Costs of Summer Youth Employment to Prevent Violence: an Analysis and Implementer's Tool.

Gun homicide rates have risen 35% across the USA since the start of the COVID-19 pandemic. One promising intervention to prevent violent crime is summer youth employment programs (SYEPs), which provide youth with meaningful workplace experiences, prosocial engagements, and developmental opportunities during the summer months, when many otherwise lack structure. This paper presents a cost analysis of violence prevention-focused SYEPs to help implementers understand the costs generally and in their own community contexts-to advocate for adoption and secure funding of, effectively budget for, and successfully implement SYEPs. Researchers use an ingredient-based costing approach and provide a template for implementers to use and adapt for their context. SYEPs with the goal of reaching youth who are justice-involved or at risk of being victims or perpetrators of violence can cost $3331 per youth assisted, with 54% of this cost directly paid to youth through stipends. Cost per youth is driven by the intensity of the mentoring and support that community organizations provide to the program participants. Knowing the cost per youth assisted can inform further analysis, implementation, and expansion of SYEPs.

The effects of revised peer-counselor support on the PMTCT cascade of care: results from a cluster-randomized trial in Kenya (the EMMA study).

BACKGROUND: This study evaluated the effect of revisions to existing peer-counselor services, called Mentor Mothers (MM), at maternal and child health clinics on medication adherence for women living with HIV (WLWH) in Kenya and on early infant HIV testing. METHODS: The Enhanced Mentor Mother Program study was a 12-site, two-arm cluster-randomized trial enrolling pregnant WLWH from March 2017 to June 2018 (with data collection through September 2020). Six clinics were randomized to continued MM-supported standard care (SC). Six clinics were randomized to the intervention arm (INT = SC plus revised MM services to include more one-on-one interactions). Primary outcomes for mothers were defined as: (PO1) the proportion of days covered (PDC) with antiretroviral therapy (ART) ≥ 0.90 during the last 24-weeks of pregnancy; and (PO2) ≥ 0.90 PDC during the first 24-weeks postpartum. Secondary outcomes were infant HIV testing according to national guidelines (at 6, 24, and 48 weeks). Crude and adjusted risk differences between study arms are reported. RESULTS: We enrolled 363 pregnant WLHV. After excluding known transfers and subjects with incomplete data extraction, data were analyzed for 309 WLWH (151 SC, 158 INT). A small share achieved high PDC during the prenatal and postnatal periods (0.33 SC/0.24 INT achieved PO1; 0.30 SC/0.31 INT achieved PO2; crude or adjusted risk differences were not statistically significant). In addition, ~ 75% in both study arms completed viral load testing during year two after enrollment, with > 90% suppressed in both arms. For infants, ≥ 90% in both arms had at least one HIV test through study follow up (76 weeks) but testing on schedule according to PMTCT guidelines was uncommon. CONCLUSIONS: While national guidelines in Kenya recommended that all HIV-infected pregnant women take a daily antiretroviral regimen for life following a HIV diagnosis, results presented here indicate that a minor share achieved high medication coverage during the prenatal and postnatal periods analyzed. In addition, adjustments to Mentor-Mother services showed no improvement in study outcomes. The lack of effect for this behavioral intervention is relatively consistent with the existing literature to improve mother-infant outcomes along the PMTCT care cascade. CLINICAL TRIAL NUMBER: NCT02848235. Date of first trial registration 28/07/2016.

Cost-effectiveness of single-dose AmBisome pre-emptive treatment for the prevention of cryptococcal meningitis in African low and middle-income countries.

