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Biomedical subjects

W G Powderly

Publications and source records attributed to W G Powderly.

At least 37 records · Page 2Linked to original sources
PubMed1996

Recent advances in the management of cryptococcal meningitis in patients with AIDS.

The optimum regimen for the treatment of cryptococcal meningitis in patients with AIDS is still not totally clear. The triazoles fluconazole and itraconazole are associated with response rates of 50%-60%. Amphotericin B appears to be associated with a more rapid clearance of organisms, and there are some data suggesting that initial therapy with amphotericin B is preferable to that with triazoles; however, this finding has not been definitively shown in large comparative trials. Results of a recently completed large trial suggested that initial treatment with amphotericin B followed by triazole therapy is associated with an acute mortality rate (approximately 6%) that is substantially less than that in previous studies. Relapse is common (20%-60% of cases) if the patient does not receive chronic suppressive therapy. The drug of choice for maintenance therapy is fluconazole (200 mg/d). A recent trial showed that fluconazole was superior to itraconazole (200 mg/d) as suppressive therapy. Prophylactic use of fluconazole (200 mg/d) significantly decreases the incidence of cryptococcosis and mucosal candidiasis, especially in patients with CD4 cell counts of < 50/mm3. However, because of the lack of a survival benefit and the risk of the selection effect on fluconazole-resistant Candida, it is difficult to make the recommendation of routine prophylaxis with fluconazole for all patients with AIDS; the decision to use prophylaxis should be based on more selective criteria.

AIDS-Related Opportunistic Infections↗
PubMed1995

A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection.

BACKGROUND: Ritonavir is a potent inhibitor in vitro of human immunodeficiency virus type 1 (HIV-1) protease, which is needed for virions to mature and become infective. We assessed the safety and efficacy of ritonavir in patients with HIV-1 infection. METHODS: We administered ritonavir orally to 62 patients in one of four dosages during a 12-week trial containing a 4-week randomized, placebo-controlled, double-blinded phase followed by an 8-week dose-blinded phase. We assessed the response with serial measurements of plasma viremia and serial CD4 cell counts. RESULTS: Fifty-two patients completed the 12-week trial. Diarrhea and nausea were the most common side effects, and reversible elevations in serum triglyceride and gamma-glutamyltransferase levels were the most frequent laboratory abnormalities. Ritonavir had a rapid antiviral effect, with a mean maximal reduction in the number of copies of HIV-1 RNA per milliliter of plasma that ranged from 0.86 to 1.18 log in the four dosage groups. After 12 weeks of treatment, the antiviral effect was partially maintained, with a mean reduction in plasma viremia of 0.5 log. When we used a more sensitive assay for HIV-1 RNA in a subgroup of 20 patients, we found that plasma viremia decreased by a mean of 1.7 log. This antiviral effect was partly sustained at week 12, with a mean reduction of approximately 1.1 log. The patients' CD4 cell counts rose during treatment with ritonavir (median increase, 74 and 83 cells per cubic millimeter at weeks 4 and 12, respectively). CONCLUSIONS: The protease inhibitor ritonavir is well tolerated and has a potent antiviral effect, as shown by substantial decreases in plasma viremia and significant elevations in CD4 cell counts. Expanded clinical trials of ritonavir are warranted.

Adult↗
PubMed1995

Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection.

Dideoxynucleosides induce a dose-related toxic neuropathy; however, there is a paucity of information on whether other risk factors influence the development of neuropathy. We reviewed the records of 103 patients at an AIDS Clinical Trials Unit who were taking didanosine and/or zalcitabine to determine the risk factors for dideoxynucleoside-induced toxic neuropathy. Most were homosexual or bisexual (85%) men with a mean age of 39 years. The median CD4+ lymphocyte count was 59 cells/mm3, and 35% had a previous diagnosis of AIDS. Toxic neuropathy was more common in patients taking zalcitabine compared with those taking didanosine (14 of 51 versus seven of 55, p = 0.08). In the patients who took zalcitabine, those who had a low baseline serum cobalamin level, a history of heavy ethanol consumption, or a history of symptoms of peripheral nerve dysfunction were more likely to develop a toxic neuropathy (10 of 14 versus 12 of 37, p = 0.01). Conversely, there were no factors associated with the development of didanosine-induced toxic neuropathy. Dideoxynucleoside-induced toxic neuropathy is a common problem that can be disabling but is usually reversible. A history of symptoms of peripheral nervous system disease, heavy ethanol consumption, or a low serum cobalamin level may be useful in distinguishing patients at higher risk of developing zalcitabine-induced toxic neuropathy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.

