naphthoquinones and HIV-Infections

Topics: Atovaquone; Clindamycin; Corticosterone; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antifungal Agents; Atovaquone; Clindamycin; Dapsone; Drug Therapy, Combination; HIV Infections; Humans; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Primaquine; Trimethoprim, Sulfamethoxazole Drug Combination

To determine (i) effects of lawsone methyl ether (LME) mouthwash on antifungal drug resistance of oral Candida, (ii) effects of LME mouthwash on changes in genotype of oral Candida, and (iii) allergy and subjects' satisfaction on LME mouthwash in comparison with chlorhexidine (CHX).. A randomized clinical trial was conducted in HIV-infected subjects and denture wearers receiving either LME or CHX mouthwash. Candidal culture by oral rinse technique was performed as baseline and after using the mouthwash for 2 weeks. Antifungal drug resistance and changes in genotype of oral Candida were assessed by microdilution assay, inverted repeat polymerase chain reaction and restriction fragment length polymorphism assays, respectively. Allergy and subjects' satisfaction on the mouthwashes were recorded. Statistical analysis was performed using Chi-squared and Fisher's exact tests.. Twenty-nine HIV-infected subjects (age range, 26-54 years; mean age, 41 years) and 38 denture wearers (age range, 27-76 years; mean age, 55 years) were enrolled. C. albicans was the most common specie found in both groups followed by C. tropicalis, C. parapsilosis, and C. glabrata. Neither antifungal drug resistance nor significant changes in genotyping of Candida were noted among those receiving LME mouthwash. Subjects' satisfaction on taste and smell of LME mouthwash was comparable to that of CHX.. Use of LME mouthwash for 2 weeks neither led to antifungal drug resistance nor significant changes in genotype of oral Candida. Thus, LME may be an alternative mouthwash in prophylaxis of oral candidiasis among those at risk of developing the disease.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents, Local; Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidiasis, Oral; Chlorhexidine; Drug Resistance, Fungal; Female; Genotype; HIV Infections; Humans; Hypersensitivity; Male; Middle Aged; Mouthwashes; Naphthoquinones; Patient Satisfaction; Smell; Stomatitis, Denture; Taste

The aim of this study was to determine the antifungal activity of lawsone methyl ether mouthwash (LME) in comparison with chlorhexidine mouthwash (CHX) in vitro and in vivo.. For in vitro study, each mouthwash preparation was added into the inoculum of Candida. The turbidity was recorded after incubation at 37°C for 48 h. Candidal culture was performed and the number of colony of Candida albicans was recorded. For in vivo study, a crossover clinical trial was conducted in 22 HIV-infected subjects and 32 denture wearers. Clinical examination was performed and oral rinse technique was carried out immediately before and 0, 1, 2 h after using each mouthwash. Allergy and subjective assessment of the mouthwashes were recorded. Statistical analysis was performed using one-way ANOVA and linear mixed effect modeling.. In vitro, antifungal activity of 0.25% LME was significantly greater than that of 0.12% CHX (P < 0.05) and comparable with that of 0.2% CHX. In vivo, antifungal activity up to 2 hours of 0.025% LME mouthwash was evidenced in both groups of subjects, although significantly lower than that of 0.12% CHX. No allergic reaction was reported. LME mouthwash was graded to have less bitter taste than that of CHX. Subjects' satisfaction on taste and smell of LME mouthwash was significantly greater than that of CHX (P < 0.05).. Lawsone methyl ether mouthwash possesses potent antifungal activity both in vitro and in vivo. However, concentration of the mouthwash needs to be adjusted in addition to further clinical trials on long-term use.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Analysis of Variance; Antifungal Agents; Candida albicans; Candidiasis, Oral; Chlorhexidine; Cross-Over Studies; Dental Prosthesis; Dentures; Female; HIV Infections; Humans; Male; Middle Aged; Mouthwashes; Naphthoquinones; Statistics, Nonparametric; Young Adult

