Effect of dolutegravir-based versus efavirenz-based antiretroviral therapy on excessive weight gain in adult treatment-naïve HIV patients at Matsanjeni health center, Eswatini: a retrospective cohort study.

BACKGROUND: There is limited data on dolutegravir (DTG)-associated weight gain from settings with a dual burden of HIV and overnutrition. METHODS: In Eswatini (at Matsanjeni), among 156 and 160 adult patients on DTG-based and EFV-based antiretroviral therapy (ART), respectively, we studied excessive weight gain (BMI at 24 months ART greater than baseline and ≥25 kg/m2). RESULTS: The median BMI increase in DTG-based patients was 1.09 (IQR:-0.28,3.28) kg/m2 compared to 0.20 (IQR:-0.85,2.18) kg/m2 in EFV-based patients (p value = 0.001). DTG-based ART predicted excessive weight gain (aOR 2.61;95% CI:1.39-4.93). CONCLUSION: Practitioners should consider DTG-based regimens as one of the risk factors for overweight/obesity.

Attrition one year after starting antiretroviral therapy before and after the programmatic implementation of HIV "Treat All" in Sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Evidence on the real-world effects of "Treat All" on attrition has not been systematically reviewed. We aimed to review existing literature to compare attrition 12 months after antiretroviral therapy (ART) initiation, before and after "Treat All" was implemented in Sub-Saharan Africa and describe predictors of attrition. METHODS: We searched Embase, Google Scholar, PubMed, and Web of Science in July 2020 and created alerts up to the end of June 2023. We also searched for preprints and conference abstracts. Two co-authors screened and selected the articles. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. We extracted and tabulated data on study characteristics, attrition 12 months after ART initiation, and predictors of attrition. We calculated a pooled risk ratio for attrition using random-effects meta-analysis. RESULTS: Eight articles and one conference abstract (nine studies) out of 8179 screened records were included in the meta-analysis. The random-effects adjusted pooled risk ratio (RR) comparing attrition before and after "Treat All" 12 months after ART initiation was not significant [RR = 1.07 (95% Confidence interval (CI): 0.91-1.24)], with 92% heterogeneity (I2). Being a pregnant or breastfeeding woman, starting ART with advanced HIV, and starting ART within the same week were reported as risk factors for attrition both before and after "Treat All". CONCLUSIONS: We found no significant difference in attrition before and after "Treat All" one year after ART initiation. While "Treat All" is being implemented widely, differentiated approaches to enhance retention should be prioritised for those subgroups at risk of attrition. PROSPERO NUMBER: CRD42020191582 .

Face mask sampling (FMS) for tuberculosis shows lower diagnostic sensitivity than sputum sampling in Guinea.

BACKGROUND: Pulmonary tuberculosis (PTB) diagnosis relies on sputum examination, a challenge in sputum-scarce patients. Alternative non-invasive sampling methods such as face mask sampling (FMS) have been proposed. OBJECTIVE: To evaluate the value of FMS for PTB diagnosis by assessing its agreement with sputum samples processed by GeneXpert MTB/RIF (Ultra)(Xpert) testing, and describe FMS sensitivity and specificity. METHODS: This was a prospective study conducted at the Carrière TB clinic in Guinea. Presumptive TB patients willing to participate were asked to wear a surgical mask containing a polyvinyl alcohol (PVA) strip for thirty minutes. Subsequently, two spot sputum samples were collected, of which one was processed by microscopy on site and the other by Xpert in Guinea's National Reference Laboratory of Mycobacteriology (LNRM). The first 30 FMS were processed at the Supranational Reference Laboratory in Antwerp, Belgium, and the following 118 FMS in the LNRM. RESULTS: One hundred fifty patients participated, of whom 148 had valid results for both mask and sputum. Sputum smear microscopy was positive for 47 (31.8%) patients while sputum-Xpert detected MTB in 54 (36.5%) patients. Among the 54 patients testing sputum-Xpert positive, 26 (48.1%) yielded a positive FMS-Xpert result, while four sputum-Xpert negative patients tested positive for FMS and 90 patients were Xpert-negative for both sputum and mask samples, suggesting a moderate level of agreement (k-value of 0.47). The overall mask sensitivity was 48.1%, with 95.7% specificity. CONCLUSION: In our setting, Xpert testing on FMS did not yield a high level of agreement to sputum sample.

