Marcelo Wolff R

Prevalencia, factores de riesgo y manejo de la depresión en pacientes con infección por VIH: Revisión de la literatura

Depression is one of the main psychiatric co-morbidities in HIV infection, presenting with a significantly higher prevalence than in the general population (around 35%). Its presence has been associated with poor quality of life, HIV disease progression and poor adherence to antiretroviral therapy. Although antidepressive treatment has demonstrated effectiveness on the management of depressive symptoms, improvement of clinical and laboratory parameters, and enhancement of antiretroviral adherence, depression is frequently under diagnosed and under treated in these patients. We analyzed the main international findings on depression prevalence, risk factors, con-sequences and management in people with HIV disease.

Cambios epidemiológicos en las enfermedades infecciosas en Chile durante la década 1990-2000: 1990-2000

In the last decade in Chile, there was a large reduction in the rate of communicable diseases, especially typhoid fever, and those preventable through the universal vaccination programs. Exceptions were hepatitis A and Pertussis. The reduction in tuberculosis, has lead the country to a threshold in which the elimination of tuberculosis as a public health problem is reachable. The HIV epidemic is still expanding, at higher rate among women and heterosexual men, keeping drug addiction as a low ranked risk factor. At the end of the century, universal or expanded access to HIV therapy was still not a reality. Cholera was a well controlled emerging infection, but Hantavirus infection has become a major threat in many regions. Syphilis and especially gonorrhea have decreased, but condyloma has increased dramatically. The nosocomial infection scenario has changed somehow, due to more severely ice and complex patients admitted to hospitals. Multiresistant nosocomial pathogens continue expanding (S aureus, fermentor and non fermentor gram negative rods, especially A baumannii). The country has been able to expand control programs to almost all hospitals. Antimicrobial resistance has continued growing. The massive and indiscriminate use of antibiotics, largely responsible for the resistance, grew worse until the sale of antimicrobials in pharmacies was restricted by law. This had a major impact, with important reduction in sales of most, but not all, antibiotics. The impact in resistance rate of this reduction, if any, has yet to be assessed (Rev Med Chile 2002; 130: 353- 362

Seguimiento prospectivo de una población infectada por VIH con y sin posibilidades de terapia anti-retroviral: impacto en sobrevida y complicaciones

Background: Three-drug antiretroviral therapy (ART-3) has reduced complications and improved survival in HIV+ patients. The Chilean Public Health System began dual therapy (ART-2) in 1997, covering approximately 40% of patients in need. Aim: To report the results of a follow-up of patients with and without access to ART in a Chilean public hospital. Patient and Methods: Prospective follow-up of patients with ART-2 and 3 (cases) and patients with no access to ART (controls). All patients needed ART but it was available to a minority of them. Selection for ART was at random. Follow-up was between 6-24 months (11/96 to 3/99). Basal and periodic clinical and laboratory parameters were determined. Mortality and occurrence of new AIDS-defining events (ADE) were compared statistically using chi square. Results: One hundred and fifty cases (106 ART2, 28 ART3 and 16 ART2 expanded to ART3) and 166 controls were studied. Basal parameters were similar except prior ART (32.7 and 18.7% in cases and controls respectively). Close to 1/3 patients had AIDS. Cases had a mean follow up of 527 days; controls, 478. Six cases (4%) (5 in ART-2) and 17 controls (10%) died. Mortality x 100/pts/yr was 2.7 in cases and 7.7 in controls, p <0.05. ADE per 100/pts/yr was 21 in cases (24.4 in ART2, 15.1 in TAR3) and 54.5 in controls, p <0.05. Cases had a reduction of: esophageal candidiasis (84%), tuberculosis (75%), cryptococcosis and toxoplasmosis (66%), P carinii pneumonia (55%) and bacterial pneumonia (46%) and they had fewer hospitalizations (73%). Late assessment: 70 of 101 ART-2 patients had changed to ART-3 (1 death); 22 of 101 kept original ART-2 (12 dead, 10 alive), 39 of 43 ART-3 patients were alive and 1 died. Conclusions: Short-term ART-2 and 3 significantly reduced mortality (60% and 73%) ADE (65% and 76% respectively) and hospitalizations. Benefits of ART-2 were short lived. Resource-constrained countries cannot depend on weaker than standard ART for proper care of people with HIV disease. (Rev Med Chile 2001; 129: 886-94)

Brote de histoplasmosis aguda en viajeros chilenos a la selva ecuatoriana: un ejemplo de Medicina Geográfica

