Efectividad y seguridad del cambio a esquema basado en raltegravir en pacientes con infección por VIH dislipidémicos bajo terapia anti-retroviral en Fundación Arriarán / Efectiveness and safety of switching to raltegravir-based regimen in dyslipidemic HIV-infected patients receiving antiretroviral therapy at Arriaran Foundation

Resumen Introducción: El impacto del cambio de terapia antiretroviral (TAR) para tratar la dislipidemia en pacientes infectados por VIH no ha sido reportado en Chile. Objetivo: Evaluar la efectividad y seguridad a 12 meses del cambio de TAR a esquema con raltegravir (RAL) para tratar la dislipidemia. Material y Métodos: Cohorte retrospectiva de pacientes con infección por VIH en TAR, atendidos en Fundación Arriarán, con dislipidemia y que cambiaron a esquema con RAL para tratarla. Resultados: Se incluyó 73 casos, en TAR con inhibidores no nucleosídicos de transcriptasa reversa (INNTR; 50,7%) o inhibidores de proteasa (IP; 49,3%), con dislipidemia mixta (42,5%) o hipertrigliceridemia aislada (57,5%). La mediana de colesterol total (CT) y triglicéridos (TG) basales era 228 mg/dl y 420 mg/dl, respectivamente. El 94,5% tenía carga viral (CV) indetectable. Se modificó TAR de base en 58,4%; 89,1% recibía hipolipemiantes. Las concentraciones plasmáticas de lípidos descendieron significativamente a 12 meses (TG= −43,6%; CT= −19,3%). Ningún paciente presentó fracaso virológico, aunque 10,9% tuvo viremia detectable a 12 meses, mayoritariamente transitoria. Conclusiones: El cambio de TAR a RAL en pacientes dislipidémicos tratados con INNTR o IP reduce significativamente las concentraciones plasmáticas de TG y CT a 12 meses. Es una estrategia segura, pero puede observarse viremia transitoria.

Background: The impact of switching antiretroviral therapy (ART) regimen for dyslipidemia management in HIV-infected (HIV+) patients has not been reported in Chile. Aim: To assess effectiveness and safety at 12 months after switching to raltegravir-based regimen for dyslipidemia management. Methods: Retrospective cohort of HIV+ patients receiving ART at Arriaran Foundation, with dyslipidemia switched to raltegravir-based regimen for lipid management. Results: 73 patients were included, receiving ART based in nonnucleoside reverse transcriptase inhibitor (NNRTI; 50,7%) or protease inhibitor (PI; 49,3%), with mixed dyslipidemia (42,5%) or isolated hypertriglyceridemia (57,5%). At baseline, median total cholesterol (TC) and triglycerides (TG) were 228 mg/dl and 420 mg/dl, respectively; undetectable viral load (VL) was present in 94,5% of patients. Backbone ART was switched in 58,4% and lipid-lowering therapy was used by 89,1% of them. At 12 months, there was a significant decrease in TG (-43,6%) and TC (-19,3%). No cases of virologic failure were observed, although 10,9% of patients had detectable VL at 12 months, mostly transient. Conclusions: Switching ART to raltegravir-based regimen in dyslipidemic patients receiving NNRTI or PI is associated with a significative decrease in TG and TC at 12 months. This strategy is safe, but VL can be increased temporarily.

Síndrome de Cushing iatrogénico por corticoides inhalados en paciente VIH / Cushing syndrome in a HIV patient using inhaled steroids: report of one case

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.

Nephrotoxicity during tenofovir treatment: a three-year follow-up study in a Brazilian reference clinic

Abstract In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA) and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r) lopinavir/r or atazanavir/r. The software package STATISTICA 10® was used for statistical analysis. The patients’ mean age was 43.2 ± 10.7 years. Systemic arterial hypertension (SAH) and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF + 3TC), 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F = 3.95; p = 0.048), SAH (F = 6.964; p = 0.009), and age over 50 years (F = 45.81; p < 0.001) were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F = 2.437; p = 0.063); however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F = 32.02; p < 0.05) and there was a significant time-by-sex interaction (F = 3.117; p = 0.0149). TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7%) and 11 due to nephrotoxicity (4%). Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.

