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Antiretroviral therapy in sub-Saharan Africa
CORRESPONDENCE
2
Mergener K, Baillie J. Chronic pancreatitis. Lancet 1997; 350: 1379–85. Mok DWH, Blumgart LH. Erythema ab igne in chronic pancreatitis pain: a diagnostic sign. J R Soc Med 1984; 77: 299–31.
Antiretroviral therapy in sub-Saharan Africa SIR—Robert Hogg and colleagues (Nov 8, p 1406)1 model the economic costs of making triple-combination antiretroviral therapy available for a quarter of people with HIV-1 in sub-Saharan Africa. They calculate the per capita annual drug costs of such an intervention at US$41 or 8·3% of the gross national product (GNP) of the region. In 11 of the countries, drug costs would exceed 25% of the GNP. Although we welcome these helpful calculations, we do not agree with Hogg and colleagues’ proposal that such combination therapies be made widely available in Africa. In countries of sub-Saharan Africa, where less than $10 per capita per year is spent on health, large-scale antiretroviral drug treatment is an unrealistic option because of the prohibitive high costs. The limited availability and quality of health services in most of these countries, where patients often do not even have regular access to simple antibiotic or antimalarial treatment, calls for great caution with respect to the introduction of complex therapies. Only experts from specialised centres equipped with the necessary laboratory facilities to measure HIV-1 viral load or CD4 lymphocyte counts would be able to manage antiretroviral regimens. The large-scale introduction of antiretroviral therapy within the regular health services of sub-Saharan Africa would not ensure the safety of and compliance with these complicated combination regimens. This would lead to severe side-effects in patients and to the rapid development of drug resistance in the community. For example, the use of a short-course AZT regimen for the prevention of vertical HIV-1 transmission would be endangered through the rapid development of AZTresistance.2 Moreover, the large-scale implementation of such an intervention targeted at pregnant women infected with HIV-1 would be possible only in countries capable of creating a nondiscriminatory and supportive social environment for infected individuals and their families, together with voluntary HIV counselling and testing services.3 Despite the existing economic and logistical constraints of health services
68
in sub-Saharan Africa, good care for HIV-1/AIDS patients is possible. The value of symptomatic treatment combined with supportive psychological, pastoral, and social services has been well-documented in the region, and the establishment of such services is a prerequisite for the acceptance of preventative interventions within any comprehensive control programme.4 Instead of promoting expensive and potentially dangerous antiretroviral drug therapies, policy makers should invest limited resources into improving the infrastructure of the existing health services to enable them to cope with the increasing number of cases of tuberculosis, pneumonia, and other opportunistic infections. *Olaf Müller, Tumani Corrah, Elly Katabira, Frank Plummer, David Mabey *Department of Tropical Hygiene and Public Health, Medical School, Ruprecht-Karls-University, 69120 Heidelberg, Germany; Medical Research Council Laboratories, The Gambia, West Africa; Department of Medicine, Makarere Medical School, Uganda; Department of Medical Microbiology, University of Nairobi, Kenya; and Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, London 1
2
3
4
Hogg RS, Anis A, Weber AE, O’Shaughnessy M, Schechter MT. Triplecombination antiretroviral therapy in subSaharan Africa. Lancet 1997; 350: 1406. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 1994; 331: 1173–80. Müller O, Phanuphak P. Voluntary HIV counselling nd testing in developing countries. Lancet 1993; 342: 1117. Goodgame RW. AIDS in Uganda—clinical and social features. N Engl J Med 1990; 323: 383–89.
