Gender differences among patients with drug resistant tuberculosis and HIV co-infection in Uganda: a countrywide retrospective cohort study

Abstract

Background Gender differences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could affect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. Methods We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged ≥ 18 years, had confirmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical significance was set at p < 0.05. Results Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p < 0.001). Men were significantly more likely to be on tenofovir-based antiretroviral therapy (ART), high-dose isoniazid-containing DRTB regimen and to have history of cigarette or alcohol use. They were also more likely to have multi-drug resistant TB, isoniazid and streptomycin resistance and had higher creatinine, aspartate and gamma-glutamyl aminotransferase and total bilirubin levels. Conversely, women were more likely to be unemployed, unmarried, receive treatment from the national referral hospital and to have anemia, a capreomycin-containing DRTB regimen and zidovudine-based ART. Treatment success was observed among 437 (65.6%) and did not differ between the genders. However, mortality was higher among men than women (25.7% vs. 18.5%, p = 0.030) and men had a shorter mean (standard error) survival time (16.8 (0.42) vs. 19.0 (0.46) months), Log Rank test (p = 0.046). Predictors of mortality, after adjusting for gender, were cigarette smoking (aHR = 4.87, 95% CI 1.28–18.58, p = 0.020), an increase in alanine aminotransferase levels (aHR = 1.05, 95% CI 1.02–1.07, p < 0.001), and history of ART default (aHR = 3.86, 95% CI 1.31–11.37, p = 0.014) while a higher baseline CD4 count was associated with lower mortality (aHR = 0.94, 95% CI 0.89–0.99, p = 0.013 for every 10 cells/mm3 increment). Conclusion Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences.

Parametric Bayesian Modelling of Tuberculosis Mortality determinants and Facility level heterogeneity effect using Gamma and Gaussian shared frailty techniques

“…Interestingly, in our study, gender, was found not to be a statistically significant factor affecting the survival of TB patients. This result is consistent with the studies that were conducted in Uganda and Brazil (32,33) but contradicts the findings of other studies that were conducted in Finland, Brazil and Singapore (34-36) that have found male TB patients to be at higher risk of dying due to TB. The differences noted could be attributed to a number of reasons including use of fixed effect models without accounting for catchment area heterogeneity and arbitrary choice of distribution for the hazard function.…”

Drug Resistance Patterns and Trends in Patients with Suspected Drug-Resistant Tuberculosis in Dalian, China: A Retrospective Study

“… 29 We suggest that this finding is potentially explained by the notion that men are more likely to consume more tobacco and alcohol than women. 30 Moreover, another reason may be that men are less compliant with TB treatment than women, thus increasing their risk of developing MDR-TB. 31 In our study, it was found that patients aged 45 years and older with suspected TB were more likely to develop MDR-TB than patients aged less than 45 years.…”

Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis

“…In a similar retrospective study of 666 drug-resistant TB/HIV-1 coinfected patients in Uganda, 60.2% were men, with a median age of 37 years. In addition, mortality following treatment failure was higher in men (25.7%) than in women (18.5%, P = 0.04) [16]. Table 1 provides a summary of studies that have addressed the male sex bias in TB/HIV-1 coinfection.…”