Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

A retrospective study of survival and risk factors for mortality among people living with HIV who received antiretroviral treatment in a resource-limited setting.

BACKGROUND: The availability and accessibility of effective antiretroviral therapy (ART) for people living with HIV (PLWH) has substantially improved in the past two decades in resource-limited settings. Therefore, evaluation of survival is needed in the current setting. METHOD: We retrospectively analyzed secondary data of the national AIDS program database from national health security region number 4 among PLWH who were ART-naive between January 2014 and December 2018. All PLWH were followed until December 2019 to evaluate their survival status and possible risk factors related to death. RESULTS: A total of 42,229 PLWH were identified, of which 14,053 were ART-naive and thus enrolled in the study. Sixty-seven percent were male, the mean ± SD age was 35 ± 12 years, and the median (IQR) baseline CD4 count was 162 (44-353) cells/mm3. Regarding medical care benefits, 46% had a universal health coverage scheme, 34% had a national social security scheme, and 2% had a civil servants medical benefit scheme. A total of 2142 (15%) mortalities occurred during the total follow-up period of 28,254 patient-years. The mortality rate was 7.5 (95% CI 7.2-7.9) per 100 person-years. Survival rates at 1, 2, 3, 4 and 5 years after HIV registration were 88.2% (95% CI 87.6-88.7%), 85.3% (95% CI 84.6-85.9%), 82.9% (95% CI 81.9-83.4%), 81.3% (95% CI 80.5-82.0%) and 75.1% (95% CI 73.5-76.8%), respectively. The Cox proportional hazards model showed that all-cause mortality was associated with a history of ART switching (HR = 7.06, 95% CI 4.53-11.00), major opportunistic infections during ART (HR = 1.93, 95% CI 1.35-2.77), baseline CD4 count ≤ 200 vs. > 500 cells/mm3 (HR = 4.00, 95% CI 1.45-11.11), age ≥ 50 vs. < 30 years (HR = 1.77, 95% CI 1.12-2.78), and receiving nevirapine-based regimens(HR = 1.43, 95% CI 1.04-1.97). CONCLUSIONS: This study demonstrated the substantial mortality rate over the consecutive 5 years of the follow-up period among PLWH who received ART in a resource-limited setting. Early case finding and prompt initiation of ART as well as continuous HIV care are a cornerstone to improve survival.