Ergotismo y HIV / Ergotism and HIV

El ergotismo es una complicación de la intoxicación aguda y/o el abuso crónico de los derivados del ergot. Se manifiesta por síndrome vasomotor con enfermedad vascular periférica que frecuentemente compromete extremidades. Presentamos cuatro casos de pacientes infectados con el virus de la inmunodeficiencia humana 1 (HIV-1), en tratamiento con antirretrovirales que incluyen inhibidores de la proteasa reforzados con ritonavir, y que habían recibido ergotamina como automedicación. Ellos desarrollaron síntomas de enfermedad vascular periférica y al examen físico sus pulsos estaban disminuidos o ausentes. El Doppler arterial confirmó signos de espasmo arterial difuso en dos de ellos. Se hizo diagnóstico de ergotismo secundario a la asociación de ergotamina-inhibidores de la proteasa. Los pacientes fueron tratados con la discontinuación de las drogas involucradas (inhibidores de la proteasa y ergotamina), bloqueantes cálcicos, profilaxis antitrombótica con enoxaparina, antiagregación con ácido acetil salicílico y uno ellos recibió pentoxifilina e infusión de prostaglandinas vasodilatadoras con mejoría de los síntomas. Discutimos la presentación clínica de esta interacción medicamentosa, difícil de diagnosticar correctamente sin una fuerte sospecha de su existencia.

Ergotism is a complication of acute intoxication and/or chronic abuse of ergot derivatives. It expresses itself through a vasomotor syndrome with peripheral vascular disease which frequently involves extremities. We report four cases of HIV-1 infected patients treated with antiretroviral drugs including boosted-protease inhibitors who had self-treated themselves with ergotamine. They developed peripheral vascular disease symptoms and their pulses where diminished or absent in the physical examination. Arterial Doppler confirmed diffused arterial spasm in two of them. Ergotism following ergotamine-protease inhibitors association was diagnosed. Patients were treated through the discontinuity of involved drugs (protease inhibitors and ergotamine), calcium blockers; antithrombotic prophylaxis with enoxaparine, antiaggregant therapy with acetylsalicylic acid, and one of them received pentoxifylline and vasodilator prostaglandins infusion, with amelioration of the symptoms. We discuss the clinical presentation of this drug interaction, difficult to diagnose properly without a strong suspicion of its existence.

Infarto esplénico ¿Ergotismo inducido por ritonavir? / Splenic infarction: Ergotism induced by ritonavir?

El ergotismo es una enfermedad conocida desde la antigüedad, que se caracteriza por isquemia y, en algunos casos, gangrena de las extremidades. Muchas drogas de uso corriente tienen la capacidad de interactuar con los ergotamínicos desarrollando ergotismo como efecto adverso. Un ejemplo de ello es el ritonavir, un inhibidor de la proteasa utilizado en pacientes con el virus de la inmunodeficiencia humana (HIV). Presentamos un caso de ergotismo en un varón de 39 años con infección por HIV en tratamiento con ritonavir que, después de ingerir 1 mg de tartrato de ergotamina, además de presentar manifestaciones clásicas de la enfermedad, desarrolló un infarto esplénico. Por lo tanto, consideramos importante advertir a los pacientes sobre la posible interacción farmacológica entre los ergotamínicos y otras drogas de uso frecuente y, en particular, el ritonavir en pacientes portadores de HIV.

Ergotism is a clinical condition known since old times and whose main characteristics are ischemia and even limb gangrene. Some drugs have the capacity of interacting with small amounts of ergotamine or its derivatives producing ergotism as a side effect. This is the case of ritonavir, a widely used anti-HIV drug. Here we present a case of ergotism that developed in an HIV positive 39 year old male under treatment with ritonavir, after taking 1 mg of ergotamine tartrate. His clinical picture, apart from showing the basic manifestations of the disease, was associated with splenic infarction. For this reason, we consider important to advise patients about the potential pharmacological interaction between ergotamines and others common drugs and, in particular, ritonavir in HIV positive patients.

