Gaps in the tuberculosis preventive therapy care cascade in children in contact with TB.

BACKGROUND: Young children (<5 years) and children living with HIV in contact with an adult with tuberculosis (TB) should receive TB preventive therapy (TPT), but uptake is low. AIMS: To determine gaps in the uptake of and adherence to TPT in child TB contacts under routine primary care clinic conditions. METHODS: A cohort of child TB contacts (age <5 years or living with HIV <15 years) was followed at a primary care clinic in Johannesburg, South Africa. RESULTS: Of 170 child contacts with 119 adult TB cases, only 45% (77/170) visited the clinic for TPT eligibility screening, two of whom had already initiated TPT at another clinic. Of the 75 other children, 18/75 (24%) commenced TB treatment and 56/75 (75%) started TPT. Health-care workers followed the guidelines, with 96% (64/67) of children screened for symptoms of TB and 97% (36/37) of those symptomatic assessed for TB, but microbiological testing was low (9/36, 25%) and none had microbiologically confirmed tuberculosis. Only half (24/46, 52%) of the children initiating TPT completed the 6-month course. Neither sociodemographic determinants (age, sex) nor clinical factors (HIV status, TB source, time to TPT initiation) was associated with non-adherence to TPT. CONCLUSION: Most child contacts of an adult TB case do not visit the clinic, and half of those initiating TPT did not adhere to the full 6-month course. These programme failures result in missed opportunities for early diagnosis of active TB and prevention of progression to disease in young and vulnerable children.

Whole-genome sequencing for TB source investigations: principles of ethical precision public health.

BACKGROUND: Whole-genome sequencing (WGS) of Mycobacterium tuberculosis allows rapid, accurate inferences about the sources, location and timing of transmission. However, in an era of heightened concern for personal privacy and science distrust, such inferences could result in unintended harm and undermine the public´s trust.METHODS: We held interdisciplinary stakeholder discussions and performed ethical analyses of real-world illustrative cases to identify principles that optimise benefit and mitigate harm of M. tuberculosis WGS-driven TB source investigations.RESULTS: The speed and precision with which real-time WGS can be used to associate M. tuberculosis strains with sensitive information has raised important concerns. While detailed understanding of transmission events could mitigate harm to vulnerable patients and communities when otherwise unfairly blamed for TB outbreaks, the precision of WGS can also identify transmission events resulting in social blame, fear, discrimination, individual or location stigma, and the use of defaming language by the public, politicians and scientists. Public health programmes should balance the need to safeguard privacy with public health goals, transparency and individual rights, including the right to know who infects whom or where.CONCLUSIONS: Ethical challenges raised by real-time WGS-driven TB source investigation requires public health authorities to move beyond their current legal mandate and embrace transparency, privacy and community engagement.

Management of rifampicin-resistant TB: programme indicators and care cascade analysis in South Africa.

BACKGROUND: Xpert® MTB/RIF was expected to revolutionise the management of rifampicin-resistant TB (RR-TB) by enabling rapid and decentralised diagnosis of rifampicin (RIF) resistance.METHODS: We performed a care cascade analysis for a cohort of RR-TB patients managed under programmatic conditions. Cumulative incidences of time to completion of the RR-TB care cascade steps were estimated, reasons for delay or attrition from the cascade investigated and WHO programme indicators for monitoring of RR-TB programmes calculated.RESULTS: Of 502 patients diagnosed with RR-TB using Xpert, 64% initiated multidrug-resistant TB (MDR-TB) treatment immediately, 20% after some first-line treatment, 16% never initiated MDR-TB treatment, mainly because of death (44%) or loss to follow-up (26%) soon after diagnosis. A supplementary sputum sample was collected within 14 days of treatment in 58.8% of cases. Only 63% of RR-TB cases were assessed for isoniazid resistance, and only 65% of MDR-TB cases were evaluated for pre-XDR-TB (extensively drug-resistant TB). Treatment was individualised in 57% of pre-XDR and 68% of XDR-TB patients. Only 8% completed the entire RR-TB care cascade as intended.CONCLUSION: Fidelity to the RR-TB algorithm was poor, with substantial losses at each step of the cascade, highlighting the fact that implementation of novel technologies needs to be accompanied by health system strengthening to maximise impact.

Identifying isoniazid resistance markers to guide inclusion of high-dose isoniazid in tuberculosis treatment regimens.

