- Email: [email protected]
Needlestick injuries, surgeons, and HIV risks
546
zidovudine showed a striking rise over the same period.6 Neuropsychological studies showed no change in performance on AL721, in contrast to the improvement seen with zidovudine.5 Furthermore, no clinical benefit was seen in 6 HIV-antigen negative/borderline patients (4 AIDS , 2 ARC) given AL721 for a minimum of 3 months outside the study, all those with AIDS died within 12 months. We terminated the study early, in view of these fmdings. Out study has failed to show any clinical or laboratory evidence of benefit from the use of AL721 at this dose. We suggest that AL721 is clinically ineffective in people with AIDS or ARC; the lack of any effect on p24 antigen concentrations as a surrogate marker of in-vivo anti-HIV activity does not encourage further study at other stages of HIV infection. Experience with AL721 also underlines the need for careful early clinical studies before therapeutic agents for HIV or AIDS are widely promoted. We acknowledge our debt to the patients who helped us with this study. We thank Ethigen Corporation, Brian Whittle Associates, and Penn Pharmaceuticals for help and for supplies of AL721; and Ethigen Corporation for financial support.
Departments of Immunology, Virology, and Clinical Psychology, St Mary’s Hospital and Medical School, London W2 1 PG, UK
BARRY S. PETERS JULIE M. BENNETT DONALD J. JEFFRIES KIRSTINE KNOX AGNES KOCSIS ANTHONY J. PINCHING
PS, Gallo RC, Scheer DI, Crews F, Lippa AS. Effects of a novel compound (AL721) on HTLV-III infectivity in vitro N Engl J Med 1985; 313: 1289-90. 2. Skornik Y, Yust I, Zakreth V, Asner A, Vardinon N, Shinitsky M. Treatment of AIDS patients with AL721. IVth International Conference on AIDS, Stockholm, June, 1988: abstract 3529. 3. Grieco MH, Lange M, Klein E, et al. Open study of AL721 treatment of HIV infected subjects with generalised lymphadenopathy syndrome: an eight week open trial and follow up. Antiviral Res 1988; 9: 177-90. 4. Yarchoan R, Mitsuya H, Myers CE, Broder S. Clinical pharmacology of 3’-azido-2’,3’ -dideoxythymidine (zidovudine) and related dideoxynucleosides. N Engl J Med 1989; 321: 726-38. 5. Pinching AJ, Helbert M, Peddle B, et al. Clinical experience with zidovudine in the treatment of patients with AIDS and ARC. J Infect 1989; 18 (suppl 1): 33-40. 6. Knox KA, Peters B, Pinching AJ. Antiviral agents for AIDS: lymphocyte function as a marker of response. Vth International Conference on AIDS, Montreal, June, 1989:
intracellular glutathione resulted in improvement in mitogeninduced lymphocyte responsiveness.2 Dr Gougerot-Pocidalo and Dr Luvacier and Dr Dupuy and colleagues agree that oxidant damage to the immune system may be important in the pathogenesis of AIDS. They also point out that, at least in part, diethyldithiocarbamate (ditiocarb) owes its beneficial effects in HIV infection to its antioxidant properties, compensating for the observed glutathione deficiency. We agree that further investigation into this mechanism of ditiocarb and its relation to glutathione is warranted. Dr Jarstrand and colleagues provide additional evidence of increased lipid peroxidation and free-radical production in HIV infection. Acetylcysteine is one rational approach to replacing the antioxidant screen in HIV infection. Acetylcysteine may lead to an increase in intracellular glutathione levels too.3 Dr Cathcart’s experience with high-dose vitamin C is interesting, especially in the context of the ability of vitamin C to regenerate reduced
glutathione. The letters focused on glutathione as an antioxidant. However, glutathione also has a role in intracellular reactions involving the synthesis of proteins and DNA precursors and as a co-factor for enzymes. The relative importance of the antioxidant and metabolic properties of glutathione to immune function is not known, and such knowledge might help in the design of therapy to compensate for glutathione deficiency.