BACKGROUND: We evaluated the effectiveness of three treatment strategies for the prevention of a first episode of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). METHODS: In an open-label trial, 843 patients with HIV infection and fewer than 200 CD4+ cells per cubic millimeter received zidovudine plus one of three randomly assigned prophylactic agents, beginning with trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine and followed by a defined sequence of other drugs to be used in cases of intolerance. RESULTS: The estimated 36-month cumulative risks of P. carinii pneumonia were 18 percent, 17 percent, and 21 percent in the trimethoprim-sulfamethoxazole, dapsone, and aerosolized-pentamidine groups, respectively (P = 0.22). The difference in risk among treatment strategies was negligible in patients entering the study with 100 or more CD4+ lymphocytes per cubic millimeter. In those entering with fewer than 100 CD4+ cells per cubic millimeter, the risk was 33 percent with aerosolized pentamidine, as compared with 19 percent with trimethoprim-sulfamethoxazole and 22 percent with dapsone (P = 0.04). The lowest failure rates occurred in patients receiving trimethoprim-sulfamethoxazole, and failures were more common with 50 mg of dapsone than with 100 mg. Toxoplasmosis developed in less than 3 percent of patients. Of the patients assigned to the two systemic therapies, only 23 percent were receiving their assigned drug and dose when they completed the study. The median survival was approximately 39 months in all three groups, and the mortality attributable to P. carinii pneumonia was only 1 percent. CONCLUSIONS: In patients with advanced HIV infection, the three treatment strategies we examined have similar effectiveness in preventing P. carinii pneumonia. Strategies that start with trimethoprim-sulfamethoxazole or with high-dose dapsone, rather than aerosolized pentamidine, are superior in patients with fewer than 100 CD4+ lymphocytes per cubic millimeter.

AIDS-Related Opportunistic Infections↗
PubMed1995

A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.

BACKGROUND: Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. METHODS: We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. RESULTS: After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 years of follow-up in the fluconazole and clotrimazole groups, respectively; P < 0.001). Survival was similar in the two groups. CONCLUSIONS: Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.

AIDS-Related Opportunistic Infections↗
PubMed1995

Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group.

OBJECTIVE: To compare the safety and efficacy of continuing zidovudine therapy with that of zalcitabine alone or zalcitabine and zidovudine used together. DESIGN: A randomized, double-blind, controlled trial. SETTING: AIDS Clinical Trials units and National Hemophilia Foundation sites. PATIENTS: 1001 patients with symptomatic human immunodeficiency (HIV) disease and 300 or fewer CD4 cells/mm3 or asymptomatic HIV disease and 200 or fewer CD4 cells/mm3 who had tolerated zidovudine therapy for 6 months or more. INTERVENTION: Patients were randomly assigned to receive zidovudine, 600 mg/d; zalcitabine, 2.25 mg/d; or zidovudine, 600 mg/d, and zalcitabine, 2.25 mg/d. MEASUREMENTS: The primary end point was time to disease progression or death. RESULTS: The median follow-up time was 17.7 months. The estimated 12-month event-free rates were 70%, 67%, and 73%, respectively, for the zidovudine, zalcitabine, and combination groups (P = 0.26). A trend analysis showed significantly lower progression rates for combination therapy compared with zidovudine therapy as the pretreatment CD4 cell count increased (P = 0.027). For patients with 150 or more CD4 cells/mm3, those receiving combination therapy were less likely to have disease progression or to die than were those receiving zidovudine (relative risk, 0.51; 95% CI, 0.28 to 0.93; P = 0.029). We observed no difference between the zalcitabine and zidovudine groups (relative risk, 0.74; CI, 0.40 to 1.36; P = 0.33). For patients with 50 to 150 CD4 cells/mm3 or fewer than 50 CD4 cells/mm3, we found no differences among the treatment groups (P = 0.69 and P = 0.57, respectively). Severe toxic effects occurred less frequently among patients with 150 or more CD4 cells/mm3. CONCLUSIONS: We found no overall benefits of zalcitabine used alone or with zidovudine. However, a trend analysis suggested a better outcome for combination therapy compared with zidovudine as the pretreatment CD4 cell count increased.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Bacteremia in hospitalized patients infected with the human immunodeficiency virus: a case-control study of risk factors and outcome.