Mesalazine preparations S IR —Alastair Forbes and Claire Chadwick’s (Nov 1, p 1329) 1 report on mesalazine preparations prompts us to recount our comparison of the release profile of mesalazine from Asacol (SmithKline Beecham), Coltec EC (APS/Berk), and Salofalk (Thomas Laboratories) tablets using the standard USP II apparatus at pH 6·4. We found clear differences in the release profile (figure). The release of mesalazine was far greater from Coltec EC than it was from either Asacol or Salofalk, and there was also significant variation for Coltec EC between tablets (range <1% to 88%). A dose-for-dose switch from Asacol to Coltec EC may therefore result in increased release of mesalazine more proximally in the gastrointestinal tract and thus, a lower concentration in the
80 % mean release of mesalazine
1
60
40
20
0
Coltec EC Salofalk Asacol (400 mg) (250 mg) (400 mg)
Mean release of mesalazine from Asacol, Coltec EC, and Salofalk* Range at pH 6·4 for 1 h. *Data on file, SmithKline Beecham, 1997; available from authors, on request.
terminal ileum and colon. Staerk Laursen and colleagues 2 reported that Salofalk achieved significantly lower colonic 5-aminosalicylic acid (5-ASA) concentrations than Asacol at equivalent dosage. Since we found that the release of mesalazine from Coltec EC was greater at pH 6·4 than that from Salofalk, the data of Staerk Laursen and co-workers could imply that in terms of colonic 5-ASA concentrations, the difference between Asacol and the Coltec EC would, if anything, be more pronounced. The clinical implications of this finding are important. To our knowledge there is no in-vivo data for Coltec EC, whereas Asacol shows consistent delivery to the terminal ileum and proximal colon, and achieves high luminal concentrations at the disease site. 3 It should also be noted that Asacol is currently the only mesalazine indicated for the maintenance of remission of Crohn’s ileocolitis. *A G Benbow, Ian Gould Clinical Research and Development and Medical Affairs, SmithKline Beecham, Mundells, Welwyn Garden City, Hertfordshire AL7 1EY. UK 1 2
3
Forbes A, Chadwick C. Mesalazine preparations. Lancet 1997; 350: 1329. Staerk Laursen L, Stokholm M, Bukhave K, Rask-Madsen J, Lauritsen K. Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion. Gut 1990; 31: 1271–76. Dew MJ, Ryder REJ, Evans N, Evans BK, Rhodes J. Colonic release of 5-amino salicylic acid from an oral preparation in active ulcerative colitis. Br J Clin Pharmac 1983; 16: 185–87.
THE LANCET • Vol 351 • January 3, 1998
2
Mergener K, Baillie J. Chronic pancreatitis. Lancet 1997; 350: 1379–85. Mok DWH, Blumgart LH. Erythema ab igne in chronic pancreatitis pain: a diagnostic sign. J R Soc Med 1984; 77: 299–31.
Antiretroviral therapy in sub-Saharan Africa SIR—Robert Hogg and colleagues (Nov 8, p 1406)1 model the economic costs of making triple-combination antiretroviral therapy available for a quarter of people with HIV-1 in sub-Saharan Africa. They calculate the per capita annual drug costs of such an intervention at US$41 or 8·3% of the gross national product (GNP) of the region. In 11 of the countries, drug costs would exceed 25% of the GNP. Although we welcome these helpful calculations, we do not agree with Hogg and colleagues’ proposal that such combination therapies be made widely available in Africa. In countries of sub-Saharan Africa, where less than $10 per capita per year is spent on health, large-scale antiretroviral drug treatment is an unrealistic option because of the prohibitive high costs. The limited availability and quality of health services in most of these countries, where patients often do not even have regular access to simple antibiotic or antimalarial treatment, calls for great caution with respect to the introduction of complex therapies. Only experts from specialised centres equipped with the necessary laboratory facilities to measure HIV-1 viral load or CD4 lymphocyte counts would be able to manage antiretroviral regimens. The large-scale introduction of antiretroviral therapy within the regular health services of sub-Saharan Africa would not ensure the safety of and compliance with these complicated combination regimens. This would lead to severe side-effects in patients and to the rapid development of drug resistance in the community. For example, the use of a short-course AZT regimen for the prevention of vertical HIV-1 transmission would be endangered through the rapid development of AZTresistance.2 Moreover, the large-scale implementation of such an intervention targeted at pregnant women infected with HIV-1 would be possible only in countries capable of creating a nondiscriminatory and supportive social environment for infected individuals and their families, together with voluntary HIV counselling and testing services.3 Despite the existing economic and logistical constraints of health services
