Purpose Non-AIDS defining cancers (NADCs) now exceed rates of AIDS-defining cancers in HIV-positive patients. Treatment of NADCs may be complicated by drug-drug interactions between antiretrovirals and chemotherapy. Docetaxel is a widely used anticancer agent that is primarily metabolized by CYP3A4 enzymes and used to treat NADCs. A preclinical in vivo assessment was performed to gain a better understanding of CYP3-mediated drug-drug interactions between antiretrovirals and docetaxel, as well as to assess any alterations in gene expression with these combinations. Methods Docetaxel (20mg/kg i.v.) was administered to male FVB mice in the presence and absence of dexamethasone (10mg/kg p.o. ×4d), efavirenz (25mg/kg p.o. ×4d), ketoconazole (50mg/kg p.o.), or ritonavir (12.5mg/kg p.o.). At various time points, plasma and liver tissue were harvested. Docetaxel concentrations were determined by LC/MS/MS. Pharmacokinetic parameters were calculated. Liver tissue RNA was used to evaluate alterations in Cyp3a11 and Abcb1a gene expression. Results Docetaxel exposure was altered by CYP3A4 inhibitors but not by inducers. The CYP3A4 inducers efavirenz and dexamethasone did not have a significant effect on docetaxel exposure (AUC). However, the CYP3A4 inhibitors ritonavir and ketoconazole resulted in a 6.9 and 3.1-fold increase in AUC, respectively. Alterations in gene expression did not account for the altered docetaxel exposure. Conclusions Docetaxel exposure was significantly altered by CYP3A4 inhibitors. Until a definitive clinical trial is performed, docetaxel should be used with caution in patients on a ritonavir-containing antiretroviral regimen or an alternative antineoplastic therapy or antiretroviral regimen should be considered.

Groundwater fluoride concentration and fluoride-related health problems were studied in twenty-two villages of Indi taluk of Vijayapura district, Karnataka, India. Present study (2015) was also used to compare groundwater fluoride concentration in same 22 villages with previous government report (2000). Groundwater fluoride concentrations of 62 bore wells of 22 villages were analyzed by using an ion-sensitive electrode. A total of 660 adults and 600 children were screened for fluorosis symptoms and signs. Sixty clinically suspected fluorosis patients' urine samples were further analyzed for fluoride. The mean value (1.22 ± 0.75 mg/L) of fluoride concentration of 62 bore wells and 54.83 % bore wells with ≥1.0 mg/L of fluoride concentrations in Indi taluk indicates higher than the permissible limit of drinking water fluoride concentration recommended for India. Clinical symptoms like arthritis, joint pains, gastrointestinal discomfort and lower limb deformities with high urinary fluoride concentrations in some subjects suggest fluorosis. Results also showed an increase in groundwater fluoride concentration of the same 22 villages between previous and present study. Preliminary arthritis symptom of the villagers could be due to drinking fluoride-contaminated water. Increase in fluoride concentration with time to the bore wells definitely indicates future danger.

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