Purpose of Review The need for better drugs to treat patients with Chagas disease remains urgent. This review summarizes the advancements in drug development over the past two years. Recent Findings Drug development efforts are almost exclusively occurring as preclinical research. The exceptions being Phase I safety studies for the cruzain inhibitor, K-777, and potential Phase II studies for the antifungal drug, posaconazole, and a prodrug of ravuconazole. Several recent laboratory investigations demonstrate anti-T. cruzi activity of novel small molecules in animal models. These include nonpeptidic cruzain inhibitors, novel inhibitors of the sterol 14α-demethylase enzyme, new compounds (arylimidamides) related to pentamidine, derivatives of nifurtimox, compounds using ruthenium complexes, and several natural products. The recent implementation of a high-throughput screen of >300,000 compounds against intracellular T. cruzi amastigotes done at the Broad Institute is an important development, yielding ~300 selective inhibitors, many of which may serve as leads for medicinal chemistry efforts. Summary Progress is slow, but recent advancements in both drug development and advocacy for research on neglected diseases are encouraging. Efforts to define a target product profile and to harmonize methodologies for testing drugs for Chagas disease are described herein.

A case of false-negative serum latex agglutination cryptococcal antigen (CRAG) test in a 45-year-old HIV-positive male with Cryptococcus-positive culture is described. The patient was presented to a hospital in Botswana, with breathlessness and a diffuse papular rash. His CD4 count was 25 cells/μL. Despite the suspicion for disseminated cryptococcal disease, an initial serum CRAG latex test was negative. Results of subsequent Indian ink staining, culture of cerebrospinal fluid and skin scrapings, and serum lateral flow immunoassay (LFA) were all positive for Cryptococcus neoformans. There are several possible explanations for the false-negative CRAG latex test. Given the positive LFA result, we speculate that disease may have been caused by Cryptococcus gattii, which is estimated to be responsible for between 15% and 30% of all cryptococcal diseases in Botswana. Reduced sensitivity of CRAG latex assays for detecting C gattii may lead to underdiagnosis of cryptococcal infection.

Background The MOD Clinic in Seattle, Washington provides walk-in primary care for people with HIV who are incompletely engaged in standard care. Methods We evaluated HIV outcomes among patients enrolled in the MOD Clinic (within group analysis) and, separately, among MOD patients vs. patients who were MOD-eligible but did not enroll (comparison group analysis) during 1/1/2018-9/30/2021. The primary outcome was viral suppression (VS; viral load <200 copies/mL); secondary outcomes care engagement (≥ 2 visits ≥60 days apart) and sustained VS (≥2 consecutive suppressed viral loads ≥60 days apart). In the within group analysis, we examined outcomes at time of MOD enrollment vs. 12 months post-enrollment. In the comparison group analysis, we examined outcomes at the time of MOD eligibility vs. 12 months post-eligibility. Both analyses used modified Poisson regression. Results Most patients in MOD (N = 213) were unstably housed (52%) and had psychiatric comorbidities (86%) or hazardous substance use (81%). Among patients enrolled ≥12 months (N = 164), VS did not increase significantly from baseline to post-enrollment (63% to 71%, p = 0.11), but care engagement and sustained VS both improved (37% to 86%, p < 0.001; and 20% to 53%, p < 0.001, respectively) from pre-enrollment to 12 months post-enrollment. In the comparison group analysis, VS worsened in non-enrolled patients (N = 517) from baseline to 12-months post-eligibility (82% to 75%, p < 0.001). MOD patients who met criteria for the comparison group analysis (N = 68) were more likely than non-enrolled patients to be engaged in care at 12 months post-eligibility (RR 1.29; 95% CI 1.03-1.63). Conclusions MOD Clinic enrollment was associated with improved engagement in care. This model adds to the spectrum of differentiated HIV care services.