1. Sarin
abstract C557
Glutathione deficiency and HIV SIR,-We appreciate the many thoughtful letters (Jan 27,
p 234) Dec 2 article on systemic glutathione deficiency in symptom-free HIV seropositive individuals. Dr Horton comments on the need for functional correlations betwen the glutathione deficiency observed and immune dysfunction and on the importance of intracellular glutathione levels. We agree; our concept that glutathione deficiency contributes to the progressive immune dysfunction of HIV infection is a hypothesis, and functional correlations are needed before such a contribution is accepted as part of the pathogenesis of the disease state. We sought to show that a systemic deficiency of glutathione exists in symptom-free HIV seropositive individuals and to provide supporting evidence from elsewhere on the consequences of a reduction in glutathione, extracellular and intracellular, for immune function. Extracellular glutathione may be important in protecting immune cells from damage by oxidants and it probably influences intracellular concentrations. We cited one report of decreased intracellular glutathione in peripheral blood mononuclear cells of AIDS patients.1 Horton notes the lack of glutathione deficiency in two mouse models of immune deficiency. However, there is abundant evidence for a correlation between reduced glutathione and immune dysfunction in model systems, as referenced in our paper. The two models (one of senescence and the other of autoimmune disease), noted by Horton show only that there are examples of immune impairment in which glutathione concentrations are normal. This is not surprising since there must be many possible mechanisms of immune impairment. Interestingly, even in those two model systems, enhancement of
about
our
National Heart, Lung, and Blood Institute,
Bethesda, Maryland 20892, USA
ROLAND BUHL H. ARI JAFFE KENNETH J. HOLROYD FAITH B. WELLS ANDREA MASTRANGELI CESARE SALTINI ANDRE M. CANTIN RONALD G. CRYSTAL
1 Eck
H-P, Gmeuder H, Hartmann H, Petzoldt D, Daniel V, Droege W. Low in the blood plasma of HIV-1 infected patients. Biol Chem Hoppe Seyler 1989; 370: 101-08. 2 Fidelus RK, Tsan MF. Glutathione and lymphocyte activation: a function of ageing and autoimmune disease. Immunology 1987; 61: 503-08. 3. Issels RD, Nagele A, Eckert K-G, Wilmanns W. Promotion of cystine uptake and its utilization for glutathione biosynthesis induced by cysteamine and N-acetylcysteine. Biochem Pharmacol 1988; 23: 881-88. concentrations of acid soluble thiol (cysteine)
surgeons, and HIV risks SIR,-Health care workers are at a small, but real, risk of acquiring
Needlestick
injuries,
HIV infection via accidents with needles and instruments contaminated with blood from infected patients. The risk depends on the prevalence of HIV in the population being cared for (f), the probability of transmission per accident (p), and the number of accidents over a given time (n). The cumulative risk is (1-[I-fþ]n), assuming that the prevalence remains constant. We asked surgeons and other operating-theatre personnel in a 500-bed hospital in Amsterdam, after informing them of the purpose of the study, to report all percutaneous injuries sustained during their work in theatre over a 7-month period. If such an incident occurred, a questionnaire was filled out by the injured person. A percutaneous injury was defined as an accident during which the skin was pierced by a needle or instrument. Tom gloves without skin penetration were not. One of us went every day to the theatre to ask whether all accidents had been reported. During the study period 3101 operations were done and 42 injuries were reported (1-4 per 100, the rate differing by specialty, table). The mean number of persons present per operation was 38 (SD 0-8), giving a percutaneous injury rate of 0-37 per person per 100 operations (for a general surgeon 0-82). The 3098 patients (3 were operated on twice) were tested anonymously with informed consent for HIV antibodies. 120 patients refused. Among the other 2978, 7 (0-23%) were seropositives (ELI SA, confirmed by western blot). Over two-thirds of the refusers were women, and from studies among pregnant