Eight Chilean teenagers traveled to Ecuador in January 1999, where they were bitten by mosquitoes, had contact with parakeets and lodged in poorly hygienic places; 6/8 visited for 5-10 minutes the interior of a bat cave. About a week later these 6 began with headache, myalgia and fever that lasted 2-3 weeks. 5/6 had dry cough with no respiratory distress. The index case was seen in the 2nd week of symptoms. A chest x-ray showed multiple nodular infiltrates as in the other five. Two had histoplasma serology, one was negative and the other positive at a low titer; histoplasmin skin test showed induration of 17-27 mm in all six. An acute histoplasmosis with massive exposure was diagnosed and treated with itraconazole for 3 weeks. All became asymptomatic and chest x-rays returned to normal. Histoplasmosis (non existent endogenously in Chile) is, among other geographic and tropical diseases, a risk for Chilean travelers. Awareness of this in the general population and development of expertise in these diseases by local health care providers is required.

Impacto de la terapia anti retroviral en la mortalidad de pacientes VIH (+) chilenos: estudio caso-control (MORTAR)

Background: Combined antiretroviral therapy (AVR) has shown a protective effect (PE) on morbidity and survival in HIV (+) patients of industrialised countries where triple-drug therapy (ARV-3) is standard. In Chile the public health system began providing double-drug therapy in 1997 (ARV-2) with 2 reverse transcriptase inhibitors. Aim: To assess the impact of ARV in morbimortality of HIV (+) patients in Chile after a year of follow up. Patients and methods: Retrospective case-control (1:1) study. Cases were 97 patients followed during 1997 for 6 or more months and dying during that period. Each case had a control of the same gender and CDC stage, similar age and CD4 count, but surviving a same period of follow up. A comparison of ARV before and during follow up (rate and type) was done. P carinii prophylaxis, pneumococcal immunization at baseline or follow up, frequency of hospital admissions and occurrence of opportunistic infections in both groups were assessed. Odds ratio (OR) for mortality, hospitalisation and opportunistic infections in ARV user, as well as treatment PE were calculated. Results: Twenty four (24.7%) cases and sixty six (68%) controls received ARV during follow up (p< 0.001), OR was 0.15 (CI 95% 0.08-0.3), p < 0.001, the PE was 6.6 for ARV users versus non users, among cases 19 patients received ARV-2 and five received ARV-3. Among controls, 41 patients received ARV-2 and 25 received ARV-3. These differences established an OR of 0.20 (CI 95% 0.09-0.04) and a PE of 5 for ARV-2 versus no ARV. For ARV-3 compared with no ARV the OR was 0.08 (CI 95% 0.003-0.26), and the PE 12.5. Fifty three (54.6%) cases and 13 (13.4%) controls required hospital admission, OR 0.49 (CI 95% 0.25-0.94), p=0.03, and PE of 2.04 of ARV versus no ARV; 82 (85.3%) cases and 50 (51%) controls had opportunistic infections, OR 0.5 (CI 95% 0.26-0.96), p=0.03 and PE of 2 for ARV versus no ARV. There were no significant differences in prior ARV, prophylaxis and immunisation between cases and controls. Conclusions: This study showed the high impact of ARV in short term morbimortality of HIV(+) patients and the need to implement antiretroviral therapy to all patients as an official health policy. This study did not answer the question of the role, if any, of weaker-than standard antiretroviral therapy. (Rev Med Chile 2000; 128: 839-45).

Estudio prospectivo, randomizado, comparativo de la eficacia, seguridad y costos de cefuroxima vs cefradina en la pielonefritis aguda del embarazo

