Recognition of possible risk factors for clinically significant drug-drug interactions among Indian people living with HIV receiving highly active antiretroviral therapy and concomitant medications.

BACKGROUND: Greatest challenges for clinician is to recognize risk factors for clinically significant drug interactions (CSDIs). There is a lack of awareness about CSDIs among healthcare professionals in India. OBJECTIVE: To recognize all possible risk factors for drug-drug interactions (DDIs) and to identify clinically significant drug interactions (CSDIs), the prevalence, pattern of occurrence of DDIs in People Living with HIV (PLW-HIV) receiving highly active antiretroviral therapy (HAART) and concomitant medications. METHODS: A retrospective medical record review was carried out by clinical pharmacist with ethics committee approval. Case files of HIV patients receiving HAART with concomitant medications were analyzed for CSDIs using University of Liverpool drug interaction database and CSDIs were classified based on red flag indication (RFI) or contraindicated drug-drug interaction (XDDIs) and orange flag indication (OFI) or DDIs that needs close monitoring. Patients with DDIs (cases) and patients without DDIs (controls) were compared with Chi-square tests. P value <0.05 was considered as statistically significant. RESULTS: A total of 240 HIV patients' cases were screened. Out of which 267 DDIs were reported in 107 patients. Prevalence of DDIs was higher in male 71 (66.4%) compared to female 36 (33.6%). On zero-inflated poisson regression analysis, factors of polypharmacy, opportunistic infections, comorbid condition like Ischemic heart disease, respiratory tract infections, and psychiatric disorder were found to be predictors of high risk factors for DDIs to HAART. Fourteen XDDIs with RFI and two hundred fifty three DDIs with OFI were reported. XDDIs were atazanavir with fluconazole 4 (28.6%), ritonavir with fluconazole 4 (28.6%), nevirapine with rifampicin 2 (14.4%), ritonavir with quetiapine, atazanavir with pantoprazole. Pharmacokinetic DDIs were highest 238 (89.1%). Sixteen DDIs were reported in a single patient. The majority 97 (90.6%) patients had developed ≤5 DDIs, 8 (7.5%) developed six to eleven DDIs. The highest DDIs were reported with efavirenz 49 (18.4%) and zidovudine 44 (16.5%) based HAART regimen. CONCLUSION: In India, with the increasing access to HAART usage, Clinician must focus to pay attention to recognize possible risk factors for CSDIs associated with HAART regimen and strictly to avoid "Red Flag Indication combinations" while prescribing so as to prevent CSDIs.

A prospective study of highly active antiretroviral therapy in Indian human immunodeficiency virus positive patients.

BACKGROUND: There are no studies performed in India on the safety of highly active antiretroviral therapy (HAART) combinations which focus on the base-line CD4+ T-cell count. Further, no data on risk factors for Adverse drug reactions (ADRs) to HAART and there is a lack of data on CD4+ T-cell count recovery after HAART. OBJECTIVES: The aim of this study was to assess risk factors for ADRs to HAART. We also compared the efficacy of HAART combinations with respect to base-line CD4+ T-cell count and CD4+ T-cell counts recovery in Indian HIV positive patients. METHODS: A prospective active surveillance study was adopted at the Antiretroviral Therapy (ART) Centre, District Government Hospital, Udupi, India. HIV-infected patients were intensively monitored to identify risk factors associated with ADRs to HAART from August 2009 to May 2012. The study protocol was approved by the University ethics committee. Baseline CD4+ T-cell count before initiation of HAART and thereafter at every six months of regular follow-up up to 24 months duration was included for comparison. Multivariate logistic regression analysis was used to identify predictors of high risk factors of ADRs. CD4+ T-cell count recovery after HAART from base-line CD4+ T-cell count in different HAART groups was analyzed by test of between-subject effects. P-value <0.05 was considered as statistically significant. RESULTS: A total of 1982 HIV positive patients were enrolled with 1181 (59.6%) males, and 801 (40.4%) females. On multivariate logistic regression analysis, four factors were found to be predictors of high-risk factors for ADRs to HAART: 1) CD4+ T-cell counts, 2) female gender, 3) polypharmacy and 4) opportunistic infections. Between HAART groups, a mean increase of 98 cells/µl of CD4+ T-cell counts recovery was seen in the 3TC + NVP + D4T group (p < 0.001) at 24 months of regular follow-up. CONCLUSION: In India, Clinician should take into consideration all possible risk factors associated with the use of HAART in order to avoid and minimize ADRs. As initial CD4+ T-cell count and age of patient decides the rise of CD4+ T-cell counts with HAART. HAART should be initiated at the earliest age in order to attain maximum CD4+ T-cell counts recovery.

