Empirical treatment for TB in HIV: lessons from a cohort study of people living with HIV treated in Recife, Brazil

BMC Public Health

Laura C Rodrigues³  Marcela L Santos¹  Demócrito B Miranda-Filho⁴  Heloísa R Lacerda²  Ricardo A A Ximenes²  Magda Maruza⁵  Joanna d’Arc Batista²  Isabella Coimbra⁴  Maria de Fátima Pessoa Militão Albuquerque¹ 

[1] NESC Department, Centro de Pesquisas Aggeu Magalhães/FIOCRUZ, Recife, Brazil;Department of Tropical Medicine, Universidade Federal de Pernambuco, Recife, Brazil;London School of Hygiene and Tropical Medicine, London, UK;Department of Medical Science, Universidade de Pernambuco, Recife, Brazil;Hospital Correia Picanço, Recife, Brazil

关键词: Survival analysis;    Mortality rate;    TB/HIV;   

Others  :  1131777
DOI  :  10.1186/1471-2458-14-289

 received in 2013-04-26, accepted in 2014-03-20,  发布年份 2014

【 摘 要 】

Background

Tuberculosis (TB) is the leading cause of death related to HIV worldwide. This study analyzes the survival of People Living with HIV (PLHIV) reporting cough without bacteriological confirmation of TB and identify factors associated with death.

Methods

Prospective cohort with a consecutive sample of PLHIV, aged ≥ 18 years. Patient inclusion criteria were complaint of current cough of any duration at the time of the first study interview or during their subsequent routine visits to health services and for whom AFB sputum smear was either negative or not performed during the whole follow-up period. Kaplan-Meier method was used to calculate the probability of survival. We estimated the Hazard Ratio (HR) in bivariate and multivariate Cox regression analyses.

Results

Mortality was 4.6 per 100 py; 73% were receiving HAART at recruitment. Average time from the first recorded date of cough until empirical treatment for tuberculosis was six months. Mortality was higher when the CD4 count was low (HR = 5.3; CI 95%: 3.2-9.0; p = 0.000), in those with anemia (HR = 3.0; CI 95%: 1.6-5.6; p = 0.001) and with abnormal chest X-rays (HR = 2.4; CI 95%: 1.4-4.0; p = 0.001). Mortality was higher in those receiving empirical TB treatment (HR = 2.4; CI 95%: 1.4-4.0; p = 0.002), but only in those with normal X-rays, no history of tuberculosis and no bacteriology requests. Empirical treatment for TB was more frequent in PLHIV with low CD4 counts, anemia, history of opportunistic infections, weight loss, previous tuberculosis, negative bacteriology test (as opposed to not having a test) and abnormal chest X-ray.

Conclusions

Higher mortality in PLHIV reporting a current cough without bacteriological confirmation of tuberculosis was identified for those with a CD4 cell count <200, abnormal chest X-ray, anemia and empirical treatment for tuberculosis. Mortality was not significantly higher in those empirically treated for TB, who had three characteristics suggestive of the disease (abnormal chest X-ray, history of TB treatment, AFB sputum smear or M.tb culture testing). Routine cohorts are not an adequate setting to evaluate the impact of empirical treatment for TB on the mortality of PLHIV.

