Evolución virológica de pacientes con infección por VIH que inician terapia antirretroviral con carga viral basales muy alta / Virological evolution of patients with HIV infection that start antiretroviral therapy with a very high baseline viral load

INTRODUCCIÓN: Se desconoce el grado de supresión viral en pacientes con infección por VIH que inician terapia antirretroviral (TAR) con cargas virales (CV) muy altas. OBJETIVO: Conocer el porcentaje de supresión viral en pacientes con VIH que inician TAR con CV ≥ 500.000 copias/mL a 96 semanas. PACIENTES Y MÉTODO: Estudio retrospectivo. Se incluyeron pacientes que iniciaron TAR con CV ≥ 500.000 copias/mL, entre los años 2008 y 2018, estratificándose en base a escala logarítmica. Se determinó el porcentaje de supresión viral, y las variables asociadas a este desenlace. RESULTADOS: Se incluyeron 221 pacientes. La mediana de edad y CV era de 43 años y 6,0 log, respectivamente, estando la mayoría (37%) en estadio C3 al inicio de TAR. El 48,8 y 87,7% de los pacientes logró la supresión viral al año y dos años de seguimiento, respectivamente. Se observó que, a mayor edad, a mayor inmunosupresión, y a mayor CV, mayor el tiempo para lograr la indetectabilidad. Sólo se demostró fracaso virológico en tres pacientes. DISCUSIÓN: Los pacientes con infección por VIH que inician TAR con CV muy altas demoran más tiempo en lograr la supresión viral, lo cual es proporcional a la magnitud de ésta y al grado de inmunosupresión, sin que esto conlleve mayor riesgo de fracaso virológico.

BACKGROUND: The degree of viral suppression in HIV patients who start antiretroviral therapy (ART) with very high viral loads (CV) is unknown. AIM: To know the percentage of viral suppression in HIV patients who start ART with CV ≥ 500,000 copies/mL at 96 weeks. METHOD: Retrospective study. Patients who started ART with a CV ≥ 500,000 copies/mL between 2008 and 2018 were included, stratifying on the basis of a logarithmic scale. The percentage of viral suppression and the variables associated with this outcome were determined. RESULTS: 221 patients were included. The median age and CV were 43 years and 6.0 log, respectively, with the majority (37%) being in stage C3 at the start of ART. 48.8 and 87.7% of the patients achieved viral suppression at one year and two years of follow-up, respectively. It was observed that the older the immunosuppression, and the higher CV, the longer the time to achieve undetectability. Virological failure was only demonstrated in three patients. DISCUSSION: Patients with HIV infection who start ART with very high CVs take longer to achieve viral suppression, which is proportional to the magnitude of this and the degree of immunosuppression, without this entailing a greater risk of virological failure.

Selección del tratamiento de rescate en pacientes con VIH-1: respuesta y supervivencia / Selection method of rescue treatment in patients with HIV-1: response and survival

Resumen Objetivo: Determinar el impacto del uso de la prueba genotípica de resistencia en la respuesta y supervivencia a largo plazo de los pacientes infectados con el VIH-1 que presentaron fracaso a la terapia antirretroviral. Métodos: Se realizó un estudio de cohorte, retrospectivo, se definieron dos grupos basados en la forma de selección de la terapia de rescate utilizada: en base al resultado de la prueba genotípica de resistencia (grupo A) y en base al criterio de expertos (grupo B). Los pacientes fueron evaluados antes del cambio de la terapia de rescate según variables demográficas, clínicas y de laboratorio y evaluados a los 6, 12, 18, y 24 meses del cambio de tratamiento según respuesta virológica, respuesta de células CD4+, incidencia de enfermedades oportunistas y supervivencia. La información fue obtenida de las actas de la Comisión Nacional de Terapia Antirretroviral, la base de datos del IPK y las Historias Clínicas. Se utilizaron números absolutos y porcentajes, media y mediana, con sus respectivas desviaciones estándares (DE), Chi2, se aplicó el Riesgo Relativo (RR), prueba U de Mann-Whitney, y el método de Kaplan-Meier. Resultados: Los pacientes de grupo A tuvieron 1,44 veces mayor probabilidad de alcanzar supresión virológica completa que los pacientes del grupo B a los 6 meses, RR 1,44 (1,046- 2,054) p=0,017. El incremento promedio de Linfocitos T CD4+ fue de 117,40 células/mm3 en pacientes del grupo A y de 30,04 células/mm3 en pacientes del grupo B, p<0,005 a los 12 meses de iniciado el tratamiento. La incidencia de enfermedades oportunistas fue de 25,7% en el grupo B y de 5,6% en grupo A. El mayor porcentaje de sobrevida acumulada se observó en el grupo el grupo A (98,1%), en comparación con el grupo B (79%). Conclusiones: Los pacientes en los cuales el tratamiento de rescate se escogió basado en una prueba genotípica de resistencia tuvieron una mejor respuesta virológica, un mayor incremento de Linfocitos T CD4+ y una mayor supervivencia que aquellos en los que el tratamiento se eligió basado en el criterio de expertos.

