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Biomedical subjects

N Clumeck

Publications and source records attributed to N Clumeck.

At least 73 records · Page 4Linked to original sources
PubMed1995

Differential effect of human immunodeficiency virus infection on the IgA and IgG antibody responses to pneumococcal vaccine.

The IgA, IgM, and IgG antibody responses to pneumococcal polysaccharide vaccine were analyzed in 35 asymptomatic or mildly symptomatic human immunodeficiency virus (HIV)-infected patients stratified according to their CD4 cell counts and in 12 healthy controls. Both the antibody titers in serum and saliva and the numbers of circulating antigen-specific antibody-producing cells (Elispot technique) were measured. At the peak of the antibody responses, HIV-infected patients mounted nearly normal IgG responses, while their IgM responses were significantly depressed, regardless of their CD4 cell counts. The IgA antibody response was decreased in patients with < 500 CD4 circulating cells/mm3. Most IgG antibodies belonged to the IgG2 subclass, and most IgA antibodies were dimeric IgA2 in both controls and patients. Anti-capsular pneumococcal polysaccharide IgG titers decreased much more rapidly in HIV-infected patients so that in all groups they were significantly lower than in controls 9 months after vaccination.

Adult↗
PubMed1995

Kaposi's sarcoma in patients infected with human virus (HIV): an overview.

The emergence of Kaposi's sarcoma (KS) among patients with HIV infection has raised a number of unsolved questions. The particular epidemiology and the etiology of KS remain unclear while both inflammatory cytokines and HIV-derived proteins appear to be involved in its pathogenesis as shown with the aid of in vitro KS-like cell cultures of animal models. Since KS rarely occurs among HIV-positive Caucasian females, sexual hormones, especially beta Human Chorionic Gonadotropin, have recently been reported as providing theoretically some protection against KS both in vitro and in vivo. All these aspects will be detailed as well as the therapeutic approaches which still remain unsatisfactory. So far, there is no curative treatment for KS and drug-induced toxicity is the limiting factor for the prolonged use of the current approaches. Perspectives for therapy will be discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Survival differences in European patients with AIDS, 1979-89. The AIDS in Europe Study Group.

OBJECTIVES: To examine the pattern of survival and factors associated with the outcome of disease in patients with AIDS. DESIGN: Inception cohort. Data collected retrospectively from patients' charts. SETTING: 52 clinical centres in 17 European countries. SUBJECTS: 6578 adults diagnosed with AIDS from 1 January 1979 to 31 December 1989. MAIN OUTCOME MEASURES: Survival after the time of diagnosis. RESULTS: The median survival after diagnosis was 17 months, with an estimated survival at three years of 16% (95% confidence interval 15% to 17%). Patients diagnosed in southern Europe had a shorter survival, particularly immediately after the time of diagnosis, compared with patients diagnosed in central and northern Europe (survival at one year (95% confidence interval) 54% (52% to 56%) 66% (64% to 68%), 65% (63% to 66%), respectively. The three year survival, however, was similar for all regions. The regional differences in survival were less pronounced for patients diagnosed in 1989 compared with earlier years. Improved survival in recent years was observed for patients with a variety of manifestations used to define AIDS but was significant only for patients diagnosed with Pneumocystis carinii pneumonia. The three year survival, however, remains unchanged over time. CONCLUSIONS: Survival of AIDS patients seems to vary within Europe, being shorter in southern than central and northern Europe. The magnitude of these differences, however, has declined gradually over time. Short term survival has improved in recent years, but the long term prognosis has remained equally poor, reflecting the fact that the underlying infection with HIV and many of the complicating diseases remains essentially uncontrolled.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Comparison of long-term prognosis of patients with AIDS treated and not treated with zidovudine. AIDS in Europe Study Group.

OBJECTIVE: To determine the association between elapsed time since starting zidovudine and survival in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Inception cohort and observational study of patients treated and not treated with zidovudine. SETTING: Fifty-one centers in 17 European countries. PATIENTS: A total of 4484 patients diagnosed as having AIDS from 1979 to 1989 who survived their initial AIDS-defining event and who had not started zidovudine before AIDS diagnosis. MAIN OUTCOME MEASURES: Use of zidovudine and mortality. RESULTS: Among patients who did not receive zidovudine, the death rate was approximately constant for the first 5 years after AIDS diagnosis. For patients treated with zidovudine, the death rate within the first year since starting zidovudine was markedly lower than for untreated patients who had developed AIDS at the same time (relative rate, 0.47; 95% confidence interval [CI], 0.42 to 0.51). For longer times since starting zidovudine, the association with reduced mortality rate was diminished, and for patients surviving more than 2 years since starting zidovudine, the death rate was greater than for untreated patients who had developed AIDS at the same time (relative rate, 1.35; 95% CI, 1.15 to 1.58). Adjustment for other prognostic factors failed to substantially affect this observation. CONCLUSIONS: When initiated after the time of AIDS diagnosis, zidovudine was associated with improved prognosis but for no more than 2 years after starting therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Successful treatment of progressive mucocutaneous infection due to acyclovir- and foscarnet-resistant herpes simplex virus with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC).

