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More than 2 billion people rely on solid fuels and traditional stoves or open fires for cooking, lighting, and/or heating. Exposure to emissions caused by burning these fuels is believed to be responsible for a significant share of the global burden of disease. To achieve widespread health improvements, interventions that reduce exposures to indoor air pollution will need to be adopted and consistently used by large numbers of households in the developing world. Given that such interventions remain to be adopted by large numbers of these households, much remains to be learned about household demand for interventions designed (in part at least) to reduce indoor air pollution. A general household framework is developed that identifies in detail the determinants of household demand for indoor air pollution interventions, where demand for an intervention is expressed in terms of willingness to pay. Household demand is shown to be a combination of three terms: (1) the direct consumption effect; (2) the child health effect; and (3) the adult health effect. While micro-level data are not available to estimate directly this model, existing data and information are used to estimate just the health effects component of household demand. Based on such existing information, it might be concluded that household demand should seemingly be strong given that willingness to pay, based on existing information, is seemingly large compared to costs for common interventions like improved stoves. Given that household demand is not strong for existing interventions, this analysis shows that more clearly focused research on household demand for interventions is needed if such interventions are going to be demanded (i.e. adopted and used) by large numbers of households throughout the developing world. Four priority areas for future research are: (1) improving information on dose-response relationships between indoor air pollution and various health effects (e.g. increased mortality and morbidity risks); (2) improving information on impacts from interventions in terms of air pollution reductions and also cooking times, fuel use, and heat intensities; (3) improving information on household shadow values for improved health, with separate information for adult and child health; and (4) considering more directly household information, and its adequacy, for their ability to evaluate the relationships between fuel use and health. [ABSTRACT FROM AUTHOR]

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., (© 2023. The Author(s).)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

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., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Tenforde MW et al.)

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., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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., Competing Interests: The authors have declared that no competing interests exist.

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/mm 3 ; South Africa 193 cells/mm 3 ). 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

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.

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., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Tenforde MW et al.)

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)., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

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., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Tenforde MW et al.)

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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SR is on the editorial board of PLOS Medicine. BL and ATB are on the editorial board of PLOS ONE. WDFV sits on antiretroviral initiation guideline committees both local and international, has accepted speaking honoraria from multiple manufacturers of antiretrovirals, and is on several of their advisory boards. The remaining authors declare that they have no competing interests.

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/mm 3 ), 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., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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., Competing Interests: BL was paid by the CDC foundation for this work. GG, AJ, and TC are employed by the CDC, which is a separate, independent entity from the CDC foundation The source of this information is the Global Cryptococcal Antigen Screening Initiative, a project of the CDC Foundation funded by a grant from Pfizer Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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.

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)., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Co-authors Bii, Sugut, and Sawe work for the HJF Medical Research International, Inc., which is also providing support to the study sites as part of the Government of Kenya's national AIDS response program (also funded in part through the PEPFAR program). While we believe we have been objective in our analysis, we wanted to report the relationship. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of 'treat all' to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initiation, requiring multiple clinic visits over a several-week period., Methods and Analysis: The Simplified Algorithm for Treatment Eligibility (SLATE) study is an individually randomised evaluation of a simplified clinical algorithm for clinicians to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. SLATE will enrol and randomise (1:1) 960 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa and Kenya. Patients randomised to the standard arm will receive routine, standard of care ART initiation from clinic staff. Patients randomised to the intervention arm will be administered a symptom report, medical history, brief physical exam and readiness assessment. Patients who have positive (satisfactory) results for all four components of SLATE will be dispensed ARVs immediately, at the same clinic visit. Patients who have any negative results will be referred for further clinical investigation, counselling, tests or other services prior to being dispensed ARVs. After the initial visit, follow-up will be by passive medical record review. The primary outcomes will be ART initiation ≤28 days and retention in care 8 months after study enrolment., Ethics and Dissemination: Ethics approval has been provided by the Boston University Institutional Review Board, the University of the Witwatersrand Human Research Ethics Committee (Medical) and the KEMRI Scientific and Ethics Review Unit. Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents., Trial Registration: NCT02891135., Competing Interests: Competing interests: PDE is an employee of the Bill & Melinda Gates Foundation, which is funding this work. WDFV sits on antiretroviral initiation guideline committees, both local and international. WDFV has accepted speaking honoraria from multiple manufacturers of antiretrovirals and is on several of their advisory boards. The remaining authors declare that they have no competing interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: South Africa has a large domestically funded HIV programme with highly saturated coverage levels for most prevention and treatment interventions. To further optimise its allocative efficiency, we designed a novel optimisation method and examined whether the optimal package of interventions changes when interaction and non-linear scale-up effects are incorporated into cost-effectiveness analysis., Methods: The conventional league table method in cost-effectiveness analysis relies on the assumption of independence between interventions. We added methodology that allowed the simultaneous consideration of a large number of HIV interventions and their potentially diminishing marginal returns to scale. We analysed the incremental cost effectiveness ratio (ICER) of 16 HIV interventions based on a well-calibrated epidemiological model that accounted for interaction and non-linear scale-up effects, a custom cost model, and an optimisation routine that iteratively added the most cost-effective intervention onto a rolling baseline before evaluating all remaining options. We compared our results with those based on a league table., Results: The rank order of interventions did not differ substantially between the two methods- in each, increasing condom availability and male medical circumcision were found to be most cost-effective, followed by anti-retroviral therapy at current guidelines. However, interventions were less cost-effective throughout when evaluated under the optimisation method, indicating substantial diminishing marginal returns, with ICERs being on average 437% higher under our optimisation routine., Conclusions: Conventional league tables may exaggerate the cost-effectiveness of interventions when programmes are implemented at scale. Accounting for interaction and non-linear scale-up effects provides more realistic estimates in highly saturated real-world settings.