Abstract Objective: To determine the impact of the use of genotypic resistance testing on the response and long-term survival of HIV-1 infected patients who have failed antiretroviral therapy. Methods: A retrospective cohort study was carried out; two groups were defined based on the method of selection of the rescue therapy used: based on the result of the genotypic resistance test (group A) and based on the criteria of experts (group B). The patients were evaluated before the change of rescue therapy according to demographic, clinical and laboratory variables and evaluated at 6, 12, 18, and 24 months after the change of treatment according to virological response, CD4 + cell response, incidence of opportunistic diseases. and survival. The information was obtained from the minutes of the National Commission for Antiretroviral Therapy, the IPK database and the Medical Records. Absolute numbers and percentages, mean and median, with their respective standard deviations (SD), Chi2, were used, the Relative Risk (RR), the Mann-Whitney U test, and the Kaplan-Meier method were applied. Results: Group A patients were 1.44 times more likely to achieve complete virological suppression than group B patients at 6 months, RR 1.44 (1.046-2.054) p = 0.017. The average increase in CD4 + T lymphocytes was 117.40 cells / mm3 in group A patients and 30.04 cells / mm3 in group B patients, p <0.005 12 months after startin treatment. The incidence of opportunistic diseases was 25.7% in group B and 5.6% in group A. The highest percentage of cumulative survival was observed in group A (98.1%), compared to the group B (79%). Conclusions: Patients in whom salvage treatment was chosen based on a genotypic resistance test had a better virological response, a greater increase in CD4 + T lymphocytes, and a longer survival than those in whom treatment was chosen based on expert judgment.

Influencing factors of the effect of anti-retroviral therapy in female commercial sex workers with human immunodeficiency virus positive in Guangxi Zhuang Autonomous Region / 中华传染病杂志

Objective:To investigate the effect and influencing factors of anti-retroviral therapy (ART) in human immunodeficiency virus (HIV)-positive female commercial sex workers (CSW) in Guangxi Zhuang Autonomous Region.Methods:A retrospective cohort study was used in this study. A total of 661 HIV-positive CSW receiving ART from the Guangxi Zhuang Autonomous Region′s municipal and county-level Centers for Disease Control and Prevention (CDC) reported to Guangxi Zhuang Autonomous Region CDC from January 1, 2009 to December 31, 2018 were included.The demographic information of the patients, marital status, past medical history, acquired immunodeficiency syndrome (AIDS)-related diseases after six to 12 months of ART, medications, CD4 + T lymphocytes, virological and immunological effects after receiving ART for six to 12 months were collected. Logistic regression model was used to analyze the influencing factors of virological failure and immunological failure of HIV-positive CSW after six to 12 months of ART. Results:Among 661 HIV-positive CSW, 50(7.6%) cases experienced virological failure, 80(12.1%) cases experienced immunological failure, and 13(2.0%) had both virological failure and immunological failure.There were 85 cases (12.9%) who had a history of sexually transmitted diseases. Multivariate logistic regression analysis showed that unmarried (adjusted odds ratio (a OR)=3.298, 95% confidence interval ( CI) 1.285 to 8.461), AIDS-related diseases after six to 12 months of ART (a OR=4.391, 95% CI 1.555 to 12.402) and missed medications in the last seven days (a OR=3.731, 95% CI 1.942 to 7.166) were risk factors for virological failure. Compared with CD4 + T lymphocytes<200.00/μL at baseline, 350.00≤CD4 + T lymphocytes <500.00/μL (a OR=3.543, 95% CI 1.631 to 7.701) and CD4 + T lymphocytes≥500.00/μL (a OR=2.358, 95% CI 1.002 to 5.547) were risk factors for immunological failure. Conclusions:HIV-positive CSW in Guangxi Zhuang Autonomous Region have a better treatment effect, with low rates of virological failure and immunological failure. Marital status, baseline CD4 + T lymphocyte counts, AIDS-related diseases after six to 12 months of ART, and missed medication in the last seven days are factors influencing the effect of six to 12 months of ART.