OBJECTIVES: Effective use of antibiotics is critical to control the global tuberculosis pandemic. High-dose isoniazid (INH) can be effective in the presence of low-level resistance. We performed a systematic literature review to improve our understanding of the differential impact of genomic Mycobacterium tuberculosis (Mtb) variants on the level of INH resistance. The following online databases were searched: PubMed, Web of Science and Embase. Articles reporting on clinical Mtb isolates with linked genotypic and phenotypic data and reporting INH resistance levels were eligible for inclusion. METHODS: All genomic regions reported in the eligible studies were included in the analysis, including: katG, inhA, ahpC, oxyR-ahpC, furA, fabG1, kasA, rv1592c, iniA, iniB, iniC, rv0340, rv2242 and nat. The level of INH resistance was determined by MIC: low-level resistance was defined as 0.1-0.4 µg/mL on liquid and 0.2-1.0 µg/mL on solid media, high-level resistance as >0.4µg/mL on liquid and >1.0 µg/mL on solid media. RESULTS: A total of 1212 records were retrieved of which 46 were included. These 46 studies reported 1697 isolates of which 21% (n = 362) were INH susceptible, 17% (n = 287) had low-level, and 62% (n = 1048) high-level INH resistance. Overall, 24% (n = 402) of isolates were reported as wild type and 76% (n = 1295) had ≥1 relevant genetic variant. Among 1295 isolates with ≥1 variant, 78% (n = 1011) had a mutation in the katG gene. Of the 867 isolates with a katG mutation in codon 315, 93% (n = 810) had high-level INH resistance. In contrast, only 50% (n = 72) of the 144 isolates with a katG variant not in the 315-position had high-level resistance. Of the 284 isolates with ≥1 relevant genetic variant and wild type katG gene, 40% (n = 114) had high-level INH resistance. CONCLUSIONS: Presence of a variant in the katG gene is a good marker of high-level INH resistance only if located in codon 315.

Deciphering Within-Host Microevolution of Mycobacterium tuberculosis through Whole-Genome Sequencing: the Phenotypic Impact and Way Forward.

The Mycobacterium tuberculosis genome is more heterogenous and less genetically stable within the host than previously thought. Currently, only limited data exist on the within-host microevolution, diversity, and genetic stability of M. tuberculosis As a direct consequence, our ability to infer M. tuberculosis transmission chains and to understand the full complexity of drug resistance profiles in individual patients is limited. Furthermore, apart from the acquisition of certain drug resistance-conferring mutations, our knowledge on the function of genetic variants that emerge within a host and their phenotypic impact remains scarce. We performed a systematic literature review of whole-genome sequencing studies of serial and parallel isolates to summarize the knowledge on genetic diversity and within-host microevolution of M. tuberculosis We identified genomic loci of within-host emerged variants found across multiple studies and determined their functional relevance. We discuss important remaining knowledge gaps and finally make suggestions on the way forward.

Evaluation of the intensified tuberculosis case finding guidelines for children living with HIV.

SETTING: Out-patient paediatric human immunodeficiency virus (HIV) clinic in Soweto, South Africa. OBJECTIVE: To evaluate the yield of symptom screening for intensified tuberculosis (TB) case finding (ICF) and potential eligibility for isoniazid preventive therapy (IPT) in children living with HIV on antiretroviral treatment (ART). DESIGN: A cohort of 247 children (age 0-8 years) was systematically screened for TB symptoms during the first 2 years of ART. Children with symptoms were assessed using chest X-ray, smear microscopy and culture. RESULTS: Over 2 years, 1346 TB symptom screens were performed in 220 children not on anti-tuberculosis treatment. Only 48 (3.6%) screens in 39 children were positive for current cough, current fever, weight loss (>5%) or contact with a TB patient. The positive predictive value of symptom screening was 8.9% (95%CI 2.5-21.2); the sensitivity was 57.1% (95%CI 18.4-90.1). Most children (85.8%) were IPT-eligible according to World Health Organization guidelines; however, few (1.2%) were eligible according to South African guidelines. CONCLUSIONS: The yield of TB symptom screening was relatively poor in children on ART, highlighting the need for future research on paediatric TB symptom screening approaches in this population. The vastly different criteria for IPT eligibility between guidelines suggest that research is also needed to define the optimal use of IPT in children on ART.

The unmet needs and health priorities of the urban poor: Generating the evidence base for urban community health worker programmes in South Africa.

