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Research paper

Human immunodeficiency virus as a determinant of tuberculosis treatment outcome in tuberculosis patients treated at Arba Minch General Hospital: a five-year retrospective study

Alemu Chemeda Ifa

HIV AIDS Rev 2018; 17, 2: 74-80
Online publish date: 2018/05/21
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Introduction

Tuberculosis (TB) is still a major public health problem in developing countries. It is the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus (HIV) [1]. There were an estimated 1.4 million TB deaths in 2015, and an additional 0.4 million deaths resulting from TB disease among people living with HIV. Although the number of TB deaths fell by 22% between 2000 and 2015, TB remained one of the top 10 causes of death worldwide in 2015 [2].
Despite several efforts made to prevent and/or control the disease, many countries have not yet achieved the TB control targets. Rather, it remains a major public health problem leading to mortality in high HIV-burden countries [3, 4]. HIV drives a TB epidemic in many countries, especially in sub-Saharan Africa, where 82% of the world’s TB/HIV co-infection exists [2, 5]. The burden of HIV/TB co-infection in the community had a great impact on TB treatment success, which is why TB is a leading cause of mortality and morbidity in developing countries.
Globally, the treatment outcome data show a treatment success rate of 83% for TB, 52% for multidrug-resistant TB (MDR-TB) and 28% for extensively drug-resistant TB (XDR-TB) [2]. According to an Ethiopia Ministry of Health (EMoH) report, in 2015, the TB treatment success rate (TSR) was 92.1%, which is below the target set for the year (97%) [6]. Disparities were observed across regions, with the highest performance being observed in the Southern Nations, Nationalities, and Peoples’ (SNNP) Region (97.0%) and the lowest performance was observed in the Gambella Region (66.8%) [7].
To achieve the millennium goal, the synergic activity of HIV/TB is another problem which reduces the TSR. The HIV epidemic is believed to contribute to this inability to reduce TB incidence in Ethiopia. The monitoring of the TB treatment outcome is an essential part of TB disease surveillance to ensure that the disease is successfully eliminated. Despite strong political commitment and implementation of different strategies such as extensive expansion of directly observed therapy short-course (DOTS) services in Ethiopia [8] and the massive involvement of health extension workers (HEWs) in TB prevention and control activities at the grass-root level, and integrated TB/HIV activities in place [7], the key intervention for reducing the burden and mortality of HIV-associated TB was estimated to be low [3, 9].
Since the inception of all the above activities, only a few studies have been conducted in Ethiopia [10, 11]. Furthermore, the impact can vary between different populations and health systems; hence it is important to evaluate the HIV status and treatment outcomes of TB patients in order to perform interventional activities taking into account the specific settings. Therefore, the aim of this study was to assess the impact of HIV status on treatment outcome of TB at Arba Minch General Hospital in the SNNP region of Ethiopia.

Material and methods

Arba Minch is the capital city of the Gamo Gofa zone of the SNNP regional state, in the southern part of Ethiopia. The town is 505 km south of Addis Ababa, the capital city of Ethiopia. Arba Minch General Hospital (AMH) is one of the public health facilities that provide DOTS services for people living in and around Arba Minch town. A five-year retrospective document review of TB patients registered at the DOTS clinic of AMH was conducted to assess the impact of HIV on TB treatment outcome. The study population included all TB cases registered from August 2012 to July 2016 at the AMH DOTS clinic. Patients were diagnosed, registered, treated and referred to other DOTS clinics following the national tuberculosis, leprosy and TB/HIV prevention and control program guideline [7]. Socio-demographic characteristics such as age, sex, residence, and type of tuberculosis infection, status of HIV infection, and outcome of TB treatment were collected from January to March 2017 using a checklist set for this purpose. Patients with incomplete information were excluded. The study was approved by the ethical review committee, College of Medicine and Health Sciences, Arba Minch University. The clinical records of patients were anonymized and de-identified prior to analysis. Consent to collect the information from TB registers was obtained from the AMH administration.

