Sustained positive impact on tuberculosis treatment outcomes of TB-HIV integrated care in Uganda

Musaazi, Joseph; Sekaggya-Wiltshire, Christine; Kiragga, Agnes; Kalule, Ivan; Reynolds, Steven J.; Manabe, Yukari C.; Castelnuovo, Barbara

doi:10.5588/ijtld.18.0306

Cited by 9 publications

(9 citation statements)

References 6 publications

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“…Of note, after a peak in 2008, drug modifications due to contraindications experience a decrease. We believe this was due to both a decrease in diagnosis of TB cases in our clinic [25], and the shift to using tenofovir, lamivudine/emtricitabine, and efavirenz as the preferred first line ART choice also in child bearing age women after the implementation of the 2012 WHO guidelines (EFV recommended as the NNRTI of choice in pregnant women).…”

Section: Discussionmentioning

confidence: 99%

Reasons for first line ART modification over the years during the ART scale up in Uganda

et al. 2019

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Background During the initial scale up of ART in sub-Saharan Africa, prescribed regimens included drugs with high potential for toxicity (particularly stavudine). More recently a growing number of patients requires second line treatment due to treatment failure, especially following the expansion of viral load testing. We aim to determine the reasons and risk factors for modification of first line ART across the years. Methods We included patients started on standard first line ART (2NRTI + 1 NNRTI) between 2005 and 2016 at the Infectious Diseases Institute, Kampala, Uganda. We described the reasons for treatment modification categorized in (1) toxicity (2) treatment failure (3) other reason (new TB treatment, new pregnancy). We used Cox proportional hazard to identify factors associated with treatment modification due to toxicity. Results We included 14,261 patients; 9114 (63.9%), were female, the median age was 34 years (IQR: 29–40), 60.8% were in WHO stage 3 and 4. The median BMI and CD4 count were 21.9 (IQR: 19.6–24.8) and 188 cell/µL (IQR: 65–353) respectively; 27.5% were started on stavudine, 46% on zidovudine, and 26.5% on a tenofovir containing regimens. We observed 6248 ART modifications in 4868/14,261 patients (34.1%); 1615 were due to toxicity, 1077 to treatment failure, 1330 to contraindications, and 1860 patients following WHO recommendation of phasing out stavudine and substituting with another NRTI. Modification for drug toxicity declined rapidly after the phase out of stavudine (2008), while switches to second line regimes increased after the implementation of viral load monitoring (2015). Patients with normal BMI compared to underweight, (HR: 0.79, CI 0.69–0.91), with CD4 counts 200–350 cells/µL compared to < 200 cells/µL (HR: 0.81− CI 0.71–0.93), and started on zidovudine (HR: 0.51 CI 0.44–0.59) and tenofovir (HR: 0.16, CI 0.14–0.22) compared to stavudine were less likely to have ART modification due to toxicity. Older patients (HR: 1.14 per 5-year increase CI 1.11–1.18), those in WHO stage 3 and 4 (HR: 1.19, CI 1.06–1.34) were more likely to have ART modification due to toxicity. Conclusions Toxicity as reason for drugs substitution decreased over time mirroring the phase out of stavudine, while viral load expansion identified more patients in need of second line treatment.

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Section: Discussionmentioning

confidence: 99%

Reasons for first line ART modification over the years during the ART scale up in Uganda

et al. 2019

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“…High mortality from HIV-associated TB even in the era of increased ART availability has been documented in other sub-Saharan African settings [16,17]. In Uganda, a study from the infectious diseases clinic located within Mulago National Referral Hospital found consistently high TB mortality rates (>15%) over seven years of ART scale up [18]. In this study, presentation to care with advanced HIV disease (defined as CD4 cell count <200 cells/ul at enrollment) doubled the risk of mortality from TB.…”

