Prevalence and predictors of tuberculosis among HIV patients who completed isoniazid preventive therapy (IPT) at Reach out Mbuya community health initiative

doi:10.21203/rs.3.rs-2595504/v1

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Prevalence and predictors of tuberculosis among HIV patients who completed isoniazid preventive therapy (IPT) at Reach out Mbuya community health initiative

https://doi.org/10.21203/rs.3.rs-2595504/v1

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Background

Tuberculosis (TB) continues to be the leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals in Sub Saharan Africa, including Uganda. Isoniazid prophylaxis therapy (IPT) is a major public health intervention to avert the progression of latent tuberculosis to active tuberculosis disease among people living with HIV. However, there is limited information about the influence of IPT on TB incidence and its associated risk factors among HIV positive patients in Uganda especially at Reach out-Mbuya community health initiative hence the study.

Methods

A cross sectional study was conducted among positive adult patients who completed a 6-months long daily treatment of Isoniazid preventive therapy. Sputum samples and urine samples were collected and analysed using gene xpert and lateral flow urine Lipoarabinomannan (TF LAM) tests respectively for presence of Tuberculosis. Data analysis was performed using STATA. Bivariate and multivariate logistic regression were performed to assess the risk factors associated with tuberculosis among the study population and significance estimated at 95% confidence level.

Results

A total of 103 HIV positive adults was studied. The mean age of the participants was 42.09 ± 10.49 and median age was 43. The prevalence of tuberculosis among HIV positive adult patients who completed Isoniazid preventive therapy was 5.8% (6/103). Counselling, the only factor significantly associated with TB (aOR:0.028, P-value < 0.001) had a protective effect of influencing HIV patients to complete of IPT and reduce the risk of TB infection.

Conclusion

Administration of IPT to HIV patients effectively reduces the occurrence of TB. Counselling is a significant predictor of prevention of active TB among HIV patients.

prevalence

Isoniazid preventive therapy

risk factors

HIV patients

Worldwide, tuberculosis (TB) is the 13th leading cause of death (1). It is caused by Mycobacterium and mainly affects the lungs but it can also affect other body parts such as the brain, kidneys, or spine. HIV coinfection is the prime risk factor for developing active TB in the high-burden settings. This in turn increases the susceptibility to primary infection or reinfection and the risk of TB reactivation for patients with latent TB. Similarly, infection of Mycobacterium tuberculosis also has a negative effect on the immune response to HIV, accelerating the progression from HIV infections to AIDS (2). Furthermore, the risk of developing TB among people living with HIV (PLHIVs) is 18 times higher than the general population (1).

In 2021, an estimate of 10.6 million people fell ill with TB worldwide with Africa accounting for 25% of the cases, 8% of which were people living with HIV. An estimate of 1.6 million TB deaths were recorded including 187,000 HIV-positive people (3). According to the WHO, Sub-Saharan Africa in 2017 was home to 70% of all people living with HIV/TB co-infection in the world (1). Uganda is among the 30 high TB burden countries and these countries accounted for 87% of new TB cases (4).

The WHO recommends Isoniazid preventive therapy, intensified case finding and infection control (three ‘I’s) as the main strategies in the prevention of Tuberculosis among people living with HIV (5).

Studies have shown that IPT can significantly lower TB incidence among PLHIV after completion of the six month period of treatment (6–8). However, uptake of IPT has been relatively low in most developing countries including Uganda (9).

Information on enrolment, retention, challenges faced, lost to follow up, completion and prevalence of TB during the treatment period has been documented. However, follow up studies after completion of therapy have not been conducted to determine the effect of IPT on TB infection and associated risk factors for TB among HIV positive adults enrolled in care and treatment at Mbuya treatment centre, hence the study. The findings will inform policy makers, health workers and patients on the opportunities for improved patient outcomes and a longer protection by IPT after treatment completion if the significant risk factors are mitigated.

Study design

A cross sectional study was conducted among PLHIV above 18 years who completed Isoniazid preventive therapy and had their clinic appointments between July and September, 2022. The study was carried out at Reach out Mbuya community health initiative in Nakawa division, Kampala district, central Uganda. Reach out Mbuya is a community-based non-governmental organization providing a unique model of care to PLHIV and where necessary their families; taking care of the medical, social, emotional and economical aspect of their lives to foster dignified living. The organisation started with 14 HIV positive clients in 2001, and currently serves ≥ 7000 annually.

