Genomic rearrangements generate hypervariable mini-chromosomes in host-specific isolates of the blast fungus.

Supernumerary mini-chromosomes-a unique type of genomic structural variation-have been implicated in the emergence of virulence traits in plant pathogenic fungi. However, the mechanisms that facilitate the emergence and maintenance of mini-chromosomes across fungi remain poorly understood. In the blast fungus Magnaporthe oryzae (Syn. Pyricularia oryzae), mini-chromosomes have been first described in the early 1990s but, until very recently, have been overlooked in genomic studies. Here we investigated structural variation in four isolates of the blast fungus M. oryzae from different grass hosts and analyzed the sequences of mini-chromosomes in the rice, foxtail millet and goosegrass isolates. The mini-chromosomes of these isolates turned out to be highly diverse with distinct sequence composition. They are enriched in repetitive elements and have lower gene density than core-chromosomes. We identified several virulence-related genes in the mini-chromosome of the rice isolate, including the virulence-related polyketide synthase Ace1 and two variants of the effector gene AVR-Pik. Macrosynteny analyses around these loci revealed structural rearrangements, including inter-chromosomal translocations between core- and mini-chromosomes. Our findings provide evidence that mini-chromosomes emerge from structural rearrangements and segmental duplication of core-chromosomes and might contribute to adaptive evolution of the blast fungus.

Sexual Practice Changes Post-HIV Diagnosis Among Men Who Have Sex with Men in the United States: A Systematic Review and Meta-analysis.

Men who have sex with men (MSM) often change sexual behaviors following HIV diagnosis. This systematic review examined such changes, including sero-adaptive behaviors (i.e., deliberate safer-sex practices to reduce transmission risk) to better understand the magnitude of their association with HIV diagnosis. We searched four databases (1996-2017) and reviewed references from other systematic reviews. We included studies conducted in the United States that compared sexual behavior among HIV-infected "aware" versus "unaware" MSM. We meta-analytically pooled RRs and associated 95% confidence intervals (CI) using random-effects models, and assessed risk of bias and evidence quality. Twenty studies reported k = 131 effect sizes on sexual practices outcomes, most of which reported changes in unprotected sex (k = 85), and on sex with at-risk partners (k = 76); 11 reported sero-adaptive behaviors. Unprotected anal intercourse with an HIV-uninfected/unknown-status partner was less likely among aware MSM (insertive position: k = 2, RR 0.26, 95% CI 0.17, 0.41; receptive position: k = 2, RR 0.53, 95% CI 0.37, 0.77). Risk of not always serosorting among aware MSM (k = 3) was RR = 0.92 (0.83, 1.02). Existing evidence, although low-quality, suggests that HIV-infected MSM tend to adopt safer sexual practices once aware of their diagnosis. Variation in reporting of outcomes limits their comparability. Sero-adaptive behavior data are sparse.

Cost Analysis of the Positive Health Check Intervention to Suppress HIV Viral Load and Retain Patients in HIV Clinical Care.

CONTEXT: Digital video-based behavioral interventions are effective tools for improving HIV care and treatment outcomes. OBJECTIVE: To assess the costs of the Positive Health Check (PHC) intervention delivered in HIV primary care settings. DESIGN, SETTING, AND INTERVENTION: The PHC study was a randomized trial evaluating the effectiveness of a highly tailored, interactive video-counseling intervention delivered in 4 HIV care clinics in the United States in improving viral suppression and retention in care. Eligible patients were randomized to either the PHC intervention or the control arm. Control arm participants received standard of care (SOC), and intervention arm participants received SOC plus PHC. The intervention was delivered on computer tablets in the clinic waiting rooms. The PHC intervention improved viral suppression among male participants. A microcosting approach was used to assess the program costs, including labor hours, materials and supplies, equipment, and office overhead. PARTICIPANTS: Persons with HIV infection, receiving care in participating clinics. MAIN OUTCOME MEASURES: The primary outcome was the number of patients virally suppressed, defined as having fewer than 200 copies/mL by the end of their 12-month follow-up. RESULTS: A total of 397 (range across sites [range], 95-102) participants were enrolled in the PHC intervention arm, of whom 368 participants (range, 82-98) had viral load data at baseline and were included in the viral load analyses. Of those, 210 (range, 41-63) patients were virally suppressed at the end of their 12-month follow-up visit. The overall annual program cost was $402 274 (range, $65 581-$124 629). We estimated the average program cost per patient at $1013 (range, $649-$1259) and the cost per patient virally suppressed at $1916 (range, $1041-$3040). Recruitment and outreach costs accounted for 30% of PHC program costs. CONCLUSIONS: The costs of this interactive video-counseling intervention are comparable with other retention in care or reengagement interventions.

