Revisiting COVID-19 policies: 10 evidence-based recommendations for where to go from here.

BACKGROUND: Strategies to control coronavirus 2019 disease (COVID-19) have often been based on preliminary and limited data and have tended to be slow to evolve as new evidence emerges. Yet knowledge about COVID-19 has grown exponentially, and the expanding rollout of vaccines presents further opportunity to reassess the response to the pandemic more broadly. MAIN TEXT: We review the latest evidence concerning 10 key COVID-19 policy and strategic areas, specifically addressing: 1) the expansion of equitable vaccine distribution, 2) the need to ease restrictions as hospitalization and mortality rates eventually fall, 3) the advantages of emphasizing educational and harm reduction approaches over coercive and punitive measures, 4) the need to encourage outdoor activities, 5) the imperative to reopen schools, 6) the far-reaching and long-term economic and psychosocial consequences of sustained lockdowns, 7) the excessive focus on surface disinfection and other ineffective measures, 8) the importance of reassessing testing policies and practices, 9) the need for increasing access to outpatient therapies and prophylactics, and 10) the necessity to better prepare for future pandemics. CONCLUSIONS: While remarkably effective vaccines have engendered great hope, some widely held assumptions underlying current policy approaches call for an evidence-based reassessment. COVID-19 will require ongoing mitigation for the foreseeable future as it transforms from a pandemic into an endemic infection, but maintaining a constant state of emergency is not viable. A more realistic public health approach is to adjust current mitigation goals to be more data-driven and to minimize unintended harms associated with unfocused or ineffective control efforts. Based on the latest evidence, we therefore present recommendations for refining 10 key policy areas, and for applying lessons learned from COVID-19 to prevent and prepare for future pandemics.

The economic returns of ending the AIDS epidemic as a public health threat.

BACKGROUND: In 2016, countries agreed on a Fast-Track strategy to "end the AIDS epidemic by 2030". The treatment and prevention components of the Fast-Track strategy aim to markedly reduce new HIV infections, AIDS-related deaths and HIV-related discrimination. This study assesses the economic returns of this ambitious strategy. METHODS: We estimated the incremental costs, benefits and economic returns of the Fast-Track scenario in low- and middle-income countries, compared to a counterfactual defined as maintaining coverage of HIV-related services at 2015 levels. The benefits are calculated using the full-income approach, which values both the changes in income and in mortality, and the productivity approach. FINDINGS: The incremental costs of the Fast-Track scenario over the constant scenario for 2017-2030 represent US$86 billion or US$13.69 per capita. The full-income valuation of the incremental benefits of the decrease in mortality amounts to US$88.14 per capita, representing 6.44 times the resources invested for all countries. These returns on investment vary by region, with the largest return in the Asia-Pacific region, followed by Eastern and Southern Africa. Returns using the productivity approach are smaller but ranked similarly across regions. INTERPRETATION: In all regions, the economic and social value of the additional life-years saved by the Fast-Track approach exceeds its incremental costs, implying that this strategy for ending the AIDS epidemic is a sound economic investment.

Epidemiological metrics and benchmarks for a transition in the HIV epidemic.

Peter Godfrey-Faussett and colleagues present six epidemiological metrics for tracking progress in reducing the public health threat of HIV.

Mutual HIV status disclosure is associated with consistent condom use in public sector ART clients in Free State province, South Africa: a short report.

Risky sexual behaviour in PLWHA on antiretroviral therapy threatens both prevention and treatment efforts, but disclosure promises to support safer sexual practices. This paper investigates the association between HIV self-disclosure and consistent condom use in a cohort of public sector patients on antiretroviral (ARV) treatment. Using data from the FEATS cohort study, logistic regression analysis shows that knowledge of your partner's HIV status is positively associated with consistent condom use (OR 2.73, 95% CI 1.37-5.43, p = 0.004) and so too mutual HIV disclosure (OR 3.38, 95% CI 1.60-7.18, p = 0.001). Prevention and treatment programmes, through couple HIV counselling and testing (CHCT) and other assistance programmes, should focus on supporting the mutual disclosure of HIV status among PLWHA on ARV treatment.

Evidence for scaling up HIV treatment in sub-Saharan Africa: A call for incorporating health system constraints.

Jan Hontelez and colleagues argue that the cost-effectiveness studies of HIV treatment scale-up need to include health system constraints to be more informative.

Multi-country analysis of treatment costs for HIV/AIDS (MATCH): facility-level ART unit cost analysis in Ethiopia, Malawi, Rwanda, South Africa and Zambia.

