• Users Online: 808
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
ARTICLE
Year : 2012  |  Volume : 1  |  Issue : 2  |  Page : 82-86

Treatment outcome and mortality: Their predictors among HIV/TB co-infected patients from Iran


1 Clinical TB and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences; Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Clinical TB and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Disease, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Web Publication28-Feb-2017

Correspondence Address:
Payam Tabarsi
Masih Daneshvari Hospital, Darabad, Niavaran Sq, Tehran 1955841452
Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.1016/j.ijmyco.2012.05.002

Rights and Permissions
  Abstract 


Background: The risk of death is significantly higher in TB/HIV-infected patients than in those patients with just one disease or the other. This study aims to evaluate the impact of demographic, clinical and laboratory characteristics on the treatment outcome and mortality of TB/HIV co-infected patients in a TB tertiary center in Iran.
Materials and methods: The study was conducted at Iran's National Referral Center for Tuberculosis. In total, 111 patients were recruited between 2004 and 2007. Mycobacteriology studies were performed for all patients. Demographic, clinical, and lab data of all patients were analyzed, and predictors of unsuccessful outcomes, as well as mortality, were determined.
Results: The mean age for all 111 TB/HIV patients was 38±9 years (range 22–70) and 107 patients (96.3%) were male; 104 patients (93.7%) had a history of drug abuse, and 96 patients (86.4%) had a history of imprisonment. The route of transmission of HIV was intravenous drug use in 88 of the patients (79.3%); 23 patients (20.7%) had a history of Category 1 (CAT-1) (5.4%) and CAT-2 treatment. Highly Active Antiretroviral Therapy (HAART) was given to 48 patients (43.2%). There was no significant association found between treatment outcome or mortality with sex, smoking, drug and alcohol abuse, imprisonment, route of transmission, history of CAT-1 and CAT-2, cluster of differentiation 4 (CD4), and adverse effects (p > 0.05). Administration of HAART led to a significantly higher rate of good outcome (p < 0.001). Lower Albumin levels and body weight were significantly associated with mortality.
Conclusion: Albumin levels and weight can be predictors of mortality and an unsuccessful outcome. Administration of HAART led to a better outcome.

Keywords: Tuberculosis, HIV, Outcome, Mortality


How to cite this article:
Tabarsi P, Chitsaz E, Moradi A, Baghaei P, Marjani M, Mansouri D. Treatment outcome and mortality: Their predictors among HIV/TB co-infected patients from Iran. Int J Mycobacteriol 2012;1:82-6

How to cite this URL:
Tabarsi P, Chitsaz E, Moradi A, Baghaei P, Marjani M, Mansouri D. Treatment outcome and mortality: Their predictors among HIV/TB co-infected patients from Iran. Int J Mycobacteriol [serial online] 2012 [cited 2019 Oct 21];1:82-6. Available from: http://www.ijmyco.org/text.asp?2012/1/2/82/201212




  Introduction Top


Infection by Human Immunodeficiency Virus (HIV) kills more than 8000 people daily, while more than 5000 people die of tuberculosis (TB) every day. It is estimated that one third of the world's population are infected with TB, and this is consequently true for about 40million people currently diagnosed with HIV/AIDS. In addition, without the proper treatment, 90% of the HIV-positive patients will die within months of contracting TB. Four million people affected with HIV also have TB worldwide making TB the main killer in HIV-infected patients [1]. The risk of death is significantly higher in the HIV-infected population, even if the mycobacterium is sensitive and responds well to anti-TB medications [2],[3],[4],[5],[6].

As well, some mortality risk factors have been proposed among TB/HIV patients [7],[8]. However, in this regard, there remain controversies which are mainly owing to different settings in various regions, the major route of acquisition, diverse demographic characteristics among HIV-positive cases and dissimilar epidemiologic patterns of infections of TB and HIV [7],[8],[9],[10],[11],[12].

Similar to its global trend [13], the number of HIV-infected patients in Iran is escalating with many of them being co-infected with TB [14],[15].

