Treatment Outcome of Tuberculosis and Associated Factors among TB-HIV Co-Infected Patients at Public Hospitals of Harar Town, Eastern Ethiopia. A five-year retrospective study

The twin epidemics of Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) are the major global health challenges of the twenty-first century [1, 2]. These two infectious diseases have a bidirectional relationship that poses a dual public health burden to resource-limited countries [2]. TB-HIV co-infected people are experiencing “double trouble” that puts them at high risk of mortality, rapid disease progression, and development of other opportunistic infection [3, 4].

HIV, because of its immunosuppressive nature, is a strong risk factor for the development of TB [5] and reactivation of latent TB [4, 6]. In 2017, globally about 920,000 people who were infected with HIV developed TB [7]. Reports also indicate that people living with HIV are 20 to 21times more likely to develop active TB than those HIV negative people [7, 8]. On the other hand, TB is the most frequent life-threatening opportunistic infection and the leading cause of death among HIV positive people [1, 3, 6‐9]. About one in four deaths among HIV positive people is caused by TB [3]. TB speeds up the viral replication and load in HIV infected people [4, 6]. In general, TB affects about one-third of the 36.7 million people living with HIV worldwide [10].

Ethiopia is one of the 14 countries with high-burden of all TB, TB/HIV, and Multi-drug Resistant TB (MDR-TB) in the world [5]. According to studies and reports, the prevalence of TB-HIV co-infection in the country is so high that it has ranged from 6.1 to 40.4% [2, 4, 5, 11, 12]. The global 2018 TB report showed that in Ethiopia an estimated 3600 (95% CI: 2500–5000) TB-HIV co-infected people died while on TB treatment in the year 2017 alone [5].

In TB-HIV co-infected patients, HIV affects the effectiveness and success of TB treatment in many ways [5]. For example, the co-infected patients are exposed to many regimens including Antiretroviral Therapy (ART), anti-TB therapy, and preventive therapy of HIV-related co-morbidities which in turn is associated with an increased incidence of adverse drug reaction, poor adherence often due to pill burden, and decreased drug effectiveness. Consequently, the patient may experience a high default rate leading to TB recurrence and increased risk of death [4, 13]. Hence, well-coordinated therapeutic management is needed to ensure optimum treatment outcomes in terms of response and prevention of drug resistance.

Collaborative TB/HIV activities and management of comorbidities are the key components of the ‘end TB strategy’ [5, 13, 14]. To reduce the dual burden of TB/HIV among people living with HIV, it is recommended to scale up the three I’s, which are intensified TB case-finding followed by high-quality TB treatment, isoniazid preventive therapy (IPT), and infection control for TB in all congregate settings and health facilities providing HIV care [6, 9, 10].

According to Ethiopia national guidelines, all HIV positive patients should be evaluated for TB before ART is initiated and then at every visit. Similarly, all TB patients should be offered HIV testing services in TB clinics [4, 6, 15]. Regarding the therapeutic management, ART should be provided to all TB/HIV co-infected patients regardless of CD4 count or WHO stage. However, ant-tuberculosis treatment should be provided first, followed by ART within the first 8 weeks of treatment [6, 15]. Likewise, Co-trimoxazole prophylaxis (CPT) should be provided to all TB-HIV co-infected patients, regardless of their CD4 count [4, 6, 9, 15]. In order to prevent the reactivation of latent TB, after excluding the presence of active TB infection, IPT should be given to all people with HIV at least for six months [6, 10].

The percentage of patients treated successfully is a key indicator for monitoring and evaluating the effectiveness of the TB Directly Observed Therapy (DOT) program [10]. This is particularly necessary for patients with TB-HIV co-morbidities where the treatment outcome could be affected by many factors. Hence, it is important to conduct a periodic evaluation of the treatment outcome for this segment of the population to assess the level of quality of care and to imply possible directions for improvement. Unfortunately, there are only a few studies that have assessed TB treatment outcomes among TB-HIV co-infected people in Eastern Ethiopia. Hence, our objective was to assess the outcomes of TB treatment and the associated factors among TB-HIV co-infected patients in public hospitals in Harar town, Eastern Ethiopia.

Tuberculosis and HIV/AIDS constitute the main burden of infectious disease in resource-limited countries [1, 2]. Determining the TB treatment outcome among TB-HIV co-infected patients in different settings may provide evidence for evaluating the performance of the TB control program in the country and forward future direction.