Initial programme theory for community-based ART delivery for key populations in Benue State, Nigeria: a realist evaluation study.

BACKGROUND: The community-based antiretroviral therapy delivery (CBART) model was implemented in Benue State in Nigeria to increase access of key populations living with HIV (KPLHIV) to antiretroviral treatment. Key populations (KP) are female sex workers, men who have sex with men, persons who inject drugs, and transgender people. Evidence shows that the CBART model for KP (KP-CBART) can improve HIV outcomes along the cascade of HIV care and treatment in sub-Saharan Africa. However, how KP-CBART works, for whom, why, and under what circumstances it generates specific outcomes are not yet clear. Therefore, the aim of this study is to identify the initial programme theory (IPT) of the KP-CBART in Benue State using a realist approach. METHOD: The study design is exploratory and qualitative, exploring the implementation of KP-CBART. We reviewed the intervention logic framework & guidelines for the KP-CBART in Nigeria, conducted a desk review of KP-CBART in Sub-Saharan Africa (SSA) and interviewed programme managers in the Benue HIV programme between November 2021 and April 2022. Findings were synthesized using the Context-Mechanism-Outcome (CMO) heuristic tool to explain the relationship between the different types of CBART models, contextual factors, actors, mechanisms and outcomes. Using a generative causality logic (retroduction and abduction), we developed, following a realist approach, CMO configurations (CMOc), summarized as an empirically testable IPT. RESULT: We developed 7 CMOc and an IPT of the KP-CBART. Where KPLHIV receive ART in a safe place while living in a setting of punitive laws, harassment, stigma and discrimination, KP will adhere to treatment and be retained in care because they feel safe and trust the healthcare providers. Where KPLHIV are involved in the design, planning and implementation of HIV services; medication adherence and retention in care will improve because KP clients perceive HIV services to be KP-friendly and participate in KP-CBART. CONCLUSION: Implementation of CBART model where KPLHIV feel safe, trust healthcare providers, and participate in HIV service delivery can improve medication adherence and retention in care. This programme hypothesis will be tested and refined in the next phase of the realist evaluation of KP-CBART.

Person-centred care and short oral treatment for rifampicin-resistant tuberculosis improve retention in care in Kandahar, Afghanistan.

OBJECTIVES: To describe the effect of adaptations to a person-centred care with short oral regimens on retention in care for rifampicin-resistant TB (RR-TB) in Kandahar province, Afghanistan. METHODS: The study included people with RR-TB registered in the programme between 01 October 2016 and 18 April 2021. From 19 November 2019, the programme implemented a trial investigating the safety and effectiveness of short oral RR-TB regimens. During the trial, person-centred care was adapted. We included the data from people living with RR-TB treated in the period before and after the care model was adapted and applied Kaplan-Meier statistics to compare rates of retention in care. RESULTS: Of 236 patients registered in the RR-TB programme, 146 (61.9%) were registered before and 90 (38.1%) after the model of care was adapted. Before adaptations enhancing person-centred care, pre-treatment attrition was 23.3% (n = 34/146), whilst under the adapted care model it was 5.6% (n = 5/90). Attrition on treatment was 22.3% (n = 25/112) before adaptations, whilst during the study period none of the participants were lost-to-follow-up on treatment and 3.3% died (n = 3/90). CONCLUSIONS: As person-centred care delivery and treatment regimens were adapted to better fit-specific contextual challenges and the needs of the target population, retention in care improved amongst people with RR-TB in Kandahar, Afghanistan.

Community-Based ART Service Delivery for Key Populations in Sub-Saharan Africa: Scoping Review of Outcomes Along the Continuum of HIV Care.

