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W G Powderly

Publications and source records attributed to W G Powderly.

At least 19 recordsLinked to original sources
PubMed1997

Molecular epidemiology of mucosal candidiasis in HIV-positive women.

Mucosal candidiasis is a common complication of HIV infection and HIV-positive women may develop both oropharyngeal and vaginal disease. Colonization with Candida albicans and related species at either site is a common preceding event in asymptomatic women. To examine the molecular epidemiology of colonizing yeast strains in HIV-positive women, concurrent oropharyngeal and vaginal cultures were obtained from 32 women (mean CD4 count 392 cells/mm3, range 0-1319). Positive oropharyngeal cultures were obtained in 18 (56%) and positive vaginal cultures in 10 (31%). Candida species were isolated from both sites simultaneously in nine (28%) women. All strains were evaluated for restriction fragment length polymorphisms (RFLPs) at the ribosomal DNA locus (using a heterologous 8.4-kb NotI probe from H. capsulatum) and with a C. albicans-specific repetitive DNA probe. Isolates were grouped into three classes by the NotI probe and then members of each class were evaluated with the C. albicans-specific probe. Isolates were subsequently evaluated by random amplified polymorphic DNA (RAPD) PCR with four arbitrary primers to detect strain-specific differences. All isolates tested were unique and could be discriminated by RFLP or RAPD PCR. Vaginal and oropharyngeal isolates from the same individual in all nine cases were dissimilar, suggesting that the dominant strain of Candida colonizing different body sites is different. These findings suggest that the epidemiology of Candida infection in HIV disease is complex, that the development of oropharyngeal and vaginal disease may be disassociated, and that HIV-positive patients are each infected by their own unique strains of Candida.

AIDS-Related Opportunistic Infections↗
PubMed1997

Serum leptin concentrations in human immunodeficiency virus-infected men with low adiposity.

The product of the obese gene (ob) is the protein leptin, which is synthesized in and secreted from adipocytes. Fasting serum leptin concentrations are closely related to body fat content and are higher in obese than in normal-weight individuals. Leptin may contribute to body weight regulation. Overproduction of leptin in certain pathologic conditions such as acquired immunodeficiency syndrome (AIDS) might in principle contribute to the low body fat content associated with body wasting. We measured fasting serum leptin levels by radioimmunoassay in individuals infected with the human immunodeficiency virus (HIV) and in a group of healthy lean men to determine whether HIV infection increases leptin levels. Thirteen HIV-infected men aged 26 to 50 years with a body mass index (BMI) of 15 to 26 kg/m2 and 4 to 24 kg body fat (7% to 29% body fat) had serum leptin levels (3.4 +/- 1.6 ng/mL) that were not elevated compared with the levels in 17 healthy men (4.0 +/- 1.4 ng/mL) matched for age (23 to 47 years), BMI (18 to 26 kg/m2), and body fat (5 to 21 kg; 9% to 28%). In both groups of men, serum leptin concentrations were correlated with percent body fat and body fat content (P < .001), and these relationships were not different between the two groups. In both groups, leptin concentrations were not correlated with lean body mass (P > or = .24). Energy intake in the HIV-infected men, assessed from 3-day intake records, was within the normal range. These findings extend the hypothesis that circulating leptin concentrations directly reflect adipose tissue mass, even in HIV-infected men with low body fat content. These findings do not support the hypothesis that HIV infection is associated with high circulating leptin concentrations, and suggest that low leptin levels do not stimulate food intake in HIV-infected individuals.

Adult↗
PubMed1997

Cryptococcosis.

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AIDS-Related Opportunistic Infections↗
PubMed1996

Patterns of opportunistic infections in patients with HIV infection.

The pattern of the development of opportunistic infections (OIs) in HIV-infected patients was evaluated, based on a cohort of 1,530 patients enrolled in two AIDS Clinical Trials Group anti-retroviral studies. We quantified the increase in risk of OIs associated with the occurrence of a previous OI. This assessment was based on the observed event rates of the more common AIDS-defining OIs: Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), cytomegalovirus (CMV), and a systemic mycosis. Additionally, for each OI, we assessed the relative risks associated with a history of prior OIs, changes in CD4 levels, and baseline prognostic factors. We found that the occurrence of each of these OIs increased the risk of subsequent OIs, even after adjusting for the CD4 count. Specifically, the occurrence of PCP significantly increased the risk of MAC and CMV, and somewhat increased the risk of systemic mycoses. Diagnosis with MAC was associated with an increased risk of subsequent CMV, whereas the occurrence of CMV increased the risk of MAC. Finally, once patients were diagnosed with a systemic mycosis, they were at a somewhat increased risk of subsequently developing MAC or CMV. Although current practice for determining the timing and initiation of prophylactic therapies relies chiefly on CD4 count, the occurrence of specific AIDS-defining OIs in patients with HIV infection should also be taken into account in making decisions regarding prophylaxis strategies.

AIDS-Related Opportunistic Infections↗
PubMed1996

A phase II study of recombinant human interferon-alpha 2a and zidovudine in patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group.

To assess safety, antitumor response, and immunological and virological activity of interferon-alpha 2a and zidovudine combination therapy in patients with AIDS-related Kaposi's sarcoma, we conducted an open-label, Phase II, multicenter study. Sixty-three patients with biopsy-proven Kaposi's sarcoma and no previous interferon-alpha therapy received zidovudine 600 mg/day and interferon-alpha 2a 18 x 10(6) U/day. The median duration of follow-up was 49 weeks. Of 62 evaluable patients, 25 (40%; 95% confidence interval, 0.28-0.52) showed a complete (26%) or partial (15%) antitumor response. Eight of 30 patients (27%) with < 100 CD4 cells/mm3 and 17 of 32 patients (53%) with > or = 100 CD4 cells/mm3 had a response. The median time to response was 36 weeks. Of the 25 patients with a response, four developed tumor progression. The median duration of response was 22.4 weeks. Eight patients (13%) developed another AIDS-defining event and 13 (21%) died. The major toxicities included anemia (16%), neutropenia (27%), elevated serum transaminases (16%), weight loss (16%), malaise (14%), fatigue (14%), fever (10%), and headache (6%). Therapy with intermediate-dose interferon-alpha 2a and zidovudine resulted in tumor regression in patients with AIDS-related Kaposi's sarcoma who had a wide range of CD4 cell counts; this therapy was relatively well tolerated.

Acquired Immunodeficiency Syndrome↗
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↗