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Intrathecal zidovudine for AIDS dementia
248
infectious HIV particles in culture supernatants. MMP also augmented the HIV-induced syncytia formation between MOLT-4 and its HIV-infected counterpart, resulting in the death of fused cells. Under these conditions, a more than 3-fold greater amount of p24 was again seen in the supernatant of the culture treated with 100 ug/ml MMP. HIV-enhancing activity of MMP was also evidenced by slot-blot hybridisation, with an HIV-1 probe in which MMP stimulated HIV transcription by more than 3-fold. Other pathogenic mycoplasma strains display the same effect. These data suggest that mycoplasma might influence the progression to AIDS by interaction with HIV-infected cells, directly or indirectly through induction of some soluble factors in infected patients in vivo. AIDS patients often have pulmonary dysfunction. Mycoplasma infection in the lung, one of the severe complications of a profound immunodeficiency, must be taken
seriously.
School of Medicine, Ube, Yamaguchi 755, Japan
MD IQBAL HOSSAIN CHOWDHURY YOSHIO KOYANAGI SUSUMU KOBAYASHI NAOKI YAMAMOTO
Department of Microbiology, Kurume University School of Medicine
TETSUO MUNAKATA SUMIO ARAI
Department of Virology and Parasitology, Yamaguchi University
SC, Dawson MS, Wong DM, et al. Identification of Mycoplasma incognitus infection in patients with AIDS: an immunohistochemical, m situ hybridization and ultrastructural study. Am J Trop Med Hyg 1989; 41: 601-16. 2. Lamaitre M, Guetard D, Henin Y, Montagnier L, Zerial A. Protective activity of tetracycline analogs against the cytopathic effect of human immunodeficiency virus in CEM cells. Res Virol 1990; 141: 5-16. 3. Matsuyama T, Hamamoto Y, Soma G, Mizuno D, Yamamoto N, Kobayashi N. Cytocidal effect of tumor necrosis factor on cells chronically infected with human immunodeficiency virus (HIV). enhancement of HIV replication. J Virol 1989; 63: 2504-09. 1. Lo
pneumocystis prophylaxis with co-trimoxazole were started. In September, 1989, oesophageal candidiasis was diagnosed (CD4 count 58/ul). 2 months later a hairy tongue developed. Because of haematological toxicity zidovudine was stopped in January, 1990. Verbal and motor slowing (with unimpaired naming) and incontinence were observed in this cachectic patient. Magnetic resonance imaging yielded a diffuse increase in T2-weighted signal; CSF examination was normal. In March, 1990, intrathecal zidovudine was started. Improvement appeared after 2 weeks; the patient was no longer incontinent and his memory loss was corrected. No toxic effect was noted during 3 months of this treatment.
Patient 3 (M, 30; HIV positive since 1986, oesophagal candidiasis in September, 1989, treated by fluconazole CD4 count 4/p.l). The patient had apathy and social withdrawal. A brain scan indicated cerebral atrophy and CSF examination excluded diagnoses other than ADC. Zidovudine 1000 mg daily was started in January, 1990. 3 weeks later he was admited to intensive care in septic shock. He was neutropenic (600/ml) with a packed cell volume of 0-21, and zidovudine was stopped. In February, 1990, zidovudine was given intrathecally. The patient complained of headache for 2 weeks but there was major neuropsychiatric improvement. Neutrophils remained at 1000/ml. No other sepsis occurred during the 4 months of treatment. This pilot study suggests that zidovudine can be safely given intrathecally. Mild headache in one patient was the only adverse development and there were no seizures and no problems at the site of injection. All treatments were given on an outpatient basis. Clinical improvement in ADC can be obtained with one-tenth of the recommended systemic daily dose of zidovudine if the intrathecal route is used, and the haematological toxicity associated with zidovudine can be reduced. Replication of our study at other centres and controlled trials are the next steps.
