Burden of HIV and treatment outcomes among TB patients in rural Kenya: a 9-year longitudinal study.

BACKGROUND: Although tuberculosis (TB) patients coinfected with HIV are at risk of poor treatment outcomes, there is paucity of data on changing trends of TB/HIV co-infection and their treatment outcomes. This study aims to estimate the burden of TB/HIV co-infection over time, describe the treatment available to TB/HIV patients and estimate the effect of TB/HIV co-infection on TB treatment outcomes. METHODS: This was a retrospective data analyses from TB surveillance in two counties in Kenya (Nyeri and Kilifi): 2012‒2020. All TB patients aged ≥ 18 years were included. The main exposure was HIV status categorised as infected, negative or unknown status. World Health Organization TB treatment outcomes were explored; cured, treatment complete, failed treatment, defaulted/lost-to-follow-up, died and transferred out. Time at risk was from date of starting TB treatment to six months later/date of the event and Cox proportion with shared frailties models were used to estimate effects of TB/HIV co-infection on TB treatment outcomes. RESULTS: The study includes 27,285 patients, median (IQR) 37 (29‒49) years old and 64% male. 23,986 (88%) were new TB cases and 91% were started on 2RHZE/4RH anti-TB regimen. Overall, 7879 (29%, 95% 28‒30%) were HIV infected. The proportion of HIV infected patient was 32% in 2012 and declined to 24% in 2020 (trend P-value = 0.01). Uptake of ARTs (95%) and cotrimoxazole prophylaxis (99%) was high. Overall, 84% patients completed six months TB treatment, 2084 (7.6%) died, 4.3% LTFU, 0.9% treatment failure and 2.8% transferred out. HIV status was associated with lower odds of completing TB treatment: infected Vs negative (aOR 0.56 (95%CI 0.52‒0.61) and unknown vs negative (aOR 0.57 (95%CI 0.44‒0.73). Both HIV infected and unknown status were associated with higher hazard of death: (aHR 2.40 (95%CI 2.18‒2.63) and 1.93 (95%CI 1.44‒2.56)) respectively and defaulting treatment/LTFU: aHR 1.16 (95%CI 1.01‒1.32) and 1.55 (95%CI 1.02‒2.35)) respectively. HIV status had no effect on hazard of transferring out and treatment failure. CONCLUSION: The overall burden of TB/HIV coinfection was within previous pooled estimate. Our findings support the need for systematic HIV testing as those with unknown status had similar TB treatment outcomes as the HIV infected.

Tuberculosis poor treatment outcomes and its determinants in Kilifi County, Kenya: a retrospective cohort study from 2012 to 2019.

BACKGROUND: Tuberculosis (TB) is one of the leading causes of deaths in Africa, monitoring its treatment outcome is essential to evaluate treatment effectiveness. The study aimed to evaluate proportion of poor TB treatment outcomes (PTO) and its determinants during six-months of treatment at Kilifi County, Kenya. METHODS: We conducted a retrospective analysis of data from the TB surveillance system (TIBU) in Kilifi County, Kenya from 2012 to 2019. The outcome of interest was PTO (lost-to-follow-up (LTFU), death, transferred out, treatment failure, drug resistance) or successful treatment (cured or completed treatment). We performed time-stratified (at three months follow-up) survival regression analyses accounting for sub-county heterogeneity to determine factors associated with PTO. RESULTS: We included 14,706 TB patients, their median (IQR) age was 37 (28-50) years and 8,791 (60%) were males. A total of 13,389 (91%) were on first line anti-TB treatment (2RHZE/4RH), 4,242 (29%) were HIV infected and 192 (1.3%) had other underlying medical conditions. During 78,882 person-months of follow-up, 2,408 (16%) patients had PTO: 1,074 (7.3%) deaths, 776 (5.3%) LTFU, 415 (2.8%) transferred out, 103 (0.7%) treatment failure and 30 (0.2%) multidrug resistance. The proportion of poor outcome increased from 7.9% in 2012 peaking at 2018 (22.8%) and slightly declining to 20% in 2019 (trend test P = 0.03). Over two-thirds 1,734 (72%) poor outcomes occurred within first three months of follow-up. In the first three months of TB treatment, overweight ((aHR 0.85 (95%CI 0.73-0.98), HIV infected not on ARVS (aHR 1.72 (95% CI 1.28-2.30)) and year of starting treatment were associated with PTO. However, in the last three months of treatment, elderly age ≥50 years (aHR 1.26 (95%CI 1.02-1.55), a retreatment patient (aHR 1.57 (95%CI 1.28-1.93), HIV infected not on ARVs (aHR 2.56 (95%CI 1.39-4.72), other underlying medical conditions (aHR 2.24 (95%CI 1.41-3.54)) and year of starting treatment were positively associated with PTO while being a female (aHR 0.83 (95%CI 0.70-0.97)) was negatively associated with PTO. CONCLUSIONS: Over two-thirds of poor outcomes occur in the first three months of TB treatment, therefore greater efforts are needed during this phase. Interventions targeting HIV infected and other underlying medical conditions, the elderly and retreated patients provide an opportunity to improve TB treatment outcome.