HIV positive key population (KP) often face health system and social barriers to HIV care. KP include sex workers, men who have sex with men, persons who inject drugs, transgender people, and people in prisons and other closed settings. Community-based ART service delivery (CBART) has the potential to increase access to antiretroviral treatment (ART) and enhance retention in care. This scoping review summarized the evidence on the effect of CBART along the continuum of HIV care among KP in sub-Saharan Africa. We searched Pubmed, Web of Science, Google scholar, and NGO websites for articles published between 2010 and April 2020. We synthesized the involvement of KP community members or lay providers in medical task provision, and outcomes along the continuum of HIV care. Of 3,330 records identified, 66 were eligible for full test screening, out of which 12 were included in the review. CBART for KP was provided through: (a) community drop-in-centres, (b) community drop-in-centres plus mobile team, or (c) community-based health centres. KP were engaged as peer educators and they provided services such as community mobilisation activities for HIV testing and ART, ART adherence counselling, and referral for ART initiation. Across the KP-CBART studies, outcomes in terms of ART uptake, adherence to ART, retention in care and viral suppression were at least as good as those obtained for KP attending facility-based care. KP-CBART was as effective as facility-based care. To achieve the UNAIDS 95-95-95 target in sub-Saharan Africa, national programmes should scale-up KP-CBART to complement facility-based care.

Virological outcomes and risk factors for non-suppression for routine and repeat viral load testing after enhanced adherence counselling during viral load testing scale-up in Zimbabwe: analytic cross-sectional study using laboratory data from 2014 to 2018.

BACKGROUND: Since the scale-up of routine viral load (VL) testing started in 2016, there is limited evidence on VL suppression rates under programmatic settings and groups at risk of non-suppression. We conducted a study to estimate VL non-suppression (> 1000 copies/ml) and its risk factors using "routine" and "repeat after enhanced adherence counselling (EAC)" VL results. METHODS: We conducted an analytic cross-sectional study using secondary VL testing data collected between 2014 and 2018 from a centrally located laboratory. We analysed data from routine tests and repeat tests after an individual received EAC. Our outcome was viral load non-suppression. Bivariable and multivariable logistic regression was performed to identify factors associated with having VL non-suppression for routine and repeat VL. RESULTS: We analysed 103,609 VL test results (101,725 routine and 1884 repeat test results) collected from the country's ten provinces. Of the 101,725 routine and 1884 repeat VL tests, 13.8% and 52.9% were non-suppressed, respectively. Only one in seven (1:7) of the non-suppressed routine VL tests had a repeat test after EAC. For routine VL tests; males (vs females, adjusted odds ratio (aOR) = 1.19, [95% CI 1.14-1.24]) and adolescents (10-19 years) (vs adults (25-49 years), aOR = 3.11, [95% CI 2.9-3.31]) were more at risk of VL non-suppression. The patients who received care at the secondary level (vs primary, aOR = 1.21, [95% CI 1.17-1.26]) and tertiary level (vs primary, aOR = 1.63, [95% CI 1.44-1.85]) had a higher risk of VL non-suppression compared to the primary level. Those that started ART in 2014-2015 (vs < 2010, aOR = 0.83, [95% CI 0.79-0.88]) and from 2016 onwards (vs < 2010, aOR = 0.84, [95% CI 0.79-0.89]) had a lower risk of VL non-suppression. For repeat VL tests; young adults (20-24 years) (vs adults (25-49 years), (aOR) = 3.48, [95% CI 2.16 -5.83]), adolescents (10-19 years) (vs adults (25-49 years), aOR = 2.76, [95% CI 2.11-3.72]) and children (0-9 years) (vs adults (25-49 years), aOR = 1.51, [95% CI 1.03-2.22]) were at risk of VL non-suppression. CONCLUSION: Close to 90% suppression in routine VL shows that Zimbabwe is on track to reach the third UNAIDS target. Strategies to improve the identification of clients with high routine VL results for repeating testing after EAC and ART adherence in subpopulations (men, adolescents and young adolescents) at risk of viral non-suppression should be prioritised.

High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss.

