RESUMEN
Introduction: While pharmacists-led interventions in hypertension have proven effective in high-income countries, their implementation and impact in low- and middle-income countries (LMIC) remain limited. This study assessed the implementation and outcomes of the hypertension program FarmaTeCuida (FTC), which integrated community pharmacies into the public primary care level using information and communication technologies. The study took place during the pandemic in General Pueyrredón, Buenos Aires, Argentina, so modifications to the implementation strategy and expected outcomes were also analyzed. Methods: A mixed-methods study was conducted using the non-adoption, abandonment, scaling-up, dissemination, and sustainability (NASSS) conceptual model. Qualitative in-depth interviews were conducted with key stakeholders using snowball sampling until thematic saturation was achieved. The quantitative approach employed a quasi-experimental, prospective, longitudinal design in a cohort of hypertensive patients enrolled in the FTC program since October 2020 to March 2022. Adoption, access, adherence to follow-up, and blood pressure levels were assessed. Clinical outcomes were compared to a cohort of hypertensive patients attending primary health care centers (PHCCs) in 2021 but not enrolled in the FTC program. Routine data from this cohort was obtained from the municipal health information system (HIS). Results: Out of 33 PHCCs, 23 adopted the FTC program, but only four collaborated with community pharmacies. A total of 440 patients were recruited, with 399 (91%) enrolled at PHCCs. Hypertension was detected in 63% (279/440) of cases at the first visit (113 were possible hypertensive patients; 26 new hypertensive patients and 140 already diagnosed). During follow-up, FTC identified 52 new hypertensive patients (12% out of 440). Reduction of systolic blood pressure (SBP) was observed in patients enrolled in both the FTC program and the comparison group over 60 days. In the multivariate analysis that included all hypertensive patient (FTC and HIS) we found strong evidence that for each month of follow up, SBP was reduced by 1.12 mmHg; however, we did not find any significant effect of the FTC program on SBP trend (interaction FTC*months has a p-value = 0.23). The pandemic was identified as the main reason for the program's underperformance; in addition we identified barriers related to technology, patient suitability, implementation team characteristics, and organizational factors. Discussion: Our study, grounded in the NASSS model, highlights the profound complexity of introducing innovative strategies in low- and middle-income settings. Despite substantial challenges posed by the pandemic, these obstacles provided valuable insights, identified areas for improvement, and informed strategies essential for reshaping the care paradigm for conditions like hypertension in resource-constrained environments.
RESUMEN
Heterotopic pregnancy is a rare pathology. It is defined as the coexistence of an intrauterine pregnancy and an extrauterine pregnancy, whatever its location. The presence of an intrauterine pregnancy in a woman of childbearing age does not therefore exclude the presence of an associated ectopic pregnancy. Late diagnosis can lead to fatal consequences for the mother, subsequent fertility as well as for the intrauterine pregnancy. We report the case of a 28-year old female patient, without any notion of assisted reproduction, who was admitted to the emergency department for hemorrhagic shock. The diagnosis of ruptured tubal heterotopic pregnancy was made intraoperatively.
La grossesse hétérotopique est une pathologie rare. Elle est décrite comme la coexistence d'une grossesse intra-utérine et d'une grossesse extra-utérine, quelle que soit la localisation de cette dernière. Nous rapportons le cas d'une patiente âgée de 28 ans, sans notion de procréation médicalement assistée, qui a été admise aux soins d'urgence dans un état de choc hémorragique. Le diagnostic de grossesse hétérotopique tubaire rompue a été posé en peropératoire. Malgré la rareté de cette entité, il est fondamental pour les cliniciens de la connaître afin d'évoquer la possibilité de ce diagnostic. L'échographie endovaginale précoce est l'examen de choix pour l'aide au diagnostic. Ce dernier reste néanmoins difficile en raison d'une symptomatologie déroutante. La présence d'une grossesse intra-utérine chez une femme en âge de procréer n'exclut dès lors pas la présence d'une grossesse ectopique associée. Le diagnostic tardif peut conduire à des conséquences fatales pour la maman, pour sa fertilité ultérieure ainsi que pour l'évolution de la grossesse intra-utérine.