Cryptococcal antigen (CrAg) screening is recommended for patients with advanced HIV to reduce AIDS-related mortality. For asymptomatic CrAg-positive persons, fluconazole pre-emptive therapy is standard, despite a ∼25% failure rate. Single-dose liposomal amphotericin B (AmBisome) is non-inferior to standard treatment for cryptococcal meningitis. We evaluate the threshold of efficacy necessary for AmBisome + fluconazole to be cost-effective as pre-emptive therapy for CrAg-positive persons.We created a decision analytic model to evaluate CrAg screening and treatment in HIV-infected persons with CD4 < 100 cells/µL. Costs were estimated for screening, pre-emptive therapy, and hospitalization for an example low-income country (Uganda) and middle-income country (South Africa). We used a discounted price range of AmBisome® at ${\$}$16.25 to ${\$}$40 per 50 mg vial for both Uganda and South Africa. We estimated AmBisome efficacy from 75 to 95%. Parameter assumptions were based on prospective CrAg screening studies and clinical trials in Africa. Disability adjusted life years (DALYs) were calculated using the age-specific life expectancy in Uganda, per WHO Global Health Observatory data. We modeled the theoretical efficacy of adjunctive AmBisome to determine cost per DALY averted.In South Africa, at ${\$}$16.25 per vial cost and a minimum efficacy of 85%, adjunctive AmBisome is cost-saving compared to fluconazole monotherapy. Compared to fluconazole pre-emptive therapy in Uganda, AmBisome + fluconazole would cost ${\$}$475, ${\$}$220, or ${\$}$136 per DALY averted if meningitis-free survival efficacy was 80, 85, or 90% at ${\$}$24 per vial cost.Investing in AmBisome may be cost-effective in low-income settings compared to using fluconazole pre-emptive therapy alone, if efficacy is 85% or greater. AmBisome pre-emptive therapy appears more cost-efficient in middle-income settings where hospitalization costs for meningitis, and GDP per capita are higher. LAY SUMMARY: We evaluate the efficacy necessary for AmBisome + fluconazole to be cost-effective to prevent cryptococcal meningitis. We found that if AmBisome pre-emptive therapy has an efficacy of 85% or greater, it is likely to be cost-effective in low-income settings.

Getting resources to those who need them: the evidence we need to budget for underserved populations in sub-Saharan Africa.

INTRODUCTION: In recent years, many countries have adopted evidence-based budgeting (EBB) to encourage the best use of limited and decreasing HIV resources. The lack of data and evidence for hard to reach, marginalized and vulnerable populations could cause EBB to further disadvantage those who are already underserved and who carry a disproportionate HIV burden (USDB). We outline the critical data required to use EBB to support USDB people in the context of the generalized epidemics of sub-Saharan Africa (SSA). DISCUSSION: To be considered in an EBB cycle, an intervention needs at a minimum to have an estimate of a) the average cost, typically per recipient of the intervention; b) the effectiveness of the intervention and c) the size of the intervention target population. The methods commonly used for general populations are not sufficient for generating valid estimates for USDB populations. USDB populations may require additional resources to learn about, access, and/or successfully participate in an intervention, increasing the cost per recipient. USDB populations may experience different health outcomes and/or other benefits than in general populations, influencing the effectiveness of the interventions. Finally, USDB population size estimation is critical for accurate programming but is difficult to obtain with almost no national estimates for countries in SSA. We explain these limitations and make recommendations for addressing them. CONCLUSIONS: EBB is a strong tool to achieve efficient allocation of resources, but in SSA the evidence necessary for USDB populations may be lacking. Rather than excluding USDB populations from the budgeting process, more should be invested in understanding the needs of these populations.

Fast-track treatment initiation counselling in South Africa: A cost-outcomes analysis.

INTRODUCTION: In 2016, under its new National Adherence Guidelines (AGL), South Africa formalized an existing model of fast-track HIV treatment initiation counselling (FTIC). Rollout of the AGL included an evaluation study at 24 clinics, with staggered AGL implementation. Using routinely collected data extracted as part of the evaluation study, we estimated and compared the costs of HIV care and treatment from the provider's perspective at the 12 clinics implementing the new, formalized model (AGL-FTIC) to costs at the 12 clinics continuing to implement some earlier, less formalized, model that likely varied across clinics (denoted here as early-FTIC). METHODS: This was a cost-outcome analysis using standard methods and a composite outcome defined as initiated antiretroviral therapy (ART) within 30 days of treatment eligibility and retained in care at 9 months. Using patient-level, bottom-up resource-utilization data and local unit costs, we estimated patient-level costs of care and treatment in 2017 U.S. dollars over the 9-month evaluation follow-up period for the two models of care. Resource use and costs, disaggregated by antiretroviral medications, laboratory tests, and clinic visits, are reported by model of care and stratified by the composite outcome. RESULTS: A total of 350/343 patients in the early-FTIC/AGL-FTIC models of care are included in this analysis. Mean/median costs were similar for both models of care ($135/$153 for early-FTIC, $130/$151 for AGL-FTIC). For the subset achieving the composite outcome, resource use and therefore mean/median costs were similar but slightly higher, reflecting care consistent with treatment guidelines ($163/$166 for early-FTIC, $168/$170 for AGL-FTIC). Not surprisingly, costs for patients not achieving the composite outcome were substantially less, mainly because they only had two or fewer follow-up visits and, therefore, received substantially less ART than patients who achieved the composite outcome. CONCLUSION: The 2016 adherence guidelines clarified expectations for the content and timing of adherence counseling sessions in relation to ART initiation. Because clinics were already initiating patients on ART quickly by 2016, little room existed for the new model of fast-track initiation counseling to reduce the number of pre-ART clinic visits at the study sites and therefore to reduce costs of care and treatment. TRIAL REGISTRATION: Clinical Trial Number: NCT02536768.