The effect of empirical and laboratory-confirmed tuberculosis on treatment outcomes.

The World Health Organization (WHO) criteria for diagnosing and treating Tuberculosis (TB) includes clinical signs, therefore not requiring bacteriological laboratory confirmation. In resource-limited settings, including Kenya, this empirical TB treatment is routine practice however limited data exist on patient clinical outcomes when comparing the method of diagnosis. We evaluated TB treatment outcomes comparing clinically diagnosed and bacteriologically confirmed TB, 6 months after starting treatment of TB in a rural county in Kenya. Our analysis compared patients with a clinical versus a bacteriologically confirmed TB diagnosis. In this retrospective analysis, we included all adults (≥ 18 years) starting treatment of TB and followed up for 6 months, within the County TB surveillance database from 2012 to 2018. Patients included from both public and private facilities. The TB treatment outcomes assessed included treatment success, treatment failure, death, defaulted and transferred out. We used survival regression models to assess effect of type of diagnosis on TB treatment outcome defining time at risk from date of starting treatment to experiencing one of the treatment outcomes or completing 6-months of treatment. A total of 12,856 patients; median age 37 [IQR 28 - 50] years were included. 7639 (59%) were male while 11,339 (88%) were pulmonary TB cases. Overall, 11,633 (90%) were given first-line TB treatment and 3791 (29%) were HIV infected. 6472 (50%) of the patients were clinically diagnosed of whom 4521/6472 (70%) had a negative sputum/GeneXpert test. During the study 5565 person-years (PYs) observed, treatment success was 82% and 83% amongst clinically and bacteriologically diagnosed patients (P = 0.05). There were no significant differences in defaulting (P = 0.70) or transfer out (P = 0.19) between clinically and bacteriologically diagnosed patients. Mortality was significantly higher among clinically diagnosed patients: 639 (9.9%) deaths compared to 285 (4.5%) amongst the bacteriologically diagnosed patients; aHR 5.16 (95%CI 2.17 - 12.3) P < 0.001. Our study suggests survival during empirical TB treatment is significantly lower compared to patients with laboratory evidence, irrespective of HIV status and age. To improve TB treatment outcomes amongst clinically diagnosed patients, we recommend systematic screening for comorbidities, prompt diagnosis and management of other infections.

Mortality during treatment for tuberculosis; a review of surveillance data in a rural county in Kenya.

BACKGROUND: Globally in 2016, 1.7 million people died of Tuberculosis (TB). This study aimed to estimate all-cause mortality rate, identify features associated with mortality and describe trend in mortality rate from treatment initiation. METHOD: A 5-year (2012-2016) retrospective analysis of electronic TB surveillance data from Kilifi County, Kenya. The outcome was all-cause mortality within 180 days after starting TB treatment. The risk factors examined were demographic and clinical features at the time of starting anti-TB treatment. We performed survival analysis with time at risk defined from day of starting TB treatment to time of death, lost-to-follow-up or completing treatment. To account for 'lost-to-follow-up' we used competing risk analysis method to examine risk factors for all-cause mortality. RESULTS: 10,717 patients receiving TB treatment, median (IQR) age 33 (24-45) years were analyzed; 3,163 (30%) were HIV infected. Overall, 585 (5.5%) patients died; mortality rate of 12.2 (95% CI 11.3-13.3) deaths per 100 person-years (PY). Mortality rate increased from 7.8 (95% CI 6.4-9.5) in 2012 to 17.7 (95% CI 14.9-21.1) in 2016 per 100PY (Ptrend<0.0001). 449/585 (77%) of the deaths occurred within the first three months after starting TB treatment. The median time to death (IQR) declined from 87 (40-100) days in 2012 to 46 (18-83) days in 2016 (Ptrend = 0·04). Mortality rate per 100PY was 7.3 (95% CI 6.5-7.8) and 23.1 (95% CI 20.8-25.7) among HIV-uninfected and HIV-infected patients respectively. Age, being a female, extrapulmonary TB, being undernourished, HIV infected and year of diagnosis were significantly associated with mortality. CONCLUSIONS: We found most deaths occurred within three months and an increasing mortality rate during the time under review among patients on TB treatment. Our results therefore warrant further investigation to explore host, disease or health system factors that may explain this trend.