The short treatment regimen (STR) achieves a >80% cure in rifampicin-resistant tuberculosis (RR-TB) patients. However, ototoxicity induced by the injectable is a concern. This is the first study to evaluate the replacement of injectables by linezolid in patients with audiometry abnormalities at baseline or during the treatment.We conducted a retrospective cohort study of all RR-TB patients started on the STR between 2016 and June, 2019, in Niger. Patients underwent audiometry every 2 months in 2016 and every month since 2017.Of 195 patients, 16.9% (33 out of 195) received linezolid from the start (n=17), or switched from injectables to linezolid during treatment (n=16), based on audiometry abnormalities. In 2016, two patients developed severe ototoxicity despite switching to linezolid. Since 2017, no patient developed severe hearing loss or complete deafness. Severe haematological toxicity was observed in 18.1% (six out of 33) of patients on linezolid, none of which was life threatening. The use of linezolid was associated with severe but manageable adverse events (hazard ratio 8.9, 95% CI 2.5-31.5; p=0.001). A total of 90.9% (30 out of 33) of patients on a linezolid-containing STR were cured, and none experienced treatment failure. Three died, but not due to adverse events.Baseline and monthly audiometry monitoring and using linezolid after detection of hearing abnormalities appears effective to prevent severe ototoxicity, while keeping high treatment success and manageable adverse events.

Second-line injectable drugs for rifampicin-resistant tuberculosis: better the devil we know?

In its 2020 guidelines for the treatment of rifampicin-resistant TB (RR-TB), the WHO recommends all-oral fluoroquinolone-based regimens, with bedaquiline replacing the second-line injectable drugs (SLIDs). SLIDs were used for their strong acquired resistance-preventing activity. Data from three cohorts showed acquired bedaquiline resistance ranging between 2.5% and 30.8%, with no protection from a SLID in most cases. If bedaquiline resistance is that easily acquired, it will fail to protect fluoroquinolones and other drugs from acquiring resistance. Until evidence on resistance-preventing activity shows that SLIDs can safely be replaced, we call for more prudent use of the few potent second-line TB drugs available. Studies on new treatment regimens need to prioritize the prevention of acquired resistance along with treatment success. Meanwhile, reducing the dosing of SLIDs to thrice weekly from Day 1, and their replacement for any degree of audiometry abnormalities before or during treatment will largely avoid serious ototoxicity.

Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis.

BACKGROUND: Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. METHODS: We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months' standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox's regression was performed to identify risk factors for virological failure. RESULTS: We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0-39.1) and a median observation time of 5.4 years (IQR 3.7-7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20-1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14-1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42-1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41-1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07-1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. CONCLUSIONS: VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

"I don't know when he will be back": life-changing events challenge the community ART Group model- a qualitative research study, Tete, Mozambique.

BACKGROUND: Since 2008 in Mozambique, patients stable on antiretroviral therapy (ART) can join Community ART Groups (CAG), peer groups in which members are involved in adherence support and community ART delivery. More than 10 years after the implementation of the first CAGs, we study how changes in circumstance and daily life events of CAG members have affected the CAG dynamic. METHODS: A qualitative study using individual in-depth interviews (27) and focus group discussions (8) with CAG members and health care providers was carried out in Tete province, rural Mozambique. Purposive sampling was used to select participants. Data were transcribed and translated, and manual thematic analysis carried out to identify codes, which were then categorized in sub-themes and themes. RESULTS: Data were collected from 61 CAG members and 18 health-care providers in 2017. The CAG dynamic was affected by life events and changing circumstances including a loss of geographical proximity or a change in social relationships. Family CAGs facilitated reporting and ART distribution, but conflict between CAG members meant some CAGs ceased to function. In some CAGs, the dynamic changed as pill counts were not carried out, members met less frequently or stopped meeting entirely. Some members did not collect ART at the facility when it was their turn, and others stopped taking ART completely. Health care providers were reported to push people living with HIV to join CAGs, instead of allowing voluntary participation. Some CAGs responded to adherence challenges by strengthening peer support through counselling and observed pill intake. Health-care providers agreed that strengthening CAG rules and membership criteria could help to overcome the identified problems. CONCLUSIONS: Changing life circumstances, changes in relationships and a lack of participation by CAG members altered the CAG dynamic, which sometimes affected adherence. Some CAGs responded to challenges by intensifying peer support, including to those diagnosed with virological failure. To ensure flexible implementation and modification of CAGs to the inevitable changes in life circumstances of its members, feedback mechanisms should be implemented between CAG members and the health-care providers.

Knowledge transmission, peer support, behaviour change and satisfaction in post Natal clubs in Khayelitsha, South Africa: a qualitative study.