Estimated Lifetime HIV-Related Medical Costs in the United States.

BACKGROUND: Lifetime cost estimates are a useful tool in measuring the economic burden of HIV in the United States. Previous estimation methods need to be updated, given improving antiretroviral therapy regimens and updated costs. METHODS: We used an updated version of the agent-based model progression and transmission of HIV (PATH) 3.0 to reflect current regimens and costs. We simulated a cohort of those infected in 2015 until the last person had died to track the lifetime costs for treatment of HIV, including HIV health care utilization costs (inpatient, outpatient, opportunistic infection prophylaxis, non-HIV medication, and emergency department), opportunistic infection treatment costs, and testing costs. We assumed a median per-person diagnosis delay of 3 years and a 3% base monthly probability of dropout from care for a base-case scenario. Additionally, we modeled a most favorable scenario (median diagnosis delay of 1 year and 1% base dropout rate) and a least favorable scenario (median diagnosis delay of 5 years and 5% base dropout rate). RESULTS: We estimated an average lifetime HIV-related medical cost for a person with HIV of $420,285 (2019 US$) discounted (3%) and $1,079,999 undiscounted for a median 3-year diagnosis delay and 3% base dropout rate. Our discounted cost estimate was $490,045 in our most favorable scenario and $326,411 in our least favorable scenario. CONCLUSIONS: Lifetime per-person HIV-related medical costs depend on the time from infection to diagnosis and the likelihood of dropping out of care. Our results, which are similar to previous studies, reflect updated antiretroviral therapy regimens and costs for HIV treatment.

Optimal Allocation of Societal HIV Prevention Resources to Reduce HIV Incidence in the United States.

Objectives. To optimize combined public and private spending on HIV prevention to achieve maximum reductions in incidence.Methods. We used a national HIV model to estimate new infections from 2018 to 2027 in the United States. We estimated current spending on HIV screening, interventions that move persons with diagnosed HIV along the HIV care continuum, pre-exposure prophylaxis, and syringe services programs. We compared the current funding allocation with 2 optimal scenarios: (1) a limited-reach scenario with expanded efforts to serve eligible persons and (2) an ideal, unlimited-reach scenario in which all eligible persons could be served.Results. A continuation of the current allocation projects 331 000 new HIV cases over the next 10 years. The limited-reach scenario reduces that number by 69%, and the unlimited reach scenario by 94%. The most efficient funding allocations resulted in prompt diagnosis and sustained viral suppression through improved screening of high-risk persons and treatment adherence support for those infected.Conclusions. Optimal allocations of public and private funds for HIV prevention can achieve substantial reductions in new infections. Achieving reductions of more than 90% under current funding will require that virtually all infected receive sustained treatment.

Change in Condom Use in Populations Newly Aware of HIV Diagnosis in the United States and Canada: A Systematic Review and Meta-Analysis.