This study aims to evaluate the impact of demographic, clinical and laboratory characteristics on the treatment outcome and mortality of TB/HIV co-infected patients along with identifying risk factors affecting mortality to determine whether or not to continue with the available treatment methods in a TB tertiary center in Iran.


  Materials and methods Top


All National Research Institute of Tuberculosis and Lung Disease (NRITLD) TB/HIV patients were studied who have been hospitalized at Masih Daneshvari Hospital, Tehran-Iran, at the National Referral Center for Tuberculosis between 2004 and 2007. The study comprised a total of 117 patients; 111 of them have completed follow-up procedures. For this purpose, retrospectively, data was extracted from the patients' medical records.

For all patients, TB and HIV confirmation was undertaken. Primarily, sputum samples (smear, culture) were collected, chest X-rays were undertaken, and patients were tested for HIV antibodies; in the case of positive results, Western Blot testing was done. After initial confirmation for TB/HIV, first-line drug-susceptibility tests (DST) were performed for all culture-positive cases. TB treatment was initiated in accordance with standard CAT-1 regimens. Until the year 2005, the Iranian national guidelines for management of TB among HIV-infected patients consisted of the initiation of HAART eight weeks after the start of TB treatment if their CD4+ count was less than 200cells/ml. In order to prevent adverse drug interactions in HIV-infected patients receiving the HAART treatment, Rifampin was replaced with Rifabutin in their TB treatment. However, in 2005 and thereafter, the protocol was updated by administering HAART concurrently with TB treatment for patients with a CD4+ <100cells/ml. The new regimen consisted of Ziduvudin, Lamivudine and Efavirenz, which allowed the administration of Rifampin as well.

Once DST results were acquired, treatment was modified accordingly. It should be noted that all patients received Cotrimoxazole (trimethoprim/sulfamethoxazole) for CD4+ <200cells/ml and Azithromycin for CD4+ <50cells/ml as prophylaxis against opportunistic infections such as Pneumocystis carinii pneumonia (PCP) and Mycobacterium avium complex (MAC), respectively.

Monthly checkups were undertaken for follow-up until the completion of the treatment. TB treatment outcomes were measured in accordance with standard definitions.

Statistical analysis

For statistical analysis, SPSS software V.15.1 (Apache Software Foundation, Chicago, Illinois) was used. Continuous variables were expressed as group means±SD. Categorical data, such as ethnicity, were expressed as group frequency and proportion. Statistics without Yates' correction, Fisher's exact test, Student's t-test and the Mann–Whitney U test were used as appropriate. All reported p-values are two-sided. A p-value of less than 0.05 was considered statistically significant.

The protocol of the study was reviewed and approved by the Scientific and Ethics Committee of the NRITLD.


  Results Top


Totally, the mean age for all 111TB/HIV patients was 38±9 years (range 22–70), and 107 patients (96.3%) were male. Smokers accounted for 108 (97.3%) of the patients, 104 of the patients (93.7%) had a history of drug abuse, 53 patients (47.7%) were alcohol abusers, and 96 patients (86.4%) had a history of imprisonment. The method of transmission of HIV was heterosexual in 11 patients (9.9%), intravenous drug use in 88 patients (79.3%), homosexual in 1 patient (0.9%), and transfusion in 9 patients (8.1%). Pulmonary TB cases accounted for 79 (71.2%) patients, while 8 patients (7.2%) had extra-pulmonary TB, and simultaneous pulmonary and extra-pulmonary TB was present in 24 (21.6%) patients; 23 patients (20.7%) had a history of CAT-1 treatment and 6 patients (5.4%) had received CAT-2 treatment. HAART was given to 48 (43.2%) patients.

Outcomes were classified into two categories: good outcome and bad outcome. Good outcomes were assigned to all patients who either were cured or had completed treatment, and bad outcomes included the patients in whom the treatment led to death, failure, or default ([Table 1]). Death accounted for 21 (18.9%) patients ([Table 2]).
Table 1: Patients' characteristics with regard to their final treatment outcome.

Click here to view
Table 2: Patients' characteristics with regard to mortality.