Section: Plos Onementioning

confidence: 99%

Estimating the effect of pretreatment loss to follow up on TB associated mortality at public health facilities in Uganda

et al. 2020

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Introduction Tuberculosis (TB) mortality estimates derived only from cohorts of patients initiated on TB treatment do not consider outcomes of patients with pretreatment loss to follow-up (LFU). We aimed to assess the effect of pretreatment LFU on TB-associated mortality in the six months following TB diagnosis at public health facilities in Uganda. Methods At ten public health facilities, we retrospectively reviewed treatment data for all patients with a positive Xpert®MTB/RIF test result from January to June 2018. Pretreatment LFU was defined as not initiating TB treatment within two weeks of a positive test. We traced patients with pretreatment LFU to ascertain their vital status. We performed Kaplan Meier survival analysis to compare the cumulative incidence of mortality, six months after diagnosis among patients who did and did not experience pretreatment LFU. We also determined the health facility level estimates of TB associated mortality before and after incorporating deaths prior to treatment initiation among patients who experienced pretreatment LFU. Results Of 510 patients with positive test, 100 (19.6%) experienced pretreatment LFU. Of these, we ascertained the vital status of 49 patients. In the six months following TB diagnosis, mortality was higher among patients who experienced pretreatment LFU 48.1/1000py vs 22.9/1000py. Hazard ratio [HR] 3.18, 95% confidence interval [CI] (1.61–6.30). After incorporating deaths prior to treatment initation among patients who experienced pretreatment LFU, health facility level estimates of TB associated mortality increased from 8.4% (95% CI 6.1%-11.6%) to 10.2% (95% CI 7.7%-13.4%). Conclusion Patients with confirmed TB who experience pretreatment LFU have high mortality within the first six months. Efforts should be made to prioritise linkage to treatment for this group of patients. Deaths that occur prior to treatment initation should be included when reporting TB mortality in order to more accurately reflect the health impact of TB.

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“…Regardless of these limitations, our study has strengths resulting in significant contributions to the body of scientific evidence available to HIV programs in DRC. Our findings coupled with the emerging evidence show that patients with TB/HIV coinfection require special attention and treatment, including TB-HIV integrated care and specific first-line therapies (e.g., dolutegravir) to improve treatment outcomes [ 35 , 36 ]. Our study utilizes a robust sample size to allow stable estimates of the influence of TB/HIV coinfection on outcome variables, after controlling for several sociodemographic and clinical variables included in the multivariable analysis.…”

Section: Discussionmentioning

confidence: 94%

Risk Factors for TB/HIV Coinfection and Consequences for Patient Outcomes: Evidence from 241 Clinics in the Democratic Republic of Congo

Shah

Ewetola²,

Etheredge

et al. 2021

IJERPH

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(1) Background: In resource-limited countries, patients with tuberculosis (TB)/HIV coinfection commonly face economic, sociocultural, and behavioral barriers to effective treatment. These barriers manifest from low treatment literacy, poverty, gender inequality, malnutrition, societal stigmas regarding HIV, and an absence of available care. It is critical for intervention programs to understand and assist in overcoming these barriers and any additional risks encountered by patients with TB/HIV coinfection. This study analyzes variation in TB/HIV coinfection and risks of negative outcomes among patients with TB/HIV coinfection compared to those without coinfection. (2) Methods: This quantitative study used data from 49,460 patients receiving ART from 241 HIV/AIDS clinics in Haut-Katanga and Kinshasa, two provinces in the Democratic Republic of Congo. Chi-square and logistic regression analysis were performed. (3) Results: Significantly higher proportions of patients with TB/HIV coinfection were men (4.5%; women, 3.3%), were new patients (3.7%; transferred-in, 1.6%), resided in the Kinshasa province (4.0%; Haut-Katanga, 2.7%), and were in an urban health zone (3.9%) or semi-rural health zone (3.1%; rural, 1.2%). Logistic regression analysis showed that after controlling for demographic and clinical variables, TB/HIV coinfection increased the risk of death (adjusted odds ratio (AOR), 2.26 (95% confidence interval (CI): 1.94–2.64)) and LTFU (AOR, 2.06 (95% CI: 1.82–2.34)). TB/HIV coinfection decreased the odds of viral load suppression (AOR, 0.58 (95% CI: 0.46–0.74)). (4) Conclusions: TB/HIV coinfection raises the risk of negative outcomes such as death, LTFU, and lack of viral load suppression. Our findings can help HIV clinics in Democratic Republic of Congo and other African countries to customize their interventions to improve HIV care and reduce care disparities among patients.

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Sustained positive impact on tuberculosis treatment outcomes of TB-HIV integrated care in Uganda

Cited by 9 publications

References 6 publications

Reasons for first line ART modification over the years during the ART scale up in Uganda

Reasons for first line ART modification over the years during the ART scale up in Uganda

Estimating the effect of pretreatment loss to follow up on TB associated mortality at public health facilities in Uganda

Risk Factors for TB/HIV Coinfection and Consequences for Patient Outcomes: Evidence from 241 Clinics in the Democratic Republic of Congo

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