Evaluation of incidence of zidovudine induced anemia in Indian human immunodeficiency virus positive patients in comparison with stavudine based highly active antiretroviral therapy.

OBJECTIVES: In patients infected with human immunodeficiency virus (HIV), zidovudine has been known to cause a severe anemia that resolves promptly when the drug is stopped. The study was aimed to assess the incidence, the pattern of occurrence of zidovudine induced anemia, causality, severity, predictability, preventability and to identify risk factors for zidovudine induced anemia in Indian HIV positive patients in comparision with stavudine based highly active antiretroviral therapy (HAART). METHODS: This was a prospective observational study conducted over a period of 6 months by clinical pharmacists. Enrolled HIV positive patients were intensively monitored for zidovudine and stavudine induced anemia. zidovudine and stavudine fixed dose drug combinations of antiretroviral therapy (ART) were only included. The World Health Organization (WHO)/AIDS Clinical Trials Group (ACTG) definition of a severity grading of anemia was adopted. Each reported case of zidovudine and stavudine induced anemia was assessed for its causality by using the WHO probability scale and also with Naranjo's algorithm. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using the modified Hartwig and Siegel scale. Multivariate logistic regression was used to evaluate the influence of zidovudine induced anemia. P-value < 0.05 was considered as statistically significant. RESULTS: Monitoring of ninety eight HIV positive patients with fixed dose highly active antiretroviral therapy identified 19 cases of zidovudine induced anemia and 2 cases of stavudine induced anemia from 55 and 43 patients respectively. Incidence of zidovudine induced anemia in intensively monitored HIV positive patients was found to be 34.5%. Chi Square tests identified statistically significant incidence differences of anemia (p < 0.05) between the zidovudine group and the stavudine group. Grade 2 and grade 4 anemia accounted for 42.1%. Causality was 'probable' by WHO probability scale and 'definite' and 'probable' by Naranjo's algorithm. The Majority (89.4%) of zidovudine induced anemias were 'moderate' in severity. A total of 94.8% zidovudine induced anemias were probably preventable. Low baseline hemoglobin concentration less than 10.5 g/dl was observed as a risk factor for zidovudine induced anemia by multivariate logistic regression. CONCLUSION: With the increasing access to zidovudine usage in India, clinicians must focus to avoid zidovudine based HAART regimens if baseline hemoglobin concentration is low, (i.e. less than 8 g/dl) thereby avoiding the occurrence of zidovudine induced anemia. Frequent monitoring of complete blood count (CBC) is important in patients on zidovudine therapy to prevent zidovudine induced anemia.

[Retraction Note to] «Highly active antiretroviral therapy induced adverse drug reactions in Indian human immunodeficiency virus positive patients» / [Articulo retractado] «Reacciones adversas inducidas por tratamientos antiretrovirales altamente activos en pacientes indios positivos al virus de la inmunodeficiencia humana»

Objective: To assess the incidence, severity pattern, causality, predictability and preventability of adverse drug reactions (ADRs) and to identify risk factors for adverse drug reactions in highly active antiretroviral therapy. Methods: Enrolled patients were intensively monitored for ADRs to highly active antiretroviral therapy. Predictability was assessed based on history of previous exposure to the drug or literature incidence of ADRs. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using modified Hartwig and Siegel scale. Multivariate logistic regressions were used to identify the risk factors for ADRs. Results: Monitoring of 130 retropositive patients by active pharmacovigilance identified 74 ADRs from 57 patients. Anemia and hepatotoxicity were the most commonly observed ADRs. The organ system commonly affected by ADR was red blood cell (21.4%). The ADRs were moderate in 77% of cases. Type A reactions (77%) were more common. A total of 10.8% ADRs were definitely preventable. The incidence rate of ADRs (65.9%) was highest with Zidovudine + Lamivudine + Nevirapine combination. A total of 84% interruptions to highly active antiretroviral therapy were due to toxicity. CD4 less than 200 cells/µl, female gender and tuberculosis were observed as risk factors for ADRs. Conclusion: Incidence of ADRs in intensively monitored patients was found to be 43.8%. Anemia in HIV patients is an influential risk factor for occurrence of ADRs. With the increasing access to antiretroviral in India, clinicians must focus on early detection and prevention of ADRs to highly active antiretroviral therapy (AU)

