Johnny Daniels

Impact of Decentralized Care and the Xpert MTB/RIF Test on Rifampicin-Resistant Tuberculosis Treatment Initiation in Khayelitsha, South Africa

Decentralization of treatment for rifampicin-resistant tuberculosis was associated with high treatment initiation and resulted in reduced time to treatment initiation. Xpert for TB diagnosis resulted in a significant further reduction in time to treatment.

Programmatic treatment outcomes in HIV-infected and uninfected drug-resistant TB patients in Khayelitsha, South Africa

BACKGROUND South Africa has high burdens of HIV, TB and drug-resistant TB (DR-TB, rifampicin-resistance). Treatment outcome data for HIV-infected versus uninfected patients is limited. We assessed the impact of HIV and other factors on DR-TB treatment success, time to culture conversion, loss-from-treatment and overall mortality after second-line treatment initiation. METHODS A retrospective cohort analysis was conducted for patients initiated on DR-TB treatment from 2008 to 2012, within a community-based, decentralised programme in Khayelitsha, South Africa. RESULTS Among 853 confirmed DR-TB patients initiating second-line treatment, 605 (70.9%) were HIV infected. HIV status did not impact on time to sputum culture conversion nor did it impact treatment success; 48.1% (259/539) and 45.9% (100/218), respectively (p=0.59). In a multivariate model, HIV was not associated with treatment success. Death during treatment was higher among HIV-infected patients, but overall mortality was not significantly higher. HIV-infected patients with CD4 <=100 cells/ml were significantly more likely to die after starting treatment. CONCLUSIONS Response to DR-TB treatment did not differ with HIV infection in a programmatic setting with access to antiretroviral treatment (ART). Earlier ART initiation at a primary care level could reduce mortality among HIV-infected patients presenting with low CD4 counts.

Loss from Treatment for Drug Resistant Tuberculosis: Risk Factors and Patient Outcomes in a Community-Based Program in Khayelitsha, South Africa

Background A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from treatment (LFT), and post treatment outcomes of DR-TB patients in this setting. Methodology LFT, defined as interruption of treatment for ≥2 consecutive months was assessed among patients initiating DR-TB treatment for the first time between January 2009 and July 2011. Patients were traced through routine data sources to identify those who subsequently restarted treatment and those who died. Additional information on patient status and survival after LTF was obtained from community DR-TB counselors and from the national death registry. Post treatment outcomes were observed until July 2013. Results Among 452 patients initiating treatment for the first time within the given period, 30% (136) were LFT, with 67% retention at 18 months. Treatment was restarted in 27 (20%) patients, with additional resistance recorded in 2/25 (8%), excluding two with presumed DR-TB. Overall, 34 (25%) patients died, including 11 who restarted treatment. Males and those in the age category 15-25 years had a greater hazard of LFT; HR 1.93 (95% CI 1.35-2.75), and 2.43 (95% CI 1.52-3.88) respectively. Older age (>35 years) was associated with a greater hazard of death; HR 3.74 (1.13- 12.37) post treatment. Overall two-year survival was 62%. It was lower (45%) in older patients, and was 92% among those who received >12 months treatment. Conclusion LFT was high, occurred throughout the treatment period and was particularly high among males and those aged 15-25 years. Overall long term survival was poor. High rates of LFT should however not preclude scale up of community based care given its impact in increasing access to treatment. Further research is needed to support retention of DR-TB patients on treatment, even within community based treatment programs.

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success.

Setting Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection. Objective To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes. Design A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation. Results Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count ≤100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4). Conclusions Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.

DOT or SAT for Rifampicin-Resistant Tuberculosis? A Non-Randomized Comparison in a High HIV-Prevalence Setting

Background Daily directly-observed therapy (DOT) is recommended for rifampicin-resistant tuberculosis (RR-TB) patients throughout treatment. We assessed the impact of self-administered treatment (SAT) in a South African township with high rates of RR-TB and HIV. Methods Community-supported SAT for patients who completed the intensive phase was piloted in five primary care clinics in Khayelitsha. We compared final treatment outcomes among RR-TB patients initiating treatment before (standard-of-care (SOC)-cohort, January 2010-July 2013) and after the implementation of the pilot (SAT-cohort, January 2012-December 2014). All patients with outcomes before January 1, 2017 were considered in the analysis of outcomes. Results One-hundred-eighteen patients in the SOC-cohort and 174 patients in the SAT-cohort had final RR-TB treatment outcomes; 70% and 73% were HIV-co-infected, respectively. The proportion of patients with a final outcome of loss to follow-up (LTFU) did not differ whether treated in the SOC (25/118, 21.2%) or SAT-cohort (31/174, 17.8%) (P = 0.47). There were no significant differences in the time to 24-month LTFU among HIV-infected and uninfected patients (HR 0.90, 95% CI: 0.51–1.6, P = 0.71), or among patients enrolled in the SOC-cohort versus the SAT-cohort (HR 0.83, 95% CI: 0.49–1.4, P = 0.50) who received at least 6-months of RR-TB treatment. Conclusion The introduction of SAT during the continuation phase of RR-TB treatment does not adversely affect final RR-TB treatment outcomes in a high TB and HIV-burden setting. This differentiated, patient-centred model of care could be considered in RR-TB programmes to decrease the burden of DOT on patients and health facilities.

Delamanid for Rifampicin–Resistant Tuberculosis: A Retrospective Study from South Africa

Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa. This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF). Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation >500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred. This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options. Patients with rifampicin-resistant TB treated with delamanid had good treatment response and cardiotoxicity was rare http://ow.ly/bVQu30jGPVJ

Missed Opportunities for Earlier Diagnosis of rifampicin-resistant Tuberculosis despite access to Xpert(®) MTB/RIF

OBJECTIVE To assess the proportion of rifampicin-resistant tuberculosis (RR-TB) patients with potential earlier RR-TB diagnoses in Khayelitsha, South Africa. DESIGN We conducted a retrospective analysis among RR-TB patients diagnosed from 2012 to 2014. Patients were considered to have missed opportunities for earlier diagnosis if 1) they were incorrectly screened according to the Western Cape diagnostic algorithm; 2) the first specimen was not tested using Xpert® MTB/RIF; 3) no specimen was ever tested; or 4) the initial Xpert test showed a negative result, but no subsequent specimen was sent for follow-up testing in human immunodeficiency virus-positive patients. RESULTS Among 543 patients, 386 (71%) were diagnosed with Xpert and 112 (21%) had had at least one presentation at a health care facility within the 6 months before the presentation at which RR-TB was diagnosed. Overall, 95/543 (18%) patients were screened incorrectly at some point: 48 at diagnostic presentation only, 38 at previous presentation only, and 9 at both previous and diagnostic presentations. CONCLUSIONS These data show that a significant proportion of RR-TB patients might have been diagnosed earlier, and suggest that case detection could be improved if diagnostic algorithms were followed more closely. Further training and monitoring is required to ensure the greatest benefit from universal Xpert implementation.