A reduced grade of liver fibros-steatosis after raltegravir, maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis, cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use / Grado reducido de fibroesteatosis tras la administración de raltegravir, maraviroc y fosamprenavir en un paciente co-infectado de VIH/VHC con hepatitis crónica, cardiomiopatía, intolerancia al nelfinavir y un aumento pronunciado de los niveles de creatina fosfoquinasa sérica probablemente debido al uso del inhibidor de la integrasa

The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.

Ergotismo secundario a la asociación ergotamina-ritonavir: A propósito de 3 casos / Ergotism secondary to ergotamine-ritonavir association: Report of three cases

Ergotism is a complication of the acute intoxication or chronic abuse of ergot derivatives. It may be manifested by a vasomotor syndrome with peripheral vascular disease frequently involving extremities. We report three patients infected with human immunodeficiency virus (HIV), in antiretroviral treatment (ART) that included a protease inhibitor as ritonavir, and had received self-medicated ergotamine. They developed symptoms of peripheral vascular disease and the physical examination showed no arterial pulses in the affected vessels. Arterial Doppler confirmed signs of diffuse arterial spasm in all of them. An arteriography was performed to the second patient and it showed obliteration of the distal sector of the ulnar and radial arteries. Ergotism secondary to ergotamine-ritonavir association was diagnosed. Patients were treated discontinuing the administration of involved drugs, arterial vasodilators and prophylactic anticoagulation, with marked improvement of symptoms.

Antiretroviral therapy-associated dyslipidemia in patients from a reference center in Brazil

The aim of this study was to determine the impact of antiretroviral therapy on the lipid profile of human immunodeficiency virus (HIV) patients before and after the initiation of highly active antiretroviral therapy (HAART). This was a cross-sectional analysis of patients receiving HAART at a reference center in Belo Horizonte, Brazil, on the basis of medical records from 2002 to 2006. Patients were included if they had at least one lipid test or a clinical or laboratory diagnosis of dyslipidemia/lipodystrophy. Among the 692 patients, 620 met the eligibility criteria. The majority were males (66.5 percent), middle age (average 39 years), had a low educational level (60.4 percent), and low income (51.0 percent). HAART duration ranged from 11 days to 4.6 years, with a mean of 28.6 months (SD = ± 470.19 days). The prevalence of dyslipidemia/lipodystrophy nearly tripled (11.3 percent pre- and 32.4 percent post-HAART). Dyslipidemia was associated with older age (P = 0.007), nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI) regimens (P = 0.04), NRTI + non-NRTI (NNRTI) regimens (P = 0.026), the use of stavudine (d4T) in any regimen (P = 0.002) or in NRTI-based regimens (P = 0.006), and longer exposure to HAART (P < 0.000). In addition, there was no correlation between dyslipidemia and gender (P = 0.084). Only 2.0 percent of the patients received treatment for dyslipidemia during the trial. These results show a need for continuous monitoring of patients under antiretroviral therapy, particularly those using NRTI-based regimens, especially when combined with d4T and PIs. Secondly, interventions should be developed to correct metabolic changes.

Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities

OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.

Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy / Avaliação nutricional e do perfil lipídico em crianças e adolescentes infectadas pelo HIV tratadas com terapia antirretroviral de alta potência

INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI) can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5 (20 - 162); p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34 - 69); p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.

