raltegravir-potassium and Neoplasms

Raltegravir, the first approved integrase inhibitor, has been shown to be virologically effective in Phase II and Phase III clinical trials in both treatment naive and triple class resistant patients. It also has an excellent tolerability profile and lacks significant drug-drug interactions making it an important drug in the treatment of a number of special patient populations. In this review its use in patients undergoing solid organ and bone marrow transplantation and patients receiving cancer chemotherapy, will be discussed. In addition other indications including patients with metabolic complications of existing antiretroviral drugs as well as patients with side effects on current HAART regimens. Other groups of patients where raltegravir may play an important role are patients with renal disease and tuberculosis. Finally, although not licensed for use in pregnancy, raltegravir may need to be considered in some pregnant women with antiretroviral resistance or tolerability issues with current HAART regimens.

Topics: Female; HIV Infections; HIV Integrase Inhibitors; Humans; Neoplasms; Organ Transplantation; Pregnancy; Pregnancy Complications, Infectious; Pyrrolidinones; Raltegravir Potassium; Tuberculosis

Topics: Anti-HIV Agents; Cardiovascular Diseases; Comorbidity; Drug Interactions; Drug Substitution; Drug Therapy, Combination; Health Behavior; HIV Infections; Humans; Life Style; Neoplasms; Precision Medicine; Raltegravir Potassium

Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs.. We conducted two identical trials in different geographic regions to evaluate the safety and efficacy of raltegravir, as compared with placebo, in combination with optimized background therapy, in patients infected with HIV-1 that has triple-class drug resistance in whom antiretroviral therapy had failed. Patients were randomly assigned to raltegravir or placebo in a 2:1 ratio.. In the combined studies, 699 of 703 randomized patients (462 and 237 in the raltegravir and placebo groups, respectively) received the study drug. Seventeen of the 699 patients (2.4%) discontinued the study before week 16. Discontinuation was related to the study treatment in 13 of these 17 patients: 7 of the 462 raltegravir recipients (1.5%) and 6 of the 237 placebo recipients (2.5%). The results of the two studies were consistent. At week 16, counting noncompletion as treatment failure, 355 of 458 raltegravir recipients (77.5%) had HIV-1 RNA levels below 400 copies per milliliter, as compared with 99 of 236 placebo recipients (41.9%, P<0.001). Suppression of HIV-1 RNA to a level below 50 copies per milliliter was achieved at week 16 in 61.8% of the raltegravir recipients, as compared with 34.7% of placebo recipients, and at week 48 in 62.1% as compared with 32.9% (P<0.001 for both comparisons). Without adjustment for the length of follow-up, cancers were detected in 3.5% of raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of drug-related adverse events were similar in the raltegravir and placebo groups.. In HIV-infected patients with limited treatment options, raltegravir plus optimized background therapy provided better viral suppression than optimized background therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 and NCT00293254.)

Topics: Adolescent; Adult; Aged; CD4 Lymphocyte Count; Double-Blind Method; Drug Resistance, Viral; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; HIV Integrase Inhibitors; HIV-1; Humans; Logistic Models; Male; Middle Aged; Neoplasms; Organic Chemicals; Pyrrolidinones; Raltegravir Potassium; RNA, Viral; Treatment Outcome; Viral Load

There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association.. The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression.. The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70-0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC).. We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.

Topics: Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Neoplasms; Prospective Studies; Raltegravir Potassium; Risk Assessment; Survival Analysis

There are few data on the best combination antiretroviral therapy in patients with HIV infection who need cancer chemotherapy because of drug-drug interactions and increased risk of toxic effects.. We evaluated the safety, efficacy and interactions of a raltegravir (RAL)-based regimen in 30 HIV-infected patients who received antineoplastic agents.. A total of 17 patients had a non-AIDS-defining malignancy (7 with Hodgkin disease) and 13 had an HIV-related cancer (9 non-Hodgkin lymphoma, 2 Kaposi sarcoma and 2 anal cancer). Overall, they received 49 cycles of chemotherapy with 19 different antineoplastic drugs, including antimetabolites in 4 patients (5-FU, gemcitabine), alkylating agents in 10 cases (cyclophosphamide, ifosfamide), vinca alkaloids in 17 patients (vincristine, vinblastine), anti-tumour antibiotics in 18 cases (doxorubicin), cisplatin or carboplatin in 6, and monoclonal antibodies in 13 patients (rituximab, trastuzumab, cetuximab). Six patients modified the doses of antineoplastic agents due to toxicity not related to raltegravir. During a median follow-up of 67.8 patient-years (median 170 days in concomitant therapy) there was only 1 case of virological failure and no patient discontinued RAL. Geometric mean trough levels of RAL were 143 ng/ml (79-455). There were no opportunistic infections, median CD4(+) T-cell count increased by 49 cells/ml and four (13%) patients died during the study (not related to AIDS progression).. Our results show that a RAL-based regimen is safe and effective in patients requiring chemotherapy, irrespective of type and of duration of chemotherapy.

Topics: Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Raltegravir Potassium; Treatment Outcome; Viral Load; Young Adult