BACKGROUND: Today's uncertain HIV funding landscape threatens to slow progress towards treatment goals. Understanding the costs of antiretroviral therapy (ART) will be essential for governments to make informed policy decisions about the pace of scale-up under the 2013 WHO HIV Treatment Guidelines, which increase the number of people eligible for treatment from 17.6 million to 28.6 million. The study presented here is one of the largest of its kind and the first to describe the facility-level cost of ART in a random sample of facilities in Ethiopia, Malawi, Rwanda, South Africa and Zambia. METHODS & FINDINGS: In 2010-2011, comprehensive data on one year of facility-level ART costs and patient outcomes were collected from 161 facilities, selected using stratified random sampling. Overall, facility-level ART costs were significantly lower than expected in four of the five countries, with a simple average of $208 per patient-year (ppy) across Ethiopia, Malawi, Rwanda and Zambia. Costs were higher in South Africa, at $682 ppy. This included medications, laboratory services, direct and indirect personnel, patient support, equipment and administrative services. Facilities demonstrated the ability to retain patients alive and on treatment at these costs, although outcomes for established patients (2-8% annual loss to follow-up or death) were better than outcomes for new patients in their first year of ART (77-95% alive and on treatment). CONCLUSIONS: This study illustrated that the facility-level costs of ART are lower than previously understood in these five countries. While limitations must be considered, and costs will vary across countries, this suggests that expanded treatment coverage may be affordable. Further research is needed to understand investment costs of treatment scale-up, non-facility costs and opportunities for more efficient resource allocation.

A novel approach to accounting for loss to follow-up when estimating the relationship between CD4 Count at ART initiation and mortality.

BACKGROUND: While CD4 strongly predicts mortality on antiretroviral therapy (ART), estimates from programmatic data suffer from incomplete patient outcomes. METHODS: We conducted a pooled analysis of one-year mortality data on ART accounting for lost patients. We identified articles reporting one-year mortality by ART initiation CD4 count. We estimated the average mortality among those lost as the value that maximizes the fit of a regression of the natural log of mortality on the natural log of the imputed mean CD4 count in each band. RESULTS: We found 20 studies representing 64,426 subjects and 51 CD4 observations. Without correcting for losses, one-year mortality was >4.8% for all CD4 counts <200 cells/mm(3). When searching over different values for mortality among those lost, the best fitting model occurs at 60% mortality. In this model, those with a CD4≤200 had a one-year mortality above 8.7, while those with a CD4>500 had a one-year mortality <6.8%. Comparing those starting ART at 500 vs. 50, one-year mortality risk was reduced by 54% (6.8 vs. 12.5%). Regardless of CD4 count, mortality was substantially higher than when assuming no mortality among those lost, ranging from a 23-94% increase. CONCLUSIONS: Our best fitting regression estimates that every 10% increase in CD4 count at initiation is associated with a 2.8% decline in one-year mortality, including those lost. Our study supports the health benefits of higher thresholds for CD4 count initiation and suggests that reports of programmatic ART outcomes can and should adjust results for mortality among those lost.

HIV treatment as prevention: modelling the cost of antiretroviral treatment--state of the art and future directions.

Policy discussions about the feasibility of massively scaling up antiretroviral therapy (ART) to reduce HIV transmission and incidence hinge on accurately projecting the cost of such scale-up in comparison to the benefits from reduced HIV incidence and mortality. We review the available literature on modelled estimates of the cost of providing ART to different populations around the world, and suggest alternative methods of characterising cost when modelling several decades into the future. In past economic analyses of ART provision, costs were often assumed to vary by disease stage and treatment regimen, but for treatment as prevention, in particular, most analyses assume a uniform cost per patient. This approach disregards variables that can affect unit cost, such as differences in factor prices (i.e., the prices of supplies and services) and the scale and scope of operations (i.e., the sizes and types of facilities providing ART). We discuss several of these variables, and then present a worked example of a flexible cost function used to determine the effect of scale on the cost of a proposed scale-up of treatment as prevention in South Africa. Adjusting previously estimated costs of universal testing and treatment in South Africa for diseconomies of small scale, i.e., more patients being treated in smaller facilities, adds 42% to the expected future cost of the intervention.

Taking ART to scale: determinants of the cost and cost-effectiveness of antiretroviral therapy in 45 clinical sites in Zambia.

BACKGROUND: We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ). METHODS: We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years. RESULTS: The program cost $69.7 million for 125,436 person-years of ART, or $556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector. CONCLUSIONS AND SIGNIFICANCE: The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.