BACKGROUND: The Post Natal Club (PNC) model assures comprehensive care, including HIV and Maternal and Child Health care, for postpartum women living with HIV and their infants during an 18-month postnatal period. The PNC model was launched in 2016 in Town Two Clinic, a primary health care facility in Khayelitsha, South Africa. This qualitative research study aims to understand how participation in PNCs affected knowledge transmission, peer support, behaviour change and satisfaction with the care provided. METHODS: We conducted ten in-depth interviews; three focus group discussions and participant observation with PNC members, health-care workers and key informants selected through purposive sampling. Seventeen PNC members between 21 and 38 years old, three key informants and seven staff working in PNC participated in the research. All participants were female, except for one of the three key informants who was male. Data was collected until saturation. The data analysis was performed in an inductive way and involved an iterative process, using Nvivo11 software. RESULTS: PNC members acquired knowledge on HIV, ART, adherence, infant feeding, healthy eating habits, follow up tests and treatment for exposed infants. Participants believed that PNC created strong relationships among members and offered an environment conducive to sharing experience and advice. Most interviewees stated that participating in PNC facilitated disclosure of their HIV status, enhanced support network and provided role models. PNC members said that they adapted their behaviour based on advice received in PNCs related to infant feeding, ART adherence, monitoring of symptoms and stimulation of early childhood development. The main benefits were believed to be comprehensive care for mother-infant pairs, time-saving and the peer dynamic. The main challenge from the perspective of key informants was the sustainability of dedicating human resources to PNC. CONCLUSION: The PNC model was believed to improve knowledge acquisition, behaviour change and peer support. Participants, staff and the majority of key informants expressed a high level of satisfaction with the PNC model. Sustainability and finding adequate human resources for PNCs remained challenging. Strategies to improve sustainability may include handing over some PNC tasks to members to increase their sense of ownership.

Viral load detection and management on first line ART in rural Rwanda.

BACKGROUND: To achieve the ambitious 90-90-90 UNAIDS targets, access to routine viral load (VL) is critical. To measure VL, Rwanda has relied on a national reference laboratory for years. In 2014, a VL testing platform was implemented in a rural District in the Northern Province. Here we analyze the uptake of VL testing, identification of risks for detectable VL (≥1000 copies/ml), and the management of patients with a detectable VL. METHODS: A retrospective cohort study of patients who started ART between July 2012 and June 2015 and followed until end December 2016. Using descriptive statistics, we describe the VL cascade, from VL uptake to the start of second-line ART in patients diagnosed with virological failure. We estimate predictors of having a detectable VL using logistic regression. RESULTS: The uptake of VL testing increased progressively between 2013 and 2016, raising from 25.6% (39/152) in 2013 up to 93.2% (510/547) in 2016.In 2016, 88.5% (n = 451) of patients tested, had a suppressed VL. Predictors of having a detectable VL included being male (aOR 2.1; 95%CI 1.12-4.02; p = 0.02), being a sex worker (aOR 6.4; 95%CI 1.1-36.0; p = 0.04), having a WHO clinical stage IV when starting ART (aOR 8.8; 95%CI 1.8-43.0; p < 0.001), having had a previous detectable VL (aOR 7.2; 95%CI 3.5-14.5; p < 0.001), and having had no VL before 2016 (aOR 3.1; 95%CI 1.2-8.1; p = 0.02). Among patients with initial detectable VL between 2013 and 2016, 88% (n = 103) had a follow-up VL, of whom 60.2% (n = 62) suppressed their VL below 1000 copies/ml. The median time between the initial and follow-up VL was of 12.5 months (IQR: 8.7-19.0). Among patients with confirmed treatment failure, 63.4% (n = 26) started second-line ART within the study period. CONCLUSION: VL uptake increased after decentralizing VL testing in rural Rwanda. Virological suppression was high. An individualized follow up of patients at risk of non-suppression and a prompt management of patients with detectable VL may help to achieve and sustain the third global UNAIDS target: virological suppression in 90% of patients on ART.

Operational Research during the Ebola Emergency.

