allopurinol and HIV-Infections

Burkitt's lymphoma and small noncleaved Burkitt's-like lymphoma are rare and are highly aggressive forms of non-Hodgkin's lymphoma that are characterized by dysregulation of the c-myc oncogene. Patients with human immunodeficiency virus (HIV) also appear to be at risk for developing Burkitt's lymphomas. Treatment options for Burkitt's lymphoma involve complex chemotherapy regimens that contain as many as 10 cytotoxic agents. Approximately 50%-80% of adult patients with Burkitt's lymphoma or small, noncleaved lymphoma can be cured with these intensive chemotherapy regimens, and in pediatric populations, the cure rate is even higher. However, a number of factors often compromise the outcome of patients with Burkitt's lymphoma. For instance, the high proliferation rate of Burkitt's lymphoma enhances the risk for tumor lysis syndrome, which results from metabolic imbalances, such as hyperuricemia, that occur as large numbers of malignant cells are lysed during cytotoxic chemotherapy. Standard treatment for tumor lysis syndrome includes adjustments in the chemotherapy regimen, vigorous hydration, administration of a uric acid synthesis inhibitor like allopurinol, and alkalinization. The administration of recombinant urate oxidase (rasburicase) also has been shown to provide effective prophylaxis against hyperuricemia in pediatric and adult patients with hematologic malignancies. The lifetime risk of developing central nervous system disease is 20%-30% for Burkitt's lymphoma. Consequently all chemotherapy regimens with activity in Burkitt's lymphoma utilize some form of central nervous system prophylaxis, such as systemic or intrathecal methotrexate or cytarabine. In the past, patients with HIV who developed Burkitt's lymphoma often received inadequate chemotherapy doses because of their immunosuppression. With the discovery of highly active antiretroviral therapy, the ability to treat and control Burkitt's lymphoma in patients with HIV has improved.

Topics: Adult; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Burkitt Lymphoma; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Enzyme Inhibitors; Etoposide; HIV Infections; Humans; Ifosfamide; Leucovorin; Methotrexate; Time Factors; Treatment Outcome; Urate Oxidase; Vincristine

To assess the effectiveness of two regimens with allopurinol or pentavalent antimony as secondary prophylaxis for visceral leishmaniasis (VL) in human immunodeficiency virus (HIV)-infected patients.. Retrospective, nonrandomized, open trial.. A 1,000-bed academic tertiary institutional hospital in Barcelona.. Forty-six individuals over 14 years old with HIV infection, who recovered from an episode of VL between January 1988 and February 1995.. Twenty patients did not receive any prophylaxis, nine received 300 mg/8 h of allopurinol, and 17 received 850 mg once-a-month of pentavalent antimony. Patients were followed-up every 3 months, and the endpoint of study was relapse of VL.. Twenty-one patients had recurrent VL: 13 of 20 in the control group (65%), 5 of 9 in the allopurinol group (56%), and 3 of 17 in the antimonial group (18%). Kaplan-Meier estimates of the probability of remaining relapse-free at 12 months were 9% without prophylaxis (95% CI, 0-22%), 21% with allopurinol (95% CI, 0-51%), and 93% with antimonials (95% CI, 82-100%) (P < 0.001). Multivariate analysis showed that the only significant variables related to relapsing course of VL were assignment to the antimonial group, and the fact that the patient had experienced a previous episode of VL.. Pentavalent antimony given once a month is effective in the prevention of VL relapses in HIV-infected individuals. It is a low-cost treatment that proved to be well tolerated. Therefore, pentavalent antimony should be considered a suitable agent for secondary prophylaxis against VL.

Topics: Adult; Aged; Allopurinol; Animals; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Data Interpretation, Statistical; Female; Follow-Up Studies; HIV Infections; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Multivariate Analysis; Organometallic Compounds; Recurrence; Retrospective Studies; Time Factors

Inconclusive findings about infection risks, importantly the use of immunosuppressive medications in patients who have undergone large-joint total joint arthroplasty, challenge efforts to provide evidence-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a post-operative infection in patients undergoing TJA of a large joint (total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty) by identifying clinical and demographic factors, including the use of high-risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses [i.e., rheumatoid arthritis (RA), osteoarthritis (OA), gout, obesity, and diabetes mellitus] that are linked to infection status, controlling for length of follow-up.. A retrospective, case-control study (N = 2212) using de-identified patient health claims information from a commercially insured, U.S. dataset representing 15 million patients annually (from January 1, 2007 to December 31, 2009) was conducted. Descriptive statistics, t-test, chi-square test, Fisher's exact test, and multivariate logistic regression were used.. Male gender (OR = 1.42, p < 0.001), diagnosis of RA (OR = 1.47, p = 0.031), diabetes mellitus (OR = 1.38, p = 0.001), obesity (OR = 1.66, p < 0.001) or gout (OR = 1.95, p = 0.001), and a prescription for prednisone (OR = 1.59, p < 0.001) predicted a post-operative infection following total joint arthroplasty. Persons with post-operative joint infections were significantly more likely to be prescribed allopurinol (p = 0.002) and colchicine (p = 0.006); no significant difference was found for the use of specific disease-modifying anti-rheumatic drugs and TNF-α inhibitors.. High-risk, post-operative joint infection groups were identified allowing for precautionary clinical measures to be taken.