Trimethoprim-sulfamethoxazole (TMP-SMZ) has been used extensively for the prevention of Pneumocystis carinii (also referred to as "Pneumocystis jiroveci") pneumonia (PCP) and other opportunistic infections in human immunodeficiency virus (HIV)-infected children. Because the efficacy of TMP-SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug-resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin.. A randomized, double-blind, placebo-controlled trial was designed to determine whether atovaquone-azithromycin had equivalent efficacy to TMP-SMZ for the prevention of serious bacterial infections and to compare the long-term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIV-infected children aged 3 months to 19 years. Children qualified for PCP prophylaxis (on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone-azithromycin or TMP-SMZ daily for >or=2 years.. Data from 366 of the 369 eligible patients (median duration of follow-up, 3 years) showed that the estimated rates of serious bacterial infection-related events were lower among atovaquone-azithromycin recipients than among TMP-SMZ recipients (17.3 vs. 24.2 events per 100 patient-years; difference, 6.9 events per 100 patient-years; 95% confidence interval [CI], -0.22 to 14.12). Rates for all end points (serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection-related deaths) were 19.7 and 27.7 events per 100 patient-years, respectively (difference, 7.9 events per 100 patient-years; 95% CI, -0.28 to 15.54 events per 100 patient-years). The results marginally favored atovaquone-azithromycin therapy statistically. Atovaquone-azithromycin and TMP-SMZ therapies had similar adverse event profiles.. We conclude that, in HIV-infected children, atovaquone-azithromycin is as effective as TMP-SMZ for the prevention of serious bacterial infections and is similarly tolerated.

Topics: Adolescent; AIDS-Related Opportunistic Infections; Atovaquone; Azithromycin; Bacterial Infections; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Infant; Infant, Newborn; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Atovaquone suspensions (750 mg and 1500 mg once a day) were compared with aerosolized pentamidine (300 mg once a month) for the prevention of Pneumocystis carinii pneumonia (PCP) in subjects with human immunodeficiency virus (HIV) infection who were intolerant to trimethoprim or sulfonamides (or both). Median time using the assigned therapy was 6.6 months, and the median follow-up was 11.3 months. Intent-to-treat analyses (n=549) showed no statistically significant differences among subjects with regard to the incidence of PCP (26%, 22%, and 17%, respectively) or mortality (20%, 13%, and 18%, respectively). The incidence of treatment-limiting adverse events with atovaquone was significantly higher (P<.01). There was, however, no significant difference in the time using therapy. Incidences of PCP and death were higher in subjects receiving 750 mg of atovaquone than in subjects receiving 1500 mg. Atovaquone suspension at 1500 mg once a day has an efficacy similar to that of aerosolized pentamidine for prevention of PCP in HIV-infected subjects and is a safe, effective alternative in those who are intolerant to trimethoprim or sulfonamides.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim

In 1995 and 1997, the United States Public Health Service (USPHS) and the Infectious Disease Society of America (IDSA) published recommendations for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis in HIV-infected adults. We evaluated their implementation at four hospital-based HIV clinics in New York City in patients who initially met the CD4+ criterion for prophylaxis between January, 1995 and April, 1997. Medical records were reviewed at 6-month intervals to determine drugs prescribed. We identified 149 patients for the PCP sample, 130 for MAC, and 138 for toxoplasmosis. In the three samples, 91% were black and Hispanic, 75% to 81% were male, and 43% to 47% had a history of injection drug use (IDU); median age was between 39 and 40 years. PCP prophylaxis was prescribed during 93% of intervals and did not vary significantly by clinic or patient characteristics. Over the study period, MAC prophylaxis increased from 22% to 62%, and prescriptions for macrolides increased from 38% to 87% of all prescriptions. In the logistic regression analysis, prescription for MAC prophylaxis at any time during the study period was less likely in blacks compared with whites (odds ratio [OR] = .08; 95% confidence interval [CI] = .01, .52) and patients attending the clinic with the lowest rate of MAC prophylaxis (clinic D) compared with the clinic with the highest rate (clinic B; OR = .04; 95% CI = .01, .26). Toxoplasmosis prophylaxis was prescribed in 73% of intervals and did not differ significantly by antibody status (p = .42). Prescribing patterns were uniform across gender, HIV risk behavior, and age for PCP and MAC prophylaxis but differed by clinic and race for MAC prophylaxis. Trends in prophylaxis for opportunistic illnesses must continue to be monitored in light of the success of antiretroviral therapy in reducing the morbidity and mortality associated with HIV/AIDS.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Atovaquone; Azithromycin; Clarithromycin; Dapsone; Ethnicity; Female; HIV Infections; Humans; Longitudinal Studies; Male; Medical Records; Mycobacterium avium-intracellulare Infection; Naphthoquinones; New York City; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Regression Analysis; Rifabutin; Risk-Taking; Time Factors; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Public Health Service