68
in sub-Saharan Africa, good care for HIV-1/AIDS patients is possible. The value of symptomatic treatment combined with supportive psychological, pastoral, and social services has been well-documented in the region, and the establishment of such services is a prerequisite for the acceptance of preventative interventions within any comprehensive control programme.4 Instead of promoting expensive and potentially dangerous antiretroviral drug therapies, policy makers should invest limited resources into improving the infrastructure of the existing health services to enable them to cope with the increasing number of cases of tuberculosis, pneumonia, and other opportunistic infections. *Olaf Müller, Tumani Corrah, Elly Katabira, Frank Plummer, David Mabey *Department of Tropical Hygiene and Public Health, Medical School, Ruprecht-Karls-University, 69120 Heidelberg, Germany; Medical Research Council Laboratories, The Gambia, West Africa; Department of Medicine, Makarere Medical School, Uganda; Department of Medical Microbiology, University of Nairobi, Kenya; and Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, London 1
2
3
4
Hogg RS, Anis A, Weber AE, O’Shaughnessy M, Schechter MT. Triplecombination antiretroviral therapy in subSaharan Africa. Lancet 1997; 350: 1406. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 1994; 331: 1173–80. Müller O, Phanuphak P. Voluntary HIV counselling nd testing in developing countries. Lancet 1993; 342: 1117. Goodgame RW. AIDS in Uganda—clinical and social features. N Engl J Med 1990; 323: 383–89.
Mesalazine preparations S IR —Alastair Forbes and Claire Chadwick’s (Nov 1, p 1329) 1 report on mesalazine preparations prompts us to recount our comparison of the release profile of mesalazine from Asacol (SmithKline Beecham), Coltec EC (APS/Berk), and Salofalk (Thomas Laboratories) tablets using the standard USP II apparatus at pH 6·4. We found clear differences in the release profile (figure). The release of mesalazine was far greater from Coltec EC than it was from either Asacol or Salofalk, and there was also significant variation for Coltec EC between tablets (range <1% to 88%). A dose-for-dose switch from Asacol to Coltec EC may therefore result in increased release of mesalazine more proximally in the gastrointestinal tract and thus, a lower concentration in the
80 % mean release of mesalazine
1
60
40
20
0
Coltec EC Salofalk Asacol (400 mg) (250 mg) (400 mg)
Mean release of mesalazine from Asacol, Coltec EC, and Salofalk* Range at pH 6·4 for 1 h. *Data on file, SmithKline Beecham, 1997; available from authors, on request.
terminal ileum and colon. Staerk Laursen and colleagues 2 reported that Salofalk achieved significantly lower colonic 5-aminosalicylic acid (5-ASA) concentrations than Asacol at equivalent dosage. Since we found that the release of mesalazine from Coltec EC was greater at pH 6·4 than that from Salofalk, the data of Staerk Laursen and co-workers could imply that in terms of colonic 5-ASA concentrations, the difference between Asacol and the Coltec EC would, if anything, be more pronounced. The clinical implications of this finding are important. To our knowledge there is no in-vivo data for Coltec EC, whereas Asacol shows consistent delivery to the terminal ileum and proximal colon, and achieves high luminal concentrations at the disease site. 3 It should also be noted that Asacol is currently the only mesalazine indicated for the maintenance of remission of Crohn’s ileocolitis. *A G Benbow, Ian Gould Clinical Research and Development and Medical Affairs, SmithKline Beecham, Mundells, Welwyn Garden City, Hertfordshire AL7 1EY. UK 1 2
3
Forbes A, Chadwick C. Mesalazine preparations. Lancet 1997; 350: 1329. Staerk Laursen L, Stokholm M, Bukhave K, Rask-Madsen J, Lauritsen K. Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion. Gut 1990; 31: 1271–76. Dew MJ, Ryder REJ, Evans N, Evans BK, Rhodes J. Colonic release of 5-amino salicylic acid from an oral preparation in active ulcerative colitis. Br J Clin Pharmac 1983; 16: 185–87.
THE LANCET • Vol 351 • January 3, 1998