According to WHO 2017 Global Tuberculosis Report, the global treatment success rate for HIV-associated TB cases among the 2015 cohort was 78% and in the WHO Africa region, it was 80% [23]. In this study, the overall TB treatment success rate among the TB-HIV co-infected patients was 86.8%, which is similar to the results reported from studies carried out in rural South Africa (82.2%) [24], Ahmedabad (84.2%) [25] and Addis Ababa, Ethiopia (88.2%) [26]. Our finding is lower than that of the Chandigarh study which reported a treatment success rate of 93.1% [27]. On the other hand, TB treatment success rate of our study is higher than several studies conducted in Gondar (22.6%) [28], Mizan Aman (28.5%) [17], Mizan Tepi (30.3%) [18], Malaysia (53.4%) [29], Brazil (55%) [30], Western Ethiopia (60.7%) [31], Cameroon (60.8%) [32], Iran (64%) [33], Ebonyi State Nigeria (65.8%) [34], Karnataka India (66.1%) [35], Tigray (70.8%) [16], Viet Nam (73%) [36], Arsi Negele (73%) [37], Yavatmal India (75%) [38], South India (75%) [39] and Free State province of South Africa (75.5%) [40].

This observed variation might be due to the difference in the quality of service in the TB/HIV clinic; proper counseling, health education, and appropriate follow up by the clinician. Another possible explanation might be the inclusion of transferred out patients in the final analysis by some of the previous studies. The proportion of transferred out TB/HIV co-infected patients were ranging from 3.8% in the Ebonyi State of Nigeria [34] to 64.2% in Mizan Aman of Ethiopia [17]. But, in our study, we did not include transferred patients because their records were not available and their treatment final outcomes were unknown. Furthermore, the high success rate observed in our study could be due to the initiation of ART for all co-infected patients. As it has been reported in previous studies [16, 24, 29, 31‐33, 35, 36, 39], patients who had ART initiated were found to have high success rate compared with their counterpart. For instance, studies conducted in Tigray Ethiopia [16] and Malaysian [29] stated that TB/HIV co-infected patients who were not receiving ART were 3.42 and 5.10 times more likely to have unsuccessful TB treatment outcomes than those who received ART, respectively.

TB/HIV co-infected patients have increased mortality due to rapid disease progression, late diagnosis and other opportunistic infections [4, 6]. In the current study, the death rate among the TB/HIV co-infected patients during TB treatment was 7.7%. Also, similar death rates were seen in study carried out in Mizan Aman (6%) [17], Aurangabad city, India (8.2%) [41], Addis Ababa, Ethiopia (8.3%) [26], South India (9%) [39], WHO African Region (9%) [23], Gondar (9.6%) [28], Viet Nam (10%) [36] and South Africa (10.5%) [24]. The death rate in our study was lower than the rate reported in deferent part of Ethiopia which reported a death rate ranging from 12.8 to 20.2% [16, 18, 31, 37, 42‐44], Cameroon 29.4% [32], Karnataka India 15.7% [45], Yavatimal India 16% [38], Malaysia 21% [29], Ebonyi State Nigeria 19% [34], Free State province South Africa 17.4% [40], Iran 18.9% [33]. Moreover, the WHO reported that TB associated death rate among HIV-positive TB patients was 11% [23]. Nonetheless, smaller death rates were reported from Chandigarh India 1.14% [27], Ahmedabad 4.17% [25] and Brazil 4.3% [30]. The lower death rate in our study could be explained by the fact that all our study participants had been on ART. ART is protective against mortality treatment outcomes during TB treatment. as demonstrated by previously conducted in Tigray [16], Karnataka India [35], south India [39] and North West Ethiopia [43].

Lost for follow up from TB treatment program is a major public health problem that can be associated with adverse drug reactions, social stigma and lack of awareness of the disease [17]. The proportion of lost for follow up found in this study (1.7%) is comparable Mizan Aman 1.3% [17], Tigray 2% [16] and Gondar 2.2% [28] studies. This lost for follow up of TB/HIV co-infected patients is lower than many studies conducted in Ethiopia [18, 31], Africa [24, 32, 34, 40] and Asia [29, 35, 36, 39, 41]. The possible explanation might be a good implementation of the DOT program. In addition, an increased patient awareness, and treatment adherence, and service accessibility might have contributed to this smaller proportion of lost for follow up in our settings.

