The relation of patient satisfaction with treatment of otitis externa to clinical outcomes: development of an instrument.

This survey was undertaken to develop a short, comprehensive measure of patient satisfaction with pharmacologic treatment for otitis externa and to assess the relationships between satisfaction, disease symptoms, and medication side effects. Otitis externa was diagnosed in 41 patients recruited from 6 sites; 34 patients completed and returned the study instruments and were included in the study. Patients or their caregivers administered polymyxin/neomycin/hydrocortisone ear drops prescribed by a physician and completed a daily diary for 10 days and a satisfaction questionnaire at the end of the treatment period. The main outcome measures were the subscale scores for patient satisfaction and their relation to medication side effects, symptoms of ear infection, activity limitations, pain, and adherence to prescription regimens. The questionnaire and its subscales demonstrated good psychometric properties (ie, reliability coefficients >0.75, except for 1 subscale). Overall satisfaction was found to be significantly correlated with relief of symptoms, ability to return to normal activities, ease of administration, and medication side effects. Satisfaction subscale scores were correlated with patient-reported severity of medication side effects and disease symptoms. More than half the patients took drops for more than the prescribed number of days, and one third took more than the prescribed number of drops per administration (ie, overadherence). The relation between satisfaction and adherence was weak, perhaps due to the high rates of overadherence. Our results demonstrate that patient satisfaction with otic medication can be assessed across various aspects of satisfaction and that it is correlated with reported disease symptoms and medication side effects. This type of multifaceted assessment may help physicians select between medications with different side-effect profiles and administration schedules. Larger studies are needed to evaluate the relationship between satisfaction with an otic medication and adherence to a medication regimen.

Topical ofloxacin treatment of otorrhea in children with tympanostomy tubes.

OBJECTIVE: To determine the safety and efficacy of ofloxacin otic solution in the treatment of acute otorrhea in children with tympanostomy tubes. DESIGN: Multicenter study with an open-label, prospective ofloxacin arm and retrospective historical and current practice arms. SETTING: Ear, nose, and throat pediatric and general practice clinics and office-based practices. SUBJECTS: Children younger than 12 years with acute purulent otorrhea of presumed bacterial origin and tympanostomy tubes. INTERVENTION: Instillation of 0.3% ofloxacin, 0.25 mL, twice daily for 10 days in the prospective arm; review of medical records in the retrospective arms. MAIN OUTCOME MEASURES: The primary index of clinical efficacy was absence (cure) or presence (failure) of otorrhea at 10 to 14 days after therapy. The primary index of microbiologic efficacy (in the ofloxacin arm only) was eradication of pathogens isolated at baseline. Safety was evaluated in the ofloxacin arm only. RESULTS: Significantly more clinically evaluable ofloxacin-treated subjects were cured (84.4%; 119/141) than were historical practice subjects (64.2%; 140/218) (P< or =.001) or current practice subjects (70%; 33/47) (P< or =.03). All baseline pathogens were eradicated in 103 (96.3%) of 107 microbiologically evaluable ofloxacin subjects. Adverse events considered "possibly" or "probably" treatment related occurred in 29 (12.8%) of 226 ofloxacin-treated subjects. CONCLUSION: Ofloxacin is safe and significantly more effective than treatments used in historical or current practice for acute purulent otorrhea in children with tympanostomy tubes.

Treatment patterns for otitis externa.

BACKGROUND: Although otitis externa is a common and painful infection of the outer ear canal, there is little specific information available regarding current treatment patterns in the United States. We wanted to examine treatment patterns for otitis externa. METHODS: Data were analyzed from the 1993 National Ambulatory Medical Care Survey (NAMCS) and the 1993 National Hospital Ambulatory Medical Care Survey (NHAMCS) for adults and children treated for otitis externa. Data analyses included the reasons for physician visits, concomitant diagnoses, types of physicians seen, sources of payment, medical procedures administered, drugs prescribed, and patient disposition following a physician visit. RESULTS: Study results suggested that treatment patterns differ substantially for adults and children, as well as by physician specialty. Although otitis externa is frequently painful, few cases are classified as severe, and the data indicated that less than 20 percent of patients have concomitant diagnoses treatable by medication. Nevertheless, 40 percent of patients received both topical and systemic medication, and many of the oral antibiotics prescribed are not active against Staphylococcus aureus or Pseudomonas aeruginosa, the most common bacterial pathogens in otitis externa. CONCLUSIONS: Appropriate treatment of localized otitis externa with topical antibiotics should eliminate the need for systemic medications. Addition of systemic medications can unnecessarily increase treatment costs and the likelihood of side effects, and could reduce the likelihood of patient compliance.