Induction-phase treatment costs for cryptococcal meningitis in high HIV-burden African countries: New opportunities with lower costs.

Introduction: Access to and the cost of induction treatment for cryptococcal meningitis (CM) is rapidly changing. The newly-announced price for flucytosine ($0.75 per 500 mg pill) and possibly lower prices for liposomal amphotericin B (AmB-L) create opportunities to reduce CM treatment costs compared to the current standard treatment in low- and middle-income countries. Methods: We developed an Excel-based cost model to estimate health system treatment costs for CM over a two-week induction phase for multiple treatment combinations, newly feasible with improved access to flucytosine and AmB-L. CM treatment costs include medications, laboratory tests and other hospital-based costs (bed-day costs and healthcare worker time). We report results from applying the model using country-specific information for South Africa, Uganda, Nigeria, and Botswana. Results: A 14-day induction-phase of seven days of inpatient AmB-D with flucytosine, followed by seven days of high-dose fluconazole as an outpatient, will cost health systems less than a 14-day hospital stay with AmB-D and fluconazole. If daily AmB-L replaces AmB-D for those with baseline renal dysfunction, with a cost of $50 or less per 50 mg vial, incremental costs would still be less than the AmB-D with fluconazole regimen. Simple oral combinations (e.g., seven days of flucytosine with fluconazole as an inpatient) are practical when AmB-D is not available, and treatment costs would remain less than the current standard treatment. Conclusions: Improved access to and lower prices for flucytosine and AmB-L create opportunities for improving CM treatment regimens. An induction regimen of flucytosine and AmB-D for seven days is less costly than standard care in the settings studied here. As this regimen has also been shown to be more effective than current standard care, countries should prioritize scaling up flucytosine access. The cost of AmB-L based regimens is highly dependent on the price of AmB-L, which currently remains unclear.

Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101-200 cells/µL in Botswana.

Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101-200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101-200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101-200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved).  While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101-200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.

Prevalence of TB symptoms, diagnosis and treatment among people living with HIV (PLHIV) not on ART presenting at outpatient clinics in South Africa and Kenya: baseline results from a clinical trial.

OBJECTIVE: We used screening data and routine clinic records for intervention arm patients in the Simplified Algorithm for Treatment Eligibility (SLATE) trials to describe the prevalence of tuberculosis (TB) symptoms, diagnosis and treatment among people living with HIV (PLHIV), not on antiretroviral therapy (ART) and presenting at outpatient clinics in South Africa and Kenya. We compared the performance of the WHO four-symptom TB screening tool with a baseline Xpert test. SETTING: Outpatient HIV clinics in South Africa and Kenya. PARTICIPANTS: Eligible patients were non-pregnant, PLHIV, >18 years of age, not on ART, willing to provide written informed consent. A total of 594 patients in South Africa and 240 in Kenya were eligible. RESULTS: Prevalence of any TB symptom was 38% in Kenya, 35% (SLATE I) and 47% (SLATE II) in South Africa. During SLATE I, 70% of patients in Kenya and 57% in South Africa with ≥1 TB symptom were tested for TB. In SLATE II, 79% of patients with ≥1 TB symptom were tested. Of those, 19% tested positive for TB in Kenya, 15% (SLATE I) and 5% (SLATE II) tested positive in South Africa. Of the 28 patients who tested positive in both trials, 20 initiated TB treatment. The lowest median CD4 counts were among those with active TB (Kenya 124 cells/mm3; South Africa 193 cells/mm3). When comparing the WHO four-symptom screening tool to the Xpert test (SLATE II), we found that increasing the number of symptoms required for a positive screen from one to three or four decreased sensitivity but increased the positive predictive value to >30%. CONCLUSIONS: 80% of patients assessed for ART initiation presented with ≥1 TB symptoms. Reconsideration of the 'any symptom' rule may be appropriate, with ART initiation among patients with fewer/milder symptoms commencing while TB test results are pending. TRIAL REGISTRATION NUMBER: NCT02891135 and NCT03315013.