Operational research aims to identify interventions, strategies, or tools that can enhance the quality, effectiveness, or coverage of programs where the research is taking place. Médecins Sans Frontières admitted ≈5,200 patients with confirmed Ebola virus disease during the Ebola outbreak in West Africa and from the beginning nested operational research within its emergency response. This research covered critical areas, such as understanding how the virus spreads, clinical trials, community perceptions, challenges within Ebola treatment centers, and negative effects on non-Ebola healthcare. Importantly, operational research questions were decided to a large extent by returning volunteers who had first-hand knowledge of the immediate issues facing teams in the field. Such a method is appropriate for an emergency medical organization. Many challenges were also identified while carrying out operational research across 3 different countries, including the basic need for collecting data in standardized format to enable comparison of findings among treatment centers.

Local constraints to access appropriate malaria treatment in the context of parasite resistance in Cambodia: a qualitative study.

BACKGROUND: Despite emerging drug resistance in Cambodia, artemisinin-based combination therapy (ACT) is still the most efficacious therapy. ACT is available free of charge in the Cambodian public sector and at a subsidized rate in the private sector. However, un- and mistreated cases in combination with population movements may lead to the further spread of resistant parasites, stressing the importance of understanding how the perceived aetiology of malaria and associated health-seeking behaviour may delay access to appropriate treatment. A qualitative study explored these factors after an epidemiological survey confirmed parasite resistance in Preah Vihear province. RESULTS: In Cambodian cosmology, illnesses can be inflicted by supernatural beings or originate from 'natural' causes because of disorder in the social, domestic or outdoor environment. Initial treatment options consist of cheap and accessible home-based care (manual therapy, herbs and biomedical medication) targeting single symptoms. If there is no steady recovery or if the condition quickly aggravates, care will be sought from 'village doctors', public health facilities, private pharmacies or, in case of suspicion of a supernatural cause, from a specialized indigenous healer. The choice of provider is mostly based on the family's financial situation, access to and trust in the provider, and the congruence between the suspected aetiology of the illness and the treatment offered by the provider. Different treatment options are often combined during the same illness episode through a serial process of trial and error guided by the observable improvements in the patient's condition. CONCLUSIONS: Cambodian perceptions of illness that focus on single symptoms and their perceived severity may lead to the identification of one or multiple illnesses at the same time, rarely suspecting malaria from the start and implying different patterns of health seeking behaviour and treatment choice. However, decisions to self-diagnose and treat at home are also pragmatic and must be understood in the context of poverty, a major barrier to seeking prompt and appropriate care for malaria in an area characterized by parasite resistance.

Rational use of Xpert testing in patients with presumptive TB: clinicians should be encouraged to use the test-treat threshold.

BACKGROUND: A recently published Ugandan study on tuberculosis (TB) diagnosis in HIV-positive patients with presumptive smear-negative TB, which showed that out of 90 patients who started TB treatment, 20% (18/90) had a positive Xpert MTB/RIF (Xpert) test, 24% (22/90) had a negative Xpert test, and 56% (50/90) were started without Xpert testing. Although Xpert testing was available, clinicians did not use it systematically. Here we aim to show more objectively the process of clinical decision-making. First, we estimated that pre-test probability of TB, or the prevalence of TB in smear-negative HIV infected patients with signs of presumptive TB in Uganda, was 17%. Second, we argue that the treatment threshold, the probability of disease at which the utility of treating and not treating is the same, and above which treatment should be started, should be determined. In Uganda, the treatment threshold was not yet formally established. In Rwanda, the calculated treatment threshold was 12%. Hence, one could argue that the threshold was reached without even considering additional tests. Still, Xpert testing can be useful when the probability of disease is above the treatment threshold, but only when a negative Xpert result can lower the probability of disease enough to cross the treatment threshold. This occurs when the pre-test probability is lower than the test-treat threshold, the probability of disease at which the utility of testing and the utility of treating without testing is the same. We estimated that the test-treatment threshold was 28%. Finally, to show the effect of the presence or absence of arguments on the probability of TB, we use confirming and excluding power, and a log10 odds scale to combine arguments. CONCLUSION: If the pre-test probability is above the test-treat threshold, empirical treatment is justified, because even a negative Xpert will not lower the post-test probability below the treatment threshold. However, Xpert testing for the diagnosis of TB should be performed in patients for whom the probability of TB was lower than the test-treat threshold. Especially in resource constrained settings clinicians should be encouraged to take clinical decisions and use scarce resources rationally.