This study reveals that 42.1% of patients with TB-HIV co-infection had unsuccessful TB treatment outcome. The main socio-demographic characteristics of TB-HIV co-infected patients in this study were: aged 18 to 39 years old, male, Malaysian, Malay and residents of medium or high cost residency. Majority received formal education, unemployed and had low household income. Most of the patients with TB-HIV co-infection in this study had clinical characteristics of: non-DM, non-smoker, did not receive ART, pulmonary TB, new TB case, no or minimal CXR lesion, negative sputum smear, negative sputum culture, received DOTS, and received treatment between 6 to 12 months. The main determinants of unsuccessful TB treatment rate among patients with TB-HIV co-infection were: not receiving DOTS and TB treatment of less than six months.
In the present study, TB treatment outcome in patients TB-HIV was closely associated with that of a study performed in 2010 in the Klang Valley, Malaysia, that reported 53.4% successful treatment outcome and 46.6% unsuccessful treatment outcome. However, in the district of Kota Baharu, Malaysia, 93% of patients with TB-HIV co-infection had successful treatment outcome. By comparison, other studies conducted in South Africa also showed better TB treatment outcome in patients with TB-HIV co-infection . Therefore, these differences must be due to multifactorial aspects such as diverse outlook on sociodemographic structure and service provision settings.
Study shown that ART should be initiated as early as possible in MDR-TB patients with HIV co-infection . It is important to start ART earlier among these patients, as higher mortality were found among TB-HIV patients who had not been started with ART prior . It is also shown that higher risk for unsuccessful MDR-TB treatment occurs with the increase frequency of missed visits which were: 1.50 times, 2.25 times and 3.37 times for once missed visit, twice missed visit and thrice missed visits respectively .
Not receiving DOTS and TB treatment duration of <6 months were the most important determinants of unsuccessful TB treatment. Our findings are supported by other studies that reported that DOTS can improve the cure rate[7, 29]. By contrast, a qualitative study showed that the rigidity of DOTS was one of the factors of treatment non-adherence by patients with TB-HIV co-infection, which led to treatment default and therefore unsuccessful treatment outcome.
Taking anti-TB medications for at least 6 months is another determinant factor for successful treatment of TB, which supports the present findings. Most patients with TB-HIV co-infection are cured with a standard 6-month treatment regimen. Another study comparing 6-month and 9-month treatment reported similar treatment outcomes but with significantly lower recurrence rates compared to a 6-month, thrice-weekly regimen. It has also been proven that a longer treatment regimen can yield a more favourable treatment outcome for patients with TB-HIV co-infection , which supports our observations. Besides, low TB treatment adherence may lead to increased risk of drug resistance, treatment relapse as well as mortality. Therefore, it is important for healthcare providers to ensure that patients with TB-HIV co-infection adhere to the TB treatment regimen.
The present study shows that non-Malaysians had higher odds of having unsuccessful TB treatment outcome but it was not statistically significant; thus, it was not included as a determinant in this study. This is in concordance with another study performed in Malaysia. The small number of non-Malaysian patients with TB-HIV co-infection could have contributed to the non-significant findings of both studies. Migration is a risk factor for TB, especially for migrants from high–TB burden countries. Immigrants tend to have a higher risk for defaulting treatment, which further contributes towards unsuccessful TB treatment outcome. WHO has emphasised efforts to control TB in order to assist governments worldwide in terms of policies for migrants by preventing HIV/AIDS among migrants, as they are a vulnerable group.
In this study, lack of formal education, being unemployed and low household income were significantly associated with unsuccessful treatment outcome, compared to having received formal education, being employed and high household income. These findings are in concordance with other studies that show that people with low socioeconomic backgrounds tend to have a higher risk of poorer TB treatment outcome[30, 31]. The risk of developing TB increases among people with low socioeconomic backgrounds, as they usually live in areas with poor ventilation, have poor knowledge and behavioural practices regarding the disease itself, and are malnourished, which may lead to low immunity.
DM is a risk factor for developing TB. Similar to another study, the present findings show no significant difference in TB treatment outcome between patients with and without DM. Patients with DM tend to have poorer TB treatment outcome compared to those without DM comorbidity, as DM patients with TB can have worsened glycaemic index. However, patients with TB-HIV co-infection have low immunity due to the underlying HIV. On the other hand, patients with underlying HIV have higher chances of developing TB compared to patients with underlying DM.