Asunto(s)
Embarazo Heterotópico , Embarazo Tubario , Embarazo , Femenino , Humanos , Adulto , Rotura Espontánea , Embarazo Heterotópico/diagnóstico , Embarazo Heterotópico/cirugía , Embarazo Tubario/diagnóstico , Embarazo Tubario/cirugíaRESUMEN
We report the case of a 29-year-old man admitted to the emergency department for dyspnea and changes in mental status during a festivity. Clinically the patient presented a central cyanosis refractory to the administration of high concentration of oxygen. The consumption of poppers is increasingly used by young people for recreational purposes because they are inexpensive and easy to acquire. Methemoglobinemia is a potentially serious and little known complication of popper intoxication. This condition, known as «methemoglobinemia¼, was suspected by the emergency physician and confirmed through non-invasive measurement of methemoglobinemia in arterial blood gases. The early recognition of methemoglobinemia and prompt treatment allowed a favourable evolution of our patient avoiding the development of multi-systemic organ failure or even death.
Nous rapportons le cas d'un homme de 29 ans admis pour dyspnée et altération de l'état de conscience survenue dans le décours d'une soirée festive. Le tableau clinique est marqué par une cyanose centrale réfractaire à l'administration d'oxygène au masque à haute concentration. La consommation de poppers à usage récréatif est de plus en plus fréquente chez les jeunes adultes. C'est une substance peu coûteuse et facile d'accès, consommée, notamment, pour ses propriétés euphorisantes. La méthémoglobinémie est une complication potentiellement grave et peu connue de l'intoxication par poppers. Dans le cas présenté, la méthémoglobinémie, suspectée par le médecin urgentiste, a pu être confirmée rapidement par une mesure non invasive à la gazométrie artérielle. La reconnaissance précoce de la méthémoglobinémie et l'initiation d'un traitement efficace ont permis une évolution rapidement favorable et d'éviter une défaillance multi-systémique pouvant conduire au décès du patient.
Asunto(s)
Cianosis/etiología , Metahemoglobinemia/diagnóstico , Adulto , Análisis de los Gases de la Sangre , Cianosis/complicaciones , Diagnóstico Diferencial , Disnea/etiología , Servicios Médicos de Urgencia , Humanos , Hipoxia , Drogas Ilícitas/efectos adversos , Masculino , Metahemoglobinemia/inducido químicamente , Metahemoglobinemia/complicaciones , Metahemoglobinemia/terapiaRESUMEN
INTRODUCTION: Frailty is a transient and reversible condition that can lead to significant morbidity and mortality and to the loss of autonomy. It is one of the key issues in public health and the prevention of addiction. Physical activity is often described as a protective factor against addiction and as a factor in limiting frailty. Our goal is to analyze the relationship between physical activity and frailty among the elderly METHODS: A cross-sectional observational study was carried out in three general practice clinics located in the French department of Eure. Patients aged 65 and over were included during a consultation with their GP. Dependent patients under the ADL scale were excluded. Level of physical activity was assessed by the Ricci and Gagnon questionnaire, which defines an active profile as a score≥18 points. Frailty was sought out by the Fried scale and the SEGA A grid. Multivariate analysis was performed to adjust frailty scores to age, gender, and level of physical activity. RESULTS: Out of the 70 patients included, 36 were active (51%) and 34 inactive (49%). They were predominantly female with 47 women (67%). Average age was 75.3years. Twelve patients were diagnosed as frail (17%) with the Fried scale and 24 (34%) with the SEGA A grid. Bivariate analysis revealed a greater frailty according to the Fried criteria in the inactive than in the active patients (mean for active patients 0.56 IC95 [0.31; 0.80], compared to 1.76 [1.21; 2.32] in the inactive patients, p<0.0001). The difference in mean was likewise significant regarding the SEGA A score (6.42 IC95 [5.34, 7.49] in the active population, as opposed to 8.65 IC95 [7.15, 10.15] among the inactive, p=0.017). In multivariate analysis, the Fried scale was primarily influenced by age and ADL, while the SEGA score was impacted by female gender and level of physical activity. CONCLUSION: Physical activity seems to have a positive effect on frailty. It would be interesting to propose systematic screening for frailty in general medicine and to institute preventive measures, including physical activity. Initiatives encouraging and promoting seniors' physical activity should be strengthened.
