Factors associated with mortality in HIV patients failing antiretroviral therapy, in Salvador, Brazil

ABSTRACT Highly active antiretroviral therapy (HAART) has significantly improved survival of people living with HIV/Aids (PLWHA). However, poor treatment adherence to HAART and other problems, still cause therapy failure and contribute to increased morbidity and mortality of PLWHA. In this retrospective cohort study (2013-2015), we sought to evaluate the factors associated with mortality of PLWHA failing HAART in 2013, who were receiving care at a reference center for sexually transmitted diseases (STD) and HIV/AIDS. A total of 165 individuals over 18 years of age who were failing antiretroviral therapy were evaluated. In two-year follow-up, 19 (11.5%) deaths were documented. There were a significant association between mortality and report of illicit drug use (53%, p < 0.01), being attended by a larger number of medical professionals (6.3 ± 3.2, p = 0.02), use of firstline non-nucleoside reverse transcriptase inhibitor (74%, p = 0.01), and history of interrupting HAART ≥3 months (90%), p = 0.02). Patients who died had a significantly higher viral load (mean 49,192.4 ± 35,783.6 copies/mL) than survivors (26,389.2 ± 27,416 copies/mm3, p < 0.01), lower mean CD4 cell counts (127.8 ± 145.6 cells/mm3 vs. 303.3 ± 202.4 cells/mm3, p < 0.01), and higher frequency of previous virologic failure (89% vs. 74.7%, p < 0.01). Our results reinforce the importance of early detection and prevention of virologic failure, to reduce the mortality associated with this event.

Factores asociados a falla virológica en pacientes infectados con VIH que reciben terapia anti-retroviral en un hospital público del Perú / Risk factors associated with virologic failure in HIV- infected patients receiving antiretroviral therapy at a public hospital in Peru

Objective: To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. Materials and Methods: An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. Results: Of 1478 records of patients on HAART analyzed, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. Conclusion: This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk.

Objetivo: Describir las características clínicas y biológicas de sujetos con falla virológica participantes de la Estrategia Sanitaria de Prevención y Control de Infecciones de Transmisión Sexual (ITS) VIH/SIDA de un hospital público del Perú. Materiales y Métodos: Se realizó un estudio descriptivo exploratorio con datos de sujetos mayores de 18 años que iniciaron terapia anti-retroviral de gran actividad (TAlRGA) entre mayo de 2004 y diciembre de 2009 con al menos un control de carga viral luego de 24 semanas de TARGA. Falla virológica fue definida como un valor de carga viral superior a 1.000 copias/mL luego de 24 semanas de TARGA. Resultados: Se analizaron 1.478 registros de sujetos en TAlRGA: la mediana de edad fue 35 años (rango intercuartíl [RIQ] 2941) y 69,6% fueron varones. Se encontró falla virológica en 24%. La proporción de fallecidos fue superior en el grupo con falla virológica (9,5%) respecto al grupo sin falla virológica (1,8%). En el análisis multivariado, la edad, antecedentes de uso de anti-retrovirales antes de iniciar TARGA, cambio de anti-retrovirales por toxicidad, infecciones oportunistas durante TARGA, nivel de linfocitos CD4+ inferior a 100 céls/mL al año de inicio de TARGA, adherencia y estadio clínico se asociaron independientemente a falla virológica. En un sub-análisis limitado al grupo de pacientes sin antecedente de uso de anti-retrovirales antes del inicio de la TARGA, se encontró que adherencia, edad y aparición de infecciones oportunistas tuvieron asociación con falla virológica. Conclusión: Este estudio identificó factores asociados a falla virológica. Se necesitan estudios adicionales para evaluar si el uso de estos factores ayudaría a identificar prospectivamente pacientes en riesgo de fallar y al diseño de intervenciones para disminuir este riesgo.