BACKGROUND: There is a growing interest in involving community health workers (CHWs) into the formal healthcare system in South Africa (SA). OBJECTIVES: To generate evidence for defining CHW tasks in urban SA. METHODS: A cross-sectional survey of residents of Diepsloot, northern Johannesburg, was performed using geographically weighted random sampling, with home-based health assessment and a questionnaire on sociodemographics, medical history, experience of violence, health-seeking behaviour and perceived health priorities. RESULTS: Between May 2013 and March 2014, 1 230 adults participated. Self-reported medical conditions included hypertension (12%), HIV (10%), diabetes (3%), cancer (1%) and mental illness (1%). Health assessments identified a high prevalence of undiagnosed conditions: hypertension (26%), obesity or overweight (46%), mild to severe depression (23%), HIV infection (5.8%) and tuberculosis (TB) (0.4%). Among women, 18% had unmet family planning needs and 77% had never had a Pap smear. Sexually transmitted infection symptoms were reported by 7% of participants. Physical violence was widespread, with 13% having experienced and 16% witnessing violence in the past year, with women mostly experiencing violence at home and men in the community. Participants' top health concerns were crime, safety and violence (49%) and HIV (18%); healthy living/weight control was listed by only 8% of participants. CONCLUSIONS: Alignment of CHW roles to unmet health needs and perceived health priorities will be important for optimal impact of CHW programmes in urban communities. Our data suggest that the CHW role should expand from a traditional focus on HIV, TB and maternal health to include non-communicable diseases, healthy lifestyle, and the intersection of violence and health.

Defining the research agenda to measure and reduce tuberculosis stigmas.

Crucial to finding and treating the 4 million tuberculosis (TB) patients currently missed by national TB programmes, TB stigma is receiving well-deserved and long-delayed attention at the global level. However, the ability to measure and evaluate the success of TB stigma-reduction efforts is limited by the need for additional tools. At a 2016 TB stigma-measurement meeting held in The Hague, The Netherlands, stigma experts discussed and proposed a research agenda around four themes: 1) drivers: what are the main drivers and domains of TB stigma(s)?; 2) consequences: how consequential are TB stigmas and how are negative impacts most felt?; 3) burden: what is the global prevalence and distribution of TB stigma(s) and what explains any variation? 4): intervention: what can be done to reduce the extent and impact of TB stigma(s)? Each theme was further subdivided into research topics to be addressed to move the agenda forward. These include greater clarity on what causes TB stigmas to emerge and thrive, the difficulty of measuring the complexity of stigma, and the improbability of a universal stigma 'cure'. Nevertheless, these challenges should not hinder investments in the measurement and reduction of TB stigma. We believe it is time to focus on how, and not whether, the global community should measure and reduce TB stigma.

Evidence-based interventions to reduce tuberculosis stigma: a systematic review.

SETTING: While substantial progress is being made in tuberculosis (TB) control, the success of public health efforts is hampered by pervasive stigma. OBJECTIVE: To perform a systematic literature review to assess the effectiveness of interventions aimed at reducing TB stigma in patients, health care workers, care givers and the general community. DESIGN: Studies were eligible for inclusion if they evaluated interventions aimed at reducing TB stigma and were published between 1950 and 2015. We searched eight databases (PubMed, Cochrane Library, Ovid, Embase, PsycInfo, Sociological Abstracts, Cumulative Index to Nursing and Allied Health Literature, World Health Organization Latin American and Caribbean Health Sciences Literature), and complemented the searches by using the snowball strategy and by reviewing relevant grey literature. RESULTS: Only seven studies were identified as providing quantitative (n = 4) or qualitative (n = 3) evidence of effectiveness in reducing TB stigma. Quality assessment of the studies was poor. Knowledge-shaping and attitude-changing interventions aimed at the public, patients and their families were effective in reducing anticipated stigma. Home visits and support groups were effective in reducing both anticipated and internalised stigma. CONCLUSION: There is a dearth of reliable information on the effectiveness of TB stigma-reduction interventions. Knowledge-shaping, attitude-changing and patient-support interventions can be effective in reducing TB stigma, but more rigorous evaluations are needed.