Although trimethoprim-sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent.. We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim-sulfamethoxazole. The median follow-up period was 27 months.. Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia. P. carinii pneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P<0.001); among those not receiving dapsone at base line, it was 0.42 (95 percent confidence interval, 0.30 to 0.58; P<0.001).. Among patients who cannot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention of P. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. carinii pneumonia.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Atovaquone; Dapsone; Female; Follow-Up Studies; HIV Infections; Humans; Male; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

The pharmacokinetic interaction between atovaquone, a 1,4-hydroxynaphthoquinone, and zidovudine was examined in an open, randomized, three-phase crossover study in 14 patients infected with human immunodeficiency virus. Atovaquone (750 mg every 12 hours) and zidovudine (200 mg every 8 hours) were given orally alone and in combination. Atovaquone significantly increased the area under the zidovudine concentration-time curve (AUC) (1.82 +/- 0.62 micrograms.hr/ml versus 2.39 +/- 0.68 micrograms.hr/ml; p < 0.05) and decreased the oral clearance of zidovudine (2029 +/- 666 ml/min versus 1512 +/- 464 ml/min; p < 0.05). In contrast, atovaquone tended to decrease the AUC of zidovudine-glucuronide (7.31 +/- 1.51 micrograms.hr/ml versus 6.89 +/- 1.42 micrograms.hr/ml; p < 0.1) and significantly decreased the ratio of AUC zidovudine-glucuronide/AUC zidovudine (4.48 +/- 1.94 versus 3.12 +/- 1.1; p < 0.05). The maximum concentration of zidovudine-glucuronide was significantly lowered by atovaquone (5.7 +/- 1.5 versus 4.57 +/- 0.97 micrograms/ml; p < 0.05). Zidovudine had no effect on the pharmacokinetic disposition of atovaquone. Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine.

Topics: Adult; Analysis of Variance; Antiviral Agents; Atovaquone; Cross-Over Studies; Glucuronates; HIV Infections; Humans; Male; Middle Aged; Naphthoquinones; Zidovudine

A hydroxynaphthoquinone compound (566C80) has been shown to be effective in the prevention and treatment of murine Pneumocystis carinii pneumonitis. In a phase I study, five cohorts of four human immunodeficiency virus-infected men received 100, 250, 750, 1500, and 3000 mg of the compound orally once daily for 12 days. A sixth cohort received 750 mg three times daily for 5 days, then twice daily for 16 days. Evaluation included clinical, hematologic, and biochemical studies and the pharmacokinetics of 566C80. The only drug-related adverse effect was a maculopapular rash in one patient that resolved without discontinuation of the drug. With the largest dosage tested (3000 mg) the following pharmacokinetic measures were achieved: maximum plasma concentration, 39 micrograms/ml; time to maximum plasma concentration, 8.0 h; area under plasma concentration-time curve at steady state, 1088 h.micrograms/ml; plasma half-life, 51 h; and total plasma clearance, 4.09 l/h. Compound 566C80 offers promise as a new drug class for P. carinii pneumonia.