Background: This paper summarizes a framework for evaluating the costs of malaria elimination interventions and applies this approach to one key component of the elimination strategy-reactive case detection (RCD)-implemented through 173 health facilities across 10 districts in Southern Province of Zambia during 2014., Methods: The primary unit of analysis is the health facility catchment area (HFCA). A five-step approach was followed to estimate implementation costs: organize preliminary information; estimate basic unit costs; estimate activity unit costs; estimate and organize final unit cost database; and create the final costing database (one row of data per HFCA). By working through a specific application, the overall logic of the analysis and details of each step are presented. An electronic annex also provides all details of the analysis. Because population varies substantially across HFCAs, all results are reported per 1000 population in HFCAs., Results: During 2014, 38.9 households per HFCA were visited for RCD services; 166.8 individuals were tested and 32.3 tested positive and were treated. The mean annual cost per HFCA was $1177 (median = $923, IQR $651-$1417). Variation in costs was driven by the number of CHWs and passive cases detected. CHW-related costs and data review meetings accounted for the largest share of costs. Rapid diagnostic tests and drugs accounted for less than 10 % of total costs., Conclusions: The framework presented here follows standard methods in applied costing of public health interventions (combining ingredients- and activity-based costing approaches into one final cost analysis). Through an application to a specific programme implemented in Zambia in 2014, the details of how to apply such methods to an actual programme are presented. Such details are not typically presented in existing costing analyses but are required for applied analysts working with national malaria control programmes and other organizations to complete such analyses as part of routine programme implementation. Obtaining data and information for implementing the approach remains complicated, in part because analysts from one organization may not have easy access to information from another organization. This basic approach is transparent and easily applied to other malaria elimination interventions being implemented in sub-Saharan Africa and elsewhere.

Sydney Rosen and colleagues describe an operations research agenda to accelerating uptake of HIV treatment initiation.

Background: In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies., Methods: We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions., Results: In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment)., Conclusions: In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.

Background: Between 2010-2013, South Africa implemented WHO 'Option A' for prevention of mother to child transmission (PMTCT), where all HIV-infected pregnant women (from 14 weeks gestation) received zidovudine (AZT) as ARV prophylaxis and initiated CD4 testing at their first antenatal care (ANC) visit. After returning for a second visit to collect CD4 results, women with CD4 counts ≤ 350 were referred to the ART clinic and fast-tracked for initiation on lifelong ART while continuing to visit the ANC clinic every four weeks. Women with CD4 counts >350 were dispensed daily AZT prophylaxis at monthly follow up visits (every 4 weeks). The primary objective of this study was to evaluate adherence of HIV-infected pregnant women to recommended PMTCT services at and after their first antenatal care (ANC) visit., Methods: We conducted an observational cohort study from August 2012 to February 2013 at two primary health care clinics in Johannesburg, South Africa using routinely collected clinic data from first ANC visit for up to 60 days., Results: Of the 158 patients newly diagnosed with HIV at their first ANC visit, records indicated that 139 women initiated CD4 testing during their first ANC visit. 52 patients (33% of 158) did not return again to the clinic within 60 days. Of the 118 (84% of 139) women with known gestational age > 13 weeks and known Hb ≥ 8 g/dl who should have received a 4-week supply of daily AZT at first ANC visit, 81 women (69% of 118) had a record of AZT being dispensed. Among the 139 women with CD4 results, 72 (52%) were eligible for lifelong ART (CD4 count ≤350); however, only 2 initiated ART within 30 days., Conclusions: Loss to initiation of both single and triple ARV therapy, loss to follow-up, and treatment interruptions were common during ANC care for pregnant women with HIV after their first ANC visit.