Will differentiated care for stable HIV patients reduce healthcare systems costs?

INTRODUCTION: South Africa's National Department of Health launched the National Adherence Guidelines for Chronic Diseases in 2015. These guidelines include adherence clubs (AC) and decentralized medication delivery (DMD) as two differentiated models of care for stable HIV patients on antiretroviral therapy. While the adherence guidelines do not suggest that provider costs (costs to the healthcare system for medications, laboratory tests and visits to clinics or alternative locations) for stable patients in these differentiated models of care will be lower than conventional, clinic-based care, recent modelling exercises suggest that such differentiated models could substantially reduce provider costs. In the context of continued implementation of the guidelines, we discuss the conditions under which provider costs of care for stable HIV patients could fall, or rise, with AC and DMD models of care in South Africa. DISCUSSION: In prior studies of HIV care and treatment costs, three main cost categories are antiretroviral medications, laboratory tests and general interaction costs based on encounters with health workers. Stable patients are likely to be on the national first-line regimen (Tenofovir/Entricitabine/Efavarinz (TDF/FTC/EFV)), so no difference in the costs of medications is expected. Laboratory testing guidelines for stable patients are the same regardless of the model of care, so no difference in laboratory costs is expected as well. Based on existing information regarding the costs of clinic visits, AC visits and DMD drug pickups, we expect that for some clinics, visit costs for DMD or AC models of care could be less, but modestly so, than for conventional, clinic-based care. For other clinics, however, DMD or AC models could have higher visit costs (see Table 2). CONCLUSIONS: The standard of care for stable patients has already been "differentiated" for years in South Africa, prior to the roll out of the new adherence guidelines. AC and DMD models of care, when implemented as envisioned in the guidelines, are unlikely to generate substantive reductions or increases in provider costs of care.

Cost-Effectiveness of Focal Mass Drug Administration and Mass Drug Administration with Dihydroartemisinin-Piperaquine for Malaria Prevention in Southern Province, Zambia: Results of a Community-Randomized Controlled Trial.

Community-wide administration of antimalarial drugs in therapeutic doses is a potential tool to prevent malaria infection and reduce the malaria parasite reservoir. To measure the effectiveness and cost of using the antimalarial drug combination dihydroartemisinin-piperaquine (DHAp) through different community-wide distribution strategies, Zambia's National Malaria Control Centre conducted a three-armed community-randomized controlled trial. The trial arms were as follows: 1) standard of care (SoC) malaria interventions, 2) SoC plus focal mass drug administration (fMDA), and 3) SoC plus MDA. Mass drug administration consisted of offering all eligible individuals DHAP, irrespective of a rapid diagnostic test (RDT) result. Focal mass drug administration consisted of offering DHAP to all eligible individuals who resided in a household where anyone tested positive by RDT. Results indicate that the costs of fMDA and MDA per person targeted and reached are similar (US$9.01 versus US$8.49 per person, respectively, P = 0.87), but that MDA was superior in all cost-effectiveness measures, including cost per infection averted, cost per case averted, cost per death averted, and cost per disability-adjusted life year averted. Subsequent costing of the MDA intervention in a non-trial, operational setting yielded significantly lower costs per person reached (US$2.90). Mass drug administration with DHAp also met the WHO thresholds for "cost-effective interventions" in the Zambian setting in 90% of simulations conducted using a probabilistic sensitivity analysis based on trial costs, whereas fMDA met these criteria in approximately 50% of simulations. A sensitivity analysis using costs from operational deployment and trial effectiveness yielded improved cost-effectiveness estimates. Mass drug administration may be a cost-effective intervention in the Zambian context and can help reduce the parasite reservoir substantially. Mass drug administration was more cost-effective in relatively higher transmission settings. In all scenarios examined, the cost-effectiveness of MDA was superior to that of fMDA.