Click here to view


Having performed a univariate analysis, a significant association was not found among treatment outcome and sex, smoking, drug and alcohol abuse, history of imprisonment, and route of transmission (p > 0.05). In addition, history of CAT-1 and CAT-2 treatment were not associated with outcome (p > 0.05). HAART was started only for patients whose CD4 count was less than 200. Surprisingly, administration of HAART led to a significantly higher rate of good outcomes in these patients (p < 0.001, CI 95% = 2.1–12.8, OR = 5.2). The mean CD4 count was 175.8 and 140.09 in patients with good outcomes and bad outcomes, respectively. Nonetheless, a correlation was not found between the CD4 count and outcome (p > 0.05). Furthermore, a CD4 count above 100 and below 100 did not affect treatment outcome.

Although the study did not find an association between weight and outcome, albumin levels were significantly lower in patients with a bad outcome (p = 0.003; 3.03±0.52 vs. 2.67±0.45). During the course of treatment, 33 (29.7%) patients developed adverse effects due to either anti-TB or HAART medications. However, these adverse effects did not influence the ultimate outcome of the patients (p > 0.05).

All the aforementioned variables were also analyzed against mortality; however, only age (p = 0.02) and albumin level (p = 0.009) were found to be significantly associated with mortality. The mean age of patients with mortality was lower than that of patients without mortality (48.6±9 vs. 54.9±10.8 years). Similarly, albumin levels were lower in patients who died than in those who survived (2.59±0.45 vs. 2.99±0.51).


  Discussion Top


It is now recognized that both TB and HIV contribute to each other's progress [9],[16],[17],[18]. Patients co-infected with TB and HIV have higher mortality rates in comparison with those infected with one or the other [2],[3],[4],[5],[6],[15],[19]. In several case series, the main predictor for survival was the prompt initiation of effective anti-tuberculosis treatment, HAART administration, CD4 count, site of the disease, and other previous or concurrent opportunistic infections caused by immunosuppression [7],[8],[9],[20],[21].

All patients were followed throughout their treatment accordingly; totally, 71 (64%) of the patients reached a successful outcome, whereas the same treatment led to an unsuccessful outcome in 41 (36%) others. In addition, 21 patients (18.9%) died during the course of treatment. For those who died, the time interval between treatment initiation and death was taken into consideration. A median was then calculated. (Median = 2.50 months, IQR 25–75% = 1.25–8.50, Range = 0.30–18.00.)

As the data tables and statistical analyses illustrate, a successful outcome is associated with having received HAART treatment and higher albumin levels. Furthermore, the analysis of mortality in TB/HIV patients is associated with higher weight and albumin levels. In accordance with the collected information, mortality has no significant association with receiving HAART treatment. However, this may be owing to the evidence that those who died experienced a very short time interval between their time of admission to the hospital and death. Therefore, there was no opportunity for receiving an efficacious HAART treatment. This is supported by the fact that those who had the opportunity to receive HAART showed an increasingly better response to TB treatment, and their outcome significantly improved.

Furthermore, the significant association between albumin levels and treatment outcome and mortality can be rationalized as those who had more developed disease, more recurrent opportunistic infections and more severe malnourishments had lower weight or albumin levels, and hence were more liable to have anti-TB treatment failure or to die. This may support the fact that a thorough combat against TB-HIV co-infection not only requires a well-administered treatment plan for both infections, but also mandates the presence of a relatively competent immune system, which may be adversely affected by malnutrition.

Despite the many factors affecting the risk of mortality in TB/HIV patients, such as the site of culture-proven TB at presentation, the history of previous opportunistic infection, history of treatment for tuberculosis, etc., not many studies have been done on this topic.

Additionally, not many studies have addressed the factors such as albumin or weight as predictors of mortality or a unsuccessful outcome in TB/HIV patients.

This study denotes that TB/HIV cases presenting to the center were mostly male IV drug users. As well, most of the cases (88.1%) have been or are currently imprisoned. This confirms and emphasizes the importance of implementing efficient plans for preventing, screening, and treating TB/HIV in high risk groups such as IV drug users or prisoners, in whom there is increased risk of contracting both TB and HIV owing to close contact and more high-risk behaviors.