INTRODUÇÃO: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência (TAAP), que inclui inibidor de protease (IP) podem apresentar significante melhora clínica no estado nutricional e na qualidade de vida. O objetivo é relatar as alterações nutricionais e metabólicas em pacientes pediátricos expostos a TAAP e controles saudáveis durante 1 ano. MÉTODOS: O perfil clínico, antropométrico e lipídico, bem como dados da ingestão alimentar foram coletados prospectivamente durante aproximadamente 12 meses. RESULTADOS: Cinquenta e um indivíduos foram estudados. Dezesseis eram saudáveis. Após 12 meses de acompanhamento, indivíduos HIV-positivo permaneceram abaixo dos parâmetros do grupo controle saudável. Nenhuma mudança foi observada em relação à ingestão alimentar. Níveis séricos de triglicerídeos foram maiores em pacientes usando inibidor de protease no começo do estudo [IP grupo: 114 (43 - 336), e 136 (63 - 271) versus grupo controle: 54.5 (20 - 162); p = 0.003], porém após doze meses de acompanhamento, apenas o grupo que recebeu inibidor de protease por não mais do que dois meses apresentou maiores valores [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-colesterol foi menor nos indivíduos HIV-positivos [grupo HIV-positivo: 36 (27 - 58) e 36 (23 - 43); controle 49.5 (34 - 69); p=0.004]. CONCLUSÕES: Crianças e adolescentes infectadas pelo HIV e tratadas com terapia antirretroviral de alta potência tiveram seus parâmetros nutricionais comprometidos quando comparados com o pareado grupo controle. Indivíduos usando inibidor de protease apresentaram piores níveis séricos de triglicerídeos quando comparados com os saudáveis.

Nutritional status and lipid profile of HIV-positive children and adolescents using antiretroviral therapy

OBJECTIVE: To describe nutritional status, body composition and lipid profile in children and adolescents receiving protease inhibitors. METHODS: Fifty-nine patients, 23 treated with protease inhibitors (group 1) and 36 not using protease inhibitors (group 2). Their dietary intake, anthropometry, bioimpedance analysis and lipid profile variables were measured. RESULTS: There was no difference in nutritional status or body composition between groups at the beginning of the study. After 6 months of follow-up, there was an increase in weight and height in both groups, as well as in waist circumference and subscapular skinfold thickness. In group 2, body mass index and triceps skinfold thickness adequacy were significantly higher after 6 months of follow-up. The groups had similar energy and macronutrient intake at any time point. After 6 months, group 1 had a higher cholesterol intake and group 2 had a higher fiber intake. Triglyceride serum levels were significantly different between the groups, with higher values in G1, at any time point [G1: 153 mg/dl (30-344); 138 (58-378) versus G2: 76 mg/dl (29-378); 76 (29-378)]. After 6 months of follow-up, G1 had higher LDL-cholesterol than G2 [104 mg/dl (40-142) versus 82 (42-145)]. CONCLUSION: The use of protease inhibitors, per se, does not seem to significantly interfere with anthropometric measures, body composition and food intake of HIV-infected children and adolescents. However, this antiretroviral therapy was associated with a significant increase in triglyceride and LDL-cholesterol in our subjects.

Indinavir-associated toxicity mimicking urinary tuberculosis in a patient with AIDS

This case reported to a patient with AIDS who presented persistent sterile leukocyturia and hematuria, lower back pain, bladder suffering symptoms, and renal papillary necrosis which were thought to be secondary to urinary tuberculosis but were demonstrated to be indinavir-associated side effects. The intention of this report is to remind medical professionals involved in the care of HIV+ patients of this possible association in order to avoid unnecessary investigation and to stress the need of careful periodical assessment of renal function and urinalysis in patients treated with indinavir.

Dyslipidaemia associated with the highly active antiretroviral therapy in aids patient: reversion after switching (stavudine to tenofovir and lopinavir/ritonavir to atazanavir/ritonavir)

Antiretroviral therapy has been associated with hyperlipidemia in AIDS patients. This case illustrates the classic metabolic effects associated to the HAART including protease inhibitors and/or stavudine. It was showed that the management of the HAART-associated dyslipidaemia with conventional antihyperlipidemic therapy may fail, being the switching strategy the best option.