HIV-infected individuals "aware" of their infection are more likely to use condoms, compared to HIV-infected "unaware" persons. To quantify this likelihood, we undertook a systematic review and meta-analysis of U.S. and Canadian studies. Twenty-one eligible studies included men who have sex with men (MSM; k = 15), persons who inject drugs (PWID; k = 2), and mixed populations of high-risk heterosexuals (HRH; k = 4). Risk ratios (RR) of "not always using condoms" with partners of any serostatus were lower among aware MSM (RR 0.44 [not significant]), PWID (RR 0.70) and HRH (RR 0.27); and, in aware MSM, with partners of HIV-uninfected or unknown status (RR 0.46). Aware individuals had lower "condomless sex likelihood" with HIV-uninfected or unknown status partners (MSM: RR 0.58; male PWID: RR 0.44; female PWID: RR 0.65; HRH: RR 0.35) and with partners of any serostatus (MSM only, RR 0.72). The association diminished over time. High risk of bias compromised evidence quality.

National Trends in Drug Payments for HIV Preexposure Prophylaxis in the United States, 2014 to 2018 : A Retrospective Cohort Study.

BACKGROUND: Use of HIV preexposure prophylaxis (PrEP) has increased nationwide, but the magnitude and distribution of PrEP medication costs across the health care system are unknown. OBJECTIVE: To estimate out-of-pocket (OOP) and third-party payments using a large pharmacy database. DESIGN: Retrospective cohort study. SETTING: Prescriptions for tenofovir disoproxil fumarate with emtricitabine (TDF-FTC) for PrEP in the United States in the IQVIA Longitudinal Prescriptions database, which covers more than 90% of retail pharmacy prescriptions. MEASUREMENTS: Third-party, OOP, and total payments were compared by third-party payer, classified as commercial, Medicaid, Medicare, manufacturer assistance program, or other. Missing payment data were imputed using a generalized linear model to estimate overall PrEP medication payments. RESULTS: Annual PrEP prescriptions increased from 73 739 to 1 100 684 during 2014 to 2018. Over that period, the average total payment for 30 TDF-FTC tablets increased from $1350 to $1638 (5.0% compound annual growth rate) and the average OOP payment increased from $54 to $94 (14.9% compound annual growth rate). Of the $1638 in total payments per 30 TDF-FTC tablets in 2018, OOP payments accounted for $94 (5.7%) and third-party payments for $1544 (94.3%). Out-of-pocket payments per 30 tablets were lower among Medicaid recipients ($3) than among those with Medicare ($80) or commercial insurance ($107). Payments for PrEP medication in the IQVIA database in 2018 totaled $2.08 billion; $1.68 billion (80.7%) originated from prescriptions for persons with commercial insurance, $200 million (9.6%) for those with Medicaid, $48 million (2.3%) for those with Medicare, and $127 million (6.1%) for those with manufacturer assistance. LIMITATION: The IQVIA database does not capture every prescription nationwide. CONCLUSION: Third-party and OOP payments per 30 TDF-FTC tablets increased annually. The $2.08 billion in PrEP medication payments in 2018 is an underestimation of national costs. High costs to the health care system may hinder PrEP expansion. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Yerba mate (Ilex paraguariensis, A. St.-Hil.) de novo transcriptome assembly based on tissue specific genomic expression profiles.