Asunto(s)
Ejercicio Físico/fisiología , Fragilidad/terapia , Medicina General/métodos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Fragilidad/diagnóstico , Fragilidad/epidemiología , Medicina General/estadística & datos numéricos , Evaluación Geriátrica/estadística & datos numéricos , Humanos , Masculino , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Estudios Prospectivos , Derivación y Consulta/estadística & datos numéricosRESUMEN
We presented a case of a 73-year-old woman presenting to the emergency department with a spinal cord compression secondary to a T2 mass lesion and needing emergency surgery. The lesion was consistent with a papillary thyroid carcinoma. The patient had a previous history of thyroidectomy in a setting of a multinodular goiter 6 years before. A rereading of the previous anatomopathological thyroid tissue confirmed the presence of a papillary thyroid carcinoma that was initially misdiagnosed.
Nous présentons le cas clinique d'une femme âgée de 73 ans se présentant au service des Urgences avec une compression de la moelle épinière secondaire à une lésion de masse au niveau de la vertèbre T2 et nécessitant une intervention chirurgicale d'urgence. La lésion est compatible avec un carcinome papillaire de la thyroïde. La patiente avait bénéficié d'une thyroïdectomie dans un contexte de goitre multinodulaire 6 ans auparavant. Une relecture de la pièce anatomopathologique confirme la présence d'un carcinome papillaire de la thyroïde non diagnostiqué au départ.
Asunto(s)
Compresión de la Médula Espinal , Neoplasias de la Columna Vertebral , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Anciano , Femenino , Humanos , Compresión de la Médula Espinal/etiología , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/secundario , Cáncer Papilar Tiroideo/secundario , Neoplasias de la Tiroides/patología , TiroidectomíaRESUMEN
The elderly population is growing in our societies. Prevention policies are strongly supported by public authorities and one of them is the promotion of physical activity. We propose to detail, through a literature review, the impact of physical activity on the main geriatric criteria.
La population âgée est en augmentation croissante dans nos sociétés. Les politiques de prévention sont fortement soutenues par les pouvoirs publics et l'une d'entre elles est la promotion de l'activité physique. Nous détaillons, au travers d'une revue de littérature, l'impact de l'activité physique sur les principaux critères gériatriques.
Asunto(s)
Ejercicio Físico , Promoción de la Salud , Anciano , Evaluación Geriátrica , HumanosRESUMEN
INTRODUCTION: Anemia remains one of the main concerns of the day-today life of Internist since it ranks third among the pathologies seen in Internal Medicine Departments. OBJECTIVE: it seemed appropriate for the SiFMI Group (Common Situations in Internal Medicine of the SNFMI) to carry out a study of anemia evaluating the contribution to the diagnosis of the «classical¼ semiology of the anemic syndrome. This work reports the results from the study of 204 patients aged 75 years and more. METHOD: A prospective, non interventional multicenter study was carried out in Internal and Geriatric Departments in the period September 2015-September 2017. Clinical and biological variables were collected. RESULTS: 204 patients from 10 Internal or Geriatric Departments were included in the period September 2015-September 2017. They were assigned into two groups with and without anemia. According to this study, it seems that the following parameters : asthenia, dyspnea (NYHA stages III and IV), palpitations, chest pain, tachycardia, hypotension as well as confusion, falls, depression and MMSE showed no significant statistical difference between both groups in contrast to pallor, edema, albumin and ECG. CONCLUSION: Clinical diagnosis of anemia in elderly individuals remains a challenge. It is difficult to establish a diagnostic protocol in this population.