We reviewed all episodes of nonmycobacterial bacteremias in human immunodeficiency virus (HIV)-infected patients from 1990 to 1991 to determine the incidence, risk factors, and outcome. Forty-five patients had a total of 63 episodes of bacteremia (9% of 689 HIV-related hospitalizations). In this cohort, the median CD4+ lymphocyte count was 17 cells/mm3, 71% had AIDS, and 78% were homosexual men. The most frequently isolated bacteria were Staphylococcus aureus (25%) and coagulase-negative staphylococci (22%). The most common site of infection was intravenous catheter-related, accounting for 35% of the bacteremias. Compared to HIV-infected, nonbacteremic controls, patients with bacteremia detected at admission were more likely to have an indwelling intravenous catheter (p = 0.003) and less likely to be likely zidovudine (p = 0.04). The overall in-hospital mortality rate was 24%. There was no significant difference in the in-hospital mortality rates in bacteremic patients with or without HIV infection. Seventeen patients had more than one episode of bacteremia (71% had recurrence with the same organism). We conclude that bacteremia is a significant problem in HIV-infected persons with low CD4+ lymphocyte counts, often related to the presence of an intravenous catheter; recurrence is common. In addition, HIV infection does not appear to increase the mortality rate for bacteremia.

Adult↗
PubMed1995

Prospects for preventing cryptococcosis in persons infected with human immunodeficiency virus.

Cryptococcosis is a major cause of illness and death among persons infected with human immunodeficiency virus (HIV). Its management must include both initial and maintenance treatment. Although most authorities favor an initial period of therapy with amphotericin B for acute cryptococcosis, the triazoles play a role in both the management of acute disease and subsequent maintenance therapy. AIDS surveillance data collected by the Centers for Disease Control and Prevention document the occurrence of cryptococcosis in more than 17,000 (6.2%) of adults with AIDS in the United States, although this figure is known to be an underestimate. The risk of cryptococcosis among HIV-infected persons is highest at CD4+ lymphocyte counts of < 100/microL. Although cryptococcosis is especially frequent among AIDS patients who are black, male, or injection drug users, the explanations for these patterns remain unclear. Whether geographic differences in rates of cryptococcosis result from variations in the environmental distribution of Cryptococcus neoformans as well as in the distribution of HIV infection is also unclear. Although exposure to pigeon feces is the best known of the putative exposure-related risk factors, proof is lacking that avian excreta are the primary environmental source of the organism in most cases of cryptococcosis. Prophylaxis with triazoles can prevent cryptococcosis and may be considered for adults and adolescents with CD4+ counts of < 50/microL. However, it is uncertain whether prophylaxis will affect survival, be cost-effective, or have an adverse impact on the susceptibility of a variety of fungi to antifungal drugs. Vaccines and monoclonal antibodies designed to prevent or modify cryptococcosis in HIV-infected persons are in the experimental stage.

Adult↗
PubMed1995

Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS and CMV infection of the central nervous system.

The objective of this study was to correlate cytomegalovirus (CMV) DNA levels in the cerebrospinal fluid (CSF) of subjects with AIDS with clinical and pathologic findings attributable to CMV infection of the central nervous system (CNS). CMV polymerase chain reaction (PCR) was done on serial dilutions of CSF samples from 24 AIDS patients with autopsy-proven CNS disorders. CMV DNA was detected in CSF from 12 of 13 subjects with evidence of CMV infection of the brain or spinal cord but in none of 11 subjects without autopsy evidence of CMV CNS infection. Subjects whose CSF contained > 10(3) CMV DNA molecules/8 microL of CSF had severe CMV CNS disease (e.g., ventriculoencephalitis). PCR appears to be more useful than clinical and neuroradiologic findings for documenting CMV infection of the CNS in patients with AIDS. Quantitation of CMV DNA in CSF shows promise for evaluation of the extent of involvement.

AIDS-Related Opportunistic Infections↗
PubMed1995

Detection of Epstein-Barr virus DNA in cerebrospinal fluid for diagnosis of AIDS-related central nervous system lymphoma.

The diagnostic utility of Epstein-Barr virus (EBV) DNA detection in cerebrospinal fluid for the diagnosis of central nervous system lymphoma was evaluated with two different PCR assays to test a collection of cerebrospinal fluid samples from 24 AIDS patients with central nervous system disorders. A PCR assay amplifying a fragment from the BamHI-W region had the highest clinical and analytic sensitivity. The BamHI-W PCR assay detected EBV DNA in cerebrospinal fluid from 83% (5 of 6) of patients with pathologically proven primary central nervous system lymphoma and 7% (1 of 16) of controls with autopsy-proven nonlymphomatous central nervous system disorders. EBV DNA was also detected in one patient with autopsy-proven systemic lymphoma involving the central nervous system and one patient with probable primary central nervous system lymphoma. EBV DNA was detected consistently when central nervous system lymphoma involved meningeal surfaces. PCR for EBV in cerebrospinal fluid appears to be useful for diagnosis of AIDS-related central nervous system lymphoma, but additional studies are required to better define the sensitivity of the assay and to understand the significance of a positive test in the absence of lymphoma.

