Development and Evaluation of a Digital HIV Risk Assessment Tool Incorporated Within an App-Based Self-Testing Program.

BACKGROUND: Low-risk perception is an important barrier to the utilization of HIV services. In this context, offering an online platform for people to assess their risk of HIV and inform their decision to test can be impactful in increasing testing uptake. Using secondary data from the HIVSmart! quasirandomized trial, we aimed to identify predictors of HIV, develop a risk staging model for South African township populations, and validate it in combination with the HIVSmart! digital self-testing program. SETTING: Townships in Cape Town, South Africa. METHODS: Using Bayesian predictive projection, we identified predictors of HIV and constructed a risk assessment model that we validated in external data. RESULTS: Our analyses included 3095 participants from the HIVSmart! trial. We identified a model of 5 predictors (being unmarried, HIV testing history, having had sex with a partner living with HIV, dwelling situation, and education) that performed best during external validation (area under the receiver operating characteristic curve, 89% credible intervals: 0.71, 0.68 to 0.72). The sensitivity of our HIV risk staging model was 91.0% (89.1% to 92.7%) and the specificity was 13.2% (8.5% to 19.8%) but increased when combined with a digital HIV self-testing program, the specificity was 91.6% (95.9% to 96.4%) and sensitivity remained similar at 90.9% (89.1% to 92.6%). CONCLUSIONS: This is the first validated digital HIV risk assessment tool developed for South African township populations and the first study to evaluate the added value of a risk assessment tool with an app-based HIV self-testing program. Study findings are relevant for application of digital programs to improve utilization of HIV testing services.

Economic evaluation of microbiological and host biomarker-based tests for the diagnosis of pleural tuberculosis in a high burden setting.

Background: Pleural tuberculosis (TB) remains difficult to diagnose. Tests measuring host biomarkers, such as adenosine deaminase (ADA) and unstimulated interferon-gamma, perform better than conventional microbiological tests for TB diagnosis using pleural fluid. However, there is no data on the cost-effectiveness of these diagnostic approaches. Methods: A cost-consequence analysis was performed from the South African healthcare provider perspective to determine the cost-effectiveness of the following strategies for the diagnosis of pleural TB: (I) Smear microscopy (SM); (II) Mycobacterial-Growth-In-Tube liquid culture (MGIT); (III) adenosine deaminase (ADA); (IV) Xpert ULTRA (Xpert); (V) unstimulated interferon-gamma using IRISA-TB™ (IRISA-TB). Costs (2019 USD) were derived from national sources and outcomes from published literature. Cost-effectiveness was expressed as the cost per pleural TB case diagnosed and initiated on treatment (per 1,000 patients screened). Sensitivity analyses were performed. Results: Total strategy costs ranged from $354,632 (SM) to $390,363 (ADA). Strategies incorporating highly specific tests, including IRISA-TB and Xpert, had the lowest costs associated with unnecessary treatment. In terms of outcomes (per 1,000 screened), IRISA-TB and ADA correctly identified the most pleural TB cases (8.4 and 8.0 cases, respectively), almost double that of MGIT (4.2 cases) and Xpert ULTRA (3.7 cases). IRISA-TB was the most cost-effective strategy, as the cost per pleural TB patient diagnosed and initiated on treatment was $44,084, ~$5,000 less than ADA (the second most cost-effective strategy; $49,065). These values were most sensitive to changes in pleural TB prevalence, treatment costs, and empirical treatment rates. The cost difference, compared to ADA, equated to a potential saving of ~US$45 million per year in South Africa. Conclusions: IRISA-TB offers good value for money and is a potentially more cost-effective alternative to ADA for pleural TB diagnosis.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.

Burden of tuberculosis in intensive care units in Cape Town, South Africa, and assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a prospective burden of disease study with a nested randomised controlled trial.

BACKGROUND: There are few prospective data about the incidence and mortality associated with pulmonary tuberculosis in intensive care units (ICUs), and none on the accuracy and clinical effect of the Xpert-MTB/RIF assay in this setting. We aimed to measure the frequency of culture-positive tuberculosis in ICUs in Cape Town, South Africa and to assess the performance and effect on patient outcomes of Xpert MTB/RIF versus smear microscopy for diagnosis of tuberculosis. METHODS: We did a prospective burden of disease study with a randomised controlled substudy at the ICUs of four hospitals in Cape Town. Mechanically ventilated adults (≥18 years) with suspected pulmonary tuberculosis admitted between Aug 1, 2010, and July 31, 2013 (irrespective of the reason for admission), were prospectively investigated by culture, and by Xpert-MTB/RIF testing or smear microscopy, of tracheal aspirate samples. In the substudy, patients were randomly assigned (1:1), via a computer-generated allocation list, to smear microscopy or Xpert MTB/RIF. Participants, caregivers, and outcome assessors were not masked to group assignment. Only the laboratory staff were blinded to the clinical details of the participants. In November, 2012, Xpert MTB/RIF was adopted as the initial diagnostic test for respiratory samples in Western Cape province. Thereafter, patients received Xpert MTB/MIF and culture as standard of care. For the whole study cohort, the primary outcome was the frequency of bacteriologically confirmed tuberculosis. The primary endpoint of the randomised substudy was the proportion of culture-positive patients on treatment at 48 h after enrolment. The randomised substudy is registered with ClinicalTrials.gov, number NCT01530568. FINDINGS: We investigated 341 patients for suspected pulmonary tuberculosis out of a total of 2309 ICU admissions. 46 (15%) of 317 patients included in the final analysis had a positive test for tuberculosis (Xpert MTB/RIF or culture). Culture-positive patients who failed to initiate treatment (adjusted HR 4·49, 95% CI 1·45-13·89) or who received inotropes (4·33, 1·49-12·60) were more likely to die. However, tuberculosis status was not associated with 28-day or 90-day mortality. In the substudy, we randomly assigned 115 patients to smear microscopy and 111 to Xpert MTB/RIF. Smear microscopy detected six (43%) of 14 culture-positive patients, and Xpert MTB/RIF detected 11 (100%) of 11 culture-positive patients (p=0·002). The proportion of culture-positive patients on treatment at 48 h was higher in the Xpert MTB/RIF group than in the smear microscopy group (11 [92%] of 12 vs nine [53%] of 17; p=0·043), although use of Xpert MTB/RIF had no effect on mortality or other patient outcomes. INTERPRETATION: Tuberculosis is fairly common in ICUs in high-burden settings, and clinicians should screen and test patients for tuberculosis with Xpert MTB/RIF where available. This test improves diagnostic yield and rates of treatment initiation, and reduces unnecessary treatment, but might not increase the total number of patients on treatment when empirical treatment is widely used. A suspected diagnosis of pulmonary tuberculosis should not exclude patients from ICU care in resource-limited settings because mortality is unaffected by the presence of this disease. FUNDING: European and Developing Countries Clinical Trials Partnership, South African Medical Research Council, and the Discovery Foundation.