Topics: Adult; Antifungal Agents; Atovaquone; Cohort Studies; Drug Evaluation; Drug Tolerance; Half-Life; HIV Infections; Homosexuality; Humans; Male; Naphthoquinones; Pneumonia, Pneumocystis

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Atovaquone; Clinical Protocols; Dapsone; Drug Therapy, Combination; HIV Infections; Hospital Administration; Humans; Naphthoquinones; Pneumonia, Pneumocystis; Retreatment; Trimethoprim, Sulfamethoxazole Drug Combination

In an effort to develop new drugs preventing the growth of human immunodeficiency virus (HIV), we developed an in vitro assay method of ribonuclease H (RNase H) activity associated with reverse transcriptase (RT) from HIV-1. Some naphthoquinones, such as 1,4-naphthoquinone (1), vitamin K(3) (2), juglone (3) and plumbagin (6), moderately inhibited RNase H activity, and others, including naphthazarin (5) and shikonins (8-9, 18-23), showed weak inhibition. Diterpenoid quinones, tanshinones (24-28), had also moderate inhibition against RNase H activity. Of these quinones, compound 1 showed the most potent inhibition on RNase H activity with a 50% inhibitory concentration (IC(50)) of 9.5 microM, together with moderate inhibition against RNA-dependent and DNA-dependent DNA polymerase (RDDP and DDDP) activities with IC(50) values of 69 and 36 microM, respectively. Compounds 3 and 5 showed significant inhibition against RDDP (IC(50) = 8 and 10 microM, respectively) and DDDP (IC(50) = 5 and 7 microM, respectively) activities. The structure-activity relationship of the naphthoquinones suggested that non-hydroxylated naphthoquinones (1 and 2) showed significant inhibition of RNase H activity, whereas 5-hydroxylated naphthoquinones (3 and 5) showed potent inhibition against RDDP and DDDP activities.

Topics: Dose-Response Relationship, Drug; HIV Infections; HIV Protease Inhibitors; HIV Reverse Transcriptase; HIV-1; Humans; Inhibitory Concentration 50; Naphthoquinones; Phytotherapy; Quinones; Ribonuclease H

Collecting and documenting subjective prior beliefs from knowledgeable clinicians about the potential results of a clinical trial has many advantages. Two large trials of prophylactic treatments in an HIV-positive population are used as examples. The trials recruited patients of primary care physicians and compared treatments which were in use in clinical practice. Opinions about these trials were elicited from 58 practising HIV clinicians. It is shown how the documented opinions can be used to augment the monitoring process; the prior opinions are updated with interim data using approximate Bayesian methods to give posterior opinions incorporating interim results. These posterior opinions can be used by the monitoring board to anticipate the clinicians' reaction to the results. Eliciting prior beliefs is also ethically important for documenting the nature of the uncertainty or equipoise. Important information is provided for the informed consent process and Institutional Review Board (IRB).

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Atovaquone; Attitude of Health Personnel; Bayes Theorem; Clinical Trials as Topic; Dapsone; Ethics, Medical; HIV Infections; Humans; Naphthoquinones; Physicians; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Sample Size; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Atovaquone; Dapsone; Drug Costs; HIV Infections; Humans; Naphthoquinones; Pneumonia, Pneumocystis

Pneumocystis carinii pneumonia (PCP) remains the most frequently reported serious opportunistic infection in AIDS patients and the second highest cause of mortality among persons with AIDS in the United States, despite the availability of effective chemoprophylaxis.. To evaluate incidence of PCP and determinants of PCP chemoprophylaxis failure, we analyzed data from 2842 patients visits to infectious diseases physicians at 10 HIV clinics (eight private and two public) in eight U.S. cities from January 1992 through June 1996 as part of the HIV Outpatient Study (HOPS). We performed a time-dependent regression analysis to examine potential determinants of PCP chemoprophylaxis failure.. The incidence of chemoprophylaxis failure was 4.6 PCP cases/100 person-years on chemoprophylaxis; these cases represent 67% of all incident episodes of PCP. In a multivariate analysis, the only significant predictors of chemoprophylaxis failure were the use of agents other than trimethoprim-sulfamethoxazole (TMP-SMX), history of prior PCP, and a CD4+ T-lymphocyte cell count of <50 cells/microl. Dosing or frequency of TMP-SMX did not seem to influence risk of chemoprophylaxis failure.. Chemoprophylaxis failure, especially among those with the most advanced immunosuppression or history of prior PCP, was the most significant source of new PCP cases in the HOPS cohort and thus represents one of the largest contributors to morbidity and mortality in this cohort.