Innovative approach to the design and evaluation of treatment adherence interventions for drug-resistant TB.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) treatment is expensive, lengthy, and can cause severe side effects. Patients face socio-economic, psychosocial, and systemic barriers to adherence; poor adherence results in poor treatment outcomes. OBJECTIVE: To estimate the effects of the components of the information-motivation-behavioral skills model on DR-TB treatment adherence. DESIGN: We recruited 326 adults receiving DR-TB treatment and 86 of their health care service providers from 40 health centers in Lima, Peru. The main outcome was adherence (i.e., the proportion of prescribed doses taken by a patient). Exposure measures were adherence information, motivation, and behavioral skills; loss to follow-up during previous TB treatment(s); providers' work engagement; and patient-perceived support from his/her social network. RESULTS: Structural equation modeling revealed that adherence information and motivation had positive effects on adherence, but only if mediated through behavioral skills (ß = 0.02, P < 0.01 and ß = 0.07, P < 0.001, respectively). Behavioral skills had a direct positive effect on adherence (ß = 0.27, P < 0.001). Loss to follow-up during previous treatment had a direct negative effect, providers' work engagement had a direct positive effect, and perceived support had indirect positive effects on adherence. The model's overall R2 was 0.76. CONCLUSION: The components of the information-motivation-behavioral skills model were associated with adherence and could be used to design, monitor, and evaluate interventions targeting adherence to DR-TB treatment.

Bioavailability of two licensed paediatric rifampicin suspensions: implications for quality control programmes.

SETTING: To assess the revised World Health Organization-recommended dose of 10-20 mg/kg rifampicin (RMP), we studied the steady state pharmacokinetics of RMP in South African children who received standard treatment for drug-susceptible tuberculosis (TB). OBJECTIVE: To determine the formulation effect on the pharmacokinetics of RMP. DESIGN: RMP plasma concentrations were characterised in 146 children (median age 1.4 years, range 0.2-10.2). The morning dose on the day of the pharmacokinetic evaluation was administered as one of two RMP single-drug oral suspensions. RESULTS: While one formulation achieved 2 h concentrations in the range of those observed in adults (median 6.54 mg/l, interquartile range [IQR] 4.47-8.84), the other attained a median bioavailability of only 25% of this, with a median 2 h concentration of 1.59 mg/l (IQR 0.89-2.38). CONCLUSION: RMP is a key drug for the treatment of TB. It is critical that the quality of RMP suspensions used to treat childhood TB is ensured.

Xpert(®) MTB/RIF for smear-negative presumptive TB: impact on case notification in DR Congo.

SETTING: The impact of Xpert(®) MTB/RIF as a follow-on diagnostic test after smear microscopy on tuberculosis (TB) notification has not yet been well defined. DESIGN: Quasi-experimental design with 86 evaluation and 49 control clinics in Kinshasa, Democratic Republic of Congo. Smear microscopy was supported at all 135 clinics, Xpert was placed in 15 evaluation clinics and a sputum transport system was implemented for 25 satellite clinics. The number of cases notified before and during the project (July 2012-June 2013) was obtained from the National TB Program. RESULTS: Of 27,147 presumptive TB cases presenting in clinics with access to Xpert, 5922 (21.8%) were smear-positive. Of 18,636 individuals with ⩾ 3 negative microscopy results, 6920 (37.1%) underwent Xpert testing, 991 (14.3%) of whom tested positive. The number of bacteriologically positive cases increased equally in evaluation clinics (15.1%, 95%CI -2.3 to 32.6) and control clinics (13.6%, 95%CI 2.6-29.3), for a difference in increase of 1.5% (95%CI -28.8 to 31.8). There was no difference in the change in smear-negative cases (-42.4%, 95%CI -111.5 to 26.6), nor in all types of TB notified (-6.1%, 95%CI -32.5 to 20.4) between the evaluation and control clinics. CONCLUSION: In part due to a restrictive algorithm, Xpert as follow-on to smear microscopy did not increase the overall number of TB notifications, nor the number of bacteriologically positive cases.

The patient impact of point-of-care vs. laboratory placement of Xpert(®) MTB/RIF.