Understanding the costs and the cost structure of a community-based HIV and gender-based violence (GBV) prevention program: the Woza Asibonisane Community Responses Program in South Africa.

BACKGROUND: The Woza Asibonisane Community Responses (CR) Programme was developed to prevent HIV infections and gender-based violence (GBV) within four provinces in South Africa. The Centre for Communication Impact (CCI) in collaboration with six partner non-governmental organizations (NGOs) implemented the programme, which was comprised of multiple types of group discussion and education activities organized and facilitated by each NGO. To date, little information exists on the cost of implementing such multi-objective, multi-activity, community-based programmes. To address this information gap, we estimated the annual cost of implementing the CR Programme for each NGO. METHODS: We used standard methods to estimate the costs for each NGO, which involved a package of multiple activities targeted to distinct subpopulations in specific locations. The primary sources of information came from the implementing organizations. Costs (US dollars, 2017) are reported for each partner for one implementation year (the U.S. Government fiscal year (10/2016-09/2017). In addition to total costs disaggregated by main input categories, a common metric--cost per participant intervention hour--is used to summarize costs across partners. RESULTS: Each activity included in the CR program involve organizing and bringing together a group of people from the target population to a location and then completing the curriculum for that activity. Activities were held in community settings (meeting hall, community center, sports grounds, schools, etc.). The annual cost per NGO varied substantially, from $260,302 to $740,413, as did scale based on estimated total participant hours, from 101,703 to 187,792 participant hours. The cost per participant hour varied from $2.8-$4.6, with NGO labor disaggregated into salaries for management and salaries for service delivery (providing the activity curriculum) contributing to the largest share of costs per participant hour. CONCLUSIONS: The cost of implementing any community-based program depends on: (1) what the program implements; (2) the resources used; and (3) unit costs for such resources. Reporting on costs alone, however, does not provide enough information to evaluate if the costs are 'too high' or 'too low' without a clearer understanding of the benefits produced by the program, and if the benefits would change if resources (and therefore costs) were changed.

A tool for estimating antiretroviral medication coverage for HIV-infected women during pregnancy (PMTCT-ACT).

BACKGROUND: In the typical prevention of mother to child transmission (PMTCT) of HIV cascade of care discussion or analysis, the period of analysis begins at the first visit for antenatal care (ANC) for that pregnancy. This starting point is problematic for two reasons: (1) a large number of HIV-infected women are already on life-long antiretroviral therapy (ART) when presenting for ANC; and (2) women present to ANC at different gestational ages. The PMTCT ART Coverage Tool (PMTCT-ACT), which estimates the proportion of days covered (PDC) with ART, was developed to address each of these problems. METHODS: PDC is a preferred method to measure adherence to chronic medications, such as ART. For evaluating the PMTCT cascade of care, as indicated by PDC with ART over various time periods, a "starting point" based on a specific day before delivery must be defined that applies to all women (treatment experienced or naïve at the first ANC visit at any gestational age). Using the example of 168 days prior to delivery (24 weeks), PMTCT-ACT measures PDC with ART during that period. PMTCT-ACT is provided as a STATA do-file. Using an example dataset for two women (ID1 is treatment experienced; ID2 is treatment naïve), the details of each major portion of the tool (Parts 1-5) are presented. PMTCT-ACT along with the intermediate datasets created during the analysis are provided as supplemental files. CONCLUSIONS: Evaluating the PMTCT cascade of care requires a standard definition of the follow-up period during pregnancy that applies to all HIV-infected pregnant women and a standard measure of adherence. PMTCT-ACT is a new tool that fits this purpose. PMTCT-ACT can also be easily adjusted to evaluate other ante- and post-natal periods (e.g., final 4 weeks, final 8 weeks, complete pregnancy period, initial 24 weeks postpartum, time periods consistent with infant HIV testing guidelines).

Simplified clinical algorithm for identifying patients eligible for same-day HIV treatment initiation (SLATE): Results from an individually randomized trial in South Africa and Kenya.