547
DETAILS OF PATIENTS
PERCUTANEOUS WOUNDS BY SURGICAL SPECIALTY AT SINT LUCAS HOSPITAL, AMSTERDAM, AUGUST, 1988, TO MARCH, 1989
in Amsterdam we know that the seroprevalence in women is below 0-3%. If a general surgeon does 500 operations a year for 30 years the estimated number of accidents during this period is 120 (0-008 x 30 x 500). The risk of transmission (p) is about 0-005 and the seroprevalence of HIV in our hospital (f) is 0-002. The 30-year cumulative risk of a surgeon at this hospital contracting HIV via occupational exposure is (1-[1-0 002 x 0.005])120 or 0-0012. Routine anti-HIV screening on patients in this hospital was not recommended in the light of this calculation. women
1000 HE Amsterdam, Netherlands
A. LEENTVAAR-KUIJPERS M. M. DEKKER R. A. COUTINHO
Sint Lucas Ziekenhuis, Amsterdam
E. E. DEKKER J. N. KEEMAN M. C. ANSINK-SCHIPPER
Department of Infectious Diseases, Municipal Health Service,
Infectious and genetic factors in AIDS-associated Kaposi sarcoma SIR,-Dr Beral and colleagues (Jan 20, p 123) postulate that a sexually transmitted infection causes Kaposi sarcoma and discount the possible contribution of genetics. In 1987 we reported that the three-year incidence rate of Kaposi sarcoma was significantly higher in a cohort of homosexual men in Manhattan, New York, than in a parallel cohort in Washington, DC.1 We also noted that Kaposi sarcoma was associated with receptive fellatio and frequent enemas/rectal douches, suggesting that it may be attributable to a sexually acquired agent. This hypothesis was strengthened by the absence of similar associations with an airborne infection, Pneumocystis carinii pneumonia.l We noted no significant
associations with nitrite inhalant use, race, or ethnicity. However, we later evaluated HLA antigen frequencies in 266 white homosexual men in our cohorts. Kaposi sarcoma, but not opportunistic infection, was strongly associated with HLA-DR1 and HLA-DQwl. Thus, our investigations support the hypothesis that a Kaposi sarcoma agent is acquired during sexual activity and that the manifestation of disease could be affected by immunogenetics. The ultimate goal, effective treatment, and prevention of Kaposi sarcoma, will be reached sooner by pursuing both the environmental and host components of the hypothesis. Viral Epidemiology Section, National Cancer Institute, Rockville, MD 20892, USA
(3/3). Foscamet was maintained for 41 days (4-116) after the onset of ulcerations but the lesions did not heal. Foscamet was withdrawn in 6 cases because of worsening penile ulceration.1 patient died shortly afterwards but the ulcers healed in the other 5 in 12 days (6-30), leaving unpigmented atrophic scars. The 4 other patients died before treatment could be discontinued. Foscamet had to be restarted in 1 patient because of recurrent cytomegalovirus. Penile ulcerations recurred within 4 days and healed spontaneously after discontinuation of foscamet. The patients were taking one or more of the following:
sulphadiazine (2), pyrimethamine (4), clindamycin (2),
co-
trimoxazole (2), rifampicin (2), ansamycin (1), fluconazole (5), ketoconazole (1), pyrazinamide (1), and phenobarbitone (1). These cases strongly suggest that foscamet can cause penile ulceration, especially perhaps in patients with AIDS patients. The lesion looks like a fixed drug eruption, despite the absence of pigmented residual scar.
Infectious Disease Unit, and Dermatology Unit, Hôpital Bichat Claude-Bernard, 75018 Paris, France
S. FÉGUEUX D. SALMON C. PICARD C. SAUVAGE P. LONGUET
Laboratoire Astra France, Paris
TH. DESMOULINS
1.
Kauppinen K, Stubb QS. Causative drugs and challenge tests. Br J Dermatol 1985; 112: 575-78.
2. Moore N. Adverse drug reaction monitoring:
doing it the French way. Lancet 1985; ii:
1056-58.
