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Genomic analysis of Mycobacterium tuberculosis in postmortem biopsies provides a window into intrahost diversification of a disseminated pathogen. Mycobacterium tuberculosis remains a leading cause of death worldwide, especially among individuals infected with HIV 1 . Whereas phylogenetic analysis has revealed M. tuberculosis spread throughout history 2 , 3 , 4 , 5 and in local outbreaks 6 , 7 , 8 , much less is understood about its dissemination within the body. Here we report genomic analysis of 2,693 samples collected post mortem from lung and extrapulmonary biopsies of 44 subjects in KwaZulu-Natal, South Africa, who received minimal antitubercular treatment and most of whom were HIV seropositive. We found that purifying selection occurred within individual patients, without the need for patient-to-patient transmission. Despite negative selection, mycobacteria diversified within individuals to form sublineages that co-existed for years. These sublineages, as well as distinct strains from mixed infections, were differentially distributed throughout the lung, suggesting temporary barriers to pathogen migration. As a consequence, samples taken from the upper airway often captured only a fraction of the population diversity, challenging current methods of outbreak tracing and resistance diagnostics. Phylogenetic analysis indicated that dissemination from the lungs to extrapulmonary sites was as frequent as between lung sites, supporting the idea of similar migration routes within and between organs, at least in subjects with HIV. Genomic diversity therefore provides a record of pathogen diversification and repeated dissemination across the body.

Treatment of latent tuberculosis infection is an important control measure, especially in patients coinfected with HIV. In this international phase 3 trial, 1 month of isoniazid plus rifapentine was noninferior to the standard 9 months of isoniazid in HIV-infected patients.

By using combined positron emission and computed tomography (PET–CT), Esmail et al. show that some patients with latent tuberculosis have signs of subclinical, active disease in the lungs and a greater likelihood of progression, suggesting a spectrum of disease rather than discrete latent and active disease states. Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral-therapy-naive, HIV-1-infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were substantially more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers that are predictive of progression.

Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden. A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33-0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32-1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06-1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63-0.92, p = 0.005) and among HIV-infected participants (ITT analysis, hazard ratio 0.67, 95% CI 0.53-0.85, p = 0.001). There was no difference in 6-mo mortality with Xpert versus routine diagnosis. Study limitations included incorrect intervention allocation for a high proportion of participants and that the study was conducted in a single clinic. These data suggest that in this routine primary care setting, use of Xpert to diagnose TB increased the number of individuals with bacteriologically confirmed TB who were treated by 3 mo and reduced time to treatment initiation, particularly among HIV-infected participants. Pan African Clinical Trials Registry PACTR201010000255244. Please see later in the article for the Editors' Summary.

The incidence of tuberculosis (TB) complicated by lung cancer has been increasing yearly worldwide. The overlapping effects of these two diseases leads to difficulties in clinical treatment and care. Single-care modalities fail to meet the clinical-care requirements of these complex diseases for both psychological and physical treatment. The study intended to evaluate the clinical efficacy of integrated nursing plus a psychological intervention for patients with TB complicated by lung cancer. The research team conducted a randomized controlled study. The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China. Participants were 60 patients with pulmonary TB complicated by lung cancer who received treatment at the hospital between January 2022 and December 2022. The research team randomly assigned participants to one of two groups, each with 30 participants: (1) the control group, who received integrated nursing and (2) the intervention group who received integrated nursing plus a psychological intervention. The research team evaluated: (1) short-term clinical efficacy; (2) quality of life, using the Medical Outcomes Study's (MOS') 36-item Short-form Health Survey (SF-36); (3) levels of anxiety and depression, using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), respectively; and (4) nursing satisfaction. No significant differences existed between the groups in demographic or clinical characteristics at baseline (P > .05). Compared to the control group, the intervention group's; (1) short-term clinical efficacy was significantly higher (P = .035); (2) scores on the SF-36 were significantly higher (all P < .001; (3) scores on the SAS and SDS were significantly lower (both P < .001); and (4) nursing satisfaction was significantly higher (P = .000). Integrated nursing plus psychological intervention can improve the quality of life of patients with TB complicated by lung cancer, alleviate their negative emotions, and enhance nursing satisfaction, thereby promoting patients' recoveries.