Clinical trial of ototopical ofloxacin for treatment of chronic suppurative otitis media.

A multicenter, open-label prospective trial was performed to determine the clinical and microbiologic efficacy of ofloxacin (OFLX) otic solution in the treatment of subjects > or =12 years with chronic suppurative otitis media (CSOM) and a chronically perforated tympanic membrane in the infected ear(s). A total of 207 patients at 27 centers in the United States and Central America received OFLX 0.5 mL instilled ototopically twice daily for 14 consecutive days. The primary clinical end point was cure (dry ear) or failure (not dry ear). The primary microbiologic end point was eradication of baseline pathogens. Because there was no comparator and there were few data in the literature regarding clinical efficacy in patients treated with other regimens, the efficacy of OFLX was compared with data recorded in the clinical records of historical-practice control (HPC) or current-practice control (CPC) subjects. The incidence of clinical cure in clinically evaluable OFLX-treated patients (91%; 148 of 162 subjects) was significantly higher than in HPC subjects (67%; 124 of 185 subjects) or CPC subjects (70%; 38 of 54 subjects). OFLX eradicated all baseline pathogens isolated in microbiologically evaluable subjects. These pathogens were predominantly Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis. The most common treatment-related adverse event, bitter taste, occurred in 17% (35 of 207) of OFLX-treated subjects. Thus OFLX 0.5 mL administered twice daily for 14 days was effective in resolving the signs and symptoms of CSOM in subjects > or =12 years, was significantly more effective than therapies used to treat HPC or CPC subjects, and was well tolerated.

Topical ofloxacin versus systemic amoxicillin/clavulanate in purulent otorrhea in children with tympanostomy tubes.

Acute otitis media (AOM) in children with tympanostomy tubes in place typically presents with otorrhea (draining ear). Because therapy is not standardized, various topical and systemic antibiotics of unproven efficacy and safety have been used in this indication. This study compared the safety and efficacy of ofloxacin otic solution, 0.3% (OFLX) with that of Augmentin oral suspension (AUG) in pediatric subjects 1-12 years of age with tympanostomy tubes and acute purulent otorrhea. Subjects were randomized to receive 10d of OFLX, 0.25 ml topically bid, or of AUG, 40 mg/kg per day. Audiometry was performed in subjects > or =4 years of age. Overall cure rate for clinically evaluable subjects was 76% with OFLX (n = 140) and 69% with AUG (n = 146; P = 0.169). Overall eradication rates for OFLX and AUG were similar for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and were superior with OFLX for Staphylococcus aureus and Pseudomonas aeruginosa (P<0.05 for both). OFLX had a greater overall pathogen eradication rate (96% vs. 67%; P<0.001). Treatment-related adverse event rates were 31% for AUG and 6% for OFLX (P<0.001). Neither treatment significantly altered hearing acuity. Topical ofloxacin 0.3% otic solution 0.25 ml bid was as effective and better tolerated than systemic therapy with Augmentin oral suspension 40 mg/kg per day in treating AOM in children with tympanostomy tubes.

Ofloxacin otic solution for treatment of otitis externa in children and adults.

