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.