The purpose of this study consisted of providing standard care for all patients and administering HAART and TB treatments with a uniform protocol. All eligible patients received co-Trimoxazole/Azithromycin as prophylaxis against opportunistic disease. This helps with interpreting the findings with a more direct relation to the outcomes and mortality. Of course, this study had several limitations as well. The first was that the center is a national referral center, which means that not all acquired data is necessarily a representation of the entire Iranian society. Secondly, the main pattern of the transmission route of HIV, as is seen throughout the country, is intravenous-drug abuse, and the majority of the patients were male. This may confine the researchers from considering the obtained results as the exact representative of the Iranian population.

However, it seems that, with regard to the health concern prompted by increasing TB-HIV infections, it is crucial to conduct more comprehensive studies on this issue; particularly on the predictors and risk factors for unfavorable outcomes or mortality. These should be preferentially undertaken in different settings worldwide and with a larger sample.



 
  References Top

1.
World Health Organization, Fight AIDS, fight TB, fight now: TB/HIV information pack, WHO, Geneva, 2004.  Back to cited text no. 1
    
2.
R. Stoneburner, E. Laroche, R. Prevots, T. Singh, S. Blum, P. Terry, et al, Survival in a cohort of human immunodeficiency virus-infected tuberculosis patients in New York City. Implications for the expansion of the AIDS case definition, Arch. Intern. Med. 152 (1992) 2033–2037.  Back to cited text no. 2
    
3.
J.H. Perriens, R.L. Colebunders, C. Karahunga, J.C. Willame, J. Jeugmans, M. Kaboto, et al, Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV) seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with ‘standard’ chemotherapy in Kinshasa, Zaire, Am. Rev. Respir. Dis. 144 (1991) 750–755.  Back to cited text no. 3
    
4.
P. Nunn, R. Brindle, L. Carpenter, J. Odhiambo, K.Wasunna, R. Newnham, et al, Cohort study of human immunodeficiency virus infection in patients with tuberculosis in Nairobi, Kenya: analysis of early (six-month) mortality, Am. Rev. Respir. Dis. 146 (1992) 849–854.  Back to cited text no. 4
    
5.
P.M. Small, G.F. Schecter, P.C. Goodman, M.A. Sande, R.E. Chaisson, P.C. Hopewell, Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection, N. Engl. J. Med. 324 (1991) 289–294.  Back to cited text no. 5
    
6.
R.E. Chaisson, G.F. Schecter, C.P. Theuer, G.W. Rutherford, D.F. Echenberg, P.C. Hopewell, Tuberculosis in patients with the acquired immunodeficiency syndrome: clinical features, response to therapy, and survival, Am. Rev. Respir. Dis. 136 (1987) 570–574.  Back to cited text no. 6
    
7.
A.N. Ackah, D. Coulibaly, H. Digheu, K. Diallo, K.M. Vetter, I.M. Coulibaly, et al, Response to treatment, mortality, and CD4 lymphocyte counts in HIV-infected persons with tuberculosis in Abidjan, Cote d’Ivoire, Lancet 345 (1995) 607–610.  Back to cited text no. 7
    
8.
R.W. Shafer, A.B. Block, C. Larkin, V. Vasudavan, S. Seligman, J.D. Dehovitz, et al, Predictors of survival in HIV-infected tuberculosis patients, AIDS 10 (1996) 269–272.  Back to cited text no. 8
    
9.
C. Whalen, C. Lahart, D. Hom, M. Simberkoff, J. Ellner, C. Horsburgh, Accelerated clinical course of HIV infection after tuberculosis, Am. J. Respir. Crit. Care Med. 151 (1995) 129–135.  Back to cited text no. 9
    
10.
R. Wallis, M.S. Helfand, C.C. Whalen, J.L. Johnson, R.D. Mugerwa, M. Vjecha, et al, Immune activation allergic drug reactions, and mortality in HIV-associated pulmonary tuberculosis, Tubercle Lung Dis. 77 (1996) 516–523.  Back to cited text no. 10
    