Objetivo: Evaluar la incidencia, gravedad, causalidad y preventabilidad de las reacciones adversas medicamentosas (RAM) e identificar los factores de riesgo de esas RAM en terapias de antiretrovirales altamente activos. Métodos: Se monitorizó intensamente a los pacientes incluidos a la búsqueda de RAM. La predecibilidad se evaluó con base en la historia de exposiciones previas al medicamento o a la incidencia de RAM en la literatura. La preventabilidad se valoró usando los criterios de Schumock y Thornton y la gravedad se evaluó utilizando la escala modificada de Hartwig y Siegel. Se utilizaron regresiones logísticas multivariadas para identificar los factores de riesgo de RAM. Resultados: La monitorización retrospectiva de 130 pacientes mediante farmacovigilancia activa identificó 74 RAM de 57 pacientes. Anemia y hepatotoxicidad fueron las RAM más comúnmente observadas. El sistema comúnmente afectado por las RAM fueron las células rojas sanguíneas (21,4%). Las RAM fueron moderadas en el 77% de los casos. Las reacciones tipo A fueron las más comunes. Un total del 10,8% de RAM fueron definitivamente prevenibles. La incidencia de RAM más alta fue con la combinación Zidovudina + Lamivudina + Nevirapina. Un 84% de las interrupciones de terapias antiretrovirales altamente activas fue debido a la toxicidad. Se observaron como factores de riesgo de RAM un CD4 en menos de 200 cel/µl, el género femenino y la tuberculosis. Conclusión: La incidencia de RAM en pacientes intensivamente monitorizados fue del 43,8%. La anemia en pacientes con VIH es un factor de riesgo de influencia en la aparición de RAM. Con el creciente uso de antiretrovirales en India, los clínicos deben centrar la atención en la detección temprana y la prevención de RAM de terapias antiretrovirales altamente activos (AU)

RETRACTED by plagiarism: Highly active antiretroviral therapy induced adverse drug reactions in Indian human immunodeficiency virus positive patients.

OBJECTIVE: To assess the incidence, severity pattern, causality, predictability and preventability of adverse drug reactions (ADRs) and to identify risk factors for adverse drug reactions in highly active antiretroviral therapy. METHODS: Enrolled patients were intensively monitored for ADRs to highly active antiretroviral therapy. Predictability was assessed based on history of previous exposure to the drug or literature incidence of ADRs. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using modified Hartwig and Siegel scale. Multivariate logistic regressions were used to identify the risk factors for ADRs. RESULTS: Monitoring of 130 retropositive patients by active pharmacovigilance identified 74 ADRs from 57 patients. Anemia and hepatotoxicity were the most commonly observed ADRs. The organ system commonly affected by ADR was red blood cell (21.4%). The ADRs were moderate in 77% of cases. Type A reactions (77%) were more common. A total of 10.8% ADRs were definitely preventable. The incidence rate of ADRs (65.9%) was highest with Zidovudine + Lamivudine + Nevirapine combination. A total of 84% interruptions to highly active antiretroviral therapy were due to toxicity. CD4 less than 200 cells/µl, female gender and tuberculosis were observed as risk factors for ADRs. CONCLUSION: Incidence of ADRs in intensively monitored patients was found to be 43.8%. Anemia in HIV patients is an influential risk factor for occurrence of ADRs. With the increasing access to antiretroviral in India, clinicians must focus on early detection and prevention of ADRs to highly active antiretroviral therapy.