Background: In March 2012, The Elizabeth Glaser Pediatric AIDS Foundation trained maternal and child health workers in Southern Province of Zambia to use a new rapid syphilis test (RST) during routine antenatal care. A recent study by Bonawitz et al. (2014) evaluated the impact of this roll out in Kalomo District. This paper estimates the costs and cost-effectiveness from the provider's perspective under the actual conditions observed during the first year of the RST roll out., Methods: Information on materials used and costs were extracted from program records. A decision-analytic model was used to evaluate the costs (2012 USD) and cost-effectiveness. Basic parameters needed for the model were based on the results from the evaluation study., Results: During the evaluation study, 62% of patients received a RST, and 2.8% of patients tested were positive (and 10.4% of these were treated). Even with very high RST sensitivity and specificity (98%), true prevalence of active syphilis would be substantially less (estimated at <0.7%). For 1,000 new ANC patients, costs of screening and treatment were estimated at $2,136, and the cost per avoided disability-adjusted-life year lost (DALY) was estimated at $628. Costs change little if all positives are treated (because prevalence is low and treatment costs are small), but the cost-per-DALY avoided falls to just $66. With full adherence to guidelines, costs increase to $3,174 per 1,000 patients and the cost-per-DALY avoided falls to $60., Conclusions: Screening for syphilis is only useful for reducing adverse birth outcomes if patients testing positive are actually treated. Even with very low prevalence of syphilis (a needle in the haystack), cost effectiveness improves dramatically if those found positive are treated; additional treatment costs little but DALYs avoided are substantial. Without treatment, the needle is essentially found and thrown back into the haystack.

Background: Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia., Methods: Data on resource utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient clinic visits, and fixed resources) and retention in care were extracted from medical records for 846 patients who initiated ART at ≥15 years of age at six treatment sites between July 2007 and October 2008. Unit costs were estimated from the provider's perspective using site- and country-level data and are reported in 2011 USD., Results: Patients initiated ART at a median CD4 cell count of 145 cells/μL. Fifty-nine percent of patients initiated on a tenofovir-containing regimen, ranging from 15% to 86% depending on site. One year after ART initiation, 75% of patients were retained in care. The average cost per patient retained in care one year after ART initiation was $243 (95% CI, $194-$293), ranging from $184 (95% CI, $172-$195) to $304 (95% CI, $290-$319) depending on site. Patients retained in care one year after ART initiation received, on average, 11.4 months' worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or clinical officer. At all sites, ARV drugs were the largest cost component, ranging from 38% to 84% of total costs, depending on site., Conclusions: Patients initiate ART late in the course of disease progression and a large proportion drop out of care after initiation. The quantity of resources utilized and costs vary widely by site, and patients utilize a different mix of resources under routine clinical conditions than if they were receiving fully guideline-concordant care. Improving retention in care and guideline concordance, including increasing the use of tenofovir in first-line ART regimens, may lead to increases in overall treatment costs.