Eligibility Criteria

All the people living with HIV/AIDS above 18 years with documented records of Isoniazid preventive therapy completion and consented were included the study.

Clients below 18 years, those without a documented record of IPT completion and those that did not consent were excluded. All patients who did not complete treatment due to personal or medical reasons were also not included in the study.

Sample size estimation and sampling procedure

The sample used in the study was estimated using the Kish and Leslie (1965) the formula below.

Sample size was calculated using the prevalence (p) of 7.2% from a previous study in Uganda done by Moore et al., 2007, a margin of error (5%), (d = 0.05) and 95% level of confidence (z = 1.96). A total of 103 participants was selected using simple random sampling technique from a list of all patients who had completed IPT and had their clinic appointments in the July – September quarter, 2022.

Data Collection

A questionnaire was entered in Kobo toolbox and used to capture demographic data of each patient and data assessing potential risk factors for Tuberculosis in people living with HIV/AIDS. The patients were asked to produce sputum samples into a clean, sterile, leak proof and labelled sputum cup for gene xpert test. Those who were not able to produce the sputum were requested to provide urine in a leak proof, screw capped labelled urine sample container.

Analysis of samples

Gene xpert

The sputum samples were tested using gene xpert test with a Cepheid machine. The test is a cartridge based nucleic acid amplification rapid test, highly sensitive and specific for Mycobacterium Tuberculosis as well as Rifampicin resistance detection.

Lateral flow Lipoarabinomannan (LF-LAM)

The urine samples from the people who were not able to produce sputum were tested using a lateral flow urine lipoarabinomannan (LF-LAM) commonly known as urine LAM. The test employs highly purified antibodies specific for the major polysaccharide antigen of the Genus Mycobacterium.

Data analysis

The data collected using Kobo toolbox was extracted, cleaned in Microsoft excel and analysed using STATA statistical package. Logistic regression analysis was performed to determine the relationship between potential risk factors and prevalence of TB among HIV patients.

Socio-demographics of the participants

A total of 103 PLHIV were included in the study. Majority of the participants were female 62 (60.2%). Of the study participants, 64 (62.1%) were aged between 31–50 years. The mean age of the participants was 42.09 ± 10.49 and median age was 43. Most of the participants 54 (52.43%) were urban dwellers, followed by sub-urban dwellers (33.01%) and lastly rural area dwellers (14.56%). Most of the participants (37.7%) had attained secondary level of education followed by 28 (27.2%) who stopped at Primary level, 27 (26.2%) of the participants reached tertiary /university level and only 11 (10.7%) had not acquired any formal education. Up to 58 (56.3%) participants were married and 22 (21.4%) were separated from their partners, 11 (11.7%) were single and 12 (11.7%) had lost their partners. Up to 59 (57.3%) participants were employed while 44 (42.7%) were not employed. Majority of the participants (33.0%) were Catholics, followed by Anglicans (27.2%), Moslems (22.3%) and Pentecostal Christians (17.5%). Only 47 (45.6%) of the participants consumed alcohol while 4 (0.8%) were smokers. Details are shown in Table 1.

Table 1

Frequency distribution of social-demographic characteristics
Characteristic	Frequency	Percentage (95% CI)
Age
≤ 30	18	17.5 (0.112–0.262)
31–50	64	62.1 (0.523–0.711)
≥ 51	24	20.4 (0.136–0.620)
Gender
Male	41	39.8 (0.307–0.497)
Female	62	60.2 (0.503–0.693)
Residence
Urban	52	52.4 (0.427–0.620)
Sub-urban	34	33.0 (0.245–0.428)
Rural	15	14.6 (0.089–0.229 )
Education level
None	11	10.7 (0.060–0.184)
Primary	28	27.2 (0.194–0.367)
Secondary	37	35.9 (0.271–0.458)
Tertiary	27	26.2 (0.185–0.357)
Marital status
Divorced/separated	22	21.4 (0.144–0.305)
Lives with partner	58	56.3 (0.465–0.657)
Single	11	10.7 (0.059–0.184)
Widowed	12	11.6 (0.067–0.196)
Employment
Employed	59	57.3 (0.474–0.666)
Unemployed	44	42.7 (0.334–0.526)
Religion
Anglican	28	27.2 (0.194–0.367)
Catholic	33	33.0 (0.245–0.428)
Moslem	23	22.3 (0.152–0.315)
Pentecost	18	17.5 (0.112–0.262)

Prevalence Of Tuberculosis

The overall prevalence of TB among the study participants was 5.8%. Out of the 65 patients tested by Gene Xpert, only 3 (4.6%) were TB positive, while out of 38 patients tested by TF-LAM, 3 (7.9%) were positive as shown in Table 2.

