelos Animales de Enfermedad , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/farmacología , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral , Adulto JovenRESUMEN
After the introduction of highly active antiretroviral therapy in the 1990s, the perception of the diagnosis of HIV infection gradually shifted from a 'death sentence' to a chronic disease requiring long-term treatment. The host genetic variability has been shown to play a relevant role in both antiretroviral drugs bioavailability and adverse effects susceptibility. Knowledge about pharmacogenetics role in HIV infection treatment has largely increased over the last years, and is reviewed in the present report, as well as future perspectives for the inclusion of pharmacogenetics information in the directing of HIV infection treatment.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1/genética , Farmacogenética/métodos , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , Humanos , Variantes Farmacogenómicas/efectos de los fármacos , Variantes Farmacogenómicas/genética , Resultado del TratamientoRESUMEN
Contexto: A solicitação da exclusão dos antirretrovirais fosamprenavir (FPV) 700mg e didanosina entérica (ddI EC) 250mg e 400mg do arsenal terapêutico de antirretrovirais para tratamento do HIV/aids baseia-se na substituição desses fármacos por outros com melhor eficácia e posologia, além de menor toxicidade e menos interações medicamentosas, tendo como foco disponibilizar melhores opções de tratamento para as pessoas vivendo com HIV/aids (PVHA). Recomendação da CONITEC: Na reunião realizada no dia 30 de novembro de 2016, os membros presentes deliberaram por unanimidade recomendar a exclusão dos medicamentos antirretrovirais (ARV) na forma farmacêutica comprimido de fosamprevir (FPV) 700 mg, dianosina entérica ddI EC 250 mg e ddI EC 400 mg do arsenal terapêutico de antirretrovirais para o tratamento do HIV/aids. Recomendação da CONITEC: Na reunião realizada no dia 30 de novembro de 2016, os membros presentes deliberaram por unanimidade recomendar a exclusão dos medicamentos antirretrovirais (ARV) na forma farmacêutica comprimido de fosamprevir (FPV) 700 mg, dianosina entérica ddI EC 250 mg e ddI EC 400 mg do arsenal terapêutico de antirretrovirais para o tratamento do HIV/aids. Decisão: Excluir os medicamentos antirretrovirais (ARV) fosamprenavir (FPV) 700mg, didanosina entérica ddI EC 250mg e ddI EC 400mg do arsenal terapêutico de antirretrovirais para tratamentodo HIV/Aids, no âmbito do Sistema Único de Saúde SUS, dada pela Portaria SCTIE-MS nº 49 publicada no Diário Oficial da União (D.O.U.) nº 246, de 23 de dezembro de 2016.
Asunto(s)
Humanos , VIH , Didanosina/efectos adversos , Didanosina/uso terapéutico , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio , Insuficiencia del Tratamiento , Sustitución de MedicamentosRESUMEN
We report a 41-year-old man with HIV and a chronic obstructive pulmonary disease, treated for seven months with Fluticasone/Salmeterol and antiretroviral therapy (Lamivudine, Tenofovir, Atazanavir and Ritonavir). While using these medications, the patients developed a Cushing syndrome in a period of five months. After performing laboratory and imaging tests, it was concluded that the most probable cause of the syndrome was the interaction of inhaled steroids with Ritonavir. After discontinuing these medications the syndrome reverted in a period of 8 months.