BACKGROUND: The most common infusion in southern Latin-American countries is prepared with dried leaves of Ilex paraguariensis A. St.-Hil., an aboriginal ancestral beverage known for its high polyphenols concentration currently consumed in > 90% of homes in Argentina, in Paraguay and Uruguay. The economy of entire provinces heavily relies on the production, collection and manufacture of Ilex paraguariensis, the fifth plant species with highest antioxidant activity. Polyphenols are associated to relevant health benefits including strong antioxidant properties. Despite its regional relevance and potential biotechnological applications, little is known about functional genomics and genetics underlying phenotypic variation of relevant traits. By generating tissue specific transcriptomic profiles, we aimed to comprehensively annotate genes in the Ilex paraguariensis phenylpropanoid pathway and to evaluate differential expression profiles. RESULTS: In this study we generated a reliable transcriptome assembly based on a collection of 15 RNA-Seq libraries from different tissues of Ilex paraguariensis. A total of 554 million RNA-Seq reads were assembled into 193,897 transcripts, where 24,612 annotated full-length transcripts had complete ORF. We assessed the transcriptome assembly quality, completeness and accuracy using BUSCO and TransRate; consistency was also evaluated by experimentally validating 11 predicted genes by PCR and sequencing. Functional annotation against KEGG Pathway database identified 1395 unigenes involved in biosynthesis of secondary metabolites, 531 annotated transcripts corresponded to the phenylpropanoid pathway. The top 30 differentially expressed genes among tissue revealed genes involved in photosynthesis and stress response. These significant differences were then validated by qRT-PCR. CONCLUSIONS: Our study is the first to provide data from whole genome gene expression profiles in different Ilex paraguariensis tissues, experimentally validating in-silico predicted genes key to the phenylpropanoid (antioxidant) pathway. Our results provide essential genomic data of potential use in breeding programs for polyphenol content. Further studies are necessary to assess if the observed expression variation in the phenylpropanoid pathway annotated genes is related to variations in leaves' polyphenol content at the population scale. These results set the current reference for Ilex paraguariensis genomic studies and provide a substantial contribution to research and biotechnological applications of phenylpropanoid secondary metabolites.

Ability to develop broadly neutralizing HIV-1 antibodies is not restricted by the germline Ig gene repertoire.

The human Ig repertoire is vast, producing billions of unique Abs from a limited number of germline Ig genes. The IgH V region (IGHV) is central to Ag binding and consists of 48 functional genes. In this study, we analyzed whether HIV-1-infected individuals who develop broadly neutralizing Abs show a distinctive germline IGHV profile. Using both 454 and Illumina technologies, we sequenced the IGHV repertoire of 28 HIV-infected South African women from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 and 004 cohorts, 13 of whom developed broadly neutralizing Abs. Of the 259 IGHV alleles identified in this study, approximately half were not found in the International Immunogenetics Database (IMGT). This included 85 entirely novel alleles and 38 alleles that matched rearranged sequences in non-IMGT databases. Analysis of the rearranged H chain V region genes of mAbs isolated from seven of these women, as well as previously isolated broadly neutralizing Abs from other donors, provided evidence that at least eight novel or non-IMGT alleles contributed to functional Abs. Importantly, we found that, despite a wide range in the number of IGHV alleles in each individual, including alleles used by known broadly neutralizing Abs, there were no significant differences in germline IGHV repertoires between individuals who do and do not develop broadly neutralizing Abs. This study reports novel IGHV repertoires and highlights the importance of a fully comprehensive Ig database for germline gene usage prediction. Furthermore, these data suggest a lack of genetic bias in broadly neutralizing Ab development in HIV-1 infection, with positive implications for HIV vaccine design.

Assessing HIV acquisition risks among men who have sex with men in the United States of America.

Men who have sex with men (MSM) can reduce their risk of acquiring human immunodeficiency virus (HIV) by using various prevention strategies and by understanding the effectiveness of each option over the short- and long-term. Strategies examined were: circumcision; insertive anal sex only; consistent, 100% self-reported condom use; and pre-exposure prophylaxis (PrEP). PrEP efficacy was based on three levels of adherence. The cumulative HIV acquisition risk among MSM over periods of 1 year and 10 years were estimated with and without single and combinations of prevention strategies. A Bernoulli process model was used to estimate risk. In the base case with no prevention strategies, the 1-year risk of HIV acquisition among MSM was 8.8%. In contrast, the 1-year risk associated with circumcision alone was 6.9%; with insertive sex only, 5.5%; with 100% self-reported condom use, 2.7%; and with average, high, and very high PrEP adherence, 5.1%, 2.5%, and 0.7%, respectively. The 10-year risk of HIV acquisition among MSM with no prevention strategy was 60.3%. In contrast, that associated with circumcision alone was 51.1%; with insertive sex only, 43.1%; with 100% self-reported condom use, 24.0%; and with average, high, and very high PrEP adherence, 40.5%, 22.2%, and 7.2%, respectively. While MSM face substantial risk of HIV, there are now a number of prevention strategies that reduce risk. Very high adherence to PrEP alone or with other strategies appears to be the most powerful tool for HIV prevention.