OBJECTIVE: To compare the safety and efficacy of ofloxacin otic solution with those of Cortisporin otic solutions (neomycin sulfate, polymyxin B sulfate, and hydrocortisone) in otitis externa in adults and children. DESIGN: Two randomized, evaluator-blind, multicenter trials, 1 each in children and adults. SETTING: Twenty-three primary care and referral ambulatory care sites per trial. PATIENTS: A total of 314 adults (12 years and older) and 287 children (younger than 12 years). Of the total, data for 247 adults and 227 children were considered clinically evaluable (CE), and those for 98 children and 98 adults were microbiologically evaluable (ME). INTERVENTIONS: Ofloxacin (adults, 0.5 mL; children, 0.25 mL) twice daily or Cortisporin (adults, 0.2 mL; children, 0.15 mL) 4 times daily for 10 days. MAIN OUTCOME MEASURES: The CE subjects were cured if all signs and symptoms resolved at posttherapy (days 11-13) and test-of-cure (days 17-20) visits. The ME subjects had microbiological and clinical successes if they were cured and had microbiological eradication or presumed eradication. RESULTS: Cure was observed in 82% and 97% of CE adults and children treated with ofloxacin and 84% and 95% of CE adults and children treated with Cortisporin, respectively. The most common pathogens at the pretherapy visit were Pseudomonas aeruginosa, Staphylococcus aureus, and enteric bacilli. There were no statistically significant differences in clinical or microbiological and clinical cure or in the rates of adverse events between treatment groups. CONCLUSIONS: Ofloxacin given twice daily is as safe and effective as Cortisporin given 4 times daily for otitis externa. The bacteriological findings and treatment responses do not differ between adults and children.

Piperacillin and tazobactam versus clindamycin and gentamicin in the treatment of hospitalized women with pelvic infection. The Piperacillin/tazobactam Study Group.

OBJECTIVE: To compare the efficacy and safety of a combination of piperacillin and tazobactam with that of clindamycin and gentamicin in the treatment of hospitalized women with infections of the upper genital tract. METHODS: This was a randomized open-label trial in hospitalized women with infections of the upper genital tract. Patients were recruited at 12 hospitals in the United States and two hospitals in Canada and were randomly assigned to one of two regimens in a 2:1 ratio. One group received piperacillin, 3 g every 6 hours, and tazobactam, 375 mg every 6 hours; the other group received clindamycin, 900 mg every 8 hours, and gentamicin, 2.5-5.0 mg/kg/day in three divided doses. Therapy with the assigned regimen was to be administered for a minimum of 3 days. Cultures for aerobic and anaerobic bacteria were obtained from the site of infection before initiation of therapy. Cultures for Chlamydia trachomatis were also obtained from patients with endometritis or pelvic inflammatory disease. Subjects were evaluated for clinical and bacteriologic response at 24-72 hours and 2-4 weeks after completing therapy. RESULTS: Two hundred ninety-nine patients were enrolled; 196 were in the piperacillin-tazobactam group and 103 were in the clindamycin-gentamicin group. The most common diagnoses were endometritis (146) and pelvic inflammatory disease (115). The most common microorganisms recovered included: Peptostreptococcus sp (99), Prevotella sp (87), black pigmented Bacteroides (29), B fragilis (11), enterococci (64), group B streptococcus (26), Escherichia coli (31), Neisseria gonorrhoeae (49), and C trachomatis (19). A favorable clinical response occurred in 84.7% (166 of 196) of piperacillin-tazobactam patients and 87.3% (90 of 103) of clindamycin-gentamicin patients. Among those evaluable for bacteriologic response, 78% (67 of 86) and 82% (23 of 28), respectively, had a favorable response. Diarrhea occurred significantly more frequently in the piperacillin-tazobactam group (9.7 versus 2.9%; P = .04), but the majority of episodes were mild to moderate. None of the adverse experiences in either treatment group were considered life-threatening and drug-related. CONCLUSION: The combination of piperacillin and tazobactam is an effective and well-tolerated antibiotic regimen for the treatment of infections of the upper genital tract in women.

Heterosexual transmission of HIV in a cohort of couples in New York City.

OBJECTIVE: Since heterosexual transmission of HIV in the United States is occurring at an increasing rate, especially among black and Hispanic couples and those in which one member has a history of intravenous drug use, we sought to study the heterosexual transmission of HIV in couples. DESIGN: Multiple logistic regression analysis of risks for HIV infection in female partners. METHODS: We enrolled 158 non-intravenous drug user (IVDU) steady heterosexual partners of HIV-infected individuals (indexes) in this study. Of these, 93% were women, 54% were Hispanic whites, 23% were black and 65.6% were partners of IVDU. RESULTS: In a multiple logistic regression analysis of risks for HIV infection in female partners, the strongest predictors of transmission were AIDS or AIDS-related complex (ARC) in the index [adjusted odds ratios (OR), 16.81; P < 0.001 and 12.53; P = 0.003, respectively], a history of anal intercourse (adjusted OR, 10.81; P < 0.001) and bleeding as a result of intercourse (adjusted OR, 4.90; P < 0.05). Female-to-male transmission was detected in seven out of 11 couples at risk. Ethnicity, number of episodes of vaginal intercourse, number of other sexual partners and history of sexually transmitted infections were not significantly associated with transmission to women. CONCLUSION: Our study demonstrates that health of the index, anal intercourse and bleeding as a result of intercourse are the major determinants of sexual transmission of HIV to women in couples.