Definitions of treatment outcome

Treatment outcome definitions were used according to the standard definitions of the National Tuberculosis and Leprosy Control Program (NTLCP) [7] and World Health Organization (WHO) guideline [12]. Cured: An initially smear-positive patient who is sputum smear-negative at, or one month prior to, the completion of treatment and on at least one previous occasion (usually at the end of the 2nd or 5th month). Treatment completed: A patient who completed treatment but for whom smear results are not available at the 7th month or one month prior to the completion of treatment. Treatment failure: A patient who remains or becomes again smear-positive at the end of 5 months or later during treatment. Died: A patient who dies for any reason during the course of treatment. Defaulter: A patient who has been on treatment for at least 4 weeks and whose treatment was interrupted for 8 or more consecutive weeks. Transfer out: A patient who started treatment and has been transferred to another reporting unit and for whom the treatment outcome is not known at the time of evaluation of treatment results. Treatment success: The sum of patients who are declared “cured” and those who have “completed” treatment.

Data analysis

Data were entered, cleaned and analyzed using SPSS version 16. Odds ratios with 95% CIs were used to determine the presence and strength of a statistically significant association between HIV status and TB treatment outcome.

Results

Out of 611 TB patients registered between 2012 and 2016 at AMH, 544 patients had complete information (89%). The majority, i.e. 323 (59.4%), of them were male. The mean age was 32.8 years with ± 14.3 years standard deviation (SD). Most of them 385 (70.8%) were HIV-negative TB patients. Many TB cases (335; 61.6%) were pulmonary tuberculosis (PTB) cases. More than 64.7% (352/544) were urban residents (Table 1).

Tuberculosis treatment outcome

Overall, the treatment success rate (TSR) of TB patients with or without HIV during the study period was 406 (74.6%). The remaining 73 (13.4%) were cases of transfer out, 0 (1.8%) were dead, 38 (7%) were defaulters and 3 (0.6%) were cases of treatment failure. Of the HIV-positive patients, 45 (28.3%) were cured, 57 (35.8%) were treatment completed, 7 (4.4%) died, 12 (7.5%) were defaulters, 34 (21.4%) were transferred-out cases, and 3 (1.9) were failures. Of the HIV-negative TB patients, 130 (33.8%) were cured, 187 (48.6%) were treatment completed, 3 (0.8%) died, 26 (6.7%) were defaulters, 39 (10.1%) were cases of transfer-out, while there was no cases of treatment failure. The treatment success rate for TB among HIV-seropositive patients was 64.1% while the treatment success rate for HIV-negative patients was 79%. The treatment success rate among the patients in AMH was generally low, ranging from 60% in 2016 to 79.1% in 2012 with a mean TSR of 74.6%. Failure was reported in two of the five years, 2012 and 2015, while default was reported in all the five years. The rate of cure among the HIV-positive TB cases was 25.7% (45/175) while in HIV-negative cases it was 74.3% (130/175) (Table 2, Fig. 1).
As shown in the above bar graph, the rate of cure was similar in 2013, 2014, and 2015, while it improved in 2016 (Fig. 2).
As shown in the above bar graph, the rate of treatment failure was higher in HIV-seropositive than HIV-negative patients.

Impact of HIV status on tuberculosis treatment outcome

Logistic regression analysis was used by combining the outcome of cured and treatment completed (treatment success) as the reference. HIV-seropositive TB patients had higher odds of death (COR = 6.95; 95% CI: 1.765-27.394) and transfer-out to other health institutions (COR = 2.59; 95% CI: 1.557-4.334). Also HIV-seropositive patients had higher odds of failure (COR = 20.79; 95% CI: 1.065-406.019), and default (COR = 1.37; 95% CI: 0.669-2.825) when compared with the HIV-negative patients (Table 3).