Cost analysis of a novel HIV testing strategy in community pharmacies and retail clinics.

OBJECTIVE: To document the cost of implementing point-of-care (POC) human immunodeficiency virus (HIV) rapid testing in busy community pharmacies and retail clinics. Providing HIV testing services in community pharmacies and retail clinics is an innovative way to expand HIV testing. The cost of implementing POC HIV rapid testing in a busy retail environment needs to be documented to provide program and policy leaders with adequate information for planning and budgeting. DESIGN: Cost analysis from a pilot project that provided confidential POC HIV rapid testing services in community pharmacies and retail clinics. SETTING: The pharmacy sites were operated under several different ownership structures (for-profit, nonprofit, sole proprietorship, corporation, public, and private) in urban and rural areas. We included data from the initial six sites that participated in the project. We collected the time spent by pharmacy and retail clinic staff for pretest and posttest counseling in an activity log for time-in-motion for each interaction. PARTICIPANTS: Pharmacists and retail clinic staff. INTERVENTION: HIV rapid testing. MAIN OUTCOME MEASURES: The total cost was calculated to include costs of test kits, control kits, shipping, test supplies, training, reporting, program administration, and advertising. RESULTS: The six sites trained 22 staff to implement HIV testing. A total of 939 HIV rapid tests were conducted over a median time of 12 months, of which 17 were reactive. Median pretest counseling time was 2 minutes. Median posttest counseling time was 2 minutes for clients with a nonreactive test and 10 minutes for clients with a reactive test. The average cost per person tested was an estimated $47.21. When we considered only recurrent costs, the average cost per person tested was $32.17. CONCLUSIONS: Providing POC HIV rapid testing services required a modest amount of staff time and costs that are comparable to other services offered in these settings. HIV testing in pharmacies and retail clinics can provide an additional alternative venue for increasing the availability and accessibility of HIV testing services in the United States.

Centers for Disease Control and Prevention Funding for HIV Testing Associated With Higher State Percentage of Persons Tested.

OBJECTIVES: To assess the association between state per capita allocations of Centers for Disease Control and Prevention (CDC) funding for HIV testing and the percentage of persons tested for HIV. SETTING AND PARTICIPANTS: We examined data from 2 sources: 2011 Behavioral Risk Factor Surveillance System and 2010-2011 State HIV Budget Allocations Reports. Behavioral Risk Factor Surveillance System data were used to estimate the percentage of persons aged 18 to 64 years who had reported testing for HIV in the last 2 years in the United States by state. State HIV Budget Allocations Reports were used to calculate the state mean annual per capita allocations for CDC-funded HIV testing reported by state and local health departments in the United States. DESIGN: The association between the state fixed-effect per capita allocations for CDC-funded HIV testing and self-reported HIV testing in the last 2 years among persons aged 18 to 64 years was assessed with a hierarchical logistic regression model adjusting for individual-level characteristics. MAIN OUTCOME: The percentage of persons tested for HIV in the last 2 years. RESULTS: In 2011, 18.7% (95% confidence interval = 18.4-19.0) of persons reported being tested for HIV in last 2 years (state range, 9.7%-28.2%). During 2010-2011, the state mean annual per capita allocation for CDC-funded HIV testing was $0.34 (state range, $0.04-$1.04). A $0.30 increase in per capita allocation for CDC-funded HIV testing was associated with an increase of 2.4 percentage points (14.0% vs 16.4%) in the percentage of persons tested for HIV per state. CONCLUSIONS: Providing HIV testing resources to health departments was associated with an increased percentage of state residents tested for HIV.

Analyzing the Costs and Impact of the TakeMeHome Program, a Public-Private Partnership to Deliver HIV Self-Test Kits in the United States.