Table 2

Prevalence of Tuberculosis.
Test	Gene Xpert	TF LAM	Total
TB Negative	62	35	97
TB Positive	03	03	06
Prevalence (%)	4.6	7.9	5.8

Risk Factors Of Tb In Plhiv Who Completed Ipt

Bivariate and multivariate logistic regression were performed to assess the association between TB active infection (dependent variable) and various predisposing factors (independent variables).

Bivariate analysis showed that being married (living with a partner) (OR = 0.171, P = 0.014) and receiving counselling (OR = 0.013, P = 0.001) had a relationship with TB prevalence among HIV patients (Table 3).

Table 3

Bivariate logistic regression of predisposing factors with TB in HIV patients.
Characteristic	Number	TB (%)	Odds ratio (95%CI)	P-value
Gender
Female	62 (60.2)	02 (3.2)	Reference
Male	41 (39.8)	04 (9.8)	1.980 (0.580–6.755)	0.275
Religion
Catholic	34 (33.0)	04 (11.8)	Reference
Anglican	28 (27.2)	02 (7.1)	0.714 (0.179–2.847)	0.633
Moslems	23 (22.3)	00 (00)	1.143 (0.129–8.436)	0.968
Pentecost	18 (17.5)	00 (00)	2.234 (0.322–15.515	0.416
Marital status
Divorced/separated	22 (21.4)	01 (4.5)	Reference
Lives with partner	28 (26.3)	02 (3.4)	0.171 (0.045–0.697)	0.014*
Single	11 (10.7)	01 (9.0)	1.143 (0.124–8.512)	0.896
Widowed	12 (11.6)	02 (16.7)	2.047 (0.341–12.285	0.433
Education
None	11 (10.7)	00 (00)	Reference
Tertiary	27 (26.2)	00 (00)	1.835 (0.192–17.494)	0.598
Secondary	37 (35.9)	03 (8.1)	0.877 (0.102–7.568)	0.905
Primary	28 (27.2)	03 (10.7)	2.224 (0.334–14.385	0.401
Residence
Rural	15 (14.6	00 (00)	Reference
Urban	54 (52.4)	06 (11)	1.758 (0.728–4.242)	0.209
Sub-urban	34 (33)	00 (00)	0.843 (0.428–1.659)	0.621
Employment
Unemployed	44 (42.7)	04 (9.1)	Reference
Employed	59 (57.3)	02 (3.4)	3.326 (0.824–13.417)	0.091
Alcohol use
No	56 (54.4)	00 (00)	Reference
Yes	47 (45.6)	06 (10.7)	2.402 (0.421–13.700)	0.324
Smoking
Non-smoker	96 (93.2)	05 (5.2)	Reference
Smoker	07 (6.8)	01 (14.3)	1.648 (0.183–14.876)	0.656
Disclosure
Not disclosed	27 (26.2)	04 (14.8)	Reference
Disclosed	76 (73.8)	02 (2.6)	0.181 (0.335–4.164)	0.795
Information
Not well informed	24 (23.3)	05 (20.8)	Reference
Well informed	79 (76.7)	01 (1.3)	0.455 (0.109–1.905)	0.482
Side effects
Not affected	57 (55.3)	00 (00)	Reference
Affected	46 (44.7)	06 (13)	1.068 (0.315–3.618)	0.916
Pill Burden
Not burdened	61 (59.2)	00 (00)	Reference
Burdened	42 (40.8)	06 (14.3)	1.100 (0.220–5.503)	0.908
Stigma
Not stigmatized	70 (68.0)	00 (00)	Reference
Stigmatized	33 (32.0)	06 (18.2)	1.029 (0.170–3.123)	0.670
Adherence Counselling
Not counselled	41 (39.8)	04 (9.8)	Reference
Counselled	62 (60.2)	02 (3.2)	0.013 (0.01–0.175)	0.001*

After performing multivariate logistic regression while controlling for cofounders, it was observed that only counselling was the only significant factor associated with prevalence of TB in HIV patients (aOR:0.028, P-value < 0.001, 95% CI: 0.0041–0.1924) ( Table 4).