Discussion

In the present study, the prevalence of HIV co-infection among TB patients was 29.2%, similar to the studies conducted in northwest Ethiopia (25%) [13]. However, this finding is higher than that of a study conducted in northwest Ethiopia (11.4%)[14], a 2016 WHO report for Ethiopia (10%) [2], for Brazil (19%) [15] and for Nigeria (20%) [16].
Overall, TSR of registered TB patients with and without HIV was 74.6%, which is inconsistent with the WHO target of 85% [9] and EMoH target of 97% [7]. However, our finding is consistent with the previous report for Tigray [17], Gondor [18] and western Ethiopia [19]. The TSR was worse in tuberculosis patients with HIV than without HIV. In the present study, HIV-seropositive TB patients had higher odds of failure, transfer out and default as compared to those of HIV sero-negatives. The mortality rate in TB/HIV-positive patients was higher than in HIV-negative patients. Those who were HIV positive had about 7 times higher odds of death and threefold higher odds of transfer out to other health institutions compared with HIV-negative TB patients. This finding is slightly lower than the research conducted in Arsi Negelle Health Center [11], Addis Ababa [20], Tigray [21], central Ethiopia [22], south Ethiopia [23, 24], and northwest Ethiopia [10, 13, 25], while this result is higher relative to a study in Northwest Ethiopia [25], Northern Ethiopia [26], west Gojjam [27], and Southwest Ethiopia [28]. The possible reason for the observed difference might be differences in study population, high number of transfer-out cases [25] and increased number of unrecorded treatment outcomes in the study in south Ethiopia [23, 24].
The HIV sero-positive patients were more likely to be transferred out to other health institutions [11] as compared to the HIV-negative patients [10], which could have an adverse effect on evaluation of TB treatment outcomes because this group was included in the denominator [11]. In addition to this, the feedback system is poor and there are no ways to determine whether these patients registered to continue treatment in another health center [25]. The possible reason for transfer out of these patients may be due to lack of confidentiality associated with HIV testing or fear of disgrace associated with accessing ART. This might be an issue which needs improvements and consultancy. Although studies have shown that patients who default tend to be at higher risk of TB treatment failure (develop MDR-TB) associated with a longer period of TB transmission in the community and had a higher rate of mortality [22, 29], still there are different factors that cause the patients from developing countries to interrupt their treatment [30]. In this study, HIV-seropositive patients had about 2 times higher odds of defaulting and about 21 times higher odds of treatment failure [10, 11, 23]. This result partly indicates that HIV status [31] and being on ART [32] were factors associated with TB treatment non-adherence and lost-to-follow-up. Also our finding showed that the risk of death was significantly higher among HIV-positive TB patients than HIV-negative patients, which agrees with findings from previous studies [11, 23, 26, 27]. A number of possible explanations have been proposed for the striking difference in mortality between patients with tuberculosis only and those co-infected with HIV. Several immunological studies, from different parts of the world, have shown that the host responses to Mycobacterium tuberculosis facilitate HIV replication [33], thus accelerating the natural progression of HIV and further depressing cellular immunity. This contributes to late presentation and diagnosis of HIV [34], which indicate that HIV-seropositive TB patients have been implicated in the increased mortality. Also the difficulty of TB diagnosis and the consequent delay in treatment initiation may result in higher mortality among PTB and extrapulmonary tuberculosis (EPTB) patients [35].

Conclusions

This study showed that the successful anti-TB treatment outcome among TB/HIV co-infected patients who attended their treatment at the Arba Minch General Hospital TB DOTS clinic was below the target set by WHO and Ethiopian Ministry of Health. Also, we were able to demonstrate from our data that HIV-negative patients being treated for TB were associated with better treatment outcome. We conclude that treatment plans that emphasize DOTS for at-risk patients have the greatest success in improving tuberculosis treatment outcome in the region. Urgently strengthening the coordinated tuberculosis control program and treatment outcome monitoring is strongly recommended. Thus, we recommended that strengthening the integration of TB/HIV collaborative activities could improve the treatment outcome. In addition, to improve TB patients’ follow- up, it is better to keep them in contact with nearby health professionals.
Our study shares the inherent limitation of a retrospective study and may be subjected to random error and selection bias. As this study was based on a retrospective review of TB registers, comprehensive analysis of all relevant risk factors such as treatment adherence, CD4+ count, opportunistic infections, timing of ART, ART enrollment and provision of current procedural terminology CPT do not routinely capture from the record, which may overestimate or underestimate the impact of HIV status on TB treatment outcome.

Acknowledgements

I acknowledge the technical support provided by AMH. My special thanks and appreciation also go to the AMH administration, who gave permission for this paper’s publication.

Conflict of interest

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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