BACKGROUND: HIV testing is an entry point to access HIV care and prevention services. Building Healthy Online Communities developed a website ( TakeMeHome.org ) where participants can order HIV home test kits. The purpose of this study was to analyze the costs and impact of the TakeMeHome program. METHODS: We estimated the costs of TakeMeHome across all participating jurisdictions for the first year of the program. We estimated program costs using purchase orders and invoices, contracts, and allocation of staff time, and the costs included website design, participant recruitment, administration and overhead, HIV self-test kits, and shipping and handling. Primary outcomes of the analysis were total program cost, cost per HIV test, and cost per new HIV diagnosis. RESULTS: The TakeMeHome program distributed 5323 HIV self-tests to 4859 participants over a 12-month period. The total program cost over this period was $314,870. The cost per HIV test delivered was estimated at $59, and the cost per person tested was $65. The program identified 18 confirmed new HIV diagnoses (0.6% positivity) verified with surveillance data in 7 health jurisdictions at $169,890. The cost per confirmed new HIV diagnosis was estimated at $9440. CONCLUSIONS: The TakeMeHome program delivered HIV self-testing at a reasonable cost, and the program may be a cost-effective use of HIV prevention resources. The public-private partnership can be an effective mechanism to validate HIV diagnoses identified with self-testing and provide HIV prevention and linkage to care services.

Estimating the Cost-Effectiveness of HIV Self-Testing in the United States Using Net Benefit Regression.

BACKGROUND: Cost-effectiveness analysis of HIV self-testing using patient-level data from a randomized clinical trial can inform HIV prevention funding decisions. Cost-effectiveness analysis using net-benefit regression addresses the sampling uncertainty in the trial data and the variability of policymakers' willingness to pay (WTP). METHODS: We used published data from a 12-month longitudinal randomized clinical trial that enrolled 2665 men who had sex with men randomly assigned to the self-testing arm (participants receiving self-test kits) and control arm (participants receiving standard-of-care), and the self-testing arm identified 48 additional new HIV cases. We used net-benefit regression to investigate the cost-effectiveness of an HIV self-testing intervention, which compared the incremental cost per new HIV diagnosis with policymakers' WTP thresholds. We addressed the uncertainties in estimating the incremental cost and the policymakers' WTP per new diagnosis through the incremental net-benefit (INB) regression and cost-effectiveness acceptability curve (CEAC) analyses. RESULTS: From the health care provider's perspective, the INB analysis showed a positive net benefit of HIV self-testing compared with standard-of-care when policymakers' WTP per new HIV diagnosis was $9365 (95% confidence interval: $5700 to $25,500) or higher. The CEAC showed that the probability of HIV self-testing being cost-effective compared with standard-of-care was 58% and >99% at a WTP of $10 000 and $50 000 per new HIV diagnosis, respectively. CONCLUSION: The INB and CEAC analyses suggest that HIV self-testing has the potential to be cost-effective for relatively low values of policymakers' WTP.

Characterizing the emergence and persistence of drug resistant mutations in HIV-1 subtype C infections using 454 ultra deep pyrosequencing.

BACKGROUND: The role of HIV-1 RNA in the emergence of resistance to antiretroviral therapies (ARTs) is well documented while less is known about the role of historical viruses stored in the proviral DNA. The primary focus of this work was to characterize the genetic diversity and evolution of HIV drug resistant variants in an individual's provirus during antiretroviral therapy using next generation sequencing. METHODS: Blood samples were collected prior to antiretroviral therapy exposure and during the course of treatment from five patients in whom drug resistance mutations had previously been identified using consensus sequencing. The spectrum of viral variants present in the provirus at each sampling time-point were characterized using 454 pyrosequencing from multiple combined PCR products. The prevalence of viral variants containing drug resistant mutations (DRMs) was characterized at each time-point. RESULTS: Low abundance drug resistant viruses were identified in 14 of 15 sampling time-points from the five patients. In all individuals DRMs against current therapy were identified at one or more of the sampling time-points. In two of the five individuals studied these DRMs were present prior to treatment exposure and were present at high prevalence within the amplified and sequenced viral population. DRMs to drugs other than those being currently used were identified in four of the five individuals. CONCLUSION: The presence of DRMs in the provirus, regardless of their observed prevalence did not appear to have an effect on clinical outcomes in the short term suggesting that the drug resistant viral variants present in the proviral DNA do not appear to play a role in the short term in facilitating the emergence of drug resistance.