The acyclic nucleoside phosphonate (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was used topically for the treatment of persistent mucocutaneous infections in two cases. One patient with AIDS suffered from a perineal lesion due to infection with herpes simplex virus type 2 (HSV-2) and did not respond to acyclovir and was intolerant of foscarnet. A bone marrow transplant recipient developed orofacial lesions due to infection with herpes simplex virus type 1 (HSV-1) that failed to respond to therapy with both acyclovir and foscarnet. After topical application of HPMPC, the HSV-2 lesions completely resolved. However, the lesions recurred 3 weeks later, and, upon subsequent treatment with HPMPC, regressed. On recurrence, the virus was found to be sensitive to acyclovir, which the patient was given. Again HSV-2, which was resistant to acyclovir, emerged; similar observations were made after another cycle of HPMPC therapy. The HSV-1 isolates were resistant to acyclovir and foscarnet. Following local HPMPC treatment, the lesions regressed, but after 1 week, a second course of topical HPMPC therapy had to be instituted for recurrent infection. The lesions again regressed, and as the recurrent virus was sensitive to acyclovir, the patient was successfully treated with the drug. The results of this study point to the potential usefulness of topical HPMPC in the treatment of immunocompromised patients with HSV-related mucocutaneous infections that are refractory to therapy with acyclovir and/or foscarnet.

AIDS-Related Opportunistic Infections↗
PubMed1994

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

AIDS-Related Complex↗
PubMed1994

Possible role of granulocyte-macrophage colony stimulating factor (GM-CSF) on the rapid progression of AIDS-related Kaposi's sarcoma lesions in vivo.

Drug-related neutropenia is a common observation in AIDS patients. Haematological growth factors are therefore increasingly used in combination with myelotoxic agents to reduce the risk of infection and to improve the haematological tolerance of these regimens. We report a case of an AIDS patient with Kaposi's sarcoma who received GM-CSF for severe neutropenia due to anti-tumour chemotherapy combining alpha-interferon 2b and zidovudine. During GM-CSF administration there was a marked increase in the size of the Kaposi's sarcoma lesions as confirmed by ultrasonographic examination. As GM-CSF in vitro has been shown to promote Kaposi's sarcoma-like cell cultures, we discuss the potential role of this growth factor in increasing Kaposi's sarcoma lesions in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. The European-Australian Collaborative Group.

BACKGROUND: Zidovudine therapy is of benefit in the treatment of symptomatic and asymptomatic human immunodeficiency virus (HIV) infection in persons with CD4+ cell counts of less than 500 per cubic millimeter. The efficacy, safety, and duration of benefit of zidovudine in those with 500 or more CD4+ cells per cubic millimeter are uncertain. METHODS: In a double-blind, placebo-controlled trial, 993 patients with asymptomatic HIV infection and CD4+ cell counts above 400 per cubic millimeter were randomly assigned to receive zidovudine (500 mg twice daily) or placebo for three years. The primary end point was progression of disease, as defined by the development of Centers for Disease Control and Prevention (CDC) group IV disease (including recurrent oral candidiasis, hairy leukoplakia, or progressive diarrhea) or two CD4+ cell counts below 350 per cubic millimeter. This outcome measure was changed from the original end point of the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex to reflect changes in recommendations for management. The study was terminated after the first interim analysis. RESULTS: Disease progression was significantly less frequent in the zidovudine group (relative risk, 0.56; 95 percent confidence interval, 0.43 to 0.75; P < 0.001 by the log-rank test). The probability of disease progression at two years was 0.19 with zidovudine, as compared with 0.34 with placebo (95 percent confidence interval for the difference, -0.21 to -0.08). Progression to CDC group IV disease was reduced by half in the zidovudine recipients (relative risk, 0.49; P = 0.049) and decline in CD4+ cell counts to below 350 per cubic millimeter was reduced by 40 percent (relative risk, 0.60; P < 0.001). The inclusion of early HIV disease events (oral candidiasis, oral hairy leukoplakia, and herpes zoster) as end points confirmed the effects of zidovudine on the progression of clinical disease (relative risk, 0.55; 95 percent confidence interval, 0.37 to 0.84; P = 0.004). The median duration of treatment was 94 weeks. Severe hematologic or clinical side effects were rare. CONCLUSIONS: Treatment with zidovudine benefits HIV-infected persons with CD4+ cell counts above 400 per cubic millimeter. Despite the use of doses larger than those now generally prescribed, zidovudine was well tolerated for up to three years by most of our patients.

AIDS-Related Complex↗
PubMed1993

Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS.

BACKGROUND: Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii. METHODS: We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg). RESULTS: Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P < 0.001), and death (P < 0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group. CONCLUSIONS: For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.

AIDS-Related Opportunistic Infections↗
PubMed1993

Current use of anti-HIV drugs in AIDS.

Since 1987 major advances have been made in our understanding of the pathogenesis of infection and the possible inhibition of the HIV virus. Various drugs targeted to the different steps of viral replication have been selected, but drugs such as soluble CD4 or dextran derivatives aimed to inhibit or interfere with the GP120-CD4 attachment step have shown little or no clinical benefit. Protease inhibitors or interferons acting at the post-transcriptional level are currently under phase I to II investigation. The only group of compounds clinically active belong to the nucleosides analogues that act as DNA chain terminators and by inhibiting viral reverse transcriptase. Zidovudine (AZT), didanosine (ddI) and dideoxycytidine (ddC) have been extensively studied, and used on a large clinical scale. Stavudine (D4T), deoxyfluorothymidine (FLT) and 3'thiacytidine (3TC) are entering phase I-II studies. Being the first nucleoside analogue discovered and used since early 1985, zidovudine remains the gold standard of anti-HIV therapy. Zidovudine is indicated at a dosage varying between 500 and 1000 mg in patients with AIDS and ARC, in asymptomatic patients with CD4 < 200/mm3 and in asymptomatic patients with CD4 between 200 and 500 cells/mm3 with a rapid decrease of CD4 cell count or a positive P24 circulating antigen. There is as yet no consensus concerning patients with more than 500 cell/mm3. ddI and ddC are currently indicated for patients intolerant to AZT or in those who have not responded (clinically or biologically) to AZT. Emergence of resistance to AZT has been reported in 30 to 80% of patients at various stages of the disease and after six to nine months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