Background: Second generation cephalosporins (CFPs) are more active in the treatment of acute pyelonephritis during pregnancy but their cost is considerably higher than their predecessors. Cefuroxime, a second generation CFP with oral and parenteral presentations, might offer significant advantages and become a first choice antimicrobial in this setting. Aim: To compare the efficacy, safety and cost of cefuroxime and cephradine in the treatment of acute pyelonephritis in pregnancy. Patients and methods: Hospitalized women with 12 to 34 weeks of pregnancy, with clinical and bacteriological diagnosis of acute pyelonephritis, were randomly assigned to receive cefuroxime (Curocef (r), GlaxoWellcome) 750 mg t.i.d, i.v or cephradine 1 g q.i.d., i.v. If the isolated organism was resistant to the assigned drug the patient was excluded. Once patients were afebrile, they were switched to an oral form of the same antimicrobial. They were discharged according to the clinical status and treated for a total of 14 days. Laboratory tests, including urine culture were requested during controls and at the end of follow-up at 28 days. Results: One hundred and one patients were randomized: 49 to receive cephradine and 52 to receive cefuroxime. Patients in the cefuroxime group had fewer febrile days (mean 1.7 vs 2.2, p<0.05), faster clinical recovery (mean 2.7 vs 3.1 days, p<0.05), a higher rate of bacteriological cure at 28 days (78.8% and 59.2%, p<0.05) and lower rate of failure (21.2% vs 40.8 % p<0.05). The rate of resistance of isolated uropathogens was l4% to cephradine and 1% to cefuroxime. Conclusions: Cefuroxime can be considered as a first choice option in the treatment of acute pyelonephritis during pregnancy due to its tolerance, microbiological activity and efficacy. (Rev Med Chile 2000; 128: 749-57).

Evolución de mortalidad y estado actual de una población infectada por VIH controlada en un centro multiprofesional

Background: Chile, a middle-income country with an HIV epidemic of moderate proportions (global infection rate 0.2%) began a government sponsored, free, highly active antiretroviral therapy (HAART) for patients from the public health system in 2001 reaching in 2004 a 100% coverage. Arriaran Foundation (AF) is the largest public AIDS care center for adults in the country. Aim: To show the present status of the AF population and the evolution of mortality. Material and Methods: Review of AF database from 1991-2004 that at 12/31/2004 had a total cumulative population of 2,259 adult patients; an active census of 1,065 patients and admitting rate 160-190 patients per years. Results: The global mortality registered was 33.4%, with decreasing annual mortality from 15.7% of its active population in 1995 to 1.9% in 2004. As of 12/31/2004, 817 patients (76.7%) were receiving antiretroviral therapy (ART); and 19.3% either did not require nor accept it. Thirty one percent received Combivir ® and nevirapine, with undetectable viral load (<400 copies per ml) in 78%. Thirty percent received Combivir ® and efavirenz with undetectable viral load in 80% at last count. Both regimens were used mainly as first therapy. Lopinavir/ritonavir was received by 6.3% of patients, mainly for post failure therapy and 58% had undetectable viral load. A baseline CD4 count <200 x mm 3 was present in 70% of patients, 45.3% had a count below 100 and 47.8% had clinical AIDS. At the last follow up assessment, CD4 count was <200 in 36.8%, <100 in 10.6% and 200-350 in 44.9%. Conclusion: The expanded access program to ART in a public, comprehensive AIDS care center in Chile has been highly successful in reaching high undetectability (75%), reducing mortality and improving immune status despite very advanced baseline disease (Rev Med Chile 2006; 134: 581-8). (Key words: Acquired immunodeficiency syndrome; Antiretroviral therapy, highly active; HIV seropositivity)

Tratamiento de la neumonía del adulto adquirida en la comunidad

Appropriate antibiotic treatment reduces the duration of symptoms associated to pneumonia, the risk of complications and mortality. In most cases, it is not possible to identify the etiologic agent so antibiotic treatment is empirically prescribed. In Chile, one third of Streptococcus pneumoniae strain isolates has diminished susceptibility to penicillin; in-vitro erythromycin resistance is about 10-15% and cefotaxime resistance 2-10%. It is recommended to classify patients with community acquired pneumonia in four risk categories: Group 1: patients under 65 years without co-morbidities, in ambulatory attendance. Treatment: oral amoxicillin 1 g TID, 7 days. Group 2: patients over 65 years and / or co-morbidities, in ambulatory attendance. Treatment: oral amoxicillin/clavulanate 500/125 mg TID or 875/125 mg BID, or cefuroxime 500 mg BID, 7 days. Group 3: patients admitted to general wards with criteria of moderate severity. Treatment: ceftriaxone 1-2 g once a day or cefotaxime 1 g TID, IV, 7-10 days. Group 4: patients with severe CAP that must be interned into ICU. Treatment: ceftriaxone 2 g once a day or cefotaxime 1 g TID, IV, associated to erythromycin 500 QID, levofloxacin 500-1.000 mg once a day, or moxifloxacin 400 mg/once a day, IV, 10-14 days. In the presence of allergy to or treatment failure with betalactam drugs and/or positive serology for Mycoplasma, Chlamydia or Legionella sp it is recommended to add: erythromycin 500 mg QID, IV or oral, oral clarithromycin 500 mg BID, or oral azythromycin 500 mg once a day

