Cryptococcal meningitis (CM) is a leading cause of mortality among HIV-infected individuals in Africa. Poor outcomes from conventional antifungal therapies, unavailability of flucytosine, and difficulties administering 14 days of amphotericin B are key drivers of this mortality. Novel treatment regimes are needed. This study examines whether short-course high-dose liposomal amphotericin B (AmBisome), given with high dose fluconazole, is non-inferior (in terms of microbiological and clinical endpoints) to standard-dose 14-day courses of AmBisome plus high dose fluconazole for treatment of HIV-associated CM. This is an adaptive open-label phase II/III randomised non-inferiority trial comparing alternative short course AmBisome regimens. Step 1 (phase II) will compare four treatment arms in 160 adult patients (≥18 years old) with a first episode of HIV-associated CM, using early fungicidal activity (EFA) as the primary outcome: 1) AmBisome 10 mg/kg day one (single dose); 2) AmBisome 10 mg/kg day one and AmBisome 5 mg/kg day three (two doses); 3) AmBisome 10 mg/kg day one, and AmBisome 5 mg/kg days three and seven (three doses); and 4) AmBisome 3 mg/kg/d for 14 days (control); all given with fluconazole 1200 mg daily for 14 days. STEP 2 (phase III) will enrol 300 participants and compare two treatment arms using all-cause mortality within 70 days as the primary outcome: 1) the shortest course AmBisome regimen found to be non-inferior in terms of EFA to the 14-day control arm in STEP 1, and 2) AmBisome 3 mg/kg/d for 14 days (control), both given with fluconazole 1200 mg daily for 14 days. STEP 2 analysis will include all patients from STEP 1 and STEP 2 taking the STEP 2 regimens. All patients will be followed for ten weeks, and mortality and safety data recorded. All patients will receive consolidation therapy with fluconazole 400–800 mg daily and ART in accordance with local guidelines. The primary analysis (for both STEP 1 and STEP 2) will be intention-to-treat. ISRCTN10248064. Date of Registration: 22 January 2014

Background. Policy changes are often necessary to contain the detrimental impact of epidemics such as those brought about by coronavirus disease (COVID‐19). In the earlier phases of the emergence of COVID‐19, China was the first to impose strict restrictions on movement (lockdown) on January 23rd, 2020. A strategy whose effectiveness in curtailing COVID‐19 was yet to be determined. We, therefore, sought to study the impact of the lockdown in reducing the incidence of COVID‐19. Methods. Daily cases of COVID‐19 that occurred in China which were registered between January 12th and March 30th, 2020, were extracted from the Johns Hopkins CSSE team COVID‐19 ArcGIS® dashboards. Daily cases reported were used as data points in the series. Two interrupted series models were run: one with an interruption point of 23 January 2020 (model 1) and the other with a 14‐day deferred interruption point of 6th February (model 2). For both models, the magnitude of change (before and after) and linear trend analyses were measured, and β‐coefficients reported with 95% confidence interval (CI) for the precision. Results. Seventy‐eight data points were used in the analysis. There was an 11% versus a 163% increase in daily cases in models 1 and 2, respectively, in the preintervention periods (p ≤ 0.001). Comparing the period immediately following the intervention points to the counterfactual, there was a daily increase of 2,746% (p < 0.001) versus a decline of 207% (p = 0.802) in model 2. However, in both scenarios, there was a statistically significant drop in the daily cases predicted for this data and beyond when comparing the preintervention periods and postintervention periods (p < 0.001). Conclusion. There was a significant decrease the COVID‐19 daily cases reported in China following the institution of a lockdown, and therefore, lockdown may be used to curtail the burden of COVID‐19.

Exposure to combination antiretroviral therapy (cART) is associated with the development of diabetes mellitus related comorbidities (DRCs). This study aims to: (i) estimate the incidence of DRCs among cART recipients, (ii) assess the time-to-event (development of DRC) and, (iii) compare survival function between recipients on first-line regimen and those on second-, third-line cART regimen. The incidence of DRCs was 26.8/1000 person-years, with total time of exposure of 3316 person-years. The average time to event for all the three regimens was 11.72 ± 0.20 years. The first-line cART regimen had a shorter mean ± SE of 10.59 ± 0.26 years to the event compared to 12.69 ± 0.24 years for the second-, third-line cART regimen. Recipients on the first-line had a shorter survival than recipients on second-, third-line cART (Log-rank X2 = 8.98, p < 0.003). Data from this study showed that the risk of developing DRCs per year of exposure was significantly greater for patients on first-line compared to those who were on second-, third-line regimen; which, suggests that monitoring of cART long-term side effects and regular reviewing of cART regimens is important. Meticulous selection of drug combinations is a key to improving recipients’ survival.

