title: Benefits of combined preventive therapy with co-trimoxazole and isoniazid in adults living with HIV: time to consider a fixed-dose, single tablet coformulation.
abstract: Antiretroviral therapy (ART) is the main intervention needed to reduce morbidity and mortality and to prevent tuberculosis in adults living with HIV. However, in most resource-limited countries, especially in sub-Saharan Africa, ART is started too late to have an effect with substantial early morbidity and mortality, and in high tuberculosis burden settings ART does not reduce the tuberculosis risk to that reported in individuals not infected with HIV. Co-trimoxazole preventive therapy started before or with ART, irrespective of CD4 cell count, reduces morbidity and mortality with benefits that continue indefinitely. Isoniazid preventive therapy as an adjunct to ART prevents tuberculosis in high-exposure settings, with long-term treatment likely to be needed to sustain this benefit. Unfortunately, both preventive therapies are underused in low-income and high-burden settings. ART development has benefited from patient-centred simplification with several effective regimens now available as a one per day pill. We argue that co-trimoxazole and isoniazid should also be combined into a single fixed-dose pill, along with pyridoxine (vitamin B6), that would be taken once per day to help with individual uptake and national scale-up of therapies.
authors.affiliation: International Union against Tuberculosis and Lung Disease, Paris, France; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: adharries@theunion.org.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harries
authors.affiliation: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
authors.affiliation: South African Centre for Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa.
authors.forename: Amitabh B
authors.initials: AB
authors.lastname: Suthar
authors.affiliation: International Association of Providers of AIDS Care (IAPAC), Washington, DC, USA.
authors.forename: Reuben
authors.initials: R
authors.lastname: Granich
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D060085:Coinfection; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology; D013607:Tablets; D013997:Time Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000517:prevention & control*; D025101:Vitamin B 6 / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D004338:Drug Combinations; D013607:Tablets; D025101:Vitamin B 6; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D007538:Isoniazid