JAMES J. GOEDERT
1. Goedert JJ, Biggar, RJ, Melbye M, et al. Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency
virus. JAMA 1987; 257: 331-34. DL, Murray C, Yarchoan R. Blattner WA, Goedert JJ. HLA antigen frequencies in HIV-1 seropositive disease-free individuals and patients with AIDS. J AIDS 1988; 1: 13-17.
2. Mann
Penile ulcerations with foscarnet SIR,-To
1988-89 were among 45 patients being treated with the drug. All 10 patients were homosexual males, aged 28-44 years, and had had on average three opportunistic infections previously. 8 had Kaposi’s sarcoma. Average cell counts (/ul) were: leucocytes 2900 (6004000), neutrophils 1110 (400-1500), and CD4 60 (20-110). The patients had two to five 1-5 cm erosive, bullous, tender ulcerations of the penis. 2 had mouth ulcers and 1 had oral oesophageal ulcerations. Bacteriological culture was positive in 2/9 (gram-negative bacilli); virological culture was negative (8/8); histology showed inflammatory infiltrate without viral inclusion
cases of foscamet-induced penile ulceration reported in The Lancet of Feb 3 (pp 286 and 287) we would like to add another 10. These 10 AIDS patients were being treated with foscamet for cytomegalovirus retinitis (table). The 9 cases observed during
SIR,-We have given foscamet to 150 AIDS patients with cytomegalovirus infection at a variety of sites, but have observed penile ulceration in only 7. Only 1 had concurrent oral ulceration. In 4 of these 7 patients foscamet was discontinued, and the penile ulcers healed within 10 days. 2 patients had similar ulcers when rechallenged. 3 patients have stayed on foscamet despite persistent ulceration; they cannot be given ganciclovir because of severe neutropenia. Foscamet daily doses are calculated according to body weight and serum creatinine. At first we used 24 hour intravenous infusions; but we now give the drug in three 1 hour infusions daily, with saline hyperhydration. The shorter infusion time is more acceptable to patients but appears to be associated with a higher frequency of ulceration.
zidovudine showed a striking rise over the same period.6 Neuropsychological studies showed no change in performance on AL721, in contrast to the improvement seen with zidovudine.5 Furthermore, no clinical benefit was seen in 6 HIV-antigen negative/borderline patients (4 AIDS , 2 ARC) given AL721 for a minimum of 3 months outside the study, all those with AIDS died within 12 months. We terminated the study early, in view of these fmdings. Out study has failed to show any clinical or laboratory evidence of benefit from the use of AL721 at this dose. We suggest that AL721 is clinically ineffective in people with AIDS or ARC; the lack of any effect on p24 antigen concentrations as a surrogate marker of in-vivo anti-HIV activity does not encourage further study at other stages of HIV infection. Experience with AL721 also underlines the need for careful early clinical studies before therapeutic agents for HIV or AIDS are widely promoted. We acknowledge our debt to the patients who helped us with this study. We thank Ethigen Corporation, Brian Whittle Associates, and Penn Pharmaceuticals for help and for supplies of AL721; and Ethigen Corporation for financial support.