The management of TB and HIV co-infected individuals is challenging because of the high pill burden, increased the adverse effect and drug-drug interaction [6]. In addition, several factors play a significant role in determining the TB treatment outcome among TB/HIV co-infected patients. In this regard, our study revealed that patient category, types of TB, WHO staging, history of opportunistic infection and CPT initiation significantly associated with TB treatment outcome.

The TB/HIV co-infected patients on the retreatment category had a higher chance of unsuccessful treatment outcome than the new patients. A similar result was reported from South India [39], Brazil [30], Yavatmal India [38] and Viet Nam [36] studies. The poor treatment outcome observed in the retreatment category could be due to drug resistance because of re-exposure to the drugs [30].

Type of TB infection was identified by different previous studies [18, 26, 29, 30, 37‐39, 43, 44] as a determinant of TB treatment outcome. In our study, the chance of unsuccessful treatment was lower among the TB/HIV co-infected patients with extrapulmonary TB and smear-negative pulmonary TB compared with the smear-positive pulmonary TB. A similar, finding was reported by a study conducted in Addis Ababa Ethiopia [26], South India [39] and Yavatmal India [38].

In contrary to this, a study conducted in Mizan Tepi [18] demonstrated TB/HIV co-infected patients with Smear positive PTB had a higher chance of successful TB treatment outcome. In addition, studies conducted in many places [29, 37, 43, 44] reported that TB/HIV co-infection patients with extrapulmonary TB had a higher chance of mortality during TB treatment than pulmonary TB patients. In general, a high successful treatment outcome is expected among patients with smear-positive PTB compared with smear-negative PTB and extrapulmonary TB. However, the higher successful treatment outcome observed in our study among smear-negative PTB and extrapulmonary TB patients might be due to the close supervision and attention given by health care provides to these groups of patients. This close supervision might be associated with considering these patients are at high risk for unsuccessful treatment outcomes.

In the present study, similar to studies conducted elsewhere (MizanTepi [18] and Tigray [16]), the chance of unsuccessful TB treatment outcome was higher among the TB/HIV co-infected patients in stage 2, stage 3 and stage 4 HIV diseases than those in stage 1 disease. This might be due to the development of different opportunistic infections among the patients with advanced stages of HIV which can directly affect TB treatment outcomes.

The association between opportunistic infections and TB treatment outcomes was also demonstrated by our study. Those TB/HIV co-infected patients with opportunistic infection history had a higher chance of unsuccessful TB treatment outcome than the patients without opportunistic infection history. This is in line with a finding reported in Cameroon [32]. The possible reason could be poor adherence to anti TB drugs due to the high pill burden and associated drugs adverse effect.

Similarly, the chance of unsuccessful TB treatment outcome was higher among the TB/HIV co-infected patients who did not take CPT compared with those who took the prophylaxis. Studies conducted in North West Ethiopia [43], Cameroon [32], South Africa Free State [40], Yavatmal India [38] and Viet Nam [36] also reported similar findings. The administration of CPT can reduce the chance of co-morbidities such as pneumonia with pneumocystis, toxoplasmosis and other bacterial infections, which may then be related to a higher rate of cure and treatment completion and a lower rate of deaths.

According to the Ethiopia National Guidelines, CPT should be provided for all HIV positive TB patients as one component of the national TB/HIV collaborative activity [6]. In spite of this, only 84.8% of TB/HIV co-infected patients were on CPT. This finding was consistent with studies from western Ethiopia (80%) [31], Yavatmal India (80%) [38], Gondar (88.9%) [19] and Addis Ababa Ethiopia (77%) [26]. However, this figure was higher than a report from Ebonyi State Nigeria (55.3%) [34] and Free State province South Africa (42.1%) [40]. Hence, health care providers should apply every effort to make sure that all HIV patients took CPT.

The overall TB treatment success rate among the TB-HIV co-infected patients in this study was higher compared with many previous studies. TB/HIV patients with a history of previous TB treatment, smear-positive pulmonary TB, advanced HIV stage, history of opportunistic infection and no CPT initiated were at a high risk of getting poor treatment outcomes.

Therefore, TB treatment facilities should give special attention to those TB-HIV co-infected patients with a higher risk of unsuccessful TB treatment outcome.