The presence of a BCG scar may be a protective factor against developing TB infection. The present study suggests that patients with TB-HIV co-infection without a BCG scar have 4.2 times higher odds of having unsuccessful TB treatment outcome compared to patients with a BCG scar, but it was not significantly associated with unsuccessful TB treatment outcome. Likewise, this finding is supported by the findings of Nik Nor Ronaidi et al..
In this study, we found that not receiving ART was significantly associated with unsuccessful TB treatment outcome, and this is consistent with previous studies worldwide[6, 11, 12, 36, 37]. However, our results contradict that of a study in India. A study from Iran found that patients with TB-HIV who had not been started with ART prior had a higher chance of dying earlier. Physicians had limited time to start such patients on ART due to the shorter duration of hospitalisation because they died earlier.
In the present study, advanced CXR presentation was not significantly associated with unsuccessful TB treatment outcome. In contrast, advanced CXR findings have been suggested as a determinant factor for unsuccessful TB treatment outcome. In patients with TB-HIV, up to 10–15% of such patients with proven TB may have normal CXR due to the delayed immune response.
In this study, sputum smear upon diagnosis was not significantly associated with unsuccessful TB treatment outcome. The numbers of patients with smear-negative and smear-positive TB were almost identical in the present study, and this might explain why it was not associated with the treatment outcome. Nevertheless, this condition can also be due to the non-specific symptoms and broad-spectrum immune response among patients with TB-HIV co-infection, which may produce false negative sputum smear results among such patients[24, 39-42]. These findings were concordant with that of Nguyen et al. and Nik Nor Ronaidi et al.[19, 27]. Others have however showed that positive sputum smear is significantly associated with unsuccessful TB treatment outcome[1, 37].
In this study, positive sputum culture upon diagnosis was significantly associated with unsuccessful TB treatment outcome. This finding was supported by similar findings by Prado et al., Nguyen et al. and Swaminathan et al.[1, 19, 32]. Patients with TB-HIV co-infection with positive sputum culture may have higher TB bacterial loads, which may thus worsen the prognosis. Sputum culture is more accurate for diagnosing TB and for determining the prognosis in patients with TB-HIV co-infection, even though their sputum smear is negative. This is consistent, as sputum culture is the gold standard for TB diagnosis, especially among patients with HIV, as it has higher sensitivity compared to sputum smear[24, 43].
Nevertheless, this study has some limitations. Although the patients were selected randomly, they were all from the Kuala Lumpur Federal Territory Health Office registry. Hence, the outcome of this study is mainly limited to patients within the Federal Territory of Kuala Lumpur, and it is not known if it can be generalised to other states in Malaysia or to other countries. Second, as it was secondary data, it was very difficult to determine the sputum conversion rate after 2 months of treatment, as not all patients with TB-HIV co-infection have these data. Besides, the transferred-out patients excluded from the study would produce bias results because they could not be included in the study due to the inability to assess the treatment outcome, as their records were unavailable.
The present study identifies the determinants of TB-HIV treatment outcome, which could guide healthcare facilities, especially those in Kuala Lumpur, to focus on those areas for better treatment outcome among patients with TB-HIV co-infection so that better treatment outcome can be achieved in the future. Other than that, the TB data were obtained from a reliable source (TBIS), which represent the population studied.
This study explored the recent factors related to unsuccessful TB treatment outcome among patients with TB-HIV co-infection. As the findings showed that not receiving DOTS and TB treatment of less than six months were the determinants of unsuccessful TB treatment outcome, it is important to focus on these factors to ensure future success of TB treatment. Results of this study may provide knowledge to the clinician, researchers and the community for better TB management among patients with TB-HIV co-infection. The method of this study can also be adapted to other settings especially in Malaysia settings which had the same source of TB database, for future research.
This study adds to the literature related to the factors of unsuccessful TB treatment among patients with TB-HIV co-infection in high density population areas like Kuala Lumpur. It revealed the important factors needed to be focused in TB management to ensure future success of TB treatment especially in patients with TB-HIV co-infection.