Abstract Background The concurrent treatment of tuberculosis and human immunodeficiency virus (HIV) is challenging, owing to drug interactions, overlapping toxicities, and immune reconstitution inflammatory syndrome (IRIS). The efficacy and safety of dolutegravir (DTG) were assessed in adults with HIV and drug-susceptible tuberculosis. Methods International Study of Patients with HIV on Rifampicin ING is a noncomparative, active-control, randomized, open-label study in HIV-1–infected antiretroviral therapy–naive adults (CD4+ ≥50 cells/mm3). Participants on rifampicin-based tuberculosis treatment ≤8 weeks were randomized (3:2) to receive DTG (50 mg twice daily both during and 2 weeks after tuberculosis therapy, then 50 mg once daily) or efavirenz (EFV; 600 mg daily) with 2 nucleoside reverse transcriptase inhibitors for 52 weeks. The primary endpoint was the proportion of DTG-arm participants with plasma HIV-1-RNA <50 copies/mL (responders) by the Food and Drug Administration Snapshot algorithm (intent-to-treat exposed population) at Week 48. The study was not powered to compare arms. Results For DTG (n = 69), the baseline HIV-1 RNA was >100 000 copies/mL in 64% of participants, with a median CD4+ count of 208 cells/mm3; for EFV (n = 44), 55% of participants had HIV-1 RNA >100 000 copies/mL, with a median CD4+ count of 202 cells/mm3. The Week 48 response rates were 75% (52/69, 95% confidence interval [CI] 65–86%) for DTG and 82% (36/44, 95% CI 70–93%) for EFV. The DTG nonresponses were driven by non–treatment related discontinuations (n = 10 lost to follow-up). There were no deaths or study drug switches. There were 2 discontinuations for toxicity (EFV). There were 3 protocol-defined virological failures (2 DTG, no acquired resistance; 1 EFV, emergent resistance to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors). The tuberculosis treatment success rate was high. Tuberculosis-associated IRIS was uncommon (4/arm), with no discontinuations for IRIS. Conclusions Among adults with HIV receiving rifampicin-based tuberculosis treatment, twice-daily DTG was effective and well tolerated. Clinical Trials Registration NCT02178592. Dolutegravir (given at a dose of 50 mg twice daily) demonstrated rapid virologic and immunologic response among human immunodeficiency virus treatment-naive individuals with drug-sensitive tuberculosis. Dolutegravir with rifampicin-containing tuberculosis treatments was well tolerated, with no deaths or discontinuations for toxicity.

A cluster-randomized trial in 20 Ugandan health centers compared a multicomponent strategy (on-site molecular testing for TB, restructuring of clinic workflows, and feedback of quality metrics) with routine care (on-site sputum-smear microscopy and referral-based molecular testing). The intervention led to greater numbers of patients being tested for, receiving a diagnosis of, and being treated for confirmed TB.

A previous study demonstrated noninferior efficacy of 4-month rifapentine/moxifloxacin regimen for tuberculosis (TB) treatment compared with the standard regimen. We explored results among study participants with diabetes. Among 2,516 randomized participants, 181 (7.2%) had diabetes. Of 166 participants with diabetes in the microbiologically eligible analysis group, 26.3% (15/57) had unfavorable outcomes in the control regimen, 13.8% (8/58) in the rifapentine/moxifloxacin regimen, and 29.4% (15/51) in the rifapentine regimen. The difference in proportion of unfavorable outcomes between the control and rifapentine/moxifloxacin arms in the microbiologically eligible analysis group was -12.5% (95% CI -27.0% to 1.9%); the difference between the control and rifapentine arms was 3.1% (95% CI -13.8% to 20.0%). Safety outcomes were similar in the rifapentine/moxifloxacin regimen and control arms. Among participants with TB and diabetes, the rifapentine/moxifloxacin arm had fewest unfavorable outcomes and was safe. Our findings indicate that the rifapentine/moxifloxacin regimen can be used in persons with TB and diabetes.

When to initiate antiretroviral therapy in patients with newly diagnosed HIV infection and TB has been debated. In this study from Cambodia, giving antiretrovirals 2 weeks after the start of TB therapy was superior to therapy begun at 8 weeks, with a decrease in mortality. Tuberculosis is a major cause of death in persons infected with the human immunodeficiency virus (HIV), especially in resource-limited settings. 1 , 2 Despite effective tuberculosis therapy, mortality is particularly high among patients with severe immunosuppression. 3 , 4 Although mortality among HIV-infected patients has been reported to be approximately 30% within the first 2 months of tuberculosis treatment if antiretroviral therapy (ART) is withheld, 5 the timing for starting ART in patients with tuberculosis has remained unclear. Arguments that support delayed initiation of ART include concern about the combined toxic effects of drugs, an increased risk of the immune reconstitution inflammatory syndrome (IRIS), and . . .

In this international study involving 809 patients with HIV and TB coinfection, earlier therapy for both infections, versus waiting 8 to 12 weeks to initiate antiretrovirals after anti-TB therapy, was beneficial in patients with a low CD4+ T-cell count (<50 per cubic millimeter). The treatment of patients with tuberculosis and newly identified infection with human immunodeficiency virus type 1 (HIV-1) is one of the most challenging aspects of HIV medicine. Antiretroviral therapy (ART) must be started during treatment for tuberculosis, 1 , 2 yet starting ART very early in the course of tuberculosis therapy increases the pill burden, the potential drug toxicity, and the risk of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS). 3 , 4 For these reasons, programs, providers, and patients are reluctant to initiate ART during the intensive 8-week induction phase of tuberculosis therapy, when the pill burden and toxicity of tuberculosis medications are greatest. . . .