Produção Nacional
Revisado por pares
Co-trimoxazole in people on antiretroviral therapy for HIV
2015; Elsevier BV; Volume: 2; Issue: 6 Linguagem: Inglês
10.1016/s2352-3018(15)00084-3
ISSN2405-4704
Autores Tópico(s)HIV Research and Treatment
ResumoI read with great interest the meta-analysis of data on the initiation, discontinuation, and dosing of co-trimoxazole prophylaxis in adults with HIV by study of Suthar and colleagues.1Suthar AB Vitoria MA Nagata JM et al.Co-trimoxazole prophylaxis in adults, including pregnant women, with HIV: a systematic review and meta-analysis.Lancet HIV. 2015; 2: e137-e150Summary Full Text Full Text PDF Scopus (59) Google Scholar Their findings reinforce recent WHO recommendations for long-term co-trimoxazole prophylaxis in adults with HIV who are receiving antiretroviral therapy irrespective of CD4 cell count or WHO clinical stage, especially in resource-constrained settings with high prevalences of invasive bacterial diseases and malaria.2WHO2014 supplement to the 2013 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection.http://www.who.int/hiv/pub/guidelines/arv2013/December2014-ARVsupplement-chap8.pdfGoogle Scholar On the basis of preliminary evidence, continuous co-trimoxazole prophylaxis after antiretroviral-induced immune recovery might provide benefits in resource-rich settings as well.Patients with HIV are at risk of residual immune dysregulation syndrome even with proper viral suppression.3Lederman MM Funderburg NT Sekaly RP Klatt NR Hunt PW Residual immune dysregulation syndrome in treated HIV infection.Adv Immunol. 2013; 119: 51-83Crossref PubMed Scopus (223) Google Scholar This syndrome is characterised by deregulated immune-coagulation pathways and increased morbidity and mortality caused by non-AIDS events. In this context, the use of co-trimoxazole has been postulated as adjunct therapy, attenuating both T-cell activation and the microbial translocation across impaired gut epithelial barrier common seen in treated HIV individuals. For instance, a substudy of the ARROW trial showed that in patients with HIV on long-term antiretroviral therapy continuous co-trimoxazole prophylaxis was associated with substantially lower concentrations of plasma proinflammatory biomarkers (ie, c-reactive protein, sCD14, interleukin 6) than was interrupted prophylaxis.4Prendergast AJ, bwakura-Dangarembizi M, Musiime V, et al. Lower inflammatory biomarkers in children randomized to prolonged cotrimoxazole prophylaxis. 21st Conference on Retroviruses and Opportunistic Infections; Boston, MA, USA; March 3–6, 2014 (Poster 914).Google Scholar A randomised, placebo-controlled trial to assess the efficacy of co-trimoxazole in reducing the relapse of Wegener's granulomatosis showed a lower risk of relapses in the interventional arm, emphasising the emergent role of co-trimoxazole as a potent immunomodulatory drug with anti-inflammatory proprieties.5Stegeman CA Tervaert JW de Jong PE Kallenberg CG Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch co-trimoxazole Wegener Study Group.N Engl J Med. 1996; 335: 16-20Crossref PubMed Scopus (736) Google Scholar Further investigations are urgently required to assess the true effect of co-trimoxazole on the persistent inflammatory state associated with chronic HIV. Whether short-term or long-term prophylaxis will be needed to reduce immune activation in people receiving antiretroviral therapy is unknown; and concerns about drug interactions between and tolerability might arise.Data from the Swiss HIV Cohort Study have shown that cumulative and current co-trimoxazole prophylaxis reduce all-cause mortality and incident tuberculosis rate in ART-naive and ART-experienced patients.6Hasse B Walker AS Fehr J et al.Co-trimoxazole prophylaxis is associated with reduced risk of incident tuberculosis in participants in the Swiss HIV Cohort Study.Antimicrob Agents Chemother. 2014; 58: 2368-3068Crossref Scopus (23) Google Scholar These findings suggest that the protection attributed to co-trimoxazole prophylaxis might be of use in diverse settings including regions with low-burden of infectious diseases in more developed countries.JAdSM is supported by a scholarship from Programa de Estudantes-Convênio de Pós-graduação (PEC-PG, da CAPES/CNPQ). I declare no competing interests. I read with great interest the meta-analysis of data on the initiation, discontinuation, and dosing of co-trimoxazole prophylaxis in adults with HIV by study of Suthar and colleagues.1Suthar AB Vitoria MA Nagata JM et al.Co-trimoxazole prophylaxis in adults, including pregnant women, with HIV: a systematic review and meta-analysis.Lancet HIV. 2015; 2: e137-e150Summary Full Text Full Text PDF Scopus (59) Google Scholar Their findings reinforce recent WHO recommendations for long-term co-trimoxazole prophylaxis in adults with HIV who are receiving antiretroviral therapy irrespective