Impacto de la viremia de bajo grado en el riesgo de fallo virológico en pacientes con infección por VIH-1 / Impact of low-grade viremia on the risk of virological failure in patients with HIV-1 infection on antiretroviral therapy

Resumen Introducción: Cargas virales (CV) entre 20-200 copias/mL se consideran cargas virales de bajo grado (CVBG). Su implicancia clínica y manejo no han sido definidos. Objetivo: Evaluar el impacto de CVBG en el riesgo de desarrollo posterior de fallo virológico (FV). Pacientes y Métodos: Se incluyeron pacientes ≥ 18 años, desde enero de 2009 a diciembre de 2019, con infección por VIH-1 con CV< 20 copias/mL, por un mínimo de seis meses y/o en dos muestras consecutivas bajo tratamiento anti-retroviral . Se realizó seguimiento de las CV estrati ficándolas: CV < 20 copias/mL, CVBG (20-50 copias/mL y 51-200 copias/mL) y FV. Mediana de seguimiento 25 meses (IQR 15-31). Resultados: Fueron incluidos 1.416 pacientes con CV < 20 copias/ mL bajo TARV. De ellos, 797 permanecieron con CV< 20 copias/mL durante el seguimiento, 144 presentaron CV entre 20-50 copias/mL, 384 entre 51-200 copias/mL y 91 presentaron FV sin CVBG previa. De los 528 pacientes que tuvieron CVBG, 110 (20,1%) fallaron, riesgo 3,45 veces superior respecto a los que no tuvieron CVBG previa. El riesgo de FV fue 3,27 mayor para aquellos que tuvieron CVBG entre 51-200 copias/mL vs 20-50 copias/mL. Discusión: El estudio permite relacionar la CVBG con el FV posterior, siendo el mayor riesgo CVBG entre 51-200 copias/mL.

Abstract Background: Viral loads (VL) between 20-200 copies/mL are considered low-grade viral loads (LGVL). Its clinical implications and management have not been defined. Aim: To evaluate the impact of LGVL on the risk of subsequent development of virological failure (VF). Methods: Patients ≥ 18 years, with HIV-1 infection who had VL < 20 copies/mL for at least six months and/or in two consecutive samples under antiretroviral therapy (ART) were included, between January 1st, 2009 and December 31, 2019. Follow-up of the VLs was carried out stratifying them in VL < 20 copies/mL, LGVL (20-50 copies/mL and 51-200 copies/mL) and VF. Median follow-up 25 months (IQR 15-31). Results: 1,416 patients were included who reached VL < 20 copies/ml under ART, 797 patients remained with CV < 20 copies/mL during follow-up, 144 patients had VL between 21-50 copies/mL, 384 between 51-200 copies/mL and 91 had VF without previous LGVL. Out of 528 patients who had LGVL, 110 failed, risk 3.45 times higher than those who had no previous LGVL. Risk 3.27 times higher of VF for those who had LGVL between 51-200 copies/mL compared to 20-50 copies/mL. Discussion: The study allows to relate the LGVL with VF. This association was observed more frequently with LGVL between 51-200 copies/mL

Tuberculosis incidence among people living with HIV/AIDS with virological failure of antiretroviral therapy in Salvador, Bahia, Brazil

Abstract Antiretroviral therapy for HIV has led to increased survival of HIV-infected patients. However, tuberculosis remains the leading opportunistic infection and cause of death among people living with HIV/AIDS. Tuberculosis has been shown to be a good predictor of virological failure in this group. This study aimed to evaluate the incidence of tuberculosis and its consequences among individuals diagnosed with virological failure of HIV. This was a retrospective cohort study involving people living with HIV/AIDS being followed-up in an AIDS reference center in Salvador, Bahia, Brazil. Individuals older than 18 years with HIV infection on antiretroviral therapy for at least six months, diagnosed with virological failure (HIV-RNA greater than or equal to 1000 copies/mL), from January to December 2013 were included. Tuberculosis was diagnosed according to the criteria of the Brazilian Society of Pneumology. Fourteen out of 165 (8.5%) patients developed tuberculosis within two years of follow-up (incidence density = 4.1 patient-years). Death was directly related to tuberculosis in 6/14 (42.9%). A high incidence and tuberculosis-related mortality was observed among patients with virological failure. Diagnosis of and prophylaxis for tuberculosis in high-incidence countries such as Brazil is critical to decrease morbidity and mortality in people living with HIV/AIDS.