Table 4

Multivariate logistic regression of predisposing factors with TB in HIV patients.
Variable	aOR	Z	P-value	95% CI
Counselling	0.028	-3.64	< 0.001*	0.0041–0.1924
Marital status	0.855	-0.37	0.709	0.3756–1.9455

Tuberculosis continues to be the leading cause of mortality among PLHIVs in Sub-saharan Africa including Uganda. The risk of developing TB among people living with HIV (PLHIVs) is higher than the general population (1). Therefore, WHO strongly recommends the use of Isoniazid preventive therapy to TB among PLHIVs to fight TB incidences in addition to infection control and active case finding (5).

A number of studies have reported that IPT significantly reduces incidence of TB among PLHIV after completion of the six month period of treatment (6, 7, 12). This study recorded a TB prevalence of 5.8% among PLHIV who had completed the six months period of IPT treatment, which is lower than 8.1% and 9.0% reported respectively in studies conducted in Ethiopia (13,14 ). This difference might be attributed to the different study design and sampling techniques used. Other studies reviewed reported lower incidence rates among PLHIV that completed IPT therapy than those who were not IPT therapy (6, 7, 12).

The study observed that females had higher completion rates of IPT as compared to their male counterparts. This is in agreement with a study in Butebo, Uganda which reported that females had a higher uptake of IPT (66%) as compared to males (33.8%) in 2021 (15).

Although TB was higher in males (9.8%) than in females (3.2%) in this study, gender was not an important predictor of TB prevalence as similarly reported in previous studies (8, 16).

It was observed in this study that adherence to counselling was an important predictor of a good outcome of the IPT therapy. This concurs with previous studies in Ethiopia and Uganda that pre-counselling of HIV clients prior to enrolment of IPT significantly improved IPT uptake and completion hence preventing active TB (13).

Administration of IPT to HIV patients effectively reduces the occurrence of TB. Counselling is a significant predictor of prevention of active TB among HIV patients. Therefore, in addition to the recommended 3Is, consistent counselling (pre and during treatment) should be emphasized in ensuring effectiveness of the IPT in people living with HIV.

IPT- isoniazid preventive therapy; HIV- human immunodeficiency virus; AIDS- Acquired Immunodeficiency Syndrome; PLHIV- People Living with Human Immunodeficiency virus; WHO- World Health Organisation; ART- Antiretroviral therapy; CI- Confidence Interval; aOR- Adjusted Odds Ratio; TF LAM - lateral flow urine Lipoarabinomannan

Acknowledgement

We acknowledge all staffs of Reach out Mbuya community health initiative specifically the Laboratory Department and Makerere University for their cooperation and support towards completion of this work.

Authors contribution

WS, EN, JN and JMK developed the concept, were involved in data collection, data analysis, data interpretation, and manuscript writing. All authors read and approved the submitted version of the manuscript.

Funding

The authors did not receive any funding.

Availability of data and materials

The datasets used and analysed during the current study are available from the corresponding author on request.

Ethics approval and consent to participate

This study was approved by Mulago Hospital Research Ethics Committee (protocol MHREC 2370) and all the other ethical principles of informed consent, autonomy, beneficence, non-maleficence and confidentiality were duly observed during the study. All methods described here were carried out in accordance with relevant guidelines and regulations.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

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No competing interests reported.

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You are reading this latest preprint version

Prevalence and predictors of tuberculosis among HIV patients who completed isoniazid preventive therapy (IPT) at Reach out Mbuya community health initiative

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Version 1

Abstract

Background

Methods

Results

Conclusion

Background

Methods

Study design

Eligibility Criteria

Sample size estimation and sampling procedure

Data Collection

Analysis of samples

Gene xpert

Lateral flow Lipoarabinomannan (LF-LAM)

Data analysis

Results

Socio-demographics of the participants

Prevalence Of Tuberculosis

Risk Factors Of Tb In Plhiv Who Completed Ipt

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1