This investigation of expert witness gender used scenarios addressing threats to the expert, sexuality, parenting by the expert, and lying, and in which intrusive and non-intrusive gender cross-examinations were presented to 352 mock jurors. Male and female experts were matched carefully on attractiveness and other social desirability dimensions. In half of the situations the expert witnesses replied with defensive answers, and in the other half, they replied assertively. The assertive responses were found to be significantly more effective on a number of dependent measures, including perceived credibility. In results consistent with other studies, the male experts were evaluated more positively than the female experts. Sexism and other attitudes of the mock jurors were unrelated to credibility and expert gender. The results are discussed in the context of managing aggressive cross-examinations, role demands for women in the courtroom, and methodological approaches to the study of expert witness gender., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective. We estimated time to initiation, outpatient resource use, and costs of outpatient care during the 6 months prior to ART initiation for HIV-infected pediatric patients in Zambia. Methods. We enrolled 1,102 children who initiated ART at <15 years of age between 2006 and 2011 at 5 study sites. Of these, 832 initiated ART ≤6 months after first presenting to care at the study sites. Data on time in care and resources utilized during the 6 months prior to ART initiation were extracted from patient medical records. Costs were estimated from the provider's perspective and are reported in 2011 USD. Results. For the patients who initiated ART ≤6 months after presenting to care, median age at presentation to care was 3.9 years; median CD4 percentage was 13%. Median time to ART initiation was 26 days. Patients made, on average, 2.38 clinic visits prior to ART initiation and received 0.81 CD4 tests, 0.74 full blood count tests, and 0.49 blood chemistry tests. The mean cost of pre-ART care was $20 per patient. Conclusions. Zambian pediatric patients initiating ART ≤6 months after presenting to care do so quickly, utilize fewer resources than mandated by national guidelines, and accrue low costs.

For the removal of superficial and nodular basal cell carcinomas (BCCs), laser ablation provides certain advantages relative to other treatment modalities. However, efficacy and reliability tend to be variable because tissue is vaporized such that none is available for subsequent histopathological examination for residual BCC (and to confirm complete removal of tumor). Intra-operative reflectance confocal microscopy (RCM) may provide a means to detect residual tumor directly on the patient and guide ablation. However, optimization of ablation parameters will be necessary to control collateral thermal damage and preserve sufficient viability in the underlying layer of tissue, so as to subsequently allow labeling of nuclear morphology with a contrast agent and imaging of residual BCC. We report the results of a preliminary study of two key parameters (fluence, number of passes) vis-à-vis the feasibility of labeling and RCM imaging in human skin ex vivo, following ablation with an erbium:yttrium aluminum garnet laser.

Background: Zambia adopted Option A for prevention of mother-to-child transmission of HIV (PMTCT) in 2010 and announced a move to Option B+ in 2013. We evaluated the uptake, outcomes, and costs of antenatal, well-baby, and PMTCT services under routine care conditions in Zambia after the adoption of Option A., Methods: We enrolled 99 HIV-infected/HIV-exposed (index) mother/baby pairs with a first antenatal visit in April-September 2011 at four study sites and 99 HIV-uninfected/HIV-unexposed (comparison) mother/baby pairs matched on site, gestational age, and calendar month at first visit. Data on patient outcomes and resources utilized from the first antenatal visit through six months postpartum were extracted from site registers. Costs in 2011 USD were estimated from the provider's perspective., Results: Index mothers presented for antenatal care at a mean 23.6 weeks gestation; 55% were considered to have initiated triple-drug antiretroviral therapy (ART) based on information recorded in site registers. Six months postpartum, 62% of index and 30% of comparison mother/baby pairs were retained in care; 67% of index babies retained had an unknown HIV status. Comparison and index mother/baby pairs utilized fewer resources than under fully guideline-concordant care; index babies utilized more well-baby resources than comparison babies. The average cost per comparison pair retained in care six months postpartum was $52 for antenatal and well-baby services. The average cost per index pair retained was $88 for antenatal, well-baby, and PMTCT services and increased to $185 when costs of triple-drug ART services were included., Conclusions: HIV-infected mothers present to care late in pregnancy and many are lost to follow up by six months postpartum. HIV-exposed babies are more likely to remain in care and receive non-HIV, well-baby care than HIV-unexposed babies. Improving retention in care, guideline concordance, and moving to Option B+ will result in increased service delivery costs in the short term.

Disability-adjusted-life-years lost (DALYs) is a common outcome metric for cost-effectiveness analyses, and the equations used for such calculations have been presented previously by Fox-Rushby and Hanson (see, e.g., "Health Policy and Planning 16:326-331, 2001"). While the equations are clear, the logic behind them is opaque at best for a large share of public health practitioners and students. The objective of this paper is to show how to calculate DALYs using a discrete time formulation that is easy to teach to students and public health practitioners, is easy to apply for those with basic discounting skills, and is consistent with the discounting methods typically included on the costing side of cost-effectiveness analysis. A continuous-time adjustment factor is derived that can be used to ensure exact consistency between the continuous and discrete time approaches, but this level of precision is typically unnecessary for cost-effectiveness analyses. To illustrate the approach, both a new, simple example and the same example presented in Fox-Rushby and Hanson are used throughout the paper.

