Biomedical subjects

J Gathe

Publications and source records attributed to J Gathe.

10 recordsLinked to original sources

PubMed2001

Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial.

CONTEXT: Abacavir, a nucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a standard protease inhibitor-containing regimen for initial antiretroviral treatment. OBJECTIVE: To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen. DESIGN AND SETTING: A multicenter, phase 3, randomized, double-blind trial with an enrollment period from August 1997 to June 1998, with follow-up through 48 weeks at 73 clinical research units in the United States, Canada, Australia, and Europe. PATIENTS: Five hundred sixty-two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L. INTERVENTIONS: Patients were stratified by baseline HIV RNA level and randomly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo. After 16 weeks, patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving randomized treatment or receive open-label therapy. MAIN OUTCOME MEASURE: Virologic suppression, defined as HIV RNA concentration of 400 copies/mL or less at week 48. RESULTS: The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group (51% [133/262]) and in the indinavir group (51% [136/265]) with a treatment difference of -0.6% (95% confidence interval [CI], -9% to 8%). In patients with baseline HIV RNA levels greater than 100 000 copies/mL, the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45% (45/100) vs 31% (30/96) and a treatment diference of -14% (95% CI, -27% to 0%). The 2 treatments were comparable with respect to their effects on CD4 cell count. There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities. One death in the abacavir group was attributed to hypersensitivity reaction, which occurred following rechallenge with abacavir, approximately 3 weeks after initiating study treatment. CONCLUSIONS: In this study of antiretroviral-naive HIV-infected adults, the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks.

Adult↗

PubMed1999

Safety and antiretroviral effects of combined didanosine and stavudine therapy in HIV-infected individuals with CD4 counts of 200 to 500 cells/mm3.

The safety and antiretroviral effects of didanosine and stavudine in combination were evaluated in 86 people infected with HIV with CD4 counts between 200 and 500 cells/mm3 who had received <7 days of prior nucleoside analogue antiretroviral treatment. Patients were randomized to receive blinded treatments with one of five weight-adjusted, twice-daily regimens of didanosine and stavudine (100 + 10 mg, 100 + 20 mg, 100 + 40 mg, 200 + 20 mg, and 200 + 40 mg) for up to 1 year. Dosages were adjusted appropriately for patients weighing <60 kg and reduced in response to adverse effects. No clear dose-related differences among treatment groups were detected with regard to suppression of plasma HIV RNA level or reduction in infectious titers in peripheral blood mononuclear cells (PBMCs), improvement in CD4 count, or adverse effects. However, trends toward greater decreases in viral load and increases in CD4 count were detected when treatment groups containing the full recommended dosage of one or both agents (high-dose subgroup; arms 3, 4, and 5) were compared with the groups receiving lower dosages. At 28 weeks the mean log 10 HIV RNA decrease was 1.12 (n = 52) and at 52 weeks it was 0.97 (n = 32). Combination therapy was well tolerated, with no apparent dose-related adverse effects. Peripheral neuropathy occurred in 2 of 86 (2.3%) of patients. Didanosine and stavudine together appear to be a good nucleoside analogue foundation for aggressive triple- or quadruple-drug therapy. Full therapeutic doses of each of these two agents should be used to achieve optimal suppression of HIV replication.

Adult↗

PubMed1999

Ethnic differences in hormone replacement prescribing patterns.

OBJECTIVE: To determine whether prescription patterns of hormone replacement therapy (HRT) differ in African-American, Asian, Latina, Soviet immigrant, and white women. DESIGN: Retrospective review of computerized medical records. SETTING: The general internal medicine, family medicine, and gynecology practices of an academic medical center. PATIENTS: Women aged 50 years or older with at least one outpatient visit from January 1, 1992, to November 30, 1995. MEASUREMENTS AND MAIN RESULTS: Use of HRT was defined as documentation of systemic estrogen use. The main predictor variable was self-identified ethnicity. Age, diagnosis (coronary heart disease, hypertension, diabetes, osteoporosis, or breast cancer), and median income were included in the analysis. Of the 8,968 women (mean age, 65.4 years) included, 50% were white, 20% Asian, 15% African American, 9% Latina, and 6% Soviet immigrants. Whites (33%) were significantly more likely to be prescribed HRT than Asians (21%), African Americans (25%), Latinas (23%), or Soviet immigrants (6.6%), p < 0.01 for each. Multivariate analysis, comparing ethnic groups and controlling for confounding variables, showed that Asians (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.49, 0.64), African Americans (OR 0.70; 95% CI 0.60, 0.81), Latinas (OR 0.70; 95% CI 0.58, 0.84), and Soviet immigrants (OR 0.14; 95% CI 0.10, 0. 20) were each less likely to be prescribed HRT than were white women. Although women with osteoporosis were more likely to receive HRT (OR 2.28; 95% CI 1.71, 2.99), those with coronary heart disease were not (OR 0.88; 95% CI 0.68, 1.09). CONCLUSIONS: Physicians at this medical center were more likely to prescribe HRT for white women and women with osteoporosis. Further study is needed to address whether these differences in HRT prescribing result in different health outcomes.