The economics of effective AIDS treatment in Thailand.

INTRODUCTION: The speed with which Thailand has scaled up public provision of antiretroviral therapy (ART) has been unprecedented, with more than 80 000 individuals on treatment at the end of 2006 through Thailand's National Access to Antiretroviral Program for People Living with HIV/AIDS (NAPHA). This paper projects the cost effectiveness, the affordability and the future fiscal burden of NAPHA to the government of Thailand under several different policy scenarios until the year 2025. METHODS: An economic/epidemiological model of access to ART was constructed, and this composite model was calibrated to economic and epidemiological data from Thailand and other countries. The economic model adopts the conditional logit specification of demand allocation across multiple treatment modes, and the epidemiological model is a deterministic difference-equation model fitted to the cumulated data on HIV incidence in each risk group. RESULTS: The paper estimates that under 2005 prices NAPHA will save life-years at approximately US$736 per life-year saved with first-line drugs alone and for approximately US$2145 per life-year if second-line drugs are included. Enhancing NAPHA with policies to recruit patients soon after they are first eligible for ART or to enhance their adherence would raise the cost per life-year saved, but the cost would be small per additional life-year saved, and is therefore justifiable. The fiscal burden of a policy including second as well as first-line drugs would be substantial, rising to 23% of the total health budget by 2014, but the authors judge this cost to be affordable given Thailand's strong overall economic performance. The paper estimates that a 90% reduction in the future cost of second-line therapy by the exercise of Thailand's World Trade Organization authority to issue compulsory licences would save the government approximately US$3.2 billion to 2025 and reduce the cost of NAPHA per life-year saved from US$2145 to approximately US$940.

HIV prevention costs and program scale: data from the PANCEA project in five low and middle-income countries.

BACKGROUND: Economic theory and limited empirical data suggest that costs per unit of HIV prevention program output (unit costs) will initially decrease as small programs expand. Unit costs may then reach a nadir and start to increase if expansion continues beyond the economically optimal size. Information on the relationship between scale and unit costs is critical to project the cost of global HIV prevention efforts and to allocate prevention resources efficiently. METHODS: The "Prevent AIDS: Network for Cost-Effectiveness Analysis" (PANCEA) project collected 2003 and 2004 cost and output data from 206 HIV prevention programs of six types in five countries. The association between scale and efficiency for each intervention type was examined for each country. Our team characterized the direction, shape, and strength of this association by fitting bivariate regression lines to scatter plots of output levels and unit costs. We chose the regression forms with the highest explanatory power (R2). RESULTS: Efficiency increased with scale, across all countries and interventions. This association varied within intervention and within country, in terms of the range in scale and efficiency, the best fitting regression form, and the slope of the regression. The fraction of variation in efficiency explained by scale ranged from 26-96%. Doubling in scale resulted in reductions in unit costs averaging 34.2% (ranging from 2.4% to 58.0%). Two regression trends, in India, suggested an inflection point beyond which unit costs increased. CONCLUSION: Unit costs decrease with scale across a wide range of service types and volumes. These country and intervention-specific findings can inform projections of the global cost of scaling up HIV prevention efforts.

Antiretroviral therapy and HIV prevention in India: modeling costs and consequences of policy options.

OBJECTIVES: The objective of this study is to assess the costs, cost-effectiveness, and HIV epidemic impact of 3 antiretroviral therapy (ART) policy options. STUDY DESIGN: We constructed an epidemiologic model to predict the course of the HIV epidemic in the absence of expanded ART availability. Based on background studies of the willingness to pay for ART among patients with AIDS, of the costs to the government of the alternative treatment interventions, and of ART's likely effects on HIV transmission, we simulated the consequences of 3 possible alternative government ART policies. RESULTS: A program to reduce the negative consequences of the currently unstructured private-sector provision of ART is the most cost-effective of the 3 options at a 10% discount rate and least cost-effective at a 3% rate. The costs and cost-effectiveness of all options are highly sensitive to the effect of ART on condom use. CONCLUSION: The design of ART policy should capitalize on the potential of ART to decrease HIV transmission through institutional arrangements that reward effective prevention programs, thereby raising the likelihood that treatment has beneficial rather than negative external effects.

Will a global subsidy of new antimalarials delay the emergence of resistance and save lives?