Recomendaciones para el uso de la terapia antirretroviral en infección por el virus de la inmunodeficiencia humana en Costa Rica / Guidelines for antiretroviral treatment of human immunodefiency virus infection in Costa Rica

El siguiente documento recolecta información actualizada para el abordaje de la persona con infección por el virus de inmunodeficiencia humano, adaptado a la realidad nacional. Se considera que la terapia antirretroviral debe iniciarse lo antes posible en personas con conteo linfocitario menor de 350 linfocitos T CD4+/mm3, previa valoración clínica y asegurado seguimiento estricto por parte de un equipo interdisciplinario. La carga viral será  el parámetro que se utilizará para el seguimiento y como meta, se proyecta alcanzar indetectabilidad a los 6 meses de tratamiento...

Characterization of virologic failure after an initially successful 48-week course of antiretroviral therapy in HIV/AIDS outpatients treated in Santos, Brazil

We characterized the virologic failure after an initially successful 48-week course of antiretroviral therapy among HIV/AIDS patients in a retrospective cohort study involving patients from Santos, Brazil. Patients with plasma HIV RNA below 500 copies/mL for 48 weeks were included. Variables analyzed included gender, age, level of education, marital status, mode of HIV acquisition, viral load, and CD4 cell count upon admission. There were 4,909 patients registered with the clinic, of which 669 patients met all the inclusion criteria (41.6 percent female and 58.4 percent male). Only 27.5 percent of the patients maintained undetectable viral loads during up to one year of follow-up. After 48 weeks, virologic failure occurred earlier in females and in patients first treated with an antiretroviral regimen other than highly active antiretroviral therapy. Patients who were married or had a steady partner experienced virologic failure later than did those who were separated or widowed. The percentage of public health clinic patients who maintain undetectable viral loads for a period of over a year is much lower than that observed among patients enrolled in clinical trials. Females, individuals in unstable relationships, single individuals and widowed individuals should be given special attention in order to improve durability of viral suppression.

Enfuvirtide: el primer paso de una nueva estrategia de tratamiento antirretroviral / Enfuvirtide: the first step for a new strategy of antiretroviral therapy

Enfuvirtide (antes T-20) es el primer inhibidor de la entrada a la célula del HIV-1 en ser aprobado. Es un péptido análogo de la porción HR2 de la glucoproteína de superficie viral gp41. Su mecanismo de acción consiste en la unión competitiva a la porción HR1 de la gp41 para impedir los cambios conformacionales del complejo gp41-gp120 tras la unión del HIV-1 a los receptores celulares, impidiendo así el acercamiento y posterior fusión entre el virus y la célula. Se aplica por vía subcutánea. Los resultados de los principales estudios clínicos (TORO 1 y 2) llevados a cabo en pacientes con fallo virológico, tratamientos previos con antirretrovirales y portadores de cepas virales altamente resistentes, mostraron que quienes recibieron enfuvirtide + HAART optimizado, elegido mediante un test de resistencia, presentaron mayores beneficios que quienes sólo recibieron HAART optimizado, en términos de mejor recuperación inmune y mayor descenso de la carga viral de HIV. Los mejores resultados se observaron en el subgrupo de pacientes con más drogas útiles en el HAART según el test de resistencia, una menor carga viral de HIV y un mayor recuento de linfocitos CD4 basales. El principal efecto adverso es el desarrollo de lesiones por hipersensibilidad en los sitios de aplicación. El alto costo de enfuvirtide se vio compensado por una reducción en los costos de internación.

Enfuvirtide (T-20) is the first approved HIV-1 entry into cells' inhibitor. It is a peptide with an amino acid sequence analogue to HR2 region of the viral surface glycoprotein gp41. Its mechanism of action is the competitive binding to HR1 region of the gp41, preventing the interaction between HR1 and HR2 and impeding the conformational changes in gp41 necessary for fusion of the virus with the cell. Its application is by subcutaneous injection. The main clinical trials of enfuvirtide (TORO 1 and 2) were performed in HIV-infected patients with virological failure, high antiretroviral experience and highly resistant viral isolates. Those trials showed that the addition of enfuvirtide to an optimized HAART (chosen with a resistance test) provided better results than HAART alone, measured by drop in viral load and immunologic benefit. The best results were observed in the subgroup of patients with more useful drugs in HAART (according to the information of the resistance test), a lower viral load, and a higher CD4 cell count at baseline. The most important adverse event is the production of injection drug hypersensitivity reaction in 98% of patients. The high cost is compensated by a reduction in costs derived from admissions.