Introduction: After almost 10 years of PEPFAR funding for antiretroviral therapy (ART) treatment programmes in Kenya, little is known about the cost of care provided to HIV-positive patients receiving ART. With some 430,000 ART patients, understanding and managing costs is essential to treatment programme sustainability., Methods: Using patient-level data from medical records (n=120/site), we estimated the cost of providing ART at three treatment sites in the Rift Valley Province of Kenya (a clinic at a government hospital, a hospital run by a large agricultural company and a mission hospital). Costs included ARV and non-ARV drugs, laboratory tests, salaries to personnel providing patient care, and infrastructure and other fixed costs. We report the average cost per patient during the first 12 months after ART initiation, stratified by site, and the average cost per patient achieving the primary outcome, retention in care 12 months after treatment initiation., Results: The cost per patient initiated on ART was $206, $252 and $213 at Sites 1, 2 and 3, respectively. The proportion of patients remaining in care at 12 months was similar across all sites (0.82, 0.80 and 0.84). Average costs for the subset of patients who remained in care at 12 months was also similar (Site 1, $229; Site 2, $287; Site 3, $237). Patients not retained in care cost substantially less (Site 1, $104; Site 2, $113; Site 3, $88). For the subset of patients who remained in care at 12 months, ART medications accounted for 51%, 44% and 50% of the costs, with the remaining costs split between non-ART medications (15%, 11%, 10%), laboratory tests (14%, 15%, 15%), salaries to personnel providing patient care (9%, 11%, 12%) and fixed costs (11%, 18%, 13%)., Conclusions: At all three sites, 12-month retention in care compared favourably to retention rates reported in the literature from other low-income African countries. The cost of providing treatment was very low, averaging $224 in the first year, less than $20/month. The cost of antiretroviral medications, roughly $120 per year, accounted for approximately half of the total costs per patient retained in care after 12 months.

Objective: To estimate the impact of antiretroviral therapy (ART) on labor productivity and income using detailed employment data from two large tea plantations in western Kenya for HIV-infected tea pluckers who initiated ART., Design: Longitudinal study using primary data on key employment outcomes for a group of HIV-infected workers receiving antiretroviral therapy (ART) and workers in the general workforce., Methods: We used nearest-neighbor matching methods to estimate the impacts of HIV/AIDS and ART among 237 HIV-positive pluckers on ART (index group) over a 4-year period (2 years pre-ART and post-ART) on 4 monthly employment outcomes - days plucking tea, total kilograms (kgs) harvested, total days working, and total labor income. Outcomes for the index group were compared with those for a matched reference group from the general workforce., Results: We observed a rapid deterioration in all four outcomes for HIV-infected individuals in the period before ART initiation and then a rapid improvement after treatment initiation. By 18-24 months after treatment initiation, the index group harvested 8% (men) and 19% (women) less tea than reference individuals. The index group earned 6% (men) and 9% (women) less income from labor than reference individuals. Women's income would have dropped further if they had not been able to offset their decline in tea plucking by spending more time on nonplucking assignments., Conclusion: HIV-infected workers experienced long-term income reductions before and after initiating ART. The implications of such long-term impacts in low-income countries have not been adequately addressed.

The Community-Based Care for Orphans and Vulnerable Children (CBCO) program operated in Kenya during 2006-2010. In Eastern Province, the program provided support to approximately 3000 orphans and vulnerable children (OVC) living in 1500 households. A primary focus of the program was to support savings and loan associations composed of OVC caregivers (typically elderly women) to improve household and OVC welfare. Cross-sectional data were collected in 2011 from 1500 randomly selected households from 3 populations: program participants (CBCO group, n=500), households in the same villages as program participants but not in the program (the local-community-group = Group L, n=300), and households living in nearby villages where the program did not operate (the adjacent-community-group, Group A, n=700). Primary welfare outcomes evaluated are household food security, as measured by the Household Food Insecurity Access instrument, and OVC educational attainment. We compared outcomes between the CBCO and the subset of Group L not meeting program eligibility criteria (L-N) to investigate disparities within local communities. We compared outcomes between the CBCO group and the subset of Group A meeting eligibility criteria (A-E) to consider program impact. We compared outcomes between households not eligible for the program in the local and adjacent community groups (L-N and A-N) to consider if the adjacent communities are similar to the local communities. In May-June 2011, at the end of the OVC program, the majority of CBCO households continued to be severely food insecure, with rates similar to other households living in nearby communities. Participation rates in primary school are high, reflecting free primary education. Among the 18-22 year olds who were "children" during the program years, relatively few children completed secondary school across all study groups. Although the CBCO program likely provided useful services and benefits to program participants, disparities continued to exist in food security and educational outcomes between program participants and their non-OVC peers in the local community. Outcomes for CBCO households were similar to those observed for OVC households in adjacent communities.