Artemisinin-based combination treatments (ACTs) are seen as an important tool in the global effort to roll back malaria. With parasite resistance to chloroquine increasing rapidly in many parts of the world, there is greater recognition of the need for a globally coordinated strategy to ensure that artemisinins are not used as monotherapy, which has the potential to cut short their useful therapeutic life. We find that even a partial subsidy could delay the emergence of resistance and that a delay in implementing a subsidy for ACTs could facilitate the emergence of resistance and lower the economic value of ACTs.

Cost and efficiency of public sector sexually transmitted infection clinics in Andhra Pradesh, India.

BACKGROUND: Control of sexually transmitted infections (STIs) is an important part of the effort to reduce the risk of HIV/AIDS. STI clinics in the government hospitals in India provide services predominantly to the poor. Data on the cost and efficiency of providing STI services in India are not available to help guide efficient use of public resources for these services. METHODS: Standardised methods were used to obtain detailed cost and output data for the 2003-2004 fiscal year from written records and interviews in 14 government STI clinics in the Indian state of Andhra Pradesh. The economic cost per patient receiving STI treatment was calculated, and the variations of total and unit costs across the STI clinics analysed. Multivariate regression technique was used to estimate incremental unit costs. The optimal number of STIs that could be handled by the clinics was estimated. RESULTS: 18807 STIs were diagnosed and treated at the 14 STI clinics in fiscal year 2003-2004 (range 323-2784, median 1199). The economic cost of treating each STI varied 5-fold from Indian Rupees (INR) 225.5 ( 4.91 US dollars) to INR 1201.5 (26.15 US dollars) between 13 clinics, with one other clinic having a very high cost of INR 2478.5 (53.94 US dollars). The average cost per STI treated for all 14 clinics combined was INR 729.5 (15.88 US dollars). Personnel salaries made up 76.2% of the total cost. The number of STIs treated per doctor full-time equivalent and cost-efficiency for each STI treated had a significant direct non-linear relation (p < 0.001, R2 = 0.81; power function). With a multiple regression model, apart from the fixed costs, the incremental cost for each STI detected and cost of treatment was INR 55.57 (1.21 US dollars) and for each follow-up visit was INR 3.75 (0.08 US dollars). Based on estimates of optimal STI cases that could be handled without compromising quality by each doctor full-time equivalent available, it was projected that at 8 of the 14 clinics substantially more STI cases could be handled, which could increase the total STI cases treated at the 14 clinics combined by 38% at an additional cost of only 3.5% for service provision. CONCLUSION: There is un-utilised capacity in the public sector STI clinics in this Indian state. Efforts to facilitate utilisation of this capacity would be useful, as this would enable more poor patients with STIs to be served at minimal additional cost, and would also reduce the cost per STI treated leading to more efficient use of public resources.

Assessing the efficiency of HIV prevention around the world: methods of the PANCEA project.

OBJECTIVE: To develop data collection methods suitable to obtain data to assess the costs, cost-efficiency, and cost-effectiveness of eight types of HIV prevention programs in five countries. DATA SOURCES/STUDY SETTING: Primary data collection from prevention programs for 2002-2003 and prior years, in Uganda, South Africa, India, Mexico, and Russia. STUDY DESIGN: This study consisted of a retrospective review of HIV prevention programs covering one to several years of data. Key variables include services delivered (outputs), quality indicators, and costs. DATA COLLECTION/EXTRACTION METHODS: Data were collected by trained in-country teams during week-long site visits, by reviewing service and financial records and interviewing program managers and clients. PRINCIPAL FINDINGS: Preliminary data suggest that the unit cost of HIV prevention programs may be both higher and more variable than previous studies suggest. CONCLUSIONS: A mix of standard data collection methods can be successfully implemented across different HIV prevention program types and countries. These methods can provide comprehensive services and cost data, which may carry valuable information for the allocation of HIV prevention resources.

Impregnated nets or ddt residual spraying? Field effectiveness of malaria prevention techniques in solomon islands, 1993-1999.

The incidence of malaria in Solomon Islands has been decreasing since 1992. The control program used a combination of methods including DDT residual house spraying and insecticide-treated mosquito nets. To determine how much each method contributed to malaria control, data were analyzed on monthly incidence and on control activities for 41 of 110 malaria zones over the same time period (January 1993 to August 1999). After correction for endogeneity, then spraying, insecticide treatment of nets, and education about malaria are all independently associated with reduction in incident cases of malaria or fever, while larviciding with temephos is not. The evidence suggests that although impregnated bed nets cannot entirely replace DDT spraying without substantial increase in incidence, their use permits reduced DDT spraying. The paper shows that non-experimental data can be used to infer causal links in epidemiology, provided that instrumental variables are available to correct for endogeneity.