Relation between plasma concentrations of didanosine and markers of antiviral efficacy in adults with AIDS or AIDS-related complex.

The relation between the average steady-state plasma concentration (Cpss) of didanosine and selected measures of efficacy, such as CD4 cell count, p24 antigenemia, and weight gain, was evaluated in patients participating in a phase 1 safety and pharmacokinetics study. All patients were diagnosed as having AIDS or severe AIDS-related complex. These individuals first received intravenous didanosine for 2 weeks at doses of 0.8-33 mg/(kg.d) and then took the drug orally at twice the intravenous dose. Cpss values were calculated on the basis of apparent oral clearance after 4 weeks of oral administration and average daily dose over the first 12 weeks of the study. These data were available for 61 patients enrolled at three clinical sites. High values for Cpss were strongly correlated with an increase in CD4 count (P = .006), a decrease in serum levels of p24 antigen (P = .006), and weight gain (P = .0001) at week 12. Logistic regression analysis was used to assess the influence of Cpss on response (as judged by the three criteria just mentioned) after adjustment for other potential factors related to infection with human immunodeficiency virus. The baseline CD4 cell count and the status with regard to prior zidovudine therapy were related to the CD4 response. However, the odds that a response would include all three parameters were nearly twice as high when the Cpss value increased by twofold.(ABSTRACT TRUNCATED AT 250 WORDS)

Didanosine: long-term follow-up of patients in a phase 1 study.

Long-term follow-up of 44 patients with AIDS or AIDS-related complex (ARC) in a phase 1 trial of didanosine is reported. These patients were monitored for as long as 72 weeks (mean, 34 weeks) for toxicity and activity of didanosine. Pancreatitis and neuropathy, the major clinical toxicities, developed infrequently at the doses of didanosine (250-750 mg/d) employed during the latter part of the study. Consistent hematologic toxicity was not encountered; moreover, mean values for hematologic parameters such as hemoglobin concentration, white blood cell count, neutrophil count, lymphocyte count, and platelet count improved for up to 20-60 weeks. CD4 counts increased significantly through 10 weeks of therapy and in some patients remained at or above counts at enrollment for as long as 60 weeks. Serum concentrations of p24 antigen decreased significantly and remained at the decreased level for up to 48 weeks. An initial diagnosis of ARC (as opposed to AIDS), an initial CD4 count of > 100/mm3, and an increase in CD4 counts during the first 10 weeks of therapy were associated with a higher rate of survival and with lower rates of development of opportunistic infections and of other clinical manifestations of disease progression.

Longitudinal analysis of responses to oral didanosine therapy following zidovudine therapy in advanced infection with human immunodeficiency virus.

The effect on immunologic and virological parameters of up to 24 weeks of therapy with didanosine at daily oral doses of < or = 12.5 mg/(kg.d) was studied retrospectively in 69 patients with advanced disease due to human immunodeficiency virus--i.e., AIDS or advanced AIDS-related complex--who had previously been treated with zidovudine. Patients entered the study with a low CD4 cell count (median, 39/microL) and with evidence of an ongoing depression of bone marrow function. Didanosine therapy was associated with a significant increase in CD4 counts and a prolonged decrease in serum levels of p24 antigen relative to baseline. These changes were more pronounced in the population with baseline CD4 counts of > or = 100/microL. A beneficial effect of didanosine therapy on hematologic parameters was observed in these patients, with increases during therapy of hemoglobin levels as well as white blood cell, granulocyte, and platelet counts. These responses were maximal at weeks 16-20. Further investigations are needed to establish the clinical correlates of these observations.

Lymphocytes from some long-term seronegative heterosexual partners of HIV-infected individuals proliferate in response to HIV antigens.