Background. We evaluated whether a pilot program providing point-of-care (POC), but not rapid, CD4 testing (BD FACSCount) immediately after testing HIV-positive improved retention in care. Methods. We conducted a retrospective record review at the Themba Lethu Clinic in Johannesburg, South Africa. We compared all walk-in patients testing HIV-positive during February, July 2010 (pilot POC period) to patients testing positive during January 2008-February 2009 (baseline period). The outcome for those with a ≤250 cells/mm(3) when testing HIV-positive was initiating ART <16 weeks after HIV testing. Results. 771 patients had CD4 results from the day of HIV testing (421 pilots, 350 baselines). ART initiation within 16 weeks was 49% in the pilot period and 46% in the baseline period. While all 421 patients during the pilot period should have been offered the POC test, patient records indicate that only 73% of them were actually offered it, and among these patients only 63% accepted the offer. Conclusions. Offering CD4 testing using a point-of-care, but not rapid, technology and without other health system changes had minor impacts on the uptake of HIV care and treatment. Point-of-care technologies alone may not be enough to improve linkage to care and treatment after HIV testing.

Background: A mobile HIV counseling and testing (HCT) program around Johannesburg piloted the integration of point-of-care (POC) CD4 testing, using the Pima analyzer, to improve linkages to HIV care. We report results from this pilot program for patients testing positive (n = 508) from May to October 2010., Methods: We analyzed 3 primary outcomes: assignment to testing group (offered POC CD4 or not), successful follow-up (by telephone), and completed the referral visit for HIV care within 8 weeks after HIV testing if successfully followed up. Proportions for each outcome were calculated, and relative risks were estimated using a modified Poisson approach., Results: Three hundred eleven patients were offered the POC CD4 test, and 197 patients were not offered the test. No differences in patient characteristics were observed between the 2 groups. Approximately 62.7% of patients were successfully followed up 8 weeks after HIV testing, with no differences observed between testing groups. Among those followed up, 54.4% reported completing their referral visit. Patients offered the POC CD4 test were more likely to complete the referral visit for further HIV care (relative risk 1.25, 95% confidence interval: 1.00 to 1.57)., Conclusions: In this mobile HCT setting, patients offered POC CD4 testing as part of the HCT services were more likely to visit a referral clinic after testing, suggesting that rapid CD4 testing technology may improve linkage to HIV care. Future research can evaluate options for adjusting HCT services if POC CD4 testing was included permanently and the cost-effectiveness of the POC CD4 testing compared with other approaches for improving linkage of care.

Sixteen million children in developing and middle-income countries have been orphaned by HIV/AIDS, and at least another million children per year are rendered vulnerable by parental HIV/AIDS-related illness. Since 2003 the US government has provided approximately $1.6 billion to give four million of these children care and support through the President's Emergency Plan for AIDS Relief (PEPFAR). We conducted five studies to evaluate the effectiveness of PEPFAR's interventions for such children in East Africa and southern Africa. We found evidence of beneficial changes in school enrollment rates and on the psychosocial well-being of children. However, we could not demonstrate empirically the impact of most of the PEPFAR initiatives that we examined, primarily because of a lack of baseline data and clear outcome and impact indicators. We also found that many programs were spread so thin across a vulnerable population that little in the way of services actually reached beneficiaries, which raises questions about whether PEPFAR funds are sufficient, or if the program is attempting to do much with too few resources. We offer several recommendations, including better measuring the effect of programs for orphans and vulnerable children by collecting baseline data and conducting well-designed, rigorous outcome and impact evaluations.