Departments of Immunology, Virology, and Clinical Psychology, St Mary’s Hospital and Medical School, London W2 1 PG, UK
BARRY S. PETERS JULIE M. BENNETT DONALD J. JEFFRIES KIRSTINE KNOX AGNES KOCSIS ANTHONY J. PINCHING
PS, Gallo RC, Scheer DI, Crews F, Lippa AS. Effects of a novel compound (AL721) on HTLV-III infectivity in vitro N Engl J Med 1985; 313: 1289-90. 2. Skornik Y, Yust I, Zakreth V, Asner A, Vardinon N, Shinitsky M. Treatment of AIDS patients with AL721. IVth International Conference on AIDS, Stockholm, June, 1988: abstract 3529. 3. Grieco MH, Lange M, Klein E, et al. Open study of AL721 treatment of HIV infected subjects with generalised lymphadenopathy syndrome: an eight week open trial and follow up. Antiviral Res 1988; 9: 177-90. 4. Yarchoan R, Mitsuya H, Myers CE, Broder S. Clinical pharmacology of 3’-azido-2’,3’ -dideoxythymidine (zidovudine) and related dideoxynucleosides. N Engl J Med 1989; 321: 726-38. 5. Pinching AJ, Helbert M, Peddle B, et al. Clinical experience with zidovudine in the treatment of patients with AIDS and ARC. J Infect 1989; 18 (suppl 1): 33-40. 6. Knox KA, Peters B, Pinching AJ. Antiviral agents for AIDS: lymphocyte function as a marker of response. Vth International Conference on AIDS, Montreal, June, 1989:
intracellular glutathione resulted in improvement in mitogeninduced lymphocyte responsiveness.2 Dr Gougerot-Pocidalo and Dr Luvacier and Dr Dupuy and colleagues agree that oxidant damage to the immune system may be important in the pathogenesis of AIDS. They also point out that, at least in part, diethyldithiocarbamate (ditiocarb) owes its beneficial effects in HIV infection to its antioxidant properties, compensating for the observed glutathione deficiency. We agree that further investigation into this mechanism of ditiocarb and its relation to glutathione is warranted. Dr Jarstrand and colleagues provide additional evidence of increased lipid peroxidation and free-radical production in HIV infection. Acetylcysteine is one rational approach to replacing the antioxidant screen in HIV infection. Acetylcysteine may lead to an increase in intracellular glutathione levels too.3 Dr Cathcart’s experience with high-dose vitamin C is interesting, especially in the context of the ability of vitamin C to regenerate reduced
glutathione. The letters focused on glutathione as an antioxidant. However, glutathione also has a role in intracellular reactions involving the synthesis of proteins and DNA precursors and as a co-factor for enzymes. The relative importance of the antioxidant and metabolic properties of glutathione to immune function is not known, and such knowledge might help in the design of therapy to compensate for glutathione deficiency.
1. Sarin
abstract C557
Glutathione deficiency and HIV SIR,-We appreciate the many thoughtful letters (Jan 27,
p 234) Dec 2 article on systemic glutathione deficiency in symptom-free HIV seropositive individuals. Dr Horton comments on the need for functional correlations betwen the glutathione deficiency observed and immune dysfunction and on the importance of intracellular glutathione levels. We agree; our concept that glutathione deficiency contributes to the progressive immune dysfunction of HIV infection is a hypothesis, and functional correlations are needed before such a contribution is accepted as part of the pathogenesis of the disease state. We sought to show that a systemic deficiency of glutathione exists in symptom-free HIV seropositive individuals and to provide supporting evidence from elsewhere on the consequences of a reduction in glutathione, extracellular and intracellular, for immune function. Extracellular glutathione may be important in protecting immune cells from damage by oxidants and it probably influences intracellular concentrations. We cited one report of decreased intracellular glutathione in peripheral blood mononuclear cells of AIDS patients.1 Horton notes the lack of glutathione deficiency in two mouse models of immune deficiency. However, there is abundant evidence for a correlation between reduced glutathione and immune dysfunction in model systems, as referenced in our paper. The two models (one of senescence and the other of autoimmune disease), noted by Horton show only that there are examples of immune impairment in which glutathione concentrations are normal. This is not surprising since there must be many possible mechanisms of immune impairment. Interestingly, even in those two model systems, enhancement of