A comparison of the proliferative responses of lymphocytes to human immunodeficiency virus (HIV) antigens from long-term, seronegative heterosexual partners of HIV-infected subjects, from normal unexposed controls and from healthy seropositive heterosexual partners or seropositive, asymptomatic men, reveals that lymphocytes from healthy seropositive individuals with strong proliferative responses to recall, microbial antigens respond only minimally to HIV proteins or envelope peptides, and that even these low responses do not occur in all individuals. If the frequency of responses to several HIV antigens are analyzed, lymphocytes from both HIV-exposed seropositive and seronegative partners of infected individuals proliferate to HIV antigens to a greater degree than lymphocytes from unexposed, normal control individuals. Although lymphocytes from seropositive partners proliferate to a greater degree than those from seronegative partners, the latter are more similar to seropositive partners than they are to normal controls. This observation suggests that these seronegative partners may have become sensitized to HIV antigens through sexual exposure but without infection, and/or that the presence or development of these small immune responses in some individuals might be associated with a failure to become infected.

Pancreatitis and pancreatic dysfunction in patients taking dideoxyinosine.

OBJECTIVE: To describe the incidence, clinical characteristics and dose relationship of dideoxyinosine (ddI)-associated pancreatitis. DESIGN: Patients enrolled in a Phase I dose escalation trial of ddI [AIDS Clinical Trials Group (ACTG) 064] were evaluated for signs and symptoms of pancreatic dysfunction. SETTING: Two ACTG sites. PATIENTS: Forty-four patients with AIDS or AIDS-related complex (ARC) and a CD4 cell count less than or equal to 400 x 10(6)/l. MAIN OUTCOME MEASURES: Seven patients developed pancreatitis that lasted from 1 to 7 weeks and varied in severity from mild to life-threatening. Seven other patients had evidence of hyperamylasemia or hypertriglyceridemia. Six patients who developed pancreatitis were able to tolerate rechallenge with lower doses of ddI. RESULTS: Development of pancreatitis correlated with cumulative dose of ddI but not with stage of disease or concomitant medications. Cumulative dose was not significantly associated with development of hyperamylasemia or hypertriglyceridemia in patients without clinical pancreatitis. CONCLUSIONS: The development of pancreatitis in AIDS or ARC patients receiving ddI varies in severity and time course and is associated with cumulative dose. Patients who develop pancreatitis may be able to tolerate therapy with a lower dose after resolution of their symptoms. Patients receiving ddI require careful monitoring for the development of this complication.

The spectrum of HIV-1-related disease among outpatients in New York City.

OBJECTIVES: To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. DESIGN AND METHODS: The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. RESULTS: Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. CONCLUSIONS: These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.

Impact of bioavailability on determination of the maximal tolerated dose of 2',3'-dideoxyinosine in phase I trials.

The objective of this study was to determine the population pharmacokinetic parameters and the extent of absorption of 2',3'-dideoxyinosine, a nucleoside analog with activity against human immunodeficiency virus in vitro and in vivo, after oral and intravenous administration through the use of NON-linear Mixed Effects Modeling. The data were drawn from the pharmacokinetics section of an open-label, multicenter phase I study. One center administered ddI on a once-daily schedule. The other centers administered the drug once every 12 h. Drug was administered intravenously, and the plasma concentration-time profile was determined. Patients were then given the drug orally at twice the dose used in the intravenous portion of the study, and the pharmacokinetic profile was again determined. A 40-fold range of doses was examined. Forty-six human immunodeficiency virus-infected patients were studied. Concentrations in plasma were determined by high-pressure liquid chromatography. Clearance of the drug from plasma was 47.7 liters/h/70 kg of body weight. The terminal half-life was 1.4 h. The volume of distribution in the central compartment was 18.8 liters/70 kg. Absorption was rapid, with an absorption half-life of 0.52 h. Bioavailability with once-daily administration was 27%. For twice-daily administration, bioavailability rose to 36%. This difference was significant (P much less than 0.01). For doses of less than or equal to 5.1 mg/kg given every 12 h (10.2 mg/kg/day), bioavailability was 41%. We conclude that once-daily administration results in lower mean bioavailability, probably because of a saturation of the absorption process similar to that seen with acyclovir. This difference in bioavailability on the basis of the administration schedule explains the different short-term maximal tolerated doses identified in phase I trials of this agent.