11.
E.Walters, M.F. Cotton, H. Rabie, H.S. Schaaf, L.O.Walters, B.J. Marais, Clinical presentation and outcome of Tuberculosis in Human Immunodeficiency Virus infected children on antiretroviral therapy, BMC Pediatr. 8 (2008) 1.  Back to cited text no. 11
    
12.
M. Maruza, R.A. De Alencar Ximenes, H.R. Lacerda, Treatment outcome and laboratory confirmation of tuberculosis diagnosis in patients with HIV/AIDS in Recife, Brazil, J. Bras. Pneumol. 34 (6) (2008) 394–403.  Back to cited text no. 12
    
13.
P. Nunn, A. Reid, K.M. De Cock, Tuberculosis and HIV infection: the global setting, J. Infect. Dis. 196 (2007) S5–S14.  Back to cited text no. 13
    
14.
P. Tabarsi, S.M. Mirsaeidi, M. Amiri, S.D. Mansouri, M.R. Masjedi, A.A. Velayati, Clinical and laboratory profile of patients with tuberculosis/HIV co-infection at a national referral center: a case series, East. Mediterr. Health J. 14 (2) (2008) 283–291.  Back to cited text no. 14
    
15.
P. Tabarsi, P. Baghaei, S.M. Mirsaeidi, M. Amiri, N. Alipanah, et al, Treatment outcome of tuberculosis patients diagnosed with human immunodeficiency virus infection in Iran, Saudi Med. J. 29 (1) (2008) 148–150.  Back to cited text no. 15
    
16.
J. del Amo, S. Perez-Hoyos, I. Hernandez Aguado, M. Diez, J. Castilla, K. Porter, Impact of tuberculosis on HIV disease progression in persons with well-documented time of HIV seroconversion, Acquir. Immune Defic. Syndr. 33 (2003) 184–190.  Back to cited text no. 16
    
17.
Centers for Disease Control and Prevention, 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults, MMWR Morb. Mortal. Wkly Rep. 41 (1993) 1–19.  Back to cited text no. 17
    
18.
K.R. Collins, M.E. Quinones-Mateu, Z. Toossi, E.J. Arts, Impact of tuberculosis on HIV-1 replication, diversity, and disease progression, AIDS Rev. 4 (2002) 165–176.  Back to cited text no. 18
    
19.
M. Sande, M. Loeff, R. Bennet, M. Dowling, A. Aveika, T. Togun, et al, Incidence of tuberculosis and survival after its diagnosis in patients infected with HIV-1 and HIV-2, AIDS 18 (2004) 1933–1941.  Back to cited text no. 19
    
20.
C. Whalen, C. Horsburgh, D. Hom, C. Lahart, M. Simerkoff, J. Ellner, Site of disease and opportunistic infection predict survival in HIV-associated tuberculosis, AIDS 11 (1997) 455–460.  Back to cited text no. 20
    
21.
E. Telzak, K. Chirgwin, E. Nelson, J. Matts, K. Sepkowitz, C. Benson, et al., Predictors for multidrug resistant tuberculosis among HIV-infected patients and response to specific drug regimens, Int. J. Tuberc. Lung Dis. 3(4) (1999) 337–343.  Back to cited text no. 21
    



 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 Treatment outcome of new smear positive pulmonary tuberculosis patients in Hamadan, Iran: A registry-based cross-sectional study
Salman Khazaei,Jafar Hassanzadeh,Shahab Rezaeian,Ebrahim Ghaderi,Somayeh Khazaei,Abdollah Mohammadian Hafshejani,Hamid Salehiniya,Ali Zahiri
Egyptian Journal of Chest Diseases and Tuberculosis. 2016; 65(4): 825
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and me...
Results
Discussion
References
Article Tables

 Article Access Statistics
    Viewed626    
    Printed18    
    Emailed0    
    PDF Downloaded68    
    Comments [Add]    
    Cited by others 1    

Recommend this journal