Intrathecal zidovudine for AIDS dementia SIR,-AIDS dementia complex (ADC) is the commonest neurological problem in AIDS: 40-60% of patients with AIDS show typical neurological deficits and more than 90% have characteristic neurological changes.! Improvement in patients on zidovudine has been documented clinically, neuropsychologically, and radiographically.2 The incidence of ADC seems to have fallen with the introduction of zidovudine3 but the benefits of the drug on systemic manifestations of AIDS and on ADC do not seem to last very long.4 The causes of this limited duration, other than dose reduction because of haematological toxicity or zidovudine resistance, are not well understood.s Steady state CSF levels of zidovudine are only about 25% of those in plasma. So far only doses above 1000 mg per day have been shown to affect the central nervous
system.
To improve the therapeutic index we have given zidovudine by intrathecal injection to patients with ADC, with their written informed consent. The three patients had become zidovudine intolerant because of haematological toxicity. Zidovudine was given, via an implanted access with a catheter passing into the CSF, by bolus injections of 50 mg every 12 hours. Patient 1 (M, 36; HIV positive since 1987, Pneumocystis carinii pneumonia in July, 1989, with CD4 count of 160/ul). 1 month later he presented with memory loss and psychomotor retardation (Kamofsky score 60%). CSF examination and brain scan were normal. He met criteria for ADC, and zidovudine 800 mg daily plus pneumocystis prophylaxis with aerosolised pentamidine were started. Despite neurological improvement in December, 1989, bone marrow toxicity necessitated regular transfusions of red blood cells and he had neutropenia. Zidovudine was stopped and the bone marrow recovered in 3 weeks. In March, 1990, the patient was bedridden because of ADC and we decided to inject zidovudine intrathecally. Neurological improvement was observed after 3 weeks and no haematological toxicity occurred. After 5 months of this treatment the patient is ambulatory and able to carry out activities of daily living. Patient 2 (M, 56; HIV positive after a transfusion in 1984, P carinii pneumonia in April, 1988). Zidovudine 800 mg daily and
Departments of Haemato-oncology, Emergency Medicine, and Neurology and Laboratory of Bacteriology, Hôpital Cézanne, 13616 Aix en Provence, France, and Department of Internal Medicine,
Hôpital de Salon
de Provence
J. P. ROUTY A. P. BLANC E. RODRIGUEZ M. ESCOFFIER Y. JOLIOT P. KIEGEL F. VIALLET H. CHARDON
1. Navia BA, Jordan BD, Price RW. The AIDS dementia complex I: clinical features Ann Neurol 1986, 19: 517-24. 2 Yarchoan R, Berg G, Brouwers P, et al. Response of human immunodeficiency-virusassociated neurological disease to 3-azido-3-deoxythymidine. Lancet 1987, i: 132-35. 3. Portgies P, de Gans, Lange MA, et al. Declining incidence of AIDS dementia complex after introduction of zidovudine treatment. Br Med J 1989; 299: 299-321. 4. Dourmon E, Matheron S, Rozenbaum W, et al. Effect of Zidovudine in 365 consecutive patients with AIDS or AIDS-related-complex. Lancet 1988, ii 1297-302. 5. Yarchoan R, Mitsuya H, Myers CE. Clinical pharmacology of 3 azido2,"-dideoxythymidine (zidovudine) and related dideoxynucleosides. N Engl J Med 1989; 321: 726-38.
Risk of
non-Hodgkin lymphoma and Kaposi’s sarcoma in homosexual men SiR,—Dr Beral and her colleagues (Jan 20, p 123) comment on the proportions of US AIDS cases that have initial diagnoses of Kaposi’s sarcoma (15%) or non-Hodgkin lymphoma (3%). In our prospective cohort study of 130 homosexual men from New York and Washington,l the actuarial 10-year cumulative incidence rates of Kaposi’s sarcoma and non-Hodgkin lymphoma were 21 % (SEM 6%) and 18% (7%), respectively, after the estimated date of HIV-seroconversion. Between years 3 and 8, Kaposi’s sarcoma occurred at a constant rate of about 2-4% per year whereas the rate of non-Hodgkin lymphoma increased from 0-8% to 2-6%. During years 9 and 10 the rates of both diseases were further increased, but these rates were based on small numbers (2 patients in each disease group). By June 1, 1990, 15 men had Kaposi’s sarcoma and 9 had
non-Hodgkin lymphoma.