Relationship between dideoxyinosine exposure, CD4 counts, and p24 antigen levels in human immunodeficiency virus infection. A phase I trial.

OBJECTIVE: To determine the relation between exposure to dideoxyinosine (ddl) and increased CD4 cell counts and suppression of serum p24 antigen in patients infected with the human immunodeficiency virus (HIV). DESIGN: Open-label, phase I study. SETTING: Two university hospitals. Patients were studied in both inpatient and outpatient settings. PATIENTS: Of 36 HIV-infected patients enrolled, 18 had adequate pharmacokinetic information for analysis. INTERVENTION: Dideoxyinosine was administered intravenously every 12 hours for 2 weeks. Patients were switched to oral administration at twice the intravenous dose. Pharmacokinetic profiles were obtained twice during each period. A 40-fold range of dose was examined. MEASUREMENTS: CD4-positive T-lymphocyte counts and serum p24 antigen levels were determined. Plasma area under the ddl concentration-time curve was determined for a single dose and at steady state. RESULTS: Increases in CD4-positive T-lymphocyte counts were independent of ddl exposure and were proportional to the starting CD4 count. Suppression of circulating p24 antigen was influenced by cumulative exposure to ddl and was statistically significant. CONCLUSIONS: The CD4-positive T-lymphocyte count increased at low ddl concentrations or exposures; the extent of this increase was directly proportional to the patient's CD4 count at the start of therapy. Suppression of p24 antigen was related to cumulative exposure to ddl. Therapeutic responses can probably be obtained with ddl, while minimizing long-term toxicity, using daily doses of 10 mg/kg body weight, or less.

Extended follow-up of peripheral neuropathy in patients with AIDS and AIDS-related complex treated with dideoxyinosine.

Neuropathic complaints were frequently observed in a Phase I study of dideoxyinosine (ddI) in 44 patients with AIDS and AIDS-related complex. Ten patients (23%) were thought to have a ddI-related peripheral neuropathy. The symptoms were primarily sensory, and there was limited motor involvement. The sensory symptoms improved in all patients with discontinuation of ddI. Some patients tolerated reintroduction of ddI at lower doses without significant recurrence of the neuropathic symptoms. Although the neuropathy was usually seen in patients taking higher doses of ddI than used in current treatment protocols, clinicians must be aware of this potential toxicity as more human immunodeficiency virus-infected patients are being treated with ddI.

Comparison of Immobilon-N membrane and other membranes for the detection of HIV-1 genome in high risk patients using PCR.

The polymerase chain reaction (PCR) was used for detection of the HIV-1 genome from the peripheral blood lymphocytes of high risk patients. The gag regions of HIV-1 (SK38-SK39) were chosen to amplify viral DNA and the amplified products were spotted onto membrane filters and hybridized with a 32P-labeled SK19 probe. Nitrocellulose, nylon and polyvinylidene difluoride (PVDF) membrane filters were used and compared in dot-blot hybridization. PVDF (Immobilon-N, trade name) filter membranes were demonstrated to be the best membranes on the basis of hybridization data and showed a stronger signal on autoradiograms than the other two types (nitrocellulose and nylon).

Phase I study of 2',3'-dideoxyinosine: experience with 19 patients at New York University Medical Center.

We performed a phase I study of escalating dosages of 2',3'-dideoxyinosine (didanosine; ddI) in 19 patients with AIDS or AIDS-related complex in order (1) to establish the maximal tolerated dosage, (2) to determine the nature of toxic adverse effects, (3) to measure changes in levels of circulating human immunodeficiency virus p24 antigen and in CD4+ cell counts, and (4) to evaluate the pharmacokinetics of ddI. Almost all patients had received zidovudine therapy previously. The maximal tolerated dosage of ddI was found to be approximately 12 mg/(kg.d) when it was administered orally for 28 weeks. The major dosage-limiting adverse effects encountered were neuropathy, pancreatitis, and hepatitis. These occurred at dosages higher than those associated with decreases in levels of p24 antigen. The major toxic effects of ddI are different from those associated with zidovudine. At the proper dosage, ddI may prove to be an effective agent for the chronic treatment of infection with human immunodeficiency virus and should be especially useful in the treatment of patients who cannot tolerate zidovudine.