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Plasmodium falciparum cross resistance

2002; Elsevier BV; Volume: 359; Issue: 9300 Linguagem: Inglês

10.1016/s0140-6736(02)07300-2

1474-547X

C. W. M. Whitty, Shabbar Jaffar,

HIV/AIDS drug development and treatment

Jayasree Iyer and colleagues (Sept 29, p 1066)1Iyer JK Milhous WK Cortese JF Kublin JG Plowe CV Plasmodium falciparum cross-resistance between trimethoprim and pyrimethamine.Lancet. 2001; 358: 1066-1067Summary Full Text Full Text PDF PubMed Scopus (116) Google Scholar report cross resistance between trimethoprim, recommended by UNAIDS as prophylaxis for those with HIV infection in Africa, and sulfadoxine-pyrimethamine, the mainstay of malaria treatment in most of sub-Saharan Africa.This finding raises the possibility that if the UNAIDS policy is adopted in areas of high HIV seroprevalence, it could greatly speed the progress of sulfadoxine-pyrimethamine resistance, widely accepted as a disaster waiting to happen. In his Sept 29 Commentary, Xavier Anglaret2Anglaret X Trimethoprim-sulfamethoxazole prophylaxis in sub-Saharan Africa.Lancet. 2001; 358: 1027-1028Summary Full Text Full Text PDF PubMed Scopus (13) Google Scholar laments the decision by UNAIDS and others to stop trials prematurely in which workers were testing this treatment against placebo in areas of Africa where antibiotic resistance patterns are different. We are, therefore, faced with a policy of unknown efficacy outside west Africa that could cause future difficulties for the treatment of one of the continent's other major causes of death.The relation between malaria and HIV prophylaxis with co-trimoxa-zole (sulphamethoxazole/trimethoprim five/one) may, however, be more complex. Co-trimoxazole has substantial antimalarial activity. Some of the improved morbidity and hospital attendance seen in Anglaret and colleagues' original study3Anglaret X Chene G Attia A et al.Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial.Lancet. 1999; 353: 1463-1468Summary Full Text Full Text PDF PubMed Scopus (349) Google Scholar may have been mediated directly by this effect. In HIV-positive people taking prophylactic medication, with the exception of pneumonia, the greatest differences between morbidity in the co-trimoxazole and placebo groups were seen in malaria and fever of unexplained origin.This finding is unlikely to be the explanation in the study from Abidjan, which informed UNAIDS policy, since it focused on mortality in HIV-positive patients who had contracted tuberculosis.4Wiktor SZ Sassan-Moroko M Grant AD et al.Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.Lancet. 1999; 353: 1469-1475Summary Full Text Full Text PDF PubMed Scopus (398) Google Scholar That study did not, however, exclude the possibility that malaria may increase the rate of progression of HIV disease over the full course of the infection in areas where malaria incidence is high. Malaria is common, and causes polyclonal activation of the CD4 T-cell population. In infected individuals, this effect would be expected to lead to increased cellular infection and eventual CD4-cell death. Acute infection is associated with a seven-fold rise in viral load.5Hoffman IF Jere CJ Taylor TE et al.The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration.AIDS. 1999; 13: 487-494Crossref PubMed Scopus (206) Google Scholar Both would be expected to increase rate of progression of HIV disease. An inverse relation between malaria incidence and CD4-cell count was seen in a cohort of HIV-positive Ugandans.This point is not just academic. If some of the improved morbidity with co-trimoxazole is mediated by malaria, the use of antibiotics with antimalarial activity is justified, although co-trimoxazole may not be the ideal choice outside west Africa, given the serious worries about sulfadoxine-pyrimethamine resistance, especially in east Africa. Alternatively, if antimalarial activity is irrelevant to the improved morbidity and mortality seen in Abidjan, Iyer and colleagues' findings should prompt a rethink about what antibiotics are appropriate for prophylaxis in areas with high HIV seroprevalence and high malaria incidence. In either case, the question about whether antimalarials reduce HIV disease progression is central, and needs to be addressed directly. In the meantime, the tendency of HIV and malaria control programmes not to consider the impact of their policies on the activities of the other needs to be rectified. Jayasree Iyer and colleagues (Sept 29, p 1066)1Iyer JK Milhous WK Cortese JF Kublin JG Plowe CV Plasmodium falciparum cross-resistance between trimethoprim and pyrimethamine.Lancet. 