about
our
National Heart, Lung, and Blood Institute,
Bethesda, Maryland 20892, USA
ROLAND BUHL H. ARI JAFFE KENNETH J. HOLROYD FAITH B. WELLS ANDREA MASTRANGELI CESARE SALTINI ANDRE M. CANTIN RONALD G. CRYSTAL
1 Eck
H-P, Gmeuder H, Hartmann H, Petzoldt D, Daniel V, Droege W. Low in the blood plasma of HIV-1 infected patients. Biol Chem Hoppe Seyler 1989; 370: 101-08. 2 Fidelus RK, Tsan MF. Glutathione and lymphocyte activation: a function of ageing and autoimmune disease. Immunology 1987; 61: 503-08. 3. Issels RD, Nagele A, Eckert K-G, Wilmanns W. Promotion of cystine uptake and its utilization for glutathione biosynthesis induced by cysteamine and N-acetylcysteine. Biochem Pharmacol 1988; 23: 881-88. concentrations of acid soluble thiol (cysteine)
surgeons, and HIV risks SIR,-Health care workers are at a small, but real, risk of acquiring
Needlestick
injuries,
HIV infection via accidents with needles and instruments contaminated with blood from infected patients. The risk depends on the prevalence of HIV in the population being cared for (f), the probability of transmission per accident (p), and the number of accidents over a given time (n). The cumulative risk is (1-[I-fþ]n), assuming that the prevalence remains constant. We asked surgeons and other operating-theatre personnel in a 500-bed hospital in Amsterdam, after informing them of the purpose of the study, to report all percutaneous injuries sustained during their work in theatre over a 7-month period. If such an incident occurred, a questionnaire was filled out by the injured person. A percutaneous injury was defined as an accident during which the skin was pierced by a needle or instrument. Tom gloves without skin penetration were not. One of us went every day to the theatre to ask whether all accidents had been reported. During the study period 3101 operations were done and 42 injuries were reported (1-4 per 100, the rate differing by specialty, table). The mean number of persons present per operation was 38 (SD 0-8), giving a percutaneous injury rate of 0-37 per person per 100 operations (for a general surgeon 0-82). The 3098 patients (3 were operated on twice) were tested anonymously with informed consent for HIV antibodies. 120 patients refused. Among the other 2978, 7 (0-23%) were seropositives (ELI SA, confirmed by western blot). Over two-thirds of the refusers were women, and from studies among pregnant
547
DETAILS OF PATIENTS
PERCUTANEOUS WOUNDS BY SURGICAL SPECIALTY AT SINT LUCAS HOSPITAL, AMSTERDAM, AUGUST, 1988, TO MARCH, 1989
in Amsterdam we know that the seroprevalence in women is below 0-3%. If a general surgeon does 500 operations a year for 30 years the estimated number of accidents during this period is 120 (0-008 x 30 x 500). The risk of transmission (p) is about 0-005 and the seroprevalence of HIV in our hospital (f) is 0-002. The 30-year cumulative risk of a surgeon at this hospital contracting HIV via occupational exposure is (1-[1-0 002 x 0.005])120 or 0-0012. Routine anti-HIV screening on patients in this hospital was not recommended in the light of this calculation. women
1000 HE Amsterdam, Netherlands
A. LEENTVAAR-KUIJPERS M. M. DEKKER R. A. COUTINHO
Sint Lucas Ziekenhuis, Amsterdam
E. E. DEKKER J. N. KEEMAN M. C. ANSINK-SCHIPPER
Department of Infectious Diseases, Municipal Health Service,
Infectious and genetic factors in AIDS-associated Kaposi sarcoma SIR,-Dr Beral and colleagues (Jan 20, p 123) postulate that a sexually transmitted infection causes Kaposi sarcoma and discount the possible contribution of genetics. In 1987 we reported that the three-year incidence rate of Kaposi sarcoma was significantly higher in a cohort of homosexual men in Manhattan, New York, than in a parallel cohort in Washington, DC.1 We also noted that Kaposi sarcoma was associated with receptive fellatio and frequent enemas/rectal douches, suggesting that it may be attributable to a sexually acquired agent. This hypothesis was strengthened by the absence of similar associations with an airborne infection, Pneumocystis carinii pneumonia.l We noted no significant