Topics: Adult; AIDS-Related Opportunistic Infections; Ambulatory Care; Anti-Infective Agents; Antifungal Agents; Atovaquone; Cohort Studies; Dapsone; Drug Therapy, Combination; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Morbidity; Naphthoquinones; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Treatment Failure; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Fever; HIV Infections; Humans; Male; Naphthoquinones

We describe a child and an adult infected with the human immunodeficiency virus (HIV) who developed cerebral lesions consistent with toxoplasmosis. A biopsy in the child and IgG ELISA in both patients confirmed the diagnosis of Toxoplasma gondii. The patients were initially treated with pyrimethamine, however, computerized tomography studies (CT scan) revealed progression of a left frontal and temporoparietal lesion. Therapy in the child was changed to pyrimethamine, clindamycin, and azithromycin. Repeat CT scan showed further disease progression and therapy was changed to high-dose pyrimethamine (3 mg/kg/d) and azithromycin. A subsequent CT scan disclosed further radiologic progression with increasing edema. The adult patient developed a maculopapular rash during attempted treatment with pyrimethamine.. Introduction of 2 (trans-4[4 chlorophenol] cyclohexy[3-hydroxy-1, 4 naphthoquinone] (HNPQ) an experimental antiparasitic compound previously used only in adult HIV clinical trials, was instituted in the child and rapid oral desensitization to pyrimethamine was initiated in the adult patient.. HNPQ resulted in resolution of the cerebral lesion in the child and rapid oral desensitization to pyrimethamine produced an excellent clinical response in the adult. To our knowledge, these are the first cases of childhood and adult cerebral toxoplasmosis treated successfully with HNPQ and rapid oral desensitization to pyrimethamine.. HNPQ and pyrimethamine desensitization should be considered as alternate modes of therapy in patients who become intolerant or fail to respond to traditional therapy for toxoplasmosis.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiprotozoal Agents; Atovaquone; Child; Desensitization, Immunologic; Female; HIV Infections; Humans; Naphthoquinones; Pyrimethamine; Toxoplasmosis, Cerebral

Pneumocystis carinii pneumonia (PCP) is common in children and adults who are HIV-positive. More than half of the babies who have PCP never received preventive drugs. It is suggested that a greater number of HIV-exposed infants must be identified at an earlier stage, and preventive medication should be prescribed. It is further recommended that HIV testing and monitoring be made more available to infants at risk so that preventive PCP medication can be given at four to six weeks of age, regardless of the CD4 count and HIV test results. The first choice of treatment is Bactrim or Septra. More information can be obtained by calling the Network at (800) 734-7104.

Topics: Antifungal Agents; Atovaquone; Clinical Trials as Topic; Dapsone; HIV Infections; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Naphthoquinones; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Topics: AIDS-Related Opportunistic Infections; Antifungal Agents; Antitubercular Agents; Atovaquone; HIV Infections; Humans; Itraconazole; Ketoconazole; Naphthoquinones; Rifabutin; Rifamycins; United States; United States Food and Drug Administration; Zalcitabine

Transcription of type 1 human immunodeficiency virus (HIV-1) provirus is governed by the viral long terminal repeat (LTR). Drugs can block HIV-1 replication by inhibiting activity of its LTR. We report that topotecan, beta-lapachone, and curcumin are potent and selective inhibitors of HIV-1 LTR-directed gene expression, at concentrations that have minor effects on cells. At these concentrations, each drug inhibited p24 antigen production in cells either acutely or chronically infected with HIV-1. Their target is transcriptional function of the LTR.

Topics: Acute Disease; Antiviral Agents; Camptothecin; Cells, Cultured; Chronic Disease; Curcumin; Gene Expression Regulation, Viral; HIV Infections; HIV Long Terminal Repeat; HIV-1; In Vitro Techniques; Naphthoquinones; RNA, Viral; Topotecan; Virus Replication

Topics: Antifungal Agents; Atovaquone; HIV Infections; Humans; Naphthoquinones; Opportunistic Infections; Pneumonia, Pneumocystis