2001; 358: 1066-1067Summary Full Text Full Text PDF PubMed Scopus (116) Google Scholar report cross resistance between trimethoprim, recommended by UNAIDS as prophylaxis for those with HIV infection in Africa, and sulfadoxine-pyrimethamine, the mainstay of malaria treatment in most of sub-Saharan Africa. This finding raises the possibility that if the UNAIDS policy is adopted in areas of high HIV seroprevalence, it could greatly speed the progress of sulfadoxine-pyrimethamine resistance, widely accepted as a disaster waiting to happen. In his Sept 29 Commentary, Xavier Anglaret2Anglaret X Trimethoprim-sulfamethoxazole prophylaxis in sub-Saharan Africa.Lancet. 2001; 358: 1027-1028Summary Full Text Full Text PDF PubMed Scopus (13) Google Scholar laments the decision by UNAIDS and others to stop trials prematurely in which workers were testing this treatment against placebo in areas of Africa where antibiotic resistance patterns are different. We are, therefore, faced with a policy of unknown efficacy outside west Africa that could cause future difficulties for the treatment of one of the continent's other major causes of death. The relation between malaria and HIV prophylaxis with co-trimoxa-zole (sulphamethoxazole/trimethoprim five/one) may, however, be more complex. Co-trimoxazole has substantial antimalarial activity. Some of the improved morbidity and hospital attendance seen in Anglaret and colleagues' original study3Anglaret X Chene G Attia A et al.Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial.Lancet. 1999; 353: 1463-1468Summary Full Text Full Text PDF PubMed Scopus (349) Google Scholar may have been mediated directly by this effect. In HIV-positive people taking prophylactic medication, with the exception of pneumonia, the greatest differences between morbidity in the co-trimoxazole and placebo groups were seen in malaria and fever of unexplained origin. This finding is unlikely to be the explanation in the study from Abidjan, which informed UNAIDS policy, since it focused on mortality in HIV-positive patients who had contracted tuberculosis.4Wiktor SZ Sassan-Moroko M Grant AD et al.Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.Lancet. 1999; 353: 1469-1475Summary Full Text Full Text PDF PubMed Scopus (398) Google Scholar That study did not, however, exclude the possibility that malaria may increase the rate of progression of HIV disease over the full course of the infection in areas where malaria incidence is high. Malaria is common, and causes polyclonal activation of the CD4 T-cell population. In infected individuals, this effect would be expected to lead to increased cellular infection and eventual CD4-cell death. Acute infection is associated with a seven-fold rise in viral load.5Hoffman IF Jere CJ Taylor TE et al.The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration.AIDS. 1999; 13: 487-494Crossref PubMed Scopus (206) Google Scholar Both would be expected to increase rate of progression of HIV disease. An inverse relation between malaria incidence and CD4-cell count was seen in a cohort of HIV-positive Ugandans. This point is not just academic. If some of the improved morbidity with co-trimoxazole is mediated by malaria, the use of antibiotics with antimalarial activity is justified, although co-trimoxazole may not be the ideal choice outside west Africa, given the serious worries about sulfadoxine-pyrimethamine resistance, especially in east Africa. Alternatively, if antimalarial activity is irrelevant to the improved morbidity and mortality seen in Abidjan, Iyer and colleagues' findings should prompt a rethink about what antibiotics are appropriate for prophylaxis in areas with high HIV seroprevalence and high malaria incidence. In either case, the question about whether antimalarials reduce HIV disease progression is central, and needs to be addressed directly. In the meantime, the tendency of HIV and malaria control programmes not to consider the impact of their policies on the activities of the other needs to be rectified.