Central Nervous System Neoplasms↗
PubMed1995

Risks of HIV infection in the health care setting.

Health care workers exposed to blood and body fluids have a low but measurable risk of occupational infection with human immunodeficiency virus (HIV). This risk is related to the prevalence of HIV among patients, the frequency of exposure to infected blood, and the method of exposure. The magnitude of risk is thus difficult to assess for any given situation, although the overall risk following percutaneous exposure is approximately 0.3%. Risk can be reduced by paying close attention to infection control procedures and by minimizing risky procedures. Exposure management should include preexposure education and immediate postexposure care and counseling. Chemoprophylaxis is widely used despite doubts as to its effectiveness, and much research is clearly needed to develop more effective prophylaxis. For patients, the risk of nosocomial acquisition of HIV remains extremely low and can be minimized by strict adherence to proper infection control procedures.

Cross Infection↗
PubMed1994

Resistance to amphotericin B associated with defective sterol delta 8-->7 isomerase in a Cryptococcus neoformans strain from an AIDS patient.

Two Cryptococcus neoformans strains isolated from an AIDS patient were investigated, a pretreatment isolate (CN1) and a second isolate (CN3) following failure of fluconazole and amphotericin B treatment. No difference in fluconazole sensitivity, but relative resistance to amphotericin B was observed for CN3. The sterol composition of CN3 indicated a defect in sterol delta 8-->7 isomerase in this strain and depletion of ergosterol, the major sterol of the CN1.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Resistant candidiasis.

Mucosal (oropharyngeal, esophageal, and, in women, vaginal) candidiasis is a common infectious complication in HIV-infected patients. There is a wide range of drugs to treat or suppress Candida infections. However, with the increasingly common use of fluconazole as treatment or prophylaxis in patients with relatively advanced HIV disease, mucosal candidiasis that is clinically resistant to fluconazole is increasingly recognized. Susceptibility testing for fluconazole has not been well standardized, and laboratory and clinical correlations often have been difficult to demonstrate. However, the frequency with which Candida strains resistant to fluconazole can be isolated appears to be increasing, particularly in patients with advanced HIV disease. Anecdotal results suggest that patients who fail fluconazole therapy usually do not respond to higher doses of fluconazole, but may occasionally respond to itraconazole or ketoconazole. In vitro susceptibility to these agents does not necessarily ensure clinical efficacy. Amphotericin B is usually effective initially but requires parenteral administration. However, with any therapy, relapses tend to occur and progressively recalcitrant disease often occurs, with increasing morbidity for patients. There is a clear need for studies addressing the incidence of resistance, the risk factors for its development, and more effective therapy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis.

The value of monitoring titers of cryptococcal antigen in serum and cerebrospinal fluid (CSF) during therapy for AIDS-associated cryptococcal meningitis was evaluated. Baseline and final titers of antigen in serum and CSF from participants in two studies of such therapy were categorized as increased (a rise of at least two dilutions), unchanged, or decreased (a fall of at least two dilutions). There was no correlation between outcome and changes in serum titers of cryptococcal antigen during treatment for acute meningitis or during suppressive therapy. During therapy for acute infection, an unchanged or increased titer of antigen in CSF was correlated with clinical and microbiological failure to respond to treatment; the correlation was especially strong among patients whose baseline titer of antigen was > or = 1:8 (P = .01). A rise in CSF antigen titer during suppressive therapy was associated with relapse of cryptococcal meningitis (P < .001). We conclude that serial monitoring of cryptococcal antigen, as conducted in these studies, has a limited role in the management of AIDS patients with cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Serious Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus: a case-control study.

We conducted a case-control study to determine the incidence and clinical features of and risk factors for Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus (HIV). Twenty-five patients who had 37 episodes of P. aeruginosa infection from 1990 through 1992 were identified. Most of the patients (92%) were homosexual men with low CD4+ lymphocyte counts and a history of AIDS. The annual incidence rates of P. aeruginosa infection were 3.5% (1990), 6.3% (1991), and 8.7% (1992). Most infections were community-acquired (68%) and involved the respiratory tract (73%). Patients were more likely than HIV-infected controls to have AIDS and had more AIDS-defining opportunistic illnesses. The overall mortality was 36%. Recurrent episodes were common (39%). We conclude that P. aeruginosa infections may be an increasing problem in patients with extremely advanced HIV infection. Clinicians should consider including antibiotics with activity against P. aeruginosa in the empirical treatment for suspected bacterial infection in patients with advanced HIV infection.

AIDS-Related Opportunistic Infections↗