INTRODUCTION: L'anémie reste une des préoccupations majeures du quotidien de l'Interniste, puisque classée troisième parmi les pathologies prises en charge dans les services de Médecine Interne. Objectif : Il a semblé? opportun au Groupe SiFMI (Situations Fréquentes en Médecine Interne de la Société Nationale Française de Médecine Interne - SNFMI) de s'attacher à l'étude des anémies au travers de l'apport au diagnostic de la sémiologie «classique¼ du syndrome anémique. Méthode : Etude prospective, non interventionnelle, multicentrique, menée de septembre 2015 à septembre 2017, dans des services de Médecine Interne et de Gériatrie. Des données cliniques et biologiques ont été recueillies. Résultats : 204 patients ont été inclus par 10 services de Médecine Interne et de Gériatrie de septembre 2015 à septembre 2017. Ils ont été répartis en deux groupes, avec et sans anémie. Dans ce travail, il apparaît que les différents paramètres suivants : asthénie, dyspnée de stades III et IV de la NYHA, palpitations, douleur thoracique, tachycardie, hypotension, mais également confusion, chute, dépression et MMSE, sont sans différence notable sur le plan statistique entre les deux groupes, à l'exception de la pâleur cutanéomuqueuse, des Ådèmes des membres inférieurs, du taux d'albuminémie et de l'ECG. CONCLUSION: Le diagnostic clinique de l'anémie au sein d'une population de sujets âgés s'avère être un vrai défi. Il reste difficile d'établir une démarche diagnostique standardisée au sein de cette population.
Asunto(s)
Anemia , Anciano , Anemia/complicaciones , Anemia/diagnóstico , Arritmias Cardíacas/etiología , Dolor en el Pecho/etiología , Francia , Humanos , Estudios ProspectivosRESUMEN
The thyroid gland is usually resistant to infections due to its anatomy. However, suppurative thyroiditis could be found in immunocompromised patients or those with previous thyroid diseases. We report a case of thyroid abscess secondary to Salmonella enteritidis infection in an immunocompetent patient. We were not able to establish the source of infection. Clinical improvement was achieved under antibiotic treatment without complications. Early diagnosis is important as thyroid abcess may be a life threatening condition.
La thyroïde est une glande endocrine généralement résistante aux infections en raison de sa localisation et présentation anatomique. Cependant, une thyroïdite suppurée est susceptible de survenir chez des patients immunodéprimés ou ayant déjà présenté un dysfonctionnement thyroïdien. Nous rapportons un cas d'abcès thyroïdien consécutif à une infection à Salmonella enteritidis chez un patient immunocompétent. Nous n'avons pas pu établir la source de l'infection. Une amélioration clinique a été obtenue sous traitement antibiotique sans complications. Un diagnostic précoce est essentiel afin d'éviter toutes complications graves mettant en jeu le pronostic vital.
Asunto(s)
Infecciones por Salmonella , Tiroiditis Supurativa , Absceso , Humanos , Infecciones por Salmonella/diagnóstico , Salmonella enteritidis , Tiroiditis Supurativa/diagnósticoRESUMEN
Measles is a highly contagious viral disease and one of the biggest causes of morbidity and mortality in the world. Transmission occurs from person to person through direct contact or by aerosolization of pharyngeal secretions. It can be responsible for severe respiratory and neurological complications. The diagnosis is clinical, confirmed by serology, PCR or culture of the measles virus. Treatment is symptomatic and prevention is based on a well conducted vaccination. In severe cases, the use of vitamin A is recommended by the World Health Organization, at least in chidren. Antivirals (ribavirin) have not been shown to be effective in clinical practice. We present a severe respiratory form of measles, affecting a young immunocompetent adult.
La rougeole est une pathologie virale hautement contagieuse et l'une des plus grandes causes de morbidité et de mortalité dans le monde. La transmission se fait de personne à personne, par contact direct ou par aérosolisation des sécrétions pharyngées. Elle peut être responsable de complications graves respiratoires et neurologiques. Le diagnostic est clinique, affirmé par les sérologies, PCR ou culture du virus de la rougeole. Le traitement est symptomatique et la prévention repose sur une vaccination bien conduite. Dans les cas sévères, l'utilisation de vitamine A est préconisée par l'Organisation Mondiale de la Santé, au moins chez les enfants. Les antiviraux (ribavirine) n'ont pas démontré d'efficacité en pratique clinique. Nous présentons une forme respiratoire sévère de rougeole, touchant un jeune adulte immunocompétent.