infectious HIV particles in culture supernatants. MMP also augmented the HIV-induced syncytia formation between MOLT-4 and its HIV-infected counterpart, resulting in the death of fused cells. Under these conditions, a more than 3-fold greater amount of p24 was again seen in the supernatant of the culture treated with 100 ug/ml MMP. HIV-enhancing activity of MMP was also evidenced by slot-blot hybridisation, with an HIV-1 probe in which MMP stimulated HIV transcription by more than 3-fold. Other pathogenic mycoplasma strains display the same effect. These data suggest that mycoplasma might influence the progression to AIDS by interaction with HIV-infected cells, directly or indirectly through induction of some soluble factors in infected patients in vivo. AIDS patients often have pulmonary dysfunction. Mycoplasma infection in the lung, one of the severe complications of a profound immunodeficiency, must be taken
seriously.
School of Medicine, Ube, Yamaguchi 755, Japan
MD IQBAL HOSSAIN CHOWDHURY YOSHIO KOYANAGI SUSUMU KOBAYASHI NAOKI YAMAMOTO
Department of Microbiology, Kurume University School of Medicine
TETSUO MUNAKATA SUMIO ARAI
Department of Virology and Parasitology, Yamaguchi University
SC, Dawson MS, Wong DM, et al. Identification of Mycoplasma incognitus infection in patients with AIDS: an immunohistochemical, m situ hybridization and ultrastructural study. Am J Trop Med Hyg 1989; 41: 601-16. 2. Lamaitre M, Guetard D, Henin Y, Montagnier L, Zerial A. Protective activity of tetracycline analogs against the cytopathic effect of human immunodeficiency virus in CEM cells. Res Virol 1990; 141: 5-16. 3. Matsuyama T, Hamamoto Y, Soma G, Mizuno D, Yamamoto N, Kobayashi N. Cytocidal effect of tumor necrosis factor on cells chronically infected with human immunodeficiency virus (HIV). enhancement of HIV replication. J Virol 1989; 63: 2504-09. 1. Lo
pneumocystis prophylaxis with co-trimoxazole were started. In September, 1989, oesophageal candidiasis was diagnosed (CD4 count 58/ul). 2 months later a hairy tongue developed. Because of haematological toxicity zidovudine was stopped in January, 1990. Verbal and motor slowing (with unimpaired naming) and incontinence were observed in this cachectic patient. Magnetic resonance imaging yielded a diffuse increase in T2-weighted signal; CSF examination was normal. In March, 1990, intrathecal zidovudine was started. Improvement appeared after 2 weeks; the patient was no longer incontinent and his memory loss was corrected. No toxic effect was noted during 3 months of this treatment.
Patient 3 (M, 30; HIV positive since 1986, oesophagal candidiasis in September, 1989, treated by fluconazole CD4 count 4/p.l). The patient had apathy and social withdrawal. A brain scan indicated cerebral atrophy and CSF examination excluded diagnoses other than ADC. Zidovudine 1000 mg daily was started in January, 1990. 3 weeks later he was admited to intensive care in septic shock. He was neutropenic (600/ml) with a packed cell volume of 0-21, and zidovudine was stopped. In February, 1990, zidovudine was given intrathecally. The patient complained of headache for 2 weeks but there was major neuropsychiatric improvement. Neutrophils remained at 1000/ml. No other sepsis occurred during the 4 months of treatment. This pilot study suggests that zidovudine can be safely given intrathecally. Mild headache in one patient was the only adverse development and there were no seizures and no problems at the site of injection. All treatments were given on an outpatient basis. Clinical improvement in ADC can be obtained with one-tenth of the recommended systemic daily dose of zidovudine if the intrathecal route is used, and the haematological toxicity associated with zidovudine can be reduced. Replication of our study at other centres and controlled trials are the next steps.