【 授权许可】

   
2014 Albuquerque et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]World Health Organization, UNAIDS, UNICEF: Global HIV/AIDS Response: Epidemic Update and Health Sector Progress Towards Universal Access: Progress Report 2011. Geneva: Switzerland: WHO Press; 2011.
• [2]Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boulle A, Miotti P, Wood R, Laurent C, Sprinz E, Seyler C, Bangsberg DR, Balestre E, Sterne JA, May M, Egger M: Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006, 367:817-824.
• [3]Lawn SD, Ayles H, Egwaga S, Williams B, Mukadi YD, Santos Filho ED, Godfrey-Faussett P, Granich RM, Harries AD: Potential utility of empirical tuberculosis treatment for HIV-infected patients with advanced immunodeficiency in high TB-HIV burden settings. Int J Tuberc Lung Dis 2011, 15:287-295.
• [4]Bradshaw D, Laubscher R, Dorrington R, Bourne DE, Timaeus IM: Unabated rise in number of adult deaths in South Africa. S Afr Med J 2004, 94:278-279.
• [5]Lawn SD, Harries AD, Anglaret X, Myer L, Wood R: Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS 2008, 22:1897-1908.
• [6]World Health Organization: Treatment of Tuberculosis: Guidelines for National Programmes. Geneva: Switzerland: WHO; 2010.
• [7]Grinsztejn B, Veloso VG, Friedman RK, Moreira RI, Luz PM, Campos DP, Pilotto JH, Cardoso SW, Keruly JC, Moore RD: Early mortality and cause of deaths in patients using HAART in Brazil and the United States. AIDS 2009, 23:2107-2114.
• [8]Corbett EL, Marston B, Churchyard GJ, De Cock KM: Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment. Lancet 2006, 367:926-937.
• [9]Lopez-Gatell H, Cole SR, Margolick JB, Witt MD, Martinson J, Phair JP, Jacobson LP: Effect of tuberculosis on the survival of HIV-infected men in a country with low tuberculosis incidence. AIDS 2008, 22:1869-1873.
• [10]Manosuthi W, Chottanapand S, Thongyen S, Chaovavanich A, Sungkanuparph S: Survival rate and risk factors of mortality among HIV/tuberculosis-coinfected patients with and without antiretroviral therapy. J Acquir Immune Defic Syndr 2006, 43:42-46.
• [11]Sanguanwongse N, Cain KP, Suriya P, Nateniyom S, Yamada N, Wattanaamornkiat W, Sumnapan S, Sattayawuthipong W, Kaewsa-ard S, Ingkaseth S, Varma JK: Antiretroviral therapy for HIV-infected tuberculosis patients saves lives but needs to be used more frequently in Thailand. J Acquir Immune Defic Syndr 2008, 48:181-189.
• [12]Velasco M, Castilla V, Sanz J, Gaspar G, Condes E, Barros C, Cervero M, Torres R, Guijarro C: Effect of simultaneous use of highly active antiretroviral therapy on survival of HIV patients with tuberculosis. J Acquir Immune Defic Syndr 2009, 50:148-152.
• [13]Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, Gengiah T, Nair G, Bamber S, Singh A, Khan M, Pienaar J, El-Sadr W, Friedland G, Abdool Karim Q: Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med 2010, 362:697-706.
• [14]Hanifa Y, Fielding KL, Charalambous S, Variava E, Luke B, Churchyard GJ, Grant AD: Tuberculosis among adults starting antiretroviral therapy in South Africa: the need for routine case finding. Int J Tuberc Lung Dis 2012, 16:1252-1259.
• [15]Getahun H, Harrington M, O’Brien R, Nunn P: Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet 2007, 369:2042-2049.
• [16]Harries AD: Paying attention to tuberculosis suspects whose sputum smears are negative. Int J Tuberc Lung Dis 2011, 15:427-428.
• [17]Macpherson P, Dimairo M, Bandason T, Zezai A, Munyati SS, Butterworth AE, Mungofa S, Rusakaniko S, Fielding K, Mason PR, Corbett EL: Risk factors for mortality in smear-negative tuberculosis suspects: a cohort study in Harare, Zimbabwe. Int J Tuberc Lung Dis 2011, 15:1390-1396.
• [18]Ministry of Health, Secretaria de Vigilância em Saúde: Manual e recomendações para o controle da tuberculose no Brasil. Brazil: Ministério da Saúde; 2011:284. [in Portuguese]
• [19]World Health Organization: Guidelines for Intensified Tuberculosis Case-Finding and Isoniazid Preventive Therapy for People Living with HIV in Resource-Constrained Settings. Geneva: Switzerland: WHO; 2011.
• [20]Camargo KR Jr, Coeli CM: [Reclink: an application for database linkage implementing the probabilistic record linkage method]. Cad Saude Publica 2000, 16:439-447.
• [21]CDC: Fact Sheets in Alcohol and Public Health. Atlanta, GA: Centers for Disease Control and Prevention; 2010.
• [22]Ariyothai N, Podhipak A, Akarasewi P, Tornee S, Smithtikarn S, Thongprathum P: Cigarette smoking and its relation to pulmonary tuberculosis in adults. Southeast Asian J Trop Med Public Health 2004, 35:219-227.
• [23]Benova L, Fielding K, Greig J, Nyang’wa BT, Casas EC, da Fonseca MS, du Cros P: Association of BMI category change with TB treatment mortality in HIV-positive smear-negative and extrapulmonary TB patients in Myanmar and Zimbabwe. PloS one 2012, 7(4):e35948.
• [24]World Health Organization: Improving the diagnosis and treatment of smear-negative pulmonary and extra-pulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource-constrained settings. In WHO/HTM/HIV. Geneva, Switzerland: WHO; 2007.
• [25]Raviglione M, Marais B, Floyd K, Lonnroth K, Getahun H, Migliori GB, Harries AD, Nunn P, Lienhardt C, Graham S, Chakaya J, Weyer K, Cole S, Kaufmann SH, Zumla A: Scaling up interventions to achieve global tuberculosis control: progress and new developments. Lancet 2012, 379:1902-1913.
• [26]Slama K, Chiang CY, Enarson DA, Hassmiller K, Fanning A, Gupta P, Ray C: Tobacco and tuberculosis: a qualitative systematic review and meta-analysis. Int J Tuberc Lung Dis 2007, 11:1049-1061.
• [27]Neuman MG, Schneider M, Nanau RM, Parry C: Alcohol consumption, progression of disease and other comorbidities, and responses to antiretroviral medication in people living with HIV. AIDS Res Treat 2012, 2012:751827.
• [28]Duailibi LB, Ribeiro M, Laranjeira R: Profile of cocaine and crack users in Brazil. Cad Saude Publica 2008, 24(Suppl 4):s545-s557.
• [29]Getahun H, Kittikraisak W, Heilig CM, Corbett EL, Ayles H, Cain KP, Grant AD, Churchyard GJ, Kimerling M, Shah S, Lawn SD, Wood R, Maartens G, Granich R, Date AA, Varma JK: Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med 2011, 8:e1000391.