Consecuencias adversas inesperadas durante el uso de antimicrobianos: Cuándo el tratamiento puede ser peligroso para la salud

Los efectos adversos de medicamentos en general y antimicrobianos en particular, son comunes y esperados de enfrentar durante la atencion de los pacientes. La mayoria de ellos consiste en intolerancia, efectos colaterales y secundarios, alergia, idiosincrasia, sobredosis o interacciones farmacologicas indeseables. Durante el empleo de antimicrobianos con fines terapeuticos o preventivos en infecciones documentadas o sospechadas, pueden presentarse efectos adversos inesperados o consecuencias lamentables. Esta publicacion revisa siete situaciones en que esto puede acontecer: La terapia antimicrobiana agrava una enfermedad infecciosa o empeora su dano (i.e., tratamiento antimicrobiano precoz de la infeccion intestinal por Escherichia coli O157: H7); el antimicrobiano al ejercer su efecto causa dano al huesped (reaccion de Jarisch Herxheimer en el tratamiento de la sifilis); el antimicrobiano por si solo es insuficiente para curar la infeccion (abscesos no drenados, infeccion relacionada a protesis sin remocion del cuerpo extrano), el tratamiento antimicrobiano de infecciones no significativas o autolimitadas, el riesgo de efectos secundarios sobrepasa a los beneficios (tratamiento de bacteriuria asintomatica en mayores con bajo riesgo de morbilidad); el tratamiento antimicrobiano temprano en infecciones cronicas no aporta mayor beneficio que una terapia diferida y arriesga las opciones futuras (enfermedad por VIH, hepatitis B); la terapia antimicrobiana restaura la inmunidad deprimida gatillando una respuesta inflamatoria danina para el huesped (terapia antiretroviral durante una fase precoz de terapia antituber-culosa); la terapia antimicrobiana de infecciones intratables o condiciones no infecciosas (Enfermedad de Chagas, condiciones alergicas o autoinmunes). Ademas, poblacion especial, mas proclive a efectos adversos de farmacos son: el adulto mayor, pacientes con afecciones renales o hepaticas, enfermedad por VIH, mujeres embarazadas y, en general, pacientes que reciben varios medicamentos en forma concomitante

Guía Clínica de VIH/SIDA

n este numero de Revista Chilena de Infectologia se publican las Guias Clinicas de VIH/SIDA. Este es el fruto de un arduo trabajo de muchos meses de un grupo de especialistas con un directo quehacer en la atencion de pacientes infectados por VIH. Estas guias fueron presentadas hace meses al Ministerio de Salud y se ofi cializaron a principios de 2010. Los objetivos centrales de la guia son dos:• Detener la progresion de la enfermedad por VIH, dis-minuir la morbi-mortalidad por SIDA y enfermedades asociadas y mejorar la calidad de vida de los adultos infectados por VIH, mediante el acceso universal y oportuno a tratamiento con asociaciones de antire-trovirales (ARV) de efi cacia, durabilidad y seguridad probadas.• Disminuir la tasa de transmision vertical del VIH a menos de 2% global y a 1% o menos en los binomios madre-hijo que reciben protocolo completo, mediante la oferta universal del test de VIH en la mujer embara-zada con consejeria previa y la aplicacion de medidas farmacologicas y no farmacologicas de eficacia probada en la reduccion de la transmision, sin afectar las posibilidades terapeuticas futuras de la madre y del hijo.Un objetivo adicional de la presente guia era actualizar la terapia antiretroviral (TAR) en el pais que, a pesar de haber sido pionero, se habia quedado atras incluso a lo recomendado por la Organizacion Mundial de la Salud. Esta actualizacion se ha dado tanto en la indicacion de inicio de terapia, llevandola a etapas mas precoces, donde ya se habia demostrado su superioridad, incluyendo nuevas situaciones donde es necesario iniciar la terapia e incorporar las muy necesarias nuevos farmacos ARV. Creemos que el resultado fi nal de esta guias resuelve, en gran medida, estas nuevas necesidades y para un pais con un sistema de autorizacion y otorgamiento de la TAR tan centralizado, constituye un gran respaldo para la aplicacion por parte de los equipos tratantes de los mejores estandares de atencion posible. Son muchas las evidencias que hacen aconsejable el inicio mas precoz de TAR, por lo que se establecio empe-zarla con un recuento de linfocitos TCD4 de 350 por mm