Aged↗

PubMed1999

Hormone replacement therapy for African American women: missed opportunities for effective intervention.

OBJECTIVES: Because of the potential benefits and risks of hormone replacement therapy (HRT), information about the efficacy of HRT in different groups of women is important to patients and providers. The objectives of this study were to review the evidence on the benefits and risks of HRT in African American women and to present a quantitative analysis of the potential reduction in mortality from osteoporotic fractures and coronary heart disease and the potential increase in risk of breast and endometrial cancer. METHODS: A MEDLINE search of English-language observational studies and clinical trials on the effects of HRT on osteoporotic fractures and coronary heart disease (CHD) was conducted for the time period from 1966 to September 1998. Using available CHD mortality data for African American women and white women, potential reductions in mortality with HRT were explored for African American and white women. RESULTS: In the 30 studies on CHD and HRT, African American women were known to comprise only 173 (0.1%) of 148,437 participants. In 11 studies of HRT and osteoporotic fractures, only 128 (0.4%) of 40,299 participants were known to be African American women. An analysis of CHD mortality by decade intervals indicated that African American women, aged 55 to 64, are more likely to die from CHD each year than white women. Despite a lower incidence of breast and endometrial cancer among African American women, the mortality rates of African American women with these cancers is higher compared with white women. CONCLUSIONS: With the higher underlying CHD mortality rate among African American women, HRT is an important potential preventive therapy. The absence of African American women and other non-white women from clinical studies of HRT makes it difficult to fully assess the risks and benefits of HRT in this group of women.

Black or African American↗

PubMed1997

Clinical efficacy of monotherapy with stavudine compared with zidovudine in HIV-infected, zidovudine-experienced patients. A randomized, double-blind, controlled trial. Bristol-Myers Squibb Stavudine/019 Study Group.

BACKGROUND: Stavudine is a promising antiretroviral agent, but its clinical efficacy has not been determined. OBJECTIVE: To evaluate the clinical effect of stavudine (2',3'-didehydro-3'-deoxythymidine) monotherapy in patients with human immunodeficiency virus (HIV) infection. DESIGN: Randomized, controlled, double-blind trial. SETTING: 56 outpatient clinics in private practices, universities, and contract research organizations in the United States, France, and Italy. PATIENTS: 822 HIV-infected adults who had 50 to 500 CD4+ cells/mm3 and had previously received at least 6 months of zidovudine treatment. INTERVENTION: Monotherapy with peroral stavudine capsules or peroral zidovudine capsules. MEASUREMENTS: The primary end point was clinical progression, which was defined as all occurrences of acquired immunodeficiency syndrome (AIDS)-defining events or death. RESULTS: Patients receiving stavudine reached clinical end points at a rate of 26 per 100 person-years, compared with 32 per 100 person-years for patients receiving zidovudine (relative risk, 0.75 [95% CI, 0.58 to 0.98]; P = 0.03). The risk for death alone was 26% lower in the stavudine group than in the zidovudine group, but the comparison was not statistically significant (relative risk, 0.74 [CI, 0.53 to 1.02]; P = 0.066). The benefit of stavudine therapy was seen in all CD4+ cell strata (< or = 100 cells/mm3, 101 to 300 cells/mm3, and > 300 cells/mm3) and clinical stages of HIV disease (asymptomatic, symptomatic, and AIDS). Four weeks after treatment began, CD4+ cell counts were 30 cells/mm3 higher in the stavudine group than in the zidovudine group; this difference was sustained for 96 weeks (P < 0.001). Nausea and vomiting were more common in patients receiving zidovudine (P < 0.01), and neuropathy occurred more frequently in those receiving stavudine (12% in the stavudine group compared with 4% in the zidovudine group; P < 0.001). Neuropathy resolved completely in many patients (63%) after interruption of stavudine treatment; these patients could resume stavudine therapy at a lower dose. CONCLUSIONS: Stavudine was well tolerated and delayed progression of HIV disease in patients who had previously received 6 or more months of zidovudine treatment. Benefits were apparent in all CD4+ cell strata and clinical stages of HIV disease. Stavudine is an important agent to consider for trials of combination chemotherapy.

Adult↗

PubMed1997

Surgical therapy for 101 patients with acquired immunodeficiency syndrome and symptomatic cholecystitis.

BACKGROUND: Hepatobiliary disease in patients with acquired immunodeficiency syndrome (AIDS) has been well documented. Cytomegalovirus and Cryptosporidium are the pathogens most frequently associated. Previous reports of cholecystectomies and AIDS have had conflicting results on morbidity and mortality. METHOD: Retrospective review of 101 patients with AIDS and symptomatic cholecystitis who underwent cholecystectomy from December 1989 to May 1995. RESULTS: All patients had symptoms characteristic of gallbladder disease, the most common being abdominal pain and fever. Thickening of the gallbladder was the most common diagnostic finding. Fifty-six patients underwent open cholecystectomy and 45 laparoscopic cholecystectomy. Pathologic examination revealed an abnormal gallbladder in all cases and gallstones in 29%. A specific pathogen or malignancy was identified as the etiologic agent in 44% of patients. Perioperative morbidity was similar (<5%) in both surgical groups. Perioperative mortality was 4% among all the patients treated. CONCLUSIONS: Both open and laparoscopic cholecystectomy improved the quality of life of these patients and should be considered as the treatment for persistent hepatobiliary symptoms in patients with AIDS.