BACKGROUND: The Xpert(®) MTB/RIF assay can diagnose tuberculosis (TB) rapidly and with great accuracy. The effect of Xpert placement at point of care (POC) vs. at an off-site laboratory on patient management remains unknown. DESIGN: At a primary care clinic in Johannesburg, South Africa, we compared TB diagnosis and treatment initiation among 1861 individuals evaluated for pulmonary TB using Xpert performed either at POC or offsite. RESULTS: When Xpert was performed at POC, a higher proportion of Xpert-positive individuals started treatment (95% vs. 87%, P = 0.047) and time to treatment initiation was shorter (median 0 vs. 5 days, P < 0.001). In contrast, among Xpert-negative TB cases, a higher proportion (87% vs. 72%, P = 0.001) started treatment when the sample was sent to the laboratory, with a shorter time to treatment (median 9 vs. 13 days, P = 0.056). While the overall proportion of presumed TB patients starting treatment was independent of Xpert placement, the proportion started based on a bacteriologically confirmed diagnosis was higher when Xpert was performed at POC (73% vs. 58%, P = 0.006). CONCLUSIONS: Placement of Xpert at POC resulted in more Xpert-positive patients receiving treatment, but did not increase the total number of presumed TB patients starting treatment. When samples were sent to a laboratory for Xpert testing, empiric decision making increased.

High incidence of latent tuberculous infection among South African health workers: an urgent call for action.

SETTING: In South Africa, health care workers (HCWs) are at two-fold greater risk of acquiring tuberculosis (TB) disease than the general population. Few studies have evaluated the risk of incident tuberculous infection. OBJECTIVE: To determine the incidence and risk factors for latent tuberculous infection (LTBI) among HCWs and to compare the results of the interferon-gamma release assay (IGRA) with those of the tuberculin skin test (TST). DESIGN: HCWs, including medical students, underwent a TST and human immunodeficiency virus (HIV) and IGRA testing at baseline and 12 months, and IGRA at 6 months. The participants kept 12-month TB exposure logs. RESULTS: Among 199 participants (150 [76%] females, median age 31 years [range 20-61]), incident LTBI was documented using IGRA in 25/97 (26%; incident rate 29 cases/100 person-years [py], 95%CI 20-44) and using TST in 25/93 (27%; incident rate 29 cases/100 py, 95%CI 19-42). Agreement between TST and IGRA was poor (44.8%, κ = 0.23). Higher annual exposure to TB cases was reported among persons with LTBI than in those who were persistently IGRA-negative (81 cases, 95%CI 61-102 vs. 50 cases, 95%CI 43-57, P < 0.01). CONCLUSION: The high LTBI incidence and the association of incident LTBI with annual TB caseload among HCWs indicate that more effective TB infection control should be implemented in South African health care facilities.

The impact of Xpert(®) MTB/RIF in sparsely populated rural settings.

BACKGROUND: The impact of implementing Xpert(®) MTB/RIF and the choice of instrument placement on patient care in sparsely populated areas with poor access to laboratory and radiology services have not yet been elucidated. METHODS: Prospective evaluation of three diagnostic approaches in the Central Karoo, South Africa: smear microscopy as the initial diagnostic, with sputum processing at centralised laboratories, and Xpert as the initial diagnostic with instrument placement at facility level or centralised laboratory. RESULTS: Of 1449 individuals, 196 were diagnosed with TB. The proportion positive on initial testing was respectively 8%, 20% and 8% during the smear microscopy, decentralised Xpert and centralised Xpert periods. The proportion of bacteriologically confirmed cases was respectively 88%, 99% and 91% during the smear microscopy, decentralised Xpert and centralised Xpert periods. The median time to treatment was respectively 11.5 (interquartile range [IQR] 6-24), 1 (IQR 0-2) and 6 days (IQR 2-9) during the smear microscopy, decentralised Xpert and centralised Xpert periods. CONCLUSION: Introducing Xpert as the initial diagnostic in areas with poor access to TB diagnostics increased the proportion of cases with bacteriological confirmation and reduced time to treatment initiation; however, point-of-care placement may have resulted in fewer people being evaluated for TB.

The complexities of Xpert® MTB/RIF interpretation.

The Xpert(®) MTB/RIF assay has demonstrated robust capability for diagnosing tuberculosis (TB) and rifampin (RMP) resistance. Optimal use of Xpert in diverse settings will require knowledge of challenges when interpreting the results. We present three selected cases from the United States, a low-burden TB setting, to highlight important clinical scenarios encountered with Xpert testing: rapid RMP resistance detection in a patient with pre-extensively drug-resistant TB who immigrated from the Philippines, false-positive RMP resistance detection, and Mycobacterium tuberculosis detection in a culture-negative patient. These cases demonstrate that a low pre-test probability of TB or drug-resistant TB can complicate the interpretation of the Xpert assay.

Impact of three empirical anti-tuberculosis treatment strategies for people initiating antiretroviral therapy.

