Radhakrishnan Rajesh

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.

Assessment of hematological adverse drug reactions to antiretroviral therapy in HIV positive patients at Kasturba Hospital Manipal

Background HIV-infected patients have a higher risk of developing hematological adverse drug reactions (ADRs) than the general population and have a significant impact on patients’ current and future care options. The study was to determine the causality, the incidence rate, severity pattern of occurrence of hematological ADRs associated with highly active antiretroviral therapy in HIV positive patients. Methods Prospective observational study conducted at medicine department, Kasturba Hospital over a period of 6 months. Enrolled HIV positive patients were intensively monitored for hematological ADRs associated with fixed dose of highly active antiretroviral therapy. Causality of adverse drug reactions was assessed by using WHO probability scale and also with Naranjo’s algorithm. Results Monitoring of 70 HIV positive patients (58 males and 12 females) with fixed dose drug combinations of antiretroviral therapy by active pharmacovigilance identified 47.3% cases of anemia, 15.7% cases of leucopenia, 21% cases of pancytopenia, 5.2% of eosinophilia, 10.5% cases of bicytopenia. The incidence rate of hematological adverse drug reactions was 37.9% and most of the reported ADR’s were definitely predictable and preventable. Fifty percent of these ADR’s were lead to hospitalization and seventy percent of these ADR’s were of moderate in severity. Hematological ADRs were highest with Zidovudine + Lamivudine + Nevirapine (68.4%) and Zidovudine + Lamivudine + Efavirenz (31.57%) combinations. Conclusion With the increasing access to use of highly active antiretroviral in India, clinician must focus for routine monitoring of hematological investigations for early detection and prevention of adverse effects associated with highly active antiretroviral therapy. Author details 1Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal – 576 104, Karnataka, India. 2Department of Medicine, Kasturba Medical College, Manipal University, Manipal – 576 104, Karnataka, India.

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.

Evaluating the Impact of Educational Interventions on Use of Highly Active Antiretroviral Therapy and Adherence Behavior in Indian Human Immunodeficiency Virus Positive Patients: Prospective Randomized Controlled Study

Background: In India, there is a lack of awareness and inadequate knowledge about use of Highly Active Antiretroviral Therapy (HAART) due to social stigma leading to intentional non-adherence among Human Immunodeficiency Virus (HIV) infected patients thus, Educational Intervention (EI) must be sought. Need for the study: There is a need for an EI program for HIV-infected patients for improving adherence to Antiretroviral Therapy (ART). Aim: The aim of the study was to evaluate the impact of an EI on use of HAART and its effect on adherence behavior in Intervention Care Group (ICG) in comparison with Standard Care Group (SCG) in HIV infected patients. Methods: A prospective, randomized, controlled study was conducted at Kasturba hospital Manipal from August 2009 to May 2012 in HIV infected patients. The baseline response for Knowledge, Attitude, Belief, and Practice (KABP) questionnaire was assessed. Block randomization was used to assign the patients to the SCG and ICG. In ICG group, patients are educated every 4 weeks for a total of 16 weeks with Patient Information Leaflet (PIL), adherence counseling and awareness to Adverse Drug Reactions (ADRs) to ART by a clinical pharmacist. In ISG group, patients are given standard care for ART treatment by a clinician. Post KABP response was documented in both groups at 16th week and adherence rate was measured. Repeated-measures Analysis of Variance (RANOVA) was used for the comparison of pre and post total KABP responses between ICG and SCG. Results: A total of 256 HIV positive patients were enrolled. Out of which 16 patients were excluded because they were on traditional medicines and 240 HIV-infected patients with HAART were finally included in the study, of whom 120 (89 [74.2%] men, 31[25.8%] women) were randomly assigned to the ICG and 120 (99 [82.5%] men, 21[17.5%] women) to the SCG. Pre and post KABP responses significantly increased with mean ± standard deviation (SD) (p<0.001) and greater than 95% of adherence (p<0.001) was reported in ICG after EI in comparison with SCG. Conclusion: The EI program on use of HAART in this study changed their intentional non-adherence behavior, negative beliefs and social stigma.