Toxicity associated with stavudine dose reduction from 40 to 30 mg in first-line antiretroviral therapy.

BACKGROUND: To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART) for HIV treatment and to investigate associated risk factors. METHODS: Multicohort study including 23 HIV programs in resource-limited countries. Adults enrolled between January 2005 and December 2009. Four-year rates of all-cause and stavudine-specific toxicity were estimated. Multilevel mixed-effect Poisson and accelerated failure models were used to investigate factors associated with toxicity and timing of diagnosis. FINDINGS: A total of 48,785 patients contributed 62,505 person-years of follow-up. Rate of all-cause toxicity was 7.80 (95%CI 7.59-8.03) per 100 person-years, but varied greatly across sites (range 0.41-21.76). Patients treated with stavudine 40 mg had higher rates of toxicity (adjusted rate ratio [aRR] 1.18, 95%CI 1.06-1.30 during the first year of ART; and 1.51, 95%CI 1.32-1.71 during the second year). Women, older age, initial advanced clinical stage, and low CD4 count were associated with increased toxicity rate ratios. Timing of lipodystrophy and peripheral neuropathy diagnosis were 12% and 13% shorter, respectively, in patients treated with stavudine 40 mg than in those receiving 30 mg stavudine dose (P = 0.03 and 0.07, respectively). INSTERPRETATION: Higher rates of drug-related toxicity were reported in patients receiving stavudine 40 mg compared with 30 mg, and the time to toxicity diagnosis was shorter in patients treated with the higher dose. Higher rates of toxicity were observed during the first two years of ART.

[Screening of microfilariasis in blood (Loa Loa) among the immigrant population in endemic areas]. / Cribaje de microfilariasis sanguínea (Loa loa) en la poblacion inmigrante de zonas endemicas.

BACKGROUND: Given the increasing flux of immigrant population from high-risk areas to our country, the need of screening for loasis arises, despite systematic screening being a debated and poorly evaluated practice to which there is no protocol. This study is aimed at identifying the population to which loasis screening would be most appropriate, by drawing a comparison among four alternatives. METHODS: Case and control group study, involving 30 cases (all those who came to our unit for treatment and who tested positive for Loa Loa in a microfilariae in the blood detection test) and 90 control cases (three controls per case from among the subjects having tested negative for microfiliariae in the blood chosen at random without any pairing criteria). RESULTS: Of the 1,638 subjects on whom the microfilariae blood test was performed, 30 tested positive (1.8%; 1.2-2.6%). Of these 30 cases of loasis, 76.7% (23; 57.7-90.1%) had eosinophilia (OR 8.8; 3.3-23.1; p<0.0001) and 30.0% (9; 14.7-49.4%) compatible clinical symptoms (OR 2.8; 1.0-7.5; p=0.04). If we were to apply the screening test to the entire immigrant population coming from endemic areas, we would have to perform 54.6 tests to detect one case. If we were to perform the test on patients showing eosinophilia and/or compatible clinical symptoms, we would have to perform a smaller number of tests for every case detected (NNS=29; IC=21-48), but there would be 16.7% (5; 5.7-34.7%) false negatives. CONCLUSIONS: Conducting a screening test with determination of microfiliariae in the blood on the immigrant population coming from Central and West Africa, independently of the presence of eosinophilia or compatible clinical symptoms, would be indicated, provided that the necessary resources are available.

Cribaje de microfilariasis sanguínea (Loa Loa) en la población inmigrante de zonas endémicas / Screening of microfilariasis in blood (Loa Loa) among the immigrant population in endemic areas

Fundamento: Dada la creciente afluencia de población inmigrante originaria de zonas de riesgo a nuestro país se plantea la necesidad de realizar cribaje para loasis, aunque el cribaje sistemático es una práctica discutida, poco evaluada y aún no protocolizada. El objetivo de este estudio es identificar la población en la que es más adecuado realizar el cribado de loasis, comparando 4 alternativas. Métodos: Estudio de casos y controles, con 30 casos (todos los que consultaron en nuestra Unidad y con un test de detección de microfilaremia positivo para Loa loa) y 90 controles (tres controles por caso de entre los sujetos con microfilaremia negativa, escogidos aleatoriamente y sin criterios de apareamiento). Resultados: De los 1.638 sujetos a los que se realizó la prueba de microfilaremia 30 (1,8%;1,2-2,6%) resultaron positivos. De estos 30 casos con loasis 76,7% (23;57,7-90,1%) presentaban eosinofilia (OR 8,8; 3,3-23,1; p<0,0001) y un 30,0% (9;14,7-49,4%) presentaba clínica (OR 2,8; 1,0-7,5; p=0,04). Si aplicáramos el test de cribado a toda la población inmigrante procedente de áreas endémicas deberíamos realizar 54,6 pruebas para detectar un caso. Si lo realizáramos en sujetos que presentan eosinofilia y/o clínica compatible, el número de pruebas que deberíamos realizar para cada caso detectado sería inferior (NNS=29; IC=21-48) pero habría un 16,7% (5;5,7-34,7%) de falsos negativos. Conclusiones: Estaría indicado practicar un test de cribado con determinación de microfilaremia a la población inmigrante procedente de Africa Central y Oeste, independientemente de la presencia de eosinofilia o clínica compatible, siempre que se disponga de los recursos necesarios (AU)

Background: Given the increasing flux of immigrant population from high-risk areas to our country, the need of screening for loasis arises, despite systematic screening being a debated and poorly evaluated practice to which there is no protocol. This study is aimed at identifying the population to which loasis screening would be most appropriate, by drawing a comparison among four alternatives. Methods: Case and control group study, involving 30 cases (all those who came to our unit for treatment and who tested positive for Loa Loa in a microfilariae in the blood detection test) and 90 control cases (three controls per case from among the subjects having tested negative for microfilariae in the blood chosen at random without any pairing criteria). Results: Of the 1,638 subjects on whom the microfilariae blood test was performed, 30 tested positive (1.8%; 1.2-2.6%). Of these 30 cases of loasis, 76.7% (23;57.7-90.1%) had eosinophylia (OR 8.8; 3.3-23.1; p<0.0001) and 30.0% (9;14.7-49.4%) compatible clinical symptoms (OR 2.8; 1.0-7.5; p=0.04). If we were to apply the screening test to the entire immigrant population coming from endemic areas, we would have to perform 54.6 tests to detect one case. It we were to perform the test on patients showing eosinophylia and/or compatible clinical symptoms, we would have to perform a smaller number of tests for every case detected (NNS=29; IC=21-48), but there would be 16.7% (5;5.7-34.7%) false negatives. Conclusions: Conducting a screening test with determination of microfilariae in the blood on the immigrant population coming from Central and West Africa, independently of the presence of eosinophylia or compatible clinical symptoms, would be indicated, provided that the necessary resources are available (AU)