Asunto(s)
Antivirales , Huésped Inmunocomprometido , Sarampión , Neumonía , Adulto , Humanos , Sarampión/complicaciones , Neumonía/microbiología , Reacción en Cadena de la Polimerasa , VacunaciónRESUMEN
BACKGROUND AND PURPOSE: The aim of the current study was to investigate the role of arachidonic acid (AA) metabolism via cyclooxygenase (COX) in the endothelial dysfunction of penile arteries from pre-diabetic, obese Zucker rats (OZR). EXPERIMENTAL APPROACH: Penile arteries from OZR and from lean Zucker rats (LZR) were mounted in microvascular myographs to assess vascular function and COX expression was determined by immunohistochemistry. KEY RESULTS: Acetylcholine (ACh) and AA elicited relaxations that were impaired in arteries from OZR. Inhibition of both COX-1 and COX-2 reduced the relaxant effects of ACh and AA in LZR but not in OZR. Inhibitors of COX-1 and of the TXA(2)/PGH(2) (TP) receptor enhanced the relaxations induced by AA in both LZR and OZR, whereas COX-2 inhibition enhanced these responses only in OZR. TP receptor blockade did not restore ACh relaxant responses in arteries from OZR. Inhibition of COX-1 increased basal tension in OZR and this contraction was blunted by TP receptor blockade. The vasoconstrictor responses to noradrenaline were augmented by indomethacin and by COX-2 inhibition in LZR but not in OZR. Immunohistochemical staining showed that both COX-1 and COX-2 are expressed in the endothelium of penile arteries from both LZR and OZR. CONCLUSIONS AND IMPLICATIONS: Vasoactive prostanoids were formed via constitutively active COX-1 and COX-2 pathways in normal rat penile arteries. Under conditions of insulin resistance, the release and/or effects of vasodilator prostanoids were impaired, contributing to the blunted endothelium-dependent vasodilatation and to the enhanced vasoconstriction.
Asunto(s)
Arterias/fisiología , Arterias/fisiopatología , Obesidad , Vasoconstricción/fisiología , Vasodilatación/fisiología , Acetilcolina/metabolismo , Acetilcolina/farmacología , Animales , Ácido Araquidónico/metabolismo , Ácido Araquidónico/farmacología , Arterias/metabolismo , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 1/farmacología , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/farmacología , Hiperemia/metabolismo , Hiperemia/fisiopatología , Resistencia a la Insulina , Masculino , Óxido Nítrico Sintasa de Tipo III , Norepinefrina/metabolismo , Norepinefrina/farmacología , Obesidad/metabolismo , Obesidad/fisiopatología , Pene/metabolismo , Pene/fisiopatología , Estado Prediabético/metabolismo , Estado Prediabético/fisiopatología , Ratas , Ratas Zucker , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/metabolismo , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/metabolismo , Vasodilatadores/farmacologíaRESUMEN
A 37-year-old homosexual man began antiretroviral combination therapy with didanosine (ddI), lamivudine (3TC) and indinavir (IDV) after being exposed previously to zidovudine (ZDV), ddI and 3TC in different sequential regimens. The patient's viral load did not fall below a detectable level despite his adherence to drug therapy, which was considered optimal. Stavudine (d4T) was prescribed in the third month of treatment instead of ddI without any evident improvement in the treatment response. A point mutation nested PCR assay showed that the patient carried a virus with a codon Q151M mutation, which confers multiple drug resistance to nucleoside analogues. Genetic sequence analysis showed that, despite none of the classically associated mutations to Q151M being present at the beginning of treatment, continuous genetic evolution under selective drug pressure allowed the virus to accumulate mutations at codons 62, 74 and 116 over time. As expected, the CD4+ cell count declined during the study period, and the viral load remained detectable.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Resistencia a Múltiples Medicamentos/genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Adulto , Recuento de Linfocito CD4 , Quimioterapia Combinada , Genes MDR/efectos de los fármacos , VIH-1/efectos de los fármacos , Humanos , Lamivudine/uso terapéutico , Masculino , Nucleósidos , Mutación Puntual , Zidovudina/uso terapéuticoAsunto(s)