of CD4 cell count or WHO clinical stage, especially in resource-constrained settings with high prevalences of invasive bacterial diseases and malaria.2WHO2014 supplement to the 2013 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection.http://www.who.int/hiv/pub/guidelines/arv2013/December2014-ARVsupplement-chap8.pdfGoogle Scholar On the basis of preliminary evidence, continuous co-trimoxazole prophylaxis after antiretroviral-induced immune recovery might provide benefits in resource-rich settings as well. Patients with HIV are at risk of residual immune dysregulation syndrome even with proper viral suppression.3Lederman MM Funderburg NT Sekaly RP Klatt NR Hunt PW Residual immune dysregulation syndrome in treated HIV infection.Adv Immunol. 2013; 119: 51-83Crossref PubMed Scopus (223) Google Scholar This syndrome is characterised by deregulated immune-coagulation pathways and increased morbidity and mortality caused by non-AIDS events. In this context, the use of co-trimoxazole has been postulated as adjunct therapy, attenuating both T-cell activation and the microbial translocation across impaired gut epithelial barrier common seen in treated HIV individuals. For instance, a substudy of the ARROW trial showed that in patients with HIV on long-term antiretroviral therapy continuous co-trimoxazole prophylaxis was associated with substantially lower concentrations of plasma proinflammatory biomarkers (ie, c-reactive protein, sCD14, interleukin 6) than was interrupted prophylaxis.4Prendergast AJ, bwakura-Dangarembizi M, Musiime V, et al. Lower inflammatory biomarkers in children randomized to prolonged cotrimoxazole prophylaxis. 21st Conference on Retroviruses and Opportunistic Infections; Boston, MA, USA; March 3–6, 2014 (Poster 914).Google Scholar A randomised, placebo-controlled trial to assess the efficacy of co-trimoxazole in reducing the relapse of Wegener's granulomatosis showed a lower risk of relapses in the interventional arm, emphasising the emergent role of co-trimoxazole as a potent immunomodulatory drug with anti-inflammatory proprieties.5Stegeman CA Tervaert JW de Jong PE Kallenberg CG Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch co-trimoxazole Wegener Study Group.N Engl J Med. 1996; 335: 16-20Crossref PubMed Scopus (736) Google Scholar Further investigations are urgently required to assess the true effect of co-trimoxazole on the persistent inflammatory state associated with chronic HIV. Whether short-term or long-term prophylaxis will be needed to reduce immune activation in people receiving antiretroviral therapy is unknown; and concerns about drug interactions between and tolerability might arise. Data from the Swiss HIV Cohort Study have shown that cumulative and current co-trimoxazole prophylaxis reduce all-cause mortality and incident tuberculosis rate in ART-naive and ART-experienced patients.6Hasse B Walker AS Fehr J et al.Co-trimoxazole prophylaxis is associated with reduced risk of incident tuberculosis in participants in the Swiss HIV Cohort Study.Antimicrob Agents Chemother. 2014; 58: 2368-3068Crossref Scopus (23) Google Scholar These findings suggest that the protection attributed to co-trimoxazole prophylaxis might be of use in diverse settings including regions with low-burden of infectious diseases in more developed countries. JAdSM is supported by a scholarship from Programa de Estudantes-Convênio de Pós-graduação (PEC-PG, da CAPES/CNPQ). I declare no competing interests. Co-trimoxazole prophylaxis in adults, including pregnant women, with HIV: a systematic review and meta-analysisCo-trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350 cells per μL or lower in low-income and middle-income countries. Co-trimoxazole prophylaxis should be provided irrespective of CD4 count in settings with a high burden of infectious diseases. Pregnant women with HIV in Africa should use co-trimoxazole rather than IPTp to prevent malaria complications in infants. Further research is needed to inform dose optimisation and co-trimoxazole use in the context of expanded ART in different epidemiological settings. Full-Text PDF Co-trimoxazole in people on antiretroviral therapy for HIV – Authors' replyWe thank José Alfredo de Sousa Moreira for his interest in our article.1 Moreira suggested that co-trimoxazole prophylaxis may have benefits beyond prevention of AIDS events in high-income countries, including reductions in non-AIDS events resulting from residual immune dysregulation syndrome and incident tuberculosis. We agree that these plausible benefits require further investigation. If co-trimoxazole is proven effective for these benefits, we welcome research to assess continued use with other key interventions, such as isoniazid preventive therapy and inflammatory reducing drugs in high-income countries. Full-Text PDF
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