Topics: Aged; Allopurinol; Arthritis, Rheumatoid; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Shoulder; Case-Control Studies; Comorbidity; Diabetes Mellitus; Female; Glucocorticoids; Gout; Gout Suppressants; HIV Infections; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Logistic Models; Lupus Erythematosus, Systemic; Male; Middle Aged; Multivariate Analysis; Neoplasms; Obesity; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prednisone; Prosthesis-Related Infections; Retrospective Studies; Risk Factors; Sex Factors; Shoulder Joint; Surgical Wound Infection

Noncirrhotic portal hypertension (NCPH) is a rare but potentially life-threatening complication in patients with human immunodeficiency virus (HIV). Cases of NCPH have been reported in HIV-negative individuals as result of treatment with thiopurines for leukemia or inflammatory bowel disease. Exposure to didanosine, which is also a purine analogue, predisposes to NCPH in the HIV setting. However, it is unclear why NCPH only develops in a small subset of didanosine-treated patients.. A multicenter, case-control study was conducted to investigate the role of pharmacogenomics in NCPH in HIV patients with prior didanosine exposure. Three controls were chosen for each case, adjusted for sex, age, CD4 counts, plasma HIV-RNA, and site. Tagging 36 single-nucleotide polymorphisms (SNPs) at enzymes involved in the purine metabolism (inosine triphosphatase, 5'-nucleotidase cytosolic-II, purine nucleoside phosphorylase and xanthine oxidase) was performed using SNPlex microarray technology.. Eighty individuals were examined; 22 with NCPH and 58 matched controls. Two SNPs at the 5'-nucleotidase gene were associated with NCPH: rs11191561 (48% CG/GG vs 17% CC; P=.003) and rs11598702 (40% CC/CT vs 9% TT; P=.003). SNPs at another 2 loci at the xanthine oxidase gene were also associated with NCPH: rs1429376 (71% AA vs 23% CC/AC; P=.015) and rs1594160 (71% AA vs 23% CC/AC; P=.015). There was a cumulative risk of NCPH for these 4 SNPs: 7%, 26%, 42%, 50%, and 100%, respectively, for 0, 1, 2, 3, or all SNPs (P=.001).. SNPs at the 5'-nucleotidase and xanthine oxidase genes influence the risk of NCPH in HIV patients treated with didanosine.

Topics: 5'-Nucleotidase; Adult; Anti-HIV Agents; Case-Control Studies; Didanosine; Female; Genetic Association Studies; GPI-Linked Proteins; HIV Infections; Humans; Hypertension, Portal; Male; Middle Aged; Polymorphism, Single Nucleotide; Prospective Studies; Risk; Xanthine Oxidase

To evaluate variability in cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO) activity in HIV-infected patients and compare this with data from uninfected, healthy volunteers.. Ten HIV-infected men and seven women on medication affecting CYP enzyme activity were phenotyped four times over 2 months using caffeine, dextromethorphan, and midazolam. Urinary caffeine and dextromethorphan metabolite ratios were used to phenotype CYP1A2, NAT2, XO, and CYP2D6 activity and midazolam plasma clearance was used to phenotype CYP3A activity. Plasma and urine samples were analyzed by validated LC/UV or LC/MS methods for midazolam, caffeine, and dextromethorphan. Noncompartmental pharmacokinetics and nonparametric statistical analyses were performed, and the data compared with those of healthy volunteer historic controls.. Compared with age and sex-matched healthy volunteers, HIV-infected subjects had 18% lower hepatic CYP3A4 activity, 90% lower CYP2D6 activity, 53% lower NAT2 activity, and 22% higher XO activity. No significant difference was found in CYP1A2 activity. Additionally, 25% genotype-phenotype discordance in CYP2D6 activity was noted in HIV-infected subjects. Intraindividual variability in enzyme activity increased by 42-62% in HIV-infected patients for CYP1A2, NAT2, and XO, and decreased by 33% for CYP2D6. Interindividual variability in enzyme activity increased by 27-63% in HIV-infected subjects for CYP2D6, CYP1A2, and XO, and decreased by 38% for NAT2. Higher plasma TNFalpha concentrations correlated with lower CYP2D6 and CYP3A4 activity.. Infection with HIV or stage of HIV infection may alter Phase I and II drug metabolizing enzyme activity. HIV infection was related to an increase in variability of these drug-metabolizing enzymes. Altered metabolism may be a consequence of immune activation and cytokine exposure.