Background: Simple interventions for improving health workers' adherence to malaria case-management guidelines are urgently required across Africa. A recent trial in Kenya showed that text-message reminders sent to health workers' mobile phones improved management of pediatric outpatients by 25 percentage points. In this paper we examine costs and cost-effectiveness of this intervention., Methods/findings: We evaluate costs and cost-effectiveness in 2010 USD under three implementation scenarios: (1) as implemented under study conditions in study areas; (2) if the intervention was routinely implemented by the Ministry of Health (MoH) in the same areas; and (3) if the intervention was scaled up nationally. Under study conditions, intervention costs were 19,342 USD, of which 45% were for developing and pretesting text-messages, 12% for developing text-message distribution system, 29% for collecting health workers' phone numbers, and 13% were costs of sending text-messages and monitoring of the system. If the intervention was implemented in the same areas by the MoH, the costs would be 28% lower (13,920 USD) due to lower costs of collecting health workers' numbers. The cost of national scale-up would be 97,350 USD, and the majority of these costs (66%) would be for sending text-messages. The cost per additional child correctly managed was 0.50 USD under study conditions, 0.36 USD if implemented by the MoH in the same area, and estimated at only 0.03 USD if implemented nationally. Even if the effect size was only 5% or the cost on the national scale was 400% higher than estimated, the cost per additional child correctly managed would be only 0.16 USD., Conclusions: A simple text-messaging intervention improving health worker adherence to malaria guidelines is effective and inexpensive. Further research is justified to optimize delivery of the intervention and expand targets beyond children and malaria disease.

Background: Information on the costs of implementing programmes designed to provide support of orphans and vulnerable children (OVC) in sub-Saharan Africa and elsewhere is increasingly being requested by donors for programme evaluation purposes. To date, little information exists to document the costs and structure of costs of OVC programmes as actually implemented "on the ground" by local non-governmental organizations (NGOs). This analysis provides a practical, six-step approach that NGOs can incorporate into routine operations to evaluate their costs of implementing their OVC programmes annually. This approach is applied to the Community-Based Care for Orphans and Vulnerable Children (CBCO) Program implemented by BIDII (a Kenyan NGO) in Eastern Province of Kenya., Methods and Results: The costing methodology involves the following six steps: accessing and organizing the NGO's annual financial report into logical sub-categories; reorganizing the sub-categories into input cost categories to create a financial cost profile; estimating the annual equivalent payment for programme equipment; documenting donations to the NGO for programme implementation; including a portion of NGO organizational costs not attributed to specific programmes; and including the results of Steps 3-5 into an expanded cost profile. Detailed results are provided for the CBCO programme., Conclusions: This paper shows through a concrete example how NGOs implementing OVC programmes (and other public health programmes) can organize themselves for data collection and documentation prospectively during the implementation of their OVC programmes so that costing analyses become routine practice to inform programme implementation rather than a painful and flawed retrospective activity. Such information is required if the costs and outcomes achieved by OVC programmes will ever be clearly documented and compared across OVC programmes and other types of programmes (prevention, treatment, etc.).

Objective: To estimate rates of completion of CD4+ lymphocyte testing (CD4 testing) within 12 weeks of testing positive for human immunodeficiency virus (HIV) at a large HIV/AIDS clinic in South Africa, and to identify clinical and demographic predictors for completion., Methods: In our study, CD4 testing was considered complete once a patient had retrieved the test results. To determine the rate of CD4 testing completion, we reviewed the records of all clinic patients who tested positive for HIV between January 2008 and February 2009. We identified predictors for completion through multivariate logistic regression., Findings: Of the 416 patients who tested positive for HIV, 84.6% initiated CD4 testing within the study timeframe. Of these patients, 54.3% were immediately eligible for antiretroviral therapy (ART) because of a CD4 cell count ≤ 200/µl, but only 51.3% of the patients in this category completed CD4 testing within 12 weeks of HIV testing. Among those not immediately eligible for ART (CD4 cells > 200/µl), only 14.9% completed CD4 testing within 12 weeks. Overall, of HIV+ patients who initiated CD4 testing, 65% did not complete it within 12 weeks of diagnosis. The higher the baseline CD4 cell count, the lower the odds of completing CD4 testing within 12 weeks., Conclusion: Patient losses between HIV testing, baseline CD4 cell count and the start of care and ART are high. As a result, many patients receive ART too late. Health information systems that link testing programmes with care and treatment programmes are needed.