BACKGROUND: The World Health Organization recommends "same-day" initiation of antiretroviral therapy (ART) for HIV patients who are eligible and ready. Identifying efficient, safe, and feasible procedures for determining same-day eligibility and readiness is now a priority. The Simplified Algorithm for Treatment Eligibility (SLATE) study evaluated a clinical algorithm that allows healthcare workers to determine eligibility for same-day treatment and to initiate ART at the patient's first clinic visit. METHODS AND FINDINGS: SLATE was an individually randomized trial at three outpatient clinics in urban settlements in Johannesburg, South Africa and three hospital clinics in western Kenya. Adult, nonpregnant, HIV-positive, ambulatory patients presenting for any HIV care, including HIV testing, but not yet on ART were enrolled and randomized to the SLATE algorithm arm or standard care. The SLATE algorithm used four screening tools-a symptom self-report, medical history questionnaire, physical examination, and readiness assessment-to ascertain eligibility for same-day initiation or refer for further care. Follow-up was by record review, and analysis was conducted by country. We report primary outcomes of 1) ART initiation ≤28 days and 2) initiation ≤28 days and retention in care ≤8 months of enrollment. From March 7, 2017 to April 17, 2018, we enrolled 600 patients (median [IQR] age 34 [29-40] and CD4 count 286 [128-490]; 63% female) in South Africa and 477 patients in Kenya (median [IQR] age 35 [29-43] and CD4 count 283 [117-541]; 58% female). In the intervention arm, 78% of patients initiated ≤28 days in South Africa, compared to 68% in the standard arm (risk difference [RD] [95% confidence interval (CI)] 10% [3%-17%]); in Kenya, 94% of intervention-arm patients initiated ≤28 days compared to 89% in the standard arm (6% [0.5%-11%]). By 8 months in South Africa, 161/298 (54%) intervention-arm patients had initiated and were retained, compared to 146/302 (48%) in the standard arm (6% [(2% to 14%]). By 8 months in Kenya, the corresponding retention outcomes were identical in both arms (137/240 [57%] of intervention-arm patients and 136/237 [57%] of standard-arm patients). Limitations of the trial included limited geographic representativeness, exclusion of patients too ill to participate, missing viral load data, greater study fidelity to the algorithm than might be achieved in standard care, and secular changes in standard care over the course of the study. CONCLUSIONS: In South Africa, the SLATE algorithm increased uptake of ART within 28 days by 10% and showed a numerical increase (6%) in retention at 8 months. In Kenya, the algorithm increased uptake of ART within 28 days by 6% but found no difference in retention at 8 months. Eight-month retention was poor in both arms and both countries. These results suggest that a simple structured algorithm for same-day treatment initiation procedures is feasible and can increase and accelerate ART uptake but that early retention on treatment remains problematic. TRIAL REGISTRATION: Clinicaltrials.gov NCT02891135, registered September 1, 2016. First participant enrolled March 6, 2017 in South Africa and July 13, 2017 in Kenya.

Who is seeking antiretroviral treatment for HIV now? Characteristics of patients presenting in Kenya and South Africa in 2017-2018.

INTRODUCTION: Many African countries have had at least two years' experience with universal treatment eligibility for HIV. The literature contains few descriptions, though, of populations starting treatment since adoption of universal eligibility. Using baseline data from a clinical trial of same-day ART initiation, we describe the populations presenting for HIV testing or care at study clinics in Kenya and South Africa in 2017-18, during the era of same-day initiation. METHODS: The Simplified Algorithm for Treatment Eligibility (SLATE) trials in Kenya (SLATE I) and South Africa (SLATE II) were multicenter, non-blinded, individually randomized, pragmatic trials evaluating simple, standardized algorithms to determine eligibility for same-day initiation of ART without relying on laboratory results, point of care tests or multiple clinic visits. In Kenya, enrolment occurred during July 2017 to April 2018. In South Africa, enrolment occurred during March to September 2018. We describe demographic, socioeconomic and clinical characteristics of patients randomized to the same-day initiation arm for both studies. RESULTS AND DISCUSSION: A total of 240 and 296 participants were enrolled in Kenya and South Africa. The majority were female (59% and 64% respectively), with a median age of 35 years. In both countries, most subjects were newly diagnosed with HIV on the day of enrolment (62%, 55%), believed they already had adequate knowledge to begin ART (78%, 68%), and preferred to start ART immediately (same-day) (98% in both countries). About 40% of all patients had at least one symptom related to tuberculosis (cough, fever, night sweats, weight loss) and/or cryptococcal meningitis (continuous headache). More than a third of patients (37%, 36%) presented with advanced disease (CD4 <200 cells/mm3 ), a fifth presented with very advanced disease (CD4 < 100), and approximately 1 in 20 presented with very advanced disease and were asymptomatic. CONCLUSIONS: Despite >2 years of universal eligibility for ART in Kenya and South Africa, in 2017-2018 more than half of HIV-positive patients presenting at public sector clinics were not yet aware of their status, and more than a third presented for care with advanced HIV disease. These proportions remain similar to those observed before the introduction of universal eligibility.

Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis.

BACKGROUND: Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. METHODS: We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/µL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. RESULTS: In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/µL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. CONCLUSION: CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.

Cost-effectiveness of reflex laboratory-based cryptococcal antigen screening for the prevention and treatment of cryptococcal meningitis in Botswana.

Background: Cryptococcal antigen (CrAg) screening for antiretroviral therapy (ART)-naïve adults with advanced HIV/AIDS can reduce the incidence of cryptococcal meningitis (CM) and all-cause mortality. We modeled the cost-effectiveness of laboratory-based "reflex" CrAg screening for ART-naïve CrAg-positive patients with CD4<100 cells/µL (those currently targeted in guidelines) and ART-experienced CrAg-positive patients with CD4<100 cells/µL (who make up an increasingly large proportion of individuals with advanced HIV/AIDS). Methods: A decision analytic model was developed to evaluate CrAg screening and treatment based on local CD4 count and CrAg prevalence data, and realistic assumptions regarding programmatic implementation of the CrAg screening intervention. We modeled the number of CrAg tests performed, the number of CrAg positives stratified by prior ART experience, the proportion of patients started on pre-emptive antifungal treatment, and the number of incident CM cases and CM-related deaths. Screening and treatment costs were evaluated, and cost per death or disability-adjusted life year (DALY) averted estimated. Results: We estimated that of 650,000 samples undergoing CD4 testing annually in Botswana, 16,364 would have a CD4<100 cells/µL and receive a CrAg test, with 70% of patients ART-experienced at the time of screening. Under base model assumptions, CrAg screening and pre-emptive treatment restricted to ART-naïve patients with a CD4<100 cells/µL prevented 20% (39/196) of CM-related deaths in patients undergoing CD4 testing at a cost of US$2 per DALY averted. Expansion of preemptive treatment to include ART-experienced patients with a CD4<100 cells/µL resulted in 55 additional deaths averted (a total of 48% [94/196]) and was cost-saving compared to no screening. Findings were robust across a range of model assumptions. Conclusions: Reflex laboratory-based CrAg screening for patients with CD4<100 cells/µL is a cost-effective strategy in Botswana, even in the context of a relatively low proportion of advanced HIV/AIDS in the overall HIV-infected population, the majority of whom are ART-experienced.

The Enhanced Mentor Mother ProgrAm (EMMA) for the prevention of mother-to-child transmission of HIV in Kenya: study protocol for a cluster randomized controlled trial.

BACKGROUND: As of September 2014, Kenya implemented the WHO recommended Option B+ guidelines in which all newly diagnosed HIV-infected pregnant women are immediately eligible for triple antiretroviral therapy (ART) for life regardless of CD4 count. In addition, Kenya previously established the Kenya Mentor Mother Program (KMMP) in 2012 to improve peer education and psychosocial support services within the national prevention of mother-to-child transmission (PMTCT) program. The primary objectives of the study described in the current protocol are: (1) to evaluate implementation of these new guidelines (Option B+ with Mentor Mothers) as part of routine service delivery; and (2) to evaluate potential benefits of a package of services within the KMMP (called EMMA) to improve PMTCT service delivery. METHODS: We will conduct a cluster randomized controlled trial in western Kenya. We will allocate 12 clinics providing PMTCT services including ART to two study arms using pair matching: the standard of care (SOC) arm, which includes the KMMP as implemented by the clinics; and the intervention arm, which is the SOC (including KMMP) with the EMMA package of services (a targeted exit interview, visit reminders, and targeted follow-up). At the intervention clinics, the EMMA package of services is implemented as part of routine service delivery. A total of 360 (180 in each arm) pregnant women will be enrolled in the study at or near their first visit for antenatal care for prospective records review through 72 weeks post-partum. The primary and secondary outcomes are uninterrupted supplies of ART medications throughout the PMTCT cascade of care as well as infants completing HIV testing on schedule. DISCUSSION: The EMMA package of services provides specific structure to the use of Mentor Mothers within PMTCT programs. This strategy was developed in collaboration with local health facility and PMTCT program staff based on their experience providing PMTCT services within the integrated ART-MCH facilities. If successful, this approach has the potential to improve dramatically PMTCT service delivery with minor additional costs beyond the basic mother-mentor program and support global goals to eliminate mother-to-child transmission. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02848235 . Registered on 19 July 2016.