Intrathecal zidovudine for AIDS dementia SIR,-AIDS dementia complex (ADC) is the commonest neurological problem in AIDS: 40-60% of patients with AIDS show typical neurological deficits and more than 90% have characteristic neurological changes.! Improvement in patients on zidovudine has been documented clinically, neuropsychologically, and radiographically.2 The incidence of ADC seems to have fallen with the introduction of zidovudine3 but the benefits of the drug on systemic manifestations of AIDS and on ADC do not seem to last very long.4 The causes of this limited duration, other than dose reduction because of haematological toxicity or zidovudine resistance, are not well understood.s Steady state CSF levels of zidovudine are only about 25% of those in plasma. So far only doses above 1000 mg per day have been shown to affect the central nervous
system.
To improve the therapeutic index we have given zidovudine by intrathecal injection to patients with ADC, with their written informed consent. The three patients had become zidovudine intolerant because of haematological toxicity. Zidovudine was given, via an implanted access with a catheter passing into the CSF, by bolus injections of 50 mg every 12 hours. Patient 1 (M, 36; HIV positive since 1987, Pneumocystis carinii pneumonia in July, 1989, with CD4 count of 160/ul). 1 month later he presented with memory loss and psychomotor retardation (Kamofsky score 60%). CSF examination and brain scan were normal. He met criteria for ADC, and zidovudine 800 mg daily plus pneumocystis prophylaxis with aerosolised pentamidine were started. Despite neurological improvement in December, 1989, bone marrow toxicity necessitated regular transfusions of red blood cells and he had neutropenia. Zidovudine was stopped and the bone marrow recovered in 3 weeks. In March, 1990, the patient was bedridden because of ADC and we decided to inject zidovudine intrathecally. Neurological improvement was observed after 3 weeks and no haematological toxicity occurred. After 5 months of this treatment the patient is ambulatory and able to carry out activities of daily living. Patient 2 (M, 56; HIV positive after a transfusion in 1984, P carinii pneumonia in April, 1988). Zidovudine 800 mg daily and
Departments of Haemato-oncology, Emergency Medicine, and Neurology and Laboratory of Bacteriology, Hôpital Cézanne, 13616 Aix en Provence, France, and Department of Internal Medicine,
Hôpital de Salon
de Provence
J. P. ROUTY A. P. BLANC E. RODRIGUEZ M. ESCOFFIER Y. JOLIOT P. KIEGEL F. VIALLET H. CHARDON
1. Navia BA, Jordan BD, Price RW. The AIDS dementia complex I: clinical features Ann Neurol 1986, 19: 517-24. 2 Yarchoan R, Berg G, Brouwers P, et al. Response of human immunodeficiency-virusassociated neurological disease to 3-azido-3-deoxythymidine. Lancet 1987, i: 132-35. 3. Portgies P, de Gans, Lange MA, et al. Declining incidence of AIDS dementia complex after introduction of zidovudine treatment. Br Med J 1989; 299: 299-321. 4. Dourmon E, Matheron S, Rozenbaum W, et al. Effect of Zidovudine in 365 consecutive patients with AIDS or AIDS-related-complex. Lancet 1988, ii 1297-302. 5. Yarchoan R, Mitsuya H, Myers CE. Clinical pharmacology of 3 azido2,"-dideoxythymidine (zidovudine) and related dideoxynucleosides. N Engl J Med 1989; 321: 726-38.
Risk of
non-Hodgkin lymphoma and Kaposi’s sarcoma in homosexual men SiR,—Dr Beral and her colleagues (Jan 20, p 123) comment on the proportions of US AIDS cases that have initial diagnoses of Kaposi’s sarcoma (15%) or non-Hodgkin lymphoma (3%). In our prospective cohort study of 130 homosexual men from New York and Washington,l the actuarial 10-year cumulative incidence rates of Kaposi’s sarcoma and non-Hodgkin lymphoma were 21 % (SEM 6%) and 18% (7%), respectively, after the estimated date of HIV-seroconversion. Between years 3 and 8, Kaposi’s sarcoma occurred at a constant rate of about 2-4% per year whereas the rate of non-Hodgkin lymphoma increased from 0-8% to 2-6%. During years 9 and 10 the rates of both diseases were further increased, but these rates were based on small numbers (2 patients in each disease group). By June 1, 1990, 15 men had Kaposi’s sarcoma and 9 had
non-Hodgkin lymphoma.