Toxicity and genotoxicity induced by abacavir antiretroviral medication alone or in combination with zidovudine and/or lamivudine in Drosophila melanogaster.

Abacavir (ABC), zidovudine (AZT), and lamivudine (3TC) are nucleoside analog reverse transcriptase inhibitors (NRTIs) widely used as combination-based antiretroviral therapy against human immunodeficiency virus. Despite effective viral suppression using NRTI combinations, genotoxic potential of NRTIs can be increased when administered in combination. This study investigated the toxic and genotoxic potential of ABC when administered alone or in combination with AZT and/or 3TC using the somatic mutation and recombination test in Drosophila melanogaster. This test simultaneously evaluated two events related to carcinogenic potential: mutation and somatic recombination. The results indicated that ABC was responsible for toxicity when administered alone or in combination with AZT and/or 3TC. In addition, all treatment combinations increased frequencies of mutation and somatic recombination. The combination of AZT/3TC showed the lowest genotoxic activity compared to all combinations with ABC. Therefore, our results indicated that ABC was responsible for a significant portion of genotoxic activity of these combinations. Somatic recombination was the main genetic event observed, ranging from 83.7% to 97.7%.

Durability of Efavirenz Compared With Boosted Protease Inhibitor-Based Regimens in Antiretroviral-Naïve Patients in the Caribbean and Central and South America.

BACKGROUND: Efavirenz (EFV) and boosted protease inhibitors (bPIs) are still the preferred options for firstline antiretroviral regimens (firstline ART) in Latin America and have comparable short-term efficacy. We assessed the long-term durability and outcomes of patients receiving EFV or bPIs as firstline ART in the Caribbean, Central and South America network for HIV epidemiology (CCASAnet). METHODS: We included ART-naïve, HIV-positive adults on EFV or bPIs as firstline ART in CCASAnet between 2000 and 2016. We investigated the time from starting until ending firstline ART according to changes of third component for any reason, including toxicity and treatment failure, death, and/or loss to follow-up. Use of a third-line regimen was a secondary outcome. Kaplan-Meier estimators of composite end points were generated. Crude cumulative incidence of events and adjusted hazard ratios (aHRs) were estimated accounting for competing risk events. RESULTS: We included 14 519 patients: 12 898 (89%) started EFV and 1621 (11%) bPIs. The adjusted median years on firstline ART were 4.6 (95% confidence interval [CI], 4.4-4.7) on EFV and 3.8 (95% CI, 3.8-4.0) on bPI (P < .001). Cumulative incidence of firstline ART ending at 10 years of follow-up was 32% (95% CI, 31-33) on EFV and 44% (95% CI, 39-48) on bPI (aHR, 0.88; 95% CI, 0.78-0.97). The cumulative incidence rates of third-line initiation in the bPI-based group were 6% (95% CI, 2.4-9.6) and 2% (95% CI, 1.4-2.2) among the EFV-based group (P < .01). CONCLUSIONS: Durability of firstline ART was longer with EFV than with bPIs. EFV-based regimens may continue to be the preferred firstline regimen for our region in the near future due to their high efficacy, relatively low toxicity (especially at lower doses), existence of generic formulations, and affordability for national programs.

Efectividad de la terapia triple antirretroviral en lactante menor con diagnóstico de SIDA categoría C / Effectiveness of triple antiretroviral therapy in a young infant diagnosed with AIDS category C

La falta de medicación antirretroviral durante el embarazo, la no aplicación del protocolo de prevención perinatal del VIH-1 y VIH-2 (PACTG 076) en el momento de la cesárea y la administración de inhibidores de la transcriptasa inversa al recién nacido, es la respuesta más directa a la falta de acciones de protección para los niños (as) que nacen de sus progenitoras que se encuentran viviendo con el virus de la inmunodeficiencia humana (VIH). En el caso de la nena de 4 meses de edad que nace de un vientre donde se encontraba el presente el VIH, presentan una evolución clínica, inmunológica y virológica que progresivamente la va llevando al estado de caquexia, además de presentar procesos infecciosos secundarios a oportunistas, que se complican con una sepsis determinando la necesidad de ventilación asistida. La administración de forma inmediata de los antirretrovirales (ARV) recomendados por el Programa Nacional de Lucha Contra el VIH/SIDA, sin incluso contar con resultados de carga viral materna, tampoco de la pacientita se asocia dos inhibidores nucleótidos de la transcriptasa inversa, con un inhibidor de la transcriptasa inversa no nucleósido, y los antimicóticos y antimicrobianos adecuados, la respuesta clínica, celular es satisfactoria, así ocurrió con la lactante menor que tratamos. Es cierto que nuestra preferencia es hacer asociaciones con principios químicos de mejor acción sobre este virus, como en nuestro caso ante la evidencia de que la nevirapina nos produjo al quinto día de tratamiento una reacción de alergia (la literatura relata que los casos de esta naturaleza generalmente evolucionan a la muerte), habiéndose además asociado antihistamínicos por vía venosa, y la administración de un inhibidor de la proteasa viral que también es un químico asociado (lopinavir + Ritonavir), habiéndose obtenido una respuesta espectacular, a pesar del fondo de caquexia en que se encontraba la lactante menor de 4 meses de edad. Todo estos acontecimientos de ver cada día más casos de mujeres embarazadas que se enteran de ser portadoras de este virus cuando sus bebes evolucionan atípicamente y/o se encuentran en situaciones clínicas gravísimas, tendrían un mejor pronóstico si se decidiera considerar al VIH/SIDA como el problema de salud número uno en nuestro país.

