Jonathan E. Golub

Background: Tuberculosis preventive therapy (TPT) reduces tuberculosis incidence among people living with HIV (PLHIV), yet uptake has been sub-optimal. We evaluated trends of TPT prescribing among people initiated on antiretroviral therapy (ART). Setting: Thirty-six public sector clinics in South Africa. Methods: We retrospectively analyzed individual-level clinical data abstracted from clinics in the Free State and North West provinces, South Africa. We included PLHIV who initiated ART 2005-2022 and had ≥1 HIV-related clinic visits on or after 15 September 2021. The timing of TPT prescribing was defined by the earliest recorded TPT prescription date as: (1) TPT prescription within ≤6 months, (2) TPT prescription >6 months, or (3) no recorded TPT prescription on or after ART initiation. Results: Among 48,718 ART initiators, 23,168 (47.6%) were prescribed TPT on or after ART initiation; 15,510 (31.8%) were prescribed TPT ≤6 months and 7,658 (15.7%) were prescribed TPT >6 months after ART initiation. Early TPT prescribing increased from 0.7% in the 2005-2010 cohort to 71.3% in 2022 ART initiators, while TPT prescribing >6 months after ART initiation declined from 28.5% in the 2005-2010 cohort to 1.3% among those who initiated ART in 2022. Cumulative TPT prescribing was 29.2% in the 2005-2010 cohort, 34.2% in the 2011-2015 cohort, and 72.6% in the 2022 cohort. Conclusions: Over 2005-2022, TPT prescribing shifted markedly toward initiation near the time of ART initiation, with early prescribing exceeding 70% by 2022. Cumulative prescribing remained low among people from earlier ART cohorts, underscoring the need for targeted catch-up strategies.

Background: An estimated 10% of tuberculosis (TB) survivors who recently completed treatment in India develop TB again. We sought to develop a parsimonious model for predicting TB recurrence that can help target post-treatment active case finding among the highest-risk TB survivors. Methods: The TB Aftermath trial enrolled TB survivors at treatment completion from 6 public TB clinics in Maharashtra, India, and assessed participants at 6-month intervals. Our prediction endpoint was recurrent TB diagnosed within 18 months of treatment completion. Candidate variables included risk factors for recurrence identified a priori and lung function assessments. We used LASSO (Least Absolute Shrinkage and Selection Operator) regression to shortlist predictors and estimated probability of recurrence using logistic regression. We conducted internal validation, assessed discrimination, and plotted calibration. Model selection was based on practical utility and predictive accuracy. For our selected model, we identified a cutoff for achieving 90% sensitivity. Results: Among 1033 participants, we identified 85 (8.2%) recurrences. Several 5-item models measurable at treatment completion had moderate discrimination. Our selected model included sex, household income, body mass index, peak expiratory flow from spirometry, and history of multiple TB episodes. The selected model had a cross-validated c-statistic of .69 (95% CI: .56–.77) and acceptable calibration (intercept: .03 [95% CI: −.03, .09]; slope: .66 [.08–1.24]). TB survivors with a predicted probability ≥3.7% accounted for 90% of recurrences. Conclusions: A 5-item tool, measurable at treatment completion, showed moderate predictive accuracy for recurrent TB. At scale, a simple 5-item prediction tool may increase efficiency of post-treatment active case finding.

The nicotine metabolite ratio (NMR) has been informative in selecting treatment choices for nicotine dependence and increasing treatment efficacy in Western settings; however, the clinical utility of the NMR among smokers in low-resource settings remains unclear. Prospective analysis was conducted using data from a randomized controlled trial of smoking cessation among adults living with HIV, to examine the association between the NMR and response to smoking cessation treatment. NMR was assessed using bio-banked urine samples collected at baseline. Self-reported smoking at 6 months was verified using a urine cotinine test and exhaled breath carbon monoxide (CO). We found no associations between the NMR and smoking abstinence (adjusted risk ratio (aRR) = 0.82; 95% CI: 0.45, 1.49; p = 0.53). No evidence of effect modification by treatment conditions was observed on the multiplicative scale (aRR = 1.17; 95% CI: 0.32, 4.30; p = 0.81) or additive scale (adjusted relative excess risk due to interaction (aRERI) = 0.10; 95% CI: −1.16, 1.36; p = 0.44). Our results suggest that the NMR may not be a viable approach for selecting smoking cessation treatment in this setting, given the minimal variability in our sample and racial/ethnic makeup of this population.

Tuberculosis (TB) preventive therapy (TPT) reduces the risk of TB disease in people with human immunodeficiency virus (HIV), yet uptake has been suboptimal in many countries. We assessed whether QuantiFERON Gold In-Tube (QGIT) during routine HIV care increased TB infection (TBI) testing and TPT prescriptions. This parallel-arm, 1:1 cluster-randomized controlled trial compared the standard-of-care tuberculin skin test to QGIT in South Africa. We enrolled consenting, TPT-eligible adults diagnosed with HIV ≤30 days prior and used intention-to-treat analyses for the outcomes: proportion of patients with documented TBI results, proportion with documented TPT, and time from enrollment to outcomes. We enrolled 2232 patients across 14 clinics from November 2014 to May 2017 (58% in intervention clinics). At 24 months of follow-up, more participants in intervention clinics had TBI results (69% vs 2%, P < .001) and TPT prescriptions (45% vs 30%, P = .13) than control clinics. Controlling for baseline covariates, intervention clinics had 60% (95% confidence interval, 51–68; P < .001) more participants with TBI results and 12% (95% confidence interval, −6 to 31; P = .18) more with TPT prescriptions. Among participants with results, those in intervention clinics received results and TPT faster (intervention: median of 6 and 29 days after enrollment vs control: 21 and 54 days, respectively). In this setting, QGIT in routine HIV care resulted in more patients with TBI results. Clinicians also initiated more people with HIV on TPT in QGIT intervention clinics, and did so more quickly, than the control arm. NCT02119130.