Infecciones por VIH/genética , Infecciones por VIH/transmisión , VIH-1 , Transmisión Vertical de Enfermedad Infecciosa , Receptores CCR5/genética , Progresión de la Enfermedad , Femenino , Eliminación de Gen , Genotipo , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo , EspañaRESUMEN
BACKGROUND: The rate of CD4+ T-lymphocyte decline seen in HIV-infected patients is very variable. Although older patients, a longer duration of HIV infection, and a high level of plasma viraemia, have been associated with a faster fall in CD4+ T-cells, the relationship between these variables is still not well known. PATIENTS AND METHODS: In a cross-sectional study that included a total of 107 patients of known age and date at HIV seroconversion, the current CD4+ T-cell count and plasma viraemia were examined. Patients were not taking antiretroviral drugs, nor had received immunizations nor were suffering any intercurrent infections at the time of the study. RESULTS: The mean duration of HIV infection was 8.6+/-2.9 years. The mean CD4+ T-lymphocyte count was 367+/-264 x 10(6)/l. Mean plasma viraemia was 4.3+/-0.9 logs. In a linear regression model, the current CD4+ T-cell count was explained in 21.7% by the duration of HIV infection, while the level of plasma viraemia justified separately up to 37.0%. When both parameters were combined, they explained 58.8%. of the CD4+ lymphocyte values. In this model, a variation of one logarithm in the plasma viraemia had six times greater effect on the number of CD4+ lymphocytes than each year of HIV infection. When the age at seroconversion was added to the model, the CD4+ cell count allowed the explanation of up to 62.2% of cases. CONCLUSIONS: The age at seroconversion, the duration of HIV infection, and the level of plasma viraemia independently and substantially influence the current CD4+ lymphocyte count in HIV-infected subjects. However, other variables should exist (e.g. virus syncytium-inducing phenotype, host immunogenetic repertoire, etc.), contributing to explaining the different rate of CD4+ T-cell decline seen in HIV-infected subjects.
Asunto(s)
Recuento de Linfocito CD4 , Infecciones por VIH/inmunología , Adulto , Factores de Edad , Humanos , Factores de Tiempo , Viremia/inmunologíaRESUMEN
BACKGROUND: The decline in CD4+ lymphocytes occurs at different rates in patients with HIV infection. A longer duration of HIV infection and a higher level of viral replication, represented by the viral load, are associated with a lower CD4+ lymphocyte count. However, the interelationship between these variables is still not well known. PATIENTS AND METHODS: 107 HIV-infected patients for whom the date of infection was known, were included in a transversal study, in which the CD4+ lymphocyte count and the plasma viral load were analysed, the last using an isothermal amplification method (NASBA). Patients were not receiving antiretroviral drugs or suffered intercurrent infections at the time of the study. RESULTS: The mean duration of HIV infection was 8.6 +/- 2.9 years. The mean CD4+ lymphocyte count was 366 +/- 264 x 10(6)/l. The mean plasma viraemia was 4.3 +/- 0.9 logs. In a linear regression model, the CD4+ lymphocyte count was explained in 21.7% of cases by the duration of HIV infection, meanwhile the viral load justified up to 36.2 of CD4+ cell variability. When both parameters were combined, up to 58.4% of CD4+ lymphocyte values were explained. In this model, changes of 1 log in viral load had a 4-fold higher effect on the CD4+ cell count than each year of HIV infection. CONCLUSIONS: The duration of HIV infection and, particularly the viral load strongly influences the current CD4+ lymphocyte count, although other variables should exist (virus with syncytium-inducing phenotype, age of the patient and his immunegenetic repertoire) influencing the different decline seen in CD4+ T-cells.