Topics: Adult; Arylamine N-Acetyltransferase; Caffeine; Cytochrome P-450 Enzyme System; Dextromethorphan; Female; HIV Infections; Humans; Interleukin-6; Male; Midazolam; Phenotype; Tumor Necrosis Factor-alpha; Xanthine Oxidase

Human immunodeficiency virus (HIV)-infected patients have a higher incidence of oxidative stress, endothelial dysfunction, and cardiovascular disease than uninfected individuals. Recent reports have demonstrated that viral proteins upregulate reactive oxygen species, which may contribute to elevated cardiovascular risk in HIV-1 patients. In this study we employed an HIV-1 transgenic rat model to investigate the physiological effects of viral protein expression on the vasculature. Markers of oxidative stress in wild-type and HIV-1 transgenic rats were measured using electron spin resonance, fluorescence microscopy, and various molecular techniques. Relaxation studies were completed on isolated aortic rings, and mRNA and protein were collected to measure changes in expression of nitric oxide (NO) and superoxide sources. HIV-1 transgenic rats displayed significantly less NO-hemoglobin, serum nitrite, serum S-nitrosothiols, aortic tissue NO, and impaired endothelium-dependent vasorelaxation than wild-type rats. NO reduction was not attributed to differences in endothelial NO synthase (eNOS) protein expression, eNOS-Ser1177 phosphorylation, or tetrahydrobiopterin availability. Aortas from HIV-1 transgenic rats had higher levels of superoxide and 3-nitrotyrosine but did not differ in expression of superoxide-generating sources NADPH oxidase or xanthine oxidase. However, transgenic aortas displayed decreased superoxide dismutase and glutathione. Administering the glutathione precursor procysteine decreased superoxide, restored aortic NO levels and NO-hemoglobin, and improved endothelium-dependent relaxation in HIV-1 transgenic rats. These results show that HIV-1 protein expression decreases NO and causes endothelial dysfunction. Diminished antioxidant capacity increases vascular superoxide levels, which reduce NO bioavailability and promote peroxynitrite generation. Restoring glutathione levels reverses HIV-1 protein-mediated effects on superoxide, NO, and vasorelaxation.

Topics: Acetylcholine; Animals; Animals, Genetically Modified; Antioxidants; Aorta; Biopterins; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Endothelium, Vascular; Glutathione; HIV Infections; HIV-1; Human Immunodeficiency Virus Proteins; Male; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase Type III; Nitroprusside; Oxidative Stress; Proviruses; Pyrrolidonecarboxylic Acid; Rats; Rats, Inbred F344; Superoxides; Thiazolidines; Tyrosine; Vasodilation; Vasodilator Agents; Xanthine Oxidase

Visceral leishmaniasis (VL) is endemic in Sicily. Although it is a notifiable disease, there is evidence that the actual number of cases is higher than that reported. In 1987, a regional reference center for active surveillance of VL was established and it recorded a total of 284 cases through 1995, a mean of 31.5 cases/year and about four-fold more than previously reported. Of the 284 cases, 150 (53%) were children (< or = 14 years of age), and of the 134 adults, 39 (29%) were coinfected with human immunodeficiency virus (HIV). The commonest viscerotropic zymodeme of Leishmania infantum, MON 1, was identified in 40 (93%) of 43 HIV-negative and eight (57%) of 14 HIV-positive patients. Among 280 patients evaluated (i.e., all HIV-negative and 35 of 39 HIV-positive subjects), 254 (91%) were treated with meglumine antimoniate alone or in combination with other drugs; 23 (8%) received allopurinol or amphotericin B, either conventional or in liposomal form; and three terminally ill patients were not treated. Among the 245 HIV-negative patients, 236 (96%) were successfully cured, while nine (4%) (seven adults) died during the course of antimonial treatment. None of the 35 HIV-positive patients was definitively cured, although mortality was apparently associated with other opportunistic infections.

Topics: Adolescent; Adult; Age Distribution; Aged; Allopurinol; Amphotericin B; Animals; Antiprotozoal Agents; Child; Child, Preschool; Cohort Studies; Drug Therapy, Combination; Female; HIV Infections; Humans; Infant; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Middle Aged; Organometallic Compounds; Recurrence; Sex Distribution; Sicily

We report on 11 patients with HIV infection and visceral leishmaniasis and who were treated with meglumine antimoniate plus allopurinol for 3 weeks (six patients) or 4 weeks (five patients). Clinical and parasitological cures were achieved in four of the five patients treated for 4 weeks and in one of the six patients treated for 3 weeks. Only one patient developed a severe maculopapular rash. Allopurinol plus meglumine antimoniate was found to be a safe combination of drugs for the treatment of visceral leishmaniasis in patients infected with HIV. The optimal length of this treatment is unknown but a course of at least 4 weeks' duration would appear to be necessary for obtaining parasitological cure in most cases.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Allopurinol; Antiprotozoal Agents; Drug Therapy, Combination; Female; HIV Infections; Humans; Injections, Intramuscular; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pilot Projects

Topics: Adult; Allopurinol; Heroin Dependence; HIV Infections; Humans; Leishmaniasis, Visceral; Male