Drug-resistant tuberculosis (DR-TB) poses a significant global health challenge and requires treatment with potentially toxic second-line anti-TB drugs. Assessing the health-related quality of life (HRQoL) of DR-TB patients is crucial, given the impact of disease and treatment on their well-being. This study aimed to evaluate HRQoL among DR-TB patients undergoing treatment in Botswana and identify predictors of variability during the treatment period. A cross-sectional study involving almost all the eligible clients in the DR-TB treatment database was conducted at four of the six DR-TB sites in Botswana. The SF-36v2-based questionnaire was administered to all patients receiving treatment between March 2022 and June 2023. Data analysis was performed with QualityMetric Inc., LLC PRO CoRE scoring software and Stata 13.1 for the HRQoL scoring and regression analyses, respectively. A score ≤ 47 on the norm-based scoring (NBS) indicated poor HRQoL. Shorter, all-oral DR-TB regimens were introduced since 2018 but Botswana had not yet fully implemented those in the years 2022/2023. Patients had to go on treatment for 18–24 months during the time of the study. Seventy-two of the 81 eligible participants were enrolled. Participants on treatment for 13–24 months exhibited better HRQoL scores (53.3 ± 8.4) than those in the initial (0–12 months, 46.9 ± 10.8) and latter phases of treatment (> 24 months, 44.3 ± 10.1) for the Physical Component Summary (PCS) even though it was not statistically significant (p = 0.0996). The mental component summary (MCS) scores were 41.6 ± 11.3, 51.6 ± 7.8, and 41.3 ± 10.7 for 0–12, 13–24, and > 24 months, respectively, with significant differences observed for the MCS (p = 0.0097). Multivariate analysis identified renal impairment as a predictor of PCS variability, while alcohol consumption, prior TB treatment, and lung cavity on chest X-ray imaging predicted MCS variability. DR-TB patients in Botswana demonstrated comparable or improved HRQoL (> 47 NBS) in their second year (13–24 months) of treatment, contrasting with poorer HRQoL scores in the initial and final years for both the PCS and MCS. The findings underscore the necessity for tailored psychosocial support, advocated for its integration into the Botswana National TB Program as a pilot initiative before widespread implementation.

Combination antiretroviral therapy (cARTs) regiments are known to prolong the recipients’ life even though they are risk factors for diabetes mellitus-related comorbidities (DRCs). We sought to: (i) examine cART relationship with DRCs among patients attending HIV clinics in Gaborone, Botswana (which cART regimens are associated with shorter/longer time to the event), (ii) characterize patients’ underlying biomedical and demographic risk factors of DRC and identify the most important, (iii) investigate survival of patients on different cART regimens in the presence of these risk factors. Data from two major HIV clinics in Botswana were reviewed. Relationships between different cART regimens and DRCs were investigated among 531 recipients. Recipients’ DRC risk factors were identified. Cox regression model was run. Unadjusted and adjusted hazard ratios were computed, and hazard and survival functions for different cART regimens were plotted. Major findings were: patients on second- and third-line cART were less likely to develop DRCs earlier than those on first-line cART. Patients with CD4 count ≤ 200 cells/mm3 at cART initiation were more likely to develop DRCs earlier than those who had CD4 count > 200 cells/mm3. Overweight patients at cART initiation had a higher risk of developing DRCs earlier than those who had normal body mass index. Males had a lower risk of developing DRCs earlier than females. The risk of new onset of DRC among cART recipients is a function of the type of cART regimen, duration of exposure and patients’ underlying biomedical and demographic DRC risk factors. The study has provided a survival model highlighting DRCs’ significant prognostic factors to guide clinical care, policy and management of recipients of cARTs. Further studies in the same direction will likely improve the survival to the development of DRC of every cART recipient in this community.

BackgroundPolicy changes are often necessary to contain the detrimental impact of epidemics such as the coronavirus disease (COVID-19). China imposed strict restrictions on movement on January 23^rd, 2020.Interrupted time series methods were used to study the impact of the lockdown on the incidence of COVID-19. MethodsThe number of cases of COVID-19 reported daily from January 12^thto March 30^th, 2020 were extracted from the World Health Organization (WHO) COVID-19 dashboard ArcGIS® and matched to China’s projected population of 1 408 526 449 for 2020 in order to estimate daily incidences. Data were plotted to reflect daily incidences as data points in the series. A deferred interruption point of 6^thFebruary was used to allow a 14-day period of diffusion. The magnitude of change and linear trend analyses were evaluated using the itsafunction with ordinary least-squares regression coefficients in Stata® yielding Newey-West standard errors.ResultsSeventy-eight (78) daily incidence points were used for the analysis, with 11(14.10%) before the intervention. There was a daily increase of 163 cases (β=1.16*10^-07, p=0.00) in the pre-intervention period. Although there was no statistically significant drop in the number of cases reported daily in the immediate period following 6^thFebruary 2020 when compared to the counterfactual (p=0.832), there was a 241 decrease (β=-1.71*10^-07, p=0.00) in cases reported daily when comparing the pre-intervention and post-intervention periods. A deceleration of 78(47%) cases reported daily. ConclusionThe lockdown policy managed to significantly decrease the incidence of CoVID-19 in China. Lockdown provides an effective means of curtailing the incidence of COVID-19.