Incremental treatment costs for HIV-infected women initiating antiretroviral therapy during pregnancy: A 24-month micro-costing cohort study for a maternal and child health clinic in Kenya.

BACKGROUND: To date, little information exists on the costs of providing antiretroviral therapy (ART) within maternal and child health (MCH) clinics in Kenya. The main objective of this analysis was to estimate the annual incremental cost of providing ART within a MCH clinic for adult women initiated on ART during pregnancy over the first one and two years on treatment. The study site was the District Hospital in Kericho, Kenya. METHODS: A micro-costing approach from the provider's perspective, based on a retrospective review of patient medical records, was used to evaluate incremental costs of care (2012 USD). Cost per patient in two cohorts were evaluated: the MCH clinic group comprised of adult women who initiated ART at the site's MCH clinic during pregnancy between 2008-2011; and for comparison, the ART clinic group comprised of adult, non-pregnant women who initiated ART at the site's ART clinic during 2008-2011. The two groups were matched on age and baseline CD4 count at initiation. Retention at year one/two on ART was defined as having completed a clinic visit at 365/730 days on ART +/- 90 days. RESULTS: For patients defined as retained in care at year one, average incremental costs per patient were $234 for the MCH clinic group (median: 215; IQR: 186, 282) and $292 in the ART clinic group (median: 227; IQR: 178, 357). ARV and laboratory costs were less on average for the MCH clinic group compared to the ART clinic group (due to lower cost regimens and fewer tests), while personnel costs were higher for the MCH clinic group. CONCLUSIONS: The annual incremental cost per patient of providing ART were similar in the two clinic settings in 2012. With shifts in recommended ARV regimens and lab monitoring over time, annual costs of care (using 2016 USD unit costs) have remained relatively constant in nominal terms for the MCH clinic group but have fallen substantially for the ART clinic group (from nominal $292 in 2012 to nominal $227 in 2016).

Revealed willingness-to-pay versus standard cost-effectiveness thresholds: Evidence from the South African HIV Investment Case.

BACKGROUND: The use of cost-effectiveness thresholds based on a country's income per capita has been criticized for not being relevant to decision making, in particular in middle-income countries such as South Africa. The recent South African HIV Investment Case produced an alternative cost-effectiveness threshold for HIV prevention and treatment interventions based on estimates of life years saved and the country's committed HIV budget. METHODS: We analysed the optimal mix of HIV interventions over a baseline of the current HIV programme under the committed HIV budget for 2016-2018. We calculated the incremental cost-effectiveness ratio (ICER) as cost per life-year saved (LYS) of 16 HIV prevention and treatment interventions over 20 years (2016-2035). We iteratively evaluated the most cost effective option (defined by an intervention and its coverage) over a rolling baseline to which the more cost effective options had already been added, thereby allowing for diminishing marginal returns to interventions. We constrained the list of interventions to those whose combined cost was affordable under the current HIV budget. Costs are presented from the government perspective, unadjusted for inflation and undiscounted, in 2016 USD. RESULTS: The current HIV budget of about $1.6 billion per year was sufficient to pay for the expansion of condom availability, medical male circumcision, universal treatment, and infant testing at 6 weeks to maximum coverage levels, while also implementing a social and behavior change mass media campaign with a message geared at increasing testing uptake and reducing the number of sexual partners. The combined ICER of this package of services was $547/ LYS. The ICER of the next intervention that was above the affordability threshold was $872/LYS. CONCLUSIONS: The results of the South African HIV Investment Case point to an HIV cost-effectiveness threshold based on affordability under the current budget of $547-872 per life year saved, a small fraction of the country's GDP per capita of about $6,000.