Objective: To estimate loss to follow up (LTFU) between initial enrollment and the first scheduled return medical visit of a pre-antiretroviral therapy (ART) care program for patients not eligible for ART., Methods: The study was conducted at a public-sector HIV clinic in Johannesburg. We reviewed records of all patients newly enrolled in the pre-ART care program and not yet eligible for ART between January 2007 and February 2008. Crude proportions of patients completing their first return medical visit stratified by patient characteristics were calculated. A modified-Poisson approach was used to estimate directly relative risks of returning for their first return medical visit within 1 year adjusting for patient characteristics as potential confounders., Results: A total of 356 patients were identified. Two-thirds had a CD4 count > 350 cells/microl (median [IQR] CD4 = 458 [394, 585]) and were scheduled to return in 6 months for a first medical visit. Seventy-four percent of these patients did not return within one year for this visit. The remaining 36% of all patients had a baseline CD4 count 251-350 cells/microl and were scheduled to return in 3 months. Only 6% of these patients returned within 4 months; 41% returned within one year. Relative risks were positively associated with a patient being employed and negatively associated with the baseline CD4 count., Conclusions: Given the high rate of LTFU immediately after enrolling in pre-ART care, it is clear that care programs are not expediting the timely initiation of ART. Significantly improved adherence to pre-ART care and monitoring for patients not yet eligible for ART is required for South Africa to achieve its AIDS strategy goals and reduce the problem of late presentation and initiation of ART.

Improvements in physical wellbeing during the first six months on antiretroviral therapy (ART) are well known, but little is known regarding long-term follow-up. We conducted a prospective cohort study among 222 HIV-positive adult tea plantation workers in western Kenya to assess wellbeing over their first two years on ART. Study subjects completed a standardized questionnaire during repeat ART clinic visits. A 30-day recall period was used to elicit the number of days when subjects experienced poor health and the number of days that pain made it difficult to complete usual activities at home and work. A seven-day recall period was used to assess the severity of bodily pain, nausea, fatigue, and rash. Prevalence of most symptoms declined over time. A median of seven days poor health during the first month on ART declined to three days in the 24th month (p=0.043). For pain making usual activities difficult, a median of seven days during the first month on ART fell to zero by 12 months (p< or =0.0001) but increased to three days by two years. Any bodily pain (range 59-83%) and fatigue (range 51-84%) over the past seven days were common through two years. However, pain and fatigue often over the past seven days declined over two years (from 24-10% (p=0.067) and 41-15% (p=0.002)). Skin rash was rare at all times, though higher at two years (8.6%) than any other time. Initial improvements in physical wellbeing were sustained over two years, however, increased pain and skin rash at year two may indicate problems as treatment programs mature. These improvements in physical wellbeing will be important in sustaining the long-term success of HIV treatment programs.

Background: As access to antiretroviral therapy (ART) has grown in Africa, attention has turned to evaluating the socio-economic impacts of ART. One key issue is the extent to which improvements in health resulting from ART allows individuals to return to work and earn income. Improvements in health from ART may also be associated with reduced impaired presenteeism, which is the loss of productivity when an ill or disabled individual attends work but accomplishes less at his or her usual tasks or shifts to other, possibly less valuable, tasks., Methods: Longitudinal data for this analysis come from company payroll records for 97 HIV-infected tea estate workers (the index group, 56 women, 41 men) and a comparison group of all workers assigned to the same work teams (n = 2485, 1691 men, 794 women) for a 37-month period covering two years before and one year after initiating ART. We used nearest neighbour matching methods to estimate the impacts of HIV/AIDS and ART on three monthly employment outcomes for tea estate workers in Kenya--days plucking tea, days assigned to non-plucking assignments, and kilograms harvested when plucking., Results: The female index group worked 30% fewer days plucking tea monthly than the matched female comparison group during the final 9 months pre-ART. They also worked 87% more days on non-plucking assignments. While the monthly gap between the two groups narrowed after beginning ART, the female index group worked 30% fewer days plucking tea and about 100% more days on non-plucking tasks than the comparison group after one year on ART. The male index group was able to maintain a similar pattern of work as their comparison group except during the initial five months on therapy., Conclusion: Significant impaired presenteeism continued to exist among the female index group after one year on ART. Future research needs to explore further the socio-economic implications of HIV-infected female workers on ART being less productive than the general female workforce over sustained periods of time.