Introduction: There are positive aspects regarding the prescribing of fixed dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower- and middle-income countries (LMICs) which have the greatest prevalence of both infectious and noninfectious diseases and issues of affordability. Areas covered: Review of potential advantages, disadvantages, cost-effectiveness, and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where there are concerns with their value. Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates, and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis, and hypertension are valued and listed in the country’s essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which are being addressed.

Data to inform the switch from a ritonavir-boosted protease inhibitor (PI) to dolutegravir in patients living with human immunodeficiency virus (HIV) infection who do not have genotype information and who have viral suppression with second-line therapy containing a ritonavir-boosted PI have been limited. In a prospective, multicenter, open-label trial conducted at four sites in Kenya, we randomly assigned, in a 1:1 ratio, previously treated patients without genotype information who had viral suppression while receiving treatment containing a ritonavir-boosted PI to either switch to dolutegravir or continue the current regimen. The primary end point was a plasma HIV type 1 RNA level of at least 50 copies per milliliter at week 48, assessed on the basis of the Food and Drug Administration snapshot algorithm. The noninferiority margin for the between-group difference in the percentage of participants who met the primary end point was 4 percentage points. Safety up to week 48 was assessed. A total of 795 participants were enrolled, with 398 assigned to switch to dolutegravir and 397 assigned to continue taking their ritonavir-boosted PI; 791 participants (397 in the dolutegravir group and 394 in the ritonavir-boosted PI group) were included in the intention-to-treat exposed population. At week 48, a total of 20 participants (5.0%) in the dolutegravir group and 20 (5.1%) in the ritonavir-boosted PI group met the primary end point (difference, -0.04 percentage points; 95% confidence interval, -3.1 to 3.0), a result that met the criterion for noninferiority. No mutations conferring resistance to dolutegravir or the ritonavir-boosted PI were detected at the time of treatment failure. The incidence of treatment-related grade 3 or 4 adverse events was similar in the dolutegravir group and the ritonavir-boosted PI group (5.7% and 6.9%, respectively). In previously treated patients with viral suppression for whom there were no data regarding the presence of drug-resistance mutations, dolutegravir treatment was noninferior to a regimen containing a ritonavir-boosted PI when the patients were switched from a ritonavir-boosted PI-based regimen. (Funded by ViiV Healthcare; 2SD ClinicalTrials.gov number, NCT04229290.).

Objectives To assess outcomes of patients admitted to hospital with COVID-19 and to determine the predictors of mortality. Setting This study was conducted in six facilities, which included both government and privately run secondary and tertiary level facilities in the central and coastal regions of Kenya. Participants We enrolled 787 reverse transcriptase-PCR-confirmed SARS-CoV2-infected persons. Patients whose records could not be accessed were excluded. Primary and secondary outcome measures The primary outcome was COVID-19-related death. We used Cox proportional hazards regressions to determine factors related to in-hospital mortality. Results Data from patients with 787 COVID-19 were available. The median age was 43 years (IQR 30–53), with 505 (64%) being men. At admission, 455 (58%) were symptomatic with an additional 63 (9%) developing clinical symptoms during hospitalisation. The most common symptoms were cough (337, 43%), loss of taste or smell (279, 35%) and fever (126, 16%). Comorbidities were reported in 340 (43%), with cardiovascular disease, diabetes and HIV documented in 130 (17%), 116 (15%), 53 (7%), respectively. 90 (11%) were admitted to the Intensive Care Unit (ICU) for a mean of 11 days, 52 (7%) were ventilated with a mean of 10 days, 107 (14%) died. The risk of death increased with age (HR 1.57 (95% CI 1.13 to 2.19)) for persons >60 years compared with those <60 years old; having comorbidities (HR 2.34 (1.68 to 3.25)) and among men (HR 1.76 (1.27 to 2.44)) compared with women. Elevated white cell count and aspartate aminotransferase were associated with higher risk of death. Conclusions The risk of death from COVID-19 is high among older patients, those with comorbidities and among men. Clinical parameters including patient clinical signs, haematology and liver function tests were associated with risk of death and may guide stratification of high-risk patients.

Background More than 49,000 cases of infection and 900 deaths from COVID-19 have been recorded in the Kenya. However, the characteristics and risk factors for severe outcomes among hospitalized COVID-19 patients in this setting have not been described. Methods We extracted demographic, laboratory, clinical and outcome data from medical records of RT-PCR confirmed SARS-CoV2 patients admitted in six hospitals in Kenya between March and September, 2020. We used Cox proportional hazards regressions to determine factors related to in-hospital mortality. Results Data from 787 COVID-19 patients was available. The median age was 43 years (IQR 30-53), with 505 (64%) males. At admission, 455 (58%) were symptomatic. The commonest symptoms were cough (337, 43%), loss of taste or smell (279, 35%), and fever (126, 16%). Co-morbidities were reported in 340 (43%), with cardiovascular disease, diabetes and HIV documented in 130 (17%), 116 (15%), 53 (7%) respectively. 90 (11%) were admitted to ICU for a mean of 11 days, 52 (7%) were ventilated with a mean of 10 days, 107 (14%) died. The risk of death increased with age [hazard ratio (HR) 1.57 (95% CI 1.13 – 2.19)] for persons >60 years compared to those <60 years old; having co-morbidities [HR 2.34 (1.68 – 3.25)]; and among males [HR 1.76 (1.27, 2.44)] compared to females. Elevated white blood cell count and aspartate aminotransferase were associated with higher risk of death. Conclusions We identify the risk factors for mortality that may guide stratification of high risk patients.

Among 777 virally suppressed adults with human immunodeficiency virus on protease-inhibitor–based second-line antiretroviral regimens randomized 1:1 to switch to dolutegravir or remain on a protease inhibitor, there was no difference in incident hypertension (12% in each arm, P = .868) or change in blood pressure over the 48-week study period.

This study aimed to conduct an epidemiological and genomic investigation of a hospital outbreak of Candida auris, and implement measures for its control. We collected demographic and clinical data from medical records of patients with C. auris from January 2017 to June 2019 after identifying increased cases in April 2019. Point-prevalence surveys for C. auris colonisation were conducted in the critical care units (CCU). Antifungal susceptibility testing and genomic sequencing of isolates were performed. A bundle of infection prevention and control measures was instituted. Thirty-two patients with C. auris were identified. All patients had a history of CCU admission. A total of 283 screening swabs were obtained and 57 isolates of C. auris identified. Antifungal susceptibility testing was performed on 48 isolates. All but two isolates were resistant to fluconazole; one isolate was also resistant to amphotericin B. Forty-one of 46 isolate genomes were clonally related and formed a distinct genetic cluster in Clade III. C. auris colonisation reduced from 42% in June 2019 to 1% in August 2019, and no new hospital-acquired colonisation was identified in the subsequent 9 months. We identified a new genetic subcluster of Clade III C. auris. We also show that strict implementation of infection prevention measures can lead to substantial reductions in C. auris transmission.