Progress on China's national free antiretroviral therapy strategy in 2002-2014 / 中华流行病学杂志

Objective To analyze the progress and characteristics of China' s "Free AIDS treatment strategy" since the implementation of the national "four free and one care" policy against AIDS 12 years ago.Methods Retrospective cohort study and cross-sectional analysis had been conducted in this study.368 449 cases that had received the ‘free antiviral therapy’ from 2002 to 2014 were selected from the National Treatment Database.Data from the baseline (initial time of ART,CD4 cell count,and antiretroviral regimen) and from the follow-up program (dates and status of follow-up,CD4 cell counts) were gathered and analysed by SAS 9.3.Results The number of cases that having received new treatment was increasing year by year,accounting for 75.4％ of all the cases identified from 2010 to 2014.Constituent ratios of patients with baseline CD4 cell count ＜200 cells/μl and clinical diagnosis of AIDS were decreasing from 81.0％ in 2006 to 39.7 ％ in 2014.Status on drug optimization showed that:3TC replaced DDI,EFV replaced NVP and TDF replaced D4T,making the utilization rates as 99.5％,75.7％,and 60.6％,respectively,by 2014.Regions that were covered by the treatment accounted for 75.4％ of all the counties/districts involved.The previous CDC-led AIDS treatment program and mode of management had been transferred to the hospital-based model.Proportion on the twice-CD4-testing model had been 75.2％ since 2010,with the rate of virological detection increased from 70.8％ in 2010 to 87.4％ in 2014 and the virological unsuccessful testing rate decreased from 17.6％ in 2010 to 11.8％ in 2014.Among all the patients,the 1,5 and 10 year survival rates appeared as 92.2％,80.5％ and 69.6％,respectively.For patients with baseline CD4 cell counts as ＜50 cells/μl or ＞350 cells/μl,the corresponding survival rates showed as 81.6％,69.9％,60.9％ and 97.9％,89.8％,81.0％,respectively.Conclusion China's HIV/AIDS free anti-retroviral therapy program appeared as a national treatment cohort which involved large number of participants,with new patients joining in,annually.Criterion on drug optimization and treatment were consistently following the recommendation and guidelines set by WHO.Management program on treatment had gradually turned to hospital-based,with follow-up and laboratory testing programs guaranteed,ended up with satisfactory treatment effects.

Evaluación de resistencia genotípica del VIH-1 en pacientes con fallo virológico de Guatemala / Evaluation of genotypic resistance of HIV-1 in patients with virologic failure Guatemala

La resistencia a la terapia antirretroviral (TARV) es un factor determinante para el fallo virológico en pacientes con VIH. El objetivo de este estudio fue identificar los patrones genotípicos de resistencia en pacientes con fallo virológico. Fueron incluidos pacientes de las diferentes unidades de atención integral de VIH en Guatemala, de quienes se sospechaba resistencia y que necesitaban cambios en la TARV por fallo virológico, se requirió haber evaluado la adherencia y una carga viral ≥1,000 copias/ml. La información clínica y demográfica fue recolectada a través de la forma de solicitud. El análisis de resistencia se realizó a través de la metodología TRUGENE® HIV-1. La muestra se restringió a 25 pacientes por motivos de accesibilidad. El 68% de las muestras analizadas presentaron resistencia; por familia de ARV la resistencia fue de 88.2% para ITINN, 70.5% para ITIAN y 17.6% para IP. Se identificaron 79 mutaciones entre el grupo de estudio, el 46.8% de fueron asociadas a ITINN, 76.6% a ITIAN y 26.6% a IP. Para ITIAN las mutaciones más frecuentes fueron la M184V 43%, M184I 14% y K219E 10%; el 23.8% fueron mutaciones TAMs. Para ITINN fueron la V179D 16%, K103N 14%, G190A 14% y Y181C 14%. Para los IP la mutación más frecuente fue la M36I con 29%. La resistencia identificada en este grupo, fue menor a lo reportado en otros países latinoamericanos; sin embargo es similar a lo reportado por OMS en países con bajo o medio ingreso económico.

ARV drug resistance is one of the leading causes of virologic failure among HIV patients on HAART. Theobjective of this study was to determine genotypic resistance profiles among HIV patients on virologic failure. Patients from one HIV clinic in Guatemala on whom ARV drug resistance was suspected and needed a change in their ARV regimen due to virologic failure were included. In order to perform the genotype, the patient had to demonstrate good adherence to therapy and a confirmed viral load ≥1,000 copies/ml. Demographics andclinical data were collected through the resistance-testing questionnaire. The TRUGENE® HIV-1 methodology was used for resistance analysis. The patient sample was restricted to 25 patients due to accessibility, 68% presented resistance to at least one ARV drug. By ARV class, 88.2% presented resistance to NNRTIs, 70.5% to NRTIs and 17.6% to IPs. We found 79 mutations among the samples analyzed. Of the mutations found, 46.8% were associated with NNRTI resistance, 76.6% to NRTI resistance and the remainder 26.6% to PI resistance. The most frequent NRTI associated mutations were M184V 43%, M184I 14% and K219E 10%; 23.8% were TAM. The NNRTI associated mutations were V179D 16%, K103N 14%, G190A 14% and Y181C 14%. For the PI the most frequent mutation was M36I with 29%. The resistance found in this study was lower to that reported in other Latin American studies, however, it is similar to what is reported by WHO in low and middle income countries.