BACKGROUND: Early mortality in people initiating antiretroviral treatment (ART) remains high. Empirical anti-tuberculosis treatment strategies aim to reduce early mortality by initiating anti-tuberculosis treatment in individuals at high risk of death from undiagnosed TB. METHODS: Using data from 16 913 individuals starting ART under program conditions, we simulated the impact of three empirical treatment strategies (two clinical trials and a pragmatic approach), assuming that 50% of early deaths and 100% of incident TB are averted in those eligible. RESULTS: Compared to starting anti-tuberculosis treatment on clinical or mycobacteriological grounds, 4.4-31.4% more individuals were eligible for anti-tuberculosis treatment, 5.5-25.4% of deaths were averted and 10.9-57.3% of incident TB cases were prevented under empirical anti-tuberculosis treatment strategies. The proportion receiving any anti-tuberculosis treatment during the first 6 months of ART increased from the observed 24.0% to an estimated 27.5%, 40.4% and 51.3%, under the PrOMPT, REMEMBER and pragmatic approach, respectively. CONCLUSION: The impact of empirical anti-tuberculosis treatment strategies depends greatly on the eligibility criteria chosen. The additional strain placed on anti-tuberculosis treatment facilities and the relatively limited impact of some empirical TB strategies raise the question as to whether the benefits will outweigh the risks at population level.

A home tracing program for contacts of people with tuberculosis or HIV and patients lost to care.

SETTING: Primary care clinic serving a high tuberculosis (TB) and human immunodeficiency virus (HIV) prevalence community in South Africa. OBJECTIVE: To evaluate a program combining TB and HIV contact investigation with tracing of individuals lost to TB or HIV care. DESIGN: Contacts were offered home-based HIV testing, TB symptom screening, sputum collection and referral for isoniazid preventive therapy (IPT). Effectiveness was assessed by the number needed to trace (NNT). RESULTS: Only 419/1197 (35.0%) households were successfully traced. Among 267 contacts, we diagnosed 27 new HIV cases (10 linked to care) and two TB cases (both initiated treatment) and three started IPT. Of 630 patients lost to care, 132 (21.0%) were successfully traced and 81 (61.4%) re-engaged in care. The NNT to locate one individual lost to care was 4.8 (95%CI 4.1-5.6), to re-engage one person in care 7.8 (95%CI 6.4-9.7), to diagnose one contact with HIV 44.3 (95%CI 30.6-67.0), to link one newly diagnosed contact to HIV care 120 (95%CI 65.3-249.2) and to find one contact with active TB and initiate treatment 599 (95%CI 166.0-4940.7). CONCLUSION: The effectiveness of this contact tracing approach in identifying new TB and HIV cases was low. Methods to optimize contact investigation should be explored and their cost-effectiveness assessed.

Delayed antiretroviral therapy despite integrated treatment for tuberculosis and HIV infection.

SETTING: Five primary health care clinics in Kinshasa, Democratic Republic of Congo. OBJECTIVE: To examine timing and predictors of delayed initiation of antiretroviral therapy (ART) during anti-tuberculosis treatment. DESIGN: Prospective observational cohort of adult patients receiving integrated treatment for tuberculosis (TB) and human immunodeficiency virus (HIV) who are expected to initiate ART at 1 month if CD4 count is <100 cells/mm(3) or if patient is World Health Organization (WHO) Clinical Stage 4 for reasons other than extra-pulmonary TB, at 2 months if CD4 count is 100-350 cells/mm(3), or at completion of anti-tuberculosis treatment if subsequently CD4 count is ≤ 350 cells/mm(3) or patient has WHO Clinical Stage 4. RESULTS: Of 492 patients, 235 (47.8%) experienced delayed initiation of ART: 171 (72.8%) initiated ART late, after a median delay of 12 days (interquartile range [IQR] 4-27) and 64 (27.2%) never initiated ART. Contraindication to any antiretroviral drug (aOR 2.91, 95%CI 1.22-6.95), lower baseline CD4 count (aOR 1.20, 95%CI 1.08-1.33/100 cells/mm(3)), TB drug intolerance (aOR 1.93, 95%CI 1.23-3.02) and non-disclosure of HIV infection (aOR 1.50, 95%CI 1.03-2.18) predicted delayed ART initiation. CONCLUSION: Despite fully integrated treatment, half of all patients experienced delayed ART initiation. Pragmatic approaches to ensure timely ART initiation in those at risk of delayed ART initiation are needed.