Many patients with tuberculosis (TB) have comorbidities, risk determinants and disability that co-exist at diagnosis, during and after TB treatment. We conducted an observational cohort study in 11 health facilities in China to assess under routine program conditions (i) the burden of these problems at the start and end of TB treatment and (ii) whether referral mechanisms for further care were functional. There were 603 patients registered with drug-susceptible TB who started TB treatment: 84% were symptomatic, 14% had diabetes, 14% had high blood pressure, 19% smoked cigarettes, 10% drank excess alcohol and in 45% the 6 min walking test (6MWT) was abnormal. Five patients were identified with mental health disorders. There were 586 (97%) patients who successfully completed TB treatment six months later. Of these, 18% were still symptomatic, 12% had diabetes (the remainder with diabetes failed to complete treatment), 5% had high blood pressure, 5% smoked cigarettes, 1% drank excess alcohol and 25% had an abnormal 6MWT. Referral mechanisms for the care of comorbidities and determinants worked well except for mental health and pulmonary rehabilitation for disability. There is need for more programmatic-related studies in other countries to build the evidence base for care of TB-related conditions and disability.

The nicotine metabolite ratio (NMR) is associated with race/ethnicity but has not been evaluated among smokers in the African region. We conducted a cross-sectional analysis of baseline data from a large randomized, controlled trial for smoking cessation among people with HIV (PWH) in South Africa. Urine samples were analyzed for the NMR and evaluated as a binary variable using a cutoff value of the fourth quartile to determine the fastest metabolizers. The median NMR was 0.31 (IQR: 0.31, 0.32; range: 0.29, 0.57); the cut-point for fast metabolizers was ≥0.3174 ng/mL. A high NMR was not associated with the number of cigarettes per day (OR = 1.10, 95% CI: 0.71, 1.70, p = 0.66) but was associated with 40% lower odds of a quit attempt in the past year (OR = 0.69; 95% CI: 0.44, 1.07, p = 0.09) and alcohol use (OR = 0.59, 95% CI: 0.32, 1.06, p = 0.07). No association was seen with marijuana or HIV clinical characteristics. As we found only minimal variability in the NMR and minimal associations with intensity of smoking, NMR may be of limited clinical value in this population, although it may inform which individuals are less likely to make a quit attempt.

There is growing evidence that a substantial proportion of people who complete anti-tuberculosis treatment experience significant morbidity and mortality which can negatively affect their quality of life. It is suggested that national tuberculosis programs conduct end-of-treatment assessments, but whether this is feasible is currently not known. We therefore assessed whether tuberculosis program staff could assess functional and general health status of patients at the end of treatment in five TB clinics in four provinces in China. There were 115 patients, aged 14–82 years, who completed anti-tuberculosis treatment and a post-TB assessment. There were 54 (47%) patients who continued to have symptoms, the commonest being cough, dyspnea and fatigue. Symptom continuation was significantly more common in the 22 patients with diabetes (p = 0.027) and the 12 patients previously treated for TB (p = 0.008). There were 12 (10%) current smokers, an abnormal chest X-ray was found in 106 (92%) patients and distance walked in the 6-min walking test (6MWT) ranged from 30–750 m (mean 452 ± 120); 24 (21%) patients walked less than 400 m. Time taken to perform the post-TB assessment, including the 6MWT, ranged from 8–45 min (mean 21 ± 8 min). In 98% of the completed questionnaires, health workers stated that conducting post-TB assessments was feasible and useful. This study shows that post-TB assessments can be conducted under routine programmatic conditions and that there is significant morbidity that needs to be addressed.

Purpose of Review: eHealth tools are increasingly utilized for communication with patients. Although efficacious and cost-effective, these tools face several barriers that challenge their ethical use in sexual health. We reviewed literature from the past decade to pick illustrative studies of eHealth tools that deliver results of laboratory tests for sexually transmitted infections, including the human immunodeficiency virus, as well as partner notifications. We describe ethical implications for such technologies. Recent Findings: Our review found that despite widespread research on the use of eHealth tools in delivering laboratory results and partner notifications, these studies rarely measured or reported on the ethical implications. Such implications can be organized according to the four major principles in bioethics: beneficence, patient autonomy, non-maleficence, and justice. The beneficence of eHealth typically measures efficacy in comparison to existing standards of care. Patient autonomy includes the ability to opt in or out of eHealth tools, right-based principles of consent, and sovereignty over healthcare data. To adhere to the principle of non-maleficence, relevant harms must be identified and measured—such as unintentional disclosure of illness, sexual orientation, or sexual activity. Justice must also be considered to accommodate all users equally, irrespective of their literacy level, with easy-to-use platforms that provide clear messages. Summary: Based on case studies from this review, we developed a list of recommendations for the ethical development and evaluation of eHealth platforms to deliver STI/HIV results to patients and notifications to partners.