Asunto(s)
Recuento de Linfocito CD4 , Infecciones por VIH/fisiopatología , Carga Viral , Infecciones por VIH/mortalidad , Humanos , Modelos Lineales , Análisis de SupervivenciaAsunto(s)
Fármacos Anti-VIH/uso terapéutico , Didanosina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Indinavir/uso terapéutico , Lamivudine/uso terapéutico , Estavudina/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Didanosina/administración & dosificación , Didanosina/efectos adversos , Quimioterapia Combinada , Infecciones por VIH/virología , Humanos , Indinavir/administración & dosificación , Indinavir/efectos adversos , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Estavudina/administración & dosificación , Estavudina/efectos adversos , Resultado del TratamientoAsunto(s)
Farmacorresistencia Microbiana , VIH-1/efectos de los fármacos , Infecciones por Retroviridae/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/farmacología , VIH-1/genética , Humanos , Lamivudine/farmacología , Mutación , Mycobacterium tuberculosis/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/farmacología , Zidovudina/farmacologíaRESUMEN
Most of the information available on stavudine (d4T) comes from studies in patients with advanced human immunodeficiency virus (HIV) disease to whom stavudine was administered as monotherapy. Herein, we summarize the results of adding 40 mg stavudine twice daily to previous therapies in patients with mild to advanced immunological disease (mean CD4 T cell count 178 cells/mm3; range 6-480 cells/mm3). In an intention-to-treat, prospective, open trial, 64 patients (84.4% men; mean age 35.2 years) were analysed. Their average time on previous antiretroviral therapy was 19.8 months (range 6-52). Plasma HIV RNA load fell by a mean of 0.64 and 0.74 log at 1 and 3 months, respectively, after the start of stavudine therapy (P <0.001 Sign rank test). The CD4 cell count increased by a mean of 25.1 cells/mm3 in the third month (P = 0.002 Sign rank test). Antiviral activity was independent of the CD4 cell count at baseline, but more pronounced declines in viral load were seen in patients with shorter periods of previous antiretroviral therapy and in those in whom stavudine was combined with didanosine or lamivudine rather than zidovudine. Ten (15.6%) patients discontinued the drug during the first 6 months of treatment because of the development of toxicity (neuropathy in six cases, hepatitis in two, oedema in one and rash in another); all but one of them had CD4 counts < 200 cells/mm3. Another two patients stopped treatment voluntarily. The remaining 52 patients tolerated the drug well for the first 6 months and had a high level of compliance with treatment. In conclusion, stavudine is generally well tolerated and has significant antiretroviral activity when it is administered to patients with extensive previous treatment with multiple reverse transcriptase (RT) inhibitors. It should be expected that the short-term favourable effects of stavudine on laboratory markers will further translate into a reduced progression of disease and improved survival.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Estavudina/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , ARN Viral/análisis , Estavudina/efectos adversosRESUMEN
BACKGROUND: the efficacy of zidovudine (ZDV) is lost in many treated individuals after a few weeks or months of monotherapy. The development of drug resistance seems to explain this adverse event. However, some individuals seem to persistently benefit clinically and immunologically from ongoing ZDV monotherapy. The degree and causes of this phenomenon remain unclear. PATIENTS AND METHODS: we studied 280 HIV-infected patients who have been receiving ZDV monotherapy for more than 18 months (mean 28 +/- 7 months), and whom has a CD4+ count between 200 and 500 x 10(6)/l at baseline. We classified them into two groups: Non-progressors with ZDV (NP-ZDV), subjects with an increase or a reduction < 15% in the CD4+ count; and Progressors with ZDV (P-ZDV), subjects showing a decline in the CD4 count > 15%. Epidemiological, immunological and virological features of each group were compared. RESULTS: the prevalence of NP-ZDV in this population was 15.7% (44/280). Age, gender, and risk behaviour were not significantly different in NP-ZDV and P-ZDV. Although the CD4/CD8 ratio, as well as the CD45R0/CD45RA ratio into the CD4+ subpopulation, were higher in NP-ZDV than in P-ZDV, the values did not achieve statistical significance. Virological studies were performed on 36 (81.8%) NP-ZDV and 55 (23.3%) P-ZDV. Mean HIV-RNA titer was higher in P-ZDV than in NP-ZDV (8.4 x 10(4) vs. 1.5 x 10(3) copies/ml; p < 0.01). Virus isolation from circulating mononuclear cells was made more frequently in P-ZDV than in NP-ZDV (90.9% vs. 81.5%), although it did not achieve statistical significance. The syncitium-inducing (SI) phenotype was detected in more than a quarter (27.3%) of P-ZDV but was absent in NP-ZDV (p < 0.01). The prevalence of RT mutations at codon 215 was much lower in NP-ZDV than in P-ZDV, and it showed a strong statistical significance (13.9% vs. 74.5%; p < 0.01). CONCLUSIONS: prolonged (> 2 years) lack of immunological and clinical progression can be observed in 15% of HIV-infected persons with mild immunosuppression, undertaking ZDV monotherapy. This effect seems to be associated with a characteristic virological profile, in which a low viral load, the absence of SI phenotype, and a lack of development of ZDV-resistance are the most relevant features.