associations with nitrite inhalant use, race, or ethnicity. However, we later evaluated HLA antigen frequencies in 266 white homosexual men in our cohorts. Kaposi sarcoma, but not opportunistic infection, was strongly associated with HLA-DR1 and HLA-DQwl. Thus, our investigations support the hypothesis that a Kaposi sarcoma agent is acquired during sexual activity and that the manifestation of disease could be affected by immunogenetics. The ultimate goal, effective treatment, and prevention of Kaposi sarcoma, will be reached sooner by pursuing both the environmental and host components of the hypothesis. Viral Epidemiology Section, National Cancer Institute, Rockville, MD 20892, USA
(3/3). Foscamet was maintained for 41 days (4-116) after the onset of ulcerations but the lesions did not heal. Foscamet was withdrawn in 6 cases because of worsening penile ulceration.1 patient died shortly afterwards but the ulcers healed in the other 5 in 12 days (6-30), leaving unpigmented atrophic scars. The 4 other patients died before treatment could be discontinued. Foscamet had to be restarted in 1 patient because of recurrent cytomegalovirus. Penile ulcerations recurred within 4 days and healed spontaneously after discontinuation of foscamet. The patients were taking one or more of the following:
sulphadiazine (2), pyrimethamine (4), clindamycin (2),
co-
trimoxazole (2), rifampicin (2), ansamycin (1), fluconazole (5), ketoconazole (1), pyrazinamide (1), and phenobarbitone (1). These cases strongly suggest that foscamet can cause penile ulceration, especially perhaps in patients with AIDS patients. The lesion looks like a fixed drug eruption, despite the absence of pigmented residual scar.
Infectious Disease Unit, and Dermatology Unit, Hôpital Bichat Claude-Bernard, 75018 Paris, France
S. FÉGUEUX D. SALMON C. PICARD C. SAUVAGE P. LONGUET
Laboratoire Astra France, Paris
TH. DESMOULINS
1.
Kauppinen K, Stubb QS. Causative drugs and challenge tests. Br J Dermatol 1985; 112: 575-78.
2. Moore N. Adverse drug reaction monitoring:
doing it the French way. Lancet 1985; ii:
1056-58.
JAMES J. GOEDERT
1. Goedert JJ, Biggar, RJ, Melbye M, et al. Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency
virus. JAMA 1987; 257: 331-34. DL, Murray C, Yarchoan R. Blattner WA, Goedert JJ. HLA antigen frequencies in HIV-1 seropositive disease-free individuals and patients with AIDS. J AIDS 1988; 1: 13-17.
2. Mann
Penile ulcerations with foscarnet SIR,-To
1988-89 were among 45 patients being treated with the drug. All 10 patients were homosexual males, aged 28-44 years, and had had on average three opportunistic infections previously. 8 had Kaposi’s sarcoma. Average cell counts (/ul) were: leucocytes 2900 (6004000), neutrophils 1110 (400-1500), and CD4 60 (20-110). The patients had two to five 1-5 cm erosive, bullous, tender ulcerations of the penis. 2 had mouth ulcers and 1 had oral oesophageal ulcerations. Bacteriological culture was positive in 2/9 (gram-negative bacilli); virological culture was negative (8/8); histology showed inflammatory infiltrate without viral inclusion
cases of foscamet-induced penile ulceration reported in The Lancet of Feb 3 (pp 286 and 287) we would like to add another 10. These 10 AIDS patients were being treated with foscamet for cytomegalovirus retinitis (table). The 9 cases observed during
SIR,-We have given foscamet to 150 AIDS patients with cytomegalovirus infection at a variety of sites, but have observed penile ulceration in only 7. Only 1 had concurrent oral ulceration. In 4 of these 7 patients foscamet was discontinued, and the penile ulcers healed within 10 days. 2 patients had similar ulcers when rechallenged. 3 patients have stayed on foscamet despite persistent ulceration; they cannot be given ganciclovir because of severe neutropenia. Foscamet daily doses are calculated according to body weight and serum creatinine. At first we used 24 hour intravenous infusions; but we now give the drug in three 1 hour infusions daily, with saline hyperhydration. The shorter infusion time is more acceptable to patients but appears to be associated with a higher frequency of ulceration.