Avascular necrosis of the femoral head in HIV infected patients

Avascular necrosis (AVN) of the femoral head is an emerging complication in HIV infected patients. It has been suggested that the increased incidence of AVN in this population may be caused by an increased prevalence of predisposing factors for osteonecrosis, including protease inhibitors, hyperlipidemia, corticosteroid use, alcohol and intravenous drug abuse. The aim of this study was to assess the risk factors for avascular necrosis developing in the femoral head of HIV infected individuals. This study consisted of meta-analysis of the secondary data extracted from current literature. The selected articles allowed two study groups to be drawn up for comparison. Group 1 comprised 324 individuals infected by the HIV virus, who did not present femoral head AVN. Group 2 comprised 32 HIV positive patients, who presented femoral head AVN. The parameters used for analysis were as follows: age, gender, sexual preference, use of intravenous drugs, time of diagnosis, CD4+ cell count, use of antiretroviral agents and duration, serum cholesterol and serum triglycerides. The present study found a statistically significant association between hypertriglyceridemia, hypercholesterolemia, sexual preference and intravenous drug abuse. The authors concluded that femoral head osteonecrosis is associated with hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) and intravenous drug abuse. This study supports the hypothesis that protease inhibitors play a role in the development of osteonecrosis through a tendency to cause hyperlipidemia.

Lipid profiles of Thai adult HIV-infected patients receiving protease inhibitors.

Dyslipidemia is a common metabolic complication among HIV-infected patients who receive protease inhibitor (PI)-based antiretroviral therapy (ART). In order to assess the prevalence of lipid abnormalities and related factors, a cross-sectional analytic study of the lipid profiles of 170 Thai adult HIV-infected patients receiving PI-containing HAART who attended the HIV-clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand between January and August 2005 was conducted. Studied subjects had a median age of 40 years with a median duration of taking PIs of 22.1 months. The mean serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), and triglyceride (TG) levels were 259.7, 43.7, 135.2, and 506.8 mg/dl, respectively, and the mean TC:HDL-c ratio = 6.4. According to the US National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines, high TC, low HDL-c, high TC:HDL-c ratio, high LDL-c, and high TG were found in 52.4, 36.5, 18.8, 44.1, and 42.9%, respectively. Seventy-five subjects (44.1%) were taking lipid-lowering drugs. Only 54 subjects (31.8%) had baseline serum lipid profiles tested before beginning PI. There was statistically significant association between group of PI with serum TC and TG. Subjects taking double boosted and single boosted PI had significantly higher serum TC and TG levels than unboosted PI. Males had significantly higher serum TG levels, while females had significantly higher serum HDL-c levels. Age was significantly associated with serum TC, LDL-c levels, and TC:HDL-c ratios. Serum TC and LDL-c levels were also significantly higher in subjects taking efavirenz.

High prevalence of indinavir-associated renal complications in Thai HIV-infected patients.

BACKGROUND: Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics. MATERIAL AND METHOD: The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well. RESULTS: Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy. CONCLUSION: A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

Urinary NO3 excretion and renal failure in indinavir-treated patients

Treatment with indinavir (IDV), a protease inhibitor, is frequently associated with renal abnormalities. We determined the incidence of renal failure (creatinine clearance <80 mL min-1 1.73 (m²)-1) in HIV patients treated with highly active antiretroviral therapy, including IDV, and investigated the possible mechanisms and risk factors of IDV nephrotoxicity. Thirty-six patients receiving IDV were followed for 3 years. All were assessed for age, body weight, duration of infection, duration of IDV treatment, sulfur-derivative use, total cholesterol, triglycerides, magnesium, sodium, potassium, creatinine, and urinalysis. We also determined renal function in terms of creatinine clearance, urine osmolality and fractional excretion of sodium, potassium, and water. Urinary nitrate (NO3) excretion was measured in 18 IDV-treated patients and compared with that of 8 patients treated with efavirenz, a drug without renal side effects. Sterile leukocyturia occurred in 80.5 percent of the IDV-treated patients. Creatinine clearance <80 mL min-1 1.73 (m²)-1 was observed in 22 patients (61 percent) and was associated with low body weight and the use of sulfur-derivatives. These patients also had lower osmolality, lower urine volume and a higher fractional excretion of water compared to the normal renal function group. Urinary NO3 excretion was significantly lower in IDV-treated patients (809 ± 181 æM NO3-/mg creatinine) than in efavirenz-treated patients (2247 ± 648 æM NO3-/mg creatinine, P < 0.01). The lower NO3 excretion suggests that IDV decreases nitric oxide production.