AIDS-Related Opportunistic Infections↗

PubMed1997

A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS.

The safety and efficacy of cidofovir gel for treatment of acyclovir-unresponsive herpes simplex virus infections in AIDS patients was evaluated in a randomized, double-blind, multicenter trial. Cidofovir (0.3% or 1%) or placebo gel was applied once daily for 5 days. Ten of 20 cidofovir-treated and none of 10 placebo-treated patients had complete healing or >50% decreased area (P = .008); 30% of cidofovir-treated patients versus 0 placebo recipients had complete healing (P = .031). Viral shedding ceased in 13 (87%) of 15 cidofovir-treated and 0 of 9 placebo-treated patients (P = .00004). For cidofovir-treated patients, median time to complete or good response was 21 days, and median time to negative viral culture was 2 days (P = .025, P = .0001, respectively). Median lesion area decreases were 58% for cidofovir-treated versus 0 for placebo-treated patients (P = .005), and mean pain score changes were -1.84 versus -0.34 (P = .042). Application site reactions occurred in 25% of cidofovir-treated and 20% of placebo-treated patients; none was dose-limiting. Cidofovir therapy provided significant benefits in lesion healing, virologic effect, and pain reduction.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Diagnosing and treating cytomegalovirus pneumonia in patients with AIDS.

Because cytomegalovirus (CMV) can be isolated from pulmonary secretions of human immunodeficiency virus (HIV)-infected patients without causing disease, its clinical significance as a cause of pneumonia in this patient population is frequently questioned. In a 22-month period, CMV pneumonia was diagnosed in 17 (8%) of 210 HIV-infected patients who underwent lung biopsy on the basis of microbiological and histologic criteria. The clinical presentations of these patients were nonspecific, including fever (100% of patients), shortness of breath (71%), cough (76%), and Pao2 of < 75 mm Hg (88%). A high correlation in the degree of viral burden in lung biopsy specimens was demonstrated by histologic examination, immunohistochemical analysis, and in situ hybridization. No other pulmonary pathogens were identified for nine patients, whereas other possible causes of pneumonia were present in eight: 11 patients had evidence of extrapulmonary CMV disease at presentation. Most patients initially responded to specific anti-CMV therapy; the overall mean survival +/- SD was 3.1 +/- 2.5 months. CMV should be considered as a possible cause of pneumonia in patients with advanced AIDS especially if CMV infection is documented at other sites.

AIDS-Related Opportunistic Infections↗

PubMed1987

Manifestations of sepsis.

The clinical manifestations of sepsis may be flagrant or subtle. Awareness of the signs and symptoms of sepsis allows early recognition and prompt, appropriate management. The clinical presentation, relative frequency, and current pathophysiologic understanding of the manifestations of sepsis are reviewed. Special emphasis is placed on the cardiopulmonary manifestations, which are examined in a temporal sequence of preshock, early shock, and late shock states. While therapy for the underlying infection (such as antibiotics and drainage of abscesses) is often sufficient, therapy for the specific manifestations of sepsis may also be necessary. Guidelines for therapy for these manifestations of sepsis are given.

Bacterial Infections↗

PubMedDate not supplied

Efficacy of nelfinavir in patients switched from ritonavir/saquinavir combination antiretroviral therapy.

UNLABELLED: Based on available data and expert opinion, the IAS-USA treatment guidelines recommend "selective substitution" of the medication thought most likely to be causing a side effect for one that should have a different side effect profile. PURPOSE: This study evaluates the short-term virological efficacy of selective substitution with nelfinavir-nucleoside combination therapy in individuals with plasma viral RNA below 400 copies/mL. METHOD: This study involved a retrospective chart review at five large urban HIV Clinical practice settings and included 19 patients taking combination therapy including ritonavir with saquinavir. We performed selective substitution with a nelfinavir combination. Our main outcome measure was plasma HIV-1 RNA (Amplicor) obtained during the period between weeks 12 to 18. RESULTS: We identified 19 HIV-1-infected individuals with evidence of viral suppression as defined by a viral load below 400 copies/mL while taking dual nucleoside reverse transcriptase inhibitors with ritonavir/saquinavir. Reasons for switching included adverse effects (37%) or preference for nelfinavir due to the possibility of a better defined salvage regimen (63%). We defined a composite viral endpoint indicative of continued viral suppression using the first 12 to 18 weeks following the medication change. We found that 73% maintained undetectable viral loads (plasma HIV RNA below 400 copies/mL) during this period. CONCLUSION: These data suggest that any medication adjustment should be made cautiously, as there may be some potential risk in a substitution. Selective substitution of a medication that has undesirable side effects or other characteristics should be considered when the possible risks of the loss of viral suppression are outweighed by the potential benefits of that substitution.

Anti-HIV Agents↗