The lack of antiretroviral medication during pregnancy, failure to apply the protocol perinatal HIV-1 and HIV-2 (PACTG 076) at the time of cesarean delivery and administration of inhibitors of reverse transcriptase newborn is the more directly to the lack of protective actions for children (as) that arise from their mothers who are living with human immunodeficiency virus (HIV) response. In the case of the baby 4 months of age born from a womb where HIV was present, present a clinical, immunological and virological evolution is progressively moving the state of cachexia, besides presenting secondary to opportunistic infectious processes which are complicated by sepsis determining the need for assisted ventilation. The administration immediately antiretroviral (ARV) recommended by the National Programme for the Fight Against HIV/AIDS, without even having maternal viral load results, either of two nucleotides pacientita reverse transcriptase inhibitors dela associated with an inhibitor of non-nucleoside reverse transcriptase and appropriate antifungal and antimicrobial, clinical, cellular response is satisfactory, so it happened with the lowest infant who try. It is true that our preference is to make partnerships with chemical principles of best action on this virus, as in our case given the evidence that nevirapine we came on the fifth day of treatment an allergic reaction (literature reports that cases of this nature death usually evolve), having further associated antihistamines intravenously, and administration of a viral protease inhibitor which is also an associated chemical (lopinavir + ritonavir), a dramatic response being obtained, despite the background of cachexia that infants under 4 months of age was. All these events to see more and more cases of pregnant women who learn to be carriers of this virus when their babies evolve atypically and / or are in very serious clinical situations, would have a better prognosis if it decides to treat HIV/AIDS as the number one health problem in our country.

Alterações hematológicas em pacientes infectados pelo vírus da imunodeficência humana submetidos à terapia antirretroviral com e sem inibidor de protease / Hematological abnormalities in patients infected with human immunodeficiency virus on antiretroviral therapy with and without protease inhibitors

A anemia é uma anormalidade hematológica comumente encontrada em pacientes infectados pelo vírus da imunodeficiência humana (HIV) e sua prevalência estimada entre 63 por cento a 95 por cento. O objetivo deste estudo foi avaliar as alterações hematológicas e o Índice de Massa Corporal (IMC) de pacientes HIV soropositivos com ou sem uso de terapia antirretroviral com e sem inibidor de protease. Os pacientes HIV soropositivos foram diagnosticados pelo teste de enzimaimunoensaio (ELISA) e confirmados por imunofluorescência. As alterações hematológicas foram determinadas por aparelho de automação Coulter Maxim Autoloader®, contagem de células CD4+ e CD8+ por citometria de fluxo FACSCount® e carga viral por amplificação baseada na sequência do ácido nucleico - Nucleic Acid Sequence Based Amplification (NASBA®). A avaliação dos dados hematológicos demonstrou níveis diminuídos no número de leucócitos e hemoglobina no grupo de estudo que fazia uso de terapia antirretrovial, quando comparado ao grupo controle sem uso desta terapia; resultado semelhante verificou-se também para o IMC dos pacientes HIV soropositivos (p<0,0001, p=0,006 e p<0,0001) respectivamente. Não houve diferença significativa entre os grupos que faziam uso de terapia antirretrovial com e sem inibidores de protease (IP). A avaliação dos dados hematológicos associada à contagem de células CD4+ e quantificação da carga viral pode contribuir para o monitoramento da infecção e auxiliar na tomada de decisão a respeito da intervenção clínica mais adequada nestes pacientes. Rev. Bras. Hematol. Hemoter.

Anemia is the most commonly encountered hematologic abnormality in from 63 percent to 95 percent of human immunodeficiency virus (HIV)-positive patients. This study intends to evaluate hematological alterations and changes in the body mass index of HIV-positive patients on antiretroviral therapy with or without protease inhibitors and those who are not on antiretroviral therapy. The HIV-positive patients were diagnosed by the ELISA test and confirmed by immunofluorescence. The hematological alterations were determined using a Coulter Maxim Autoloader®, CD4+ and CD8+ cell counts by FACSCount® Flux cytometry and viral load by Nucleic Acid Sequence Based Amplification (NASBA®). The evaluation of hematological alterations showed smaller numbers of leukocytes and hemoglobin in the study group who used antiretroviral therapy compared to the control group (not on antiretroviral therapy); similar results were found for the body mass index of HIV-positive patients (p<0.0001, p=0.006 and p<0.0001), respectively. There were no significant differences identified between the groups on antiretroviral therapy with or without protease inhibitors. An evaluation of the hematological alterations associated with CD4+ cell counts and measurement of the viral load may contribute to monitor HIV infection and assist in the decision of the most appropriate clinical intervention in these patients. Rev. Bras. Hematol. Hemoter.