Maja Kiselinova

Background: The Xpert assay has revolutionized the rapid detection of resistance to rifampicin. However, Xpert has its pitfalls. We explored potential determinants of false-positive rifampicin resistance when using Xpert, aiming to refine the precision of tuberculosis diagnostics and subsequently contribute to better patient outcomes. Methods: This is a retrospective cross-sectional analysis of archived Xpert files from the South Kivu province, used to diagnose Mycobacterium tuberculosis (MTB) between 2013 and 2018. Xpert cycle threshold was extracted for each molecular beacon probe, and ΔCt was calculated. We used the MTBDRplus line-probe assay, which covers the same 81-bp RRDR, as a reference test. Results: Of 1900 samples positive for MTB, 220 (11.2%) were rifampicin resistant. Of the 141 patients' sputum samples that had results for both Xpert and MTBDRplus, 45 (31.9%) showed discordant results with Xpert, indicating rifampicin resistance while MTBDRplus indicated rifampicin susceptibility, suggesting false-positive rifampicin resistance detection by Xpert, predominantly in samples with very low (Ct > 28, odds ratio [OR] = 2.23, 95% CI: 1.30–3.82) or low (Ct 22–28, OR = 1.81, 95% CI: 1.21–2.71) bacterial loads. Probe E was the most frequently missed probe, followed by multiple probe dropouts or absence of probe binding (OR = 1.5, 95% CI: .731–3.076). Conclusions: Our findings indicate that low and very low MTB bacterial loads in sputum are strongly associated with discordant rifampicin resistance results when using Xpert. Further research into underlying mechanisms is needed to establish causality definitively.

Reducing the number of active compounds for lifelong human immunodeficiency virus (HIV) treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control support the robustness and safety of 2DR (2-drug regimen) antiretroviral therapy compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts, and sustained immunological control. The RUMBA study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable second-generation integrase strand transfer inhibitor-based 3DR regimen with HIV-1 RNA < 50 copies/mL plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, n = 89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, n = 45). After 48 weeks, virological, immunological, and metabolic parameters were evaluated. We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4⁺ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in proinflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens. This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription, and inflammatory markers. NCT04553081.

Extrapulmonary nontuberculous mycobacterial (NTM) disease remains largely enigmatic, yet these mycobacteria are increasingly acknowledged as important opportunistic pathogens in humans. Traditionally, NTM infections have been identified across various anatomical locations, with the respiratory system being the most affected and best understood. Historically, extrapulmonary NTM infection was predominantly associated with HIV/AIDS, with Mycobacterium avium lymphadenopathy being the most commonly reported. Today, however, because of the expanding utilization of immunosuppressive therapies and the demographic shift towards an aging population, an increasing number of NTM infections are expected and seen. Hence, a heightened index of suspicion is essential, necessitating a multifaceted approach to identification and drug sensitivity testing to improve treatment outcomes. In extrapulmonary NTM management, expert consultation is strongly recommended to determine the most efficacious treatment regimen, as individualized, patient-tailored therapies are often required. Furthermore, the economic burden of NTM disease is considerable, accompanied by high rates of hospitalization. To optimize the management of these intricate infections, there is an urgent need for comprehensive data on incidence, prevalence, and outcomes. This case-based series delves into the intricate nature of extrapulmonary NTM infections, focusing on both rapid and slow-growing NTM species, and explores therapeutic options, resistance mechanisms, and host-related immunological factors.

Toxoplasma gondii, an obligate intracellular parasitic protozoon, usually causes a mild, acute infection followed by a latent asymptomatic phase with tissue cysts or a chronic form with recurrent retinochoroiditis. However, immunocompromised patients can cause disseminated disease due to the reactivation of the latent tissue cysts or due to a primary infection. Here, we present a rare case of bilateral ocular toxoplasmosis and concurrent subacute toxoplasma encephalitis in a 70-year-old patient on anti-CD40 treatment following his liver transplant. The diagnosis was confirmed by PCR of anterior chamber fluid and brain biopsy, and no other sites of disseminated disease were detected on PET-CT. The patient has been treated with sulfamethoxazole-trimethoprim 800/160mg with virtually complete resolution of the neurological and ocular symptoms. Iatrogenic blockade of the CD40 pathway may elicit a particular susceptibility for CNS reactivation of T. gondii.