Costs of Providing Preexposure Prophylaxis for HIV Prevention at Community Health Centers in the United States.

OBJECTIVE: Preexposure prophylaxis (PrEP) is recommended for people at risk of acquiring HIV. We assessed billable costs associated with PrEP delivery at community health centers. METHODS: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) study is an observational cohort of people receiving daily oral PrEP at participating federally qualified health centers and other community health centers. We assessed health care utilization and billable costs of providing PrEP at 2 health centers, 1 in Chicago, Illinois, and 1 in Washington, DC, from 2014 to 2018. The health centers followed the clinical practice guidelines for PrEP provision, including regular visits with health care providers and ongoing laboratory monitoring. Using clinic billing records and Current Procedural Terminology (CPT) coding, we retrospectively extracted data on the frequency and costs (in 2017 US dollars) of PrEP clinic visits and laboratory screening, for each patient, for 12 months since first PrEP prescription. RESULTS: The average annual number of PrEP clinic visits and associated laboratory screens per patient was 5.1 visits and 25.2 screens in Chicago (n = 482 patients) and 5.4 visits and 24.8 screens in Washington, DC (n = 56 patients). The average annual PrEP billable cost per patient was $583 for clinic visits and $1070 for laboratory screens in Chicago and $923 for clinic visits and $1018 for laboratory screens in Washington, DC. The average annual total cost per patient was $1653 (95% CI, $1639-$1668) in Chicago and $1941 (95% CI, $1811-$2071) in Washington, DC. CONCLUSIONS: Our analysis, which provides PrEP billable cost estimates based on empirical data, may help inform health care providers who are considering implementing this HIV prevention strategy.

Costs and cost-effectiveness of a collaborative data-to-care intervention for HIV treatment and care in the United States.

INTRODUCTION: Data-to-care programmes utilize surveillance data to identify persons who are out of HIV care, re-engage them in care and improve HIV care outcomes. We assess the costs and cost-effectiveness of re-engagement in an HIV care intervention in the United States. METHODS: The Cooperative Re-engagement Control Trial (CoRECT) employed a data-to-care collaborative model between health departments and HIV care providers, August 2016-July 2018. The health departments in Connecticut (CT), Massachusetts (MA) and Philadelphia (PHL) collaborated with HIV clinics to identify newly out-of-care patients and randomize them to receive usual linkage and engagement in care services (standard-of-care control arm) or health department-initiated active re-engagement services (intervention arm). We used a microcosting approach to identify the activities and resources involved in the CoRECT intervention, separate from the standard-of-care, and quantified the costs. The cost data were collected at the start-up and recurrent phases of the trial to incorporate potential variation in the intervention costs. The costs were estimated from the healthcare provider perspective. RESULTS: The CoRECT trial in CT, MA and PHL randomly assigned on average 327, 316 and 305 participants per year either to the intervention arm (n = 166, 159 and 155) or the standard-of-care arm (n = 161, 157 and 150), respectively. Of those randomized, the number of participants re-engaged in care within 90 days in the intervention and standard-of-care arms was 85 and 70 in CT, 84 and 70 in MA, and 98 and 67 in PHL. The additional number of participants re-engaged in care in the intervention arm compared with those in the standard-of-care arm was 15 (CT), 14 (MA) and 31 (PHL). We estimated the annual total cost of the CoRECT intervention at $490,040 in CT, $473,297 in MA and $439,237 in PHL. The average cost per participant enrolled was $2952, $2977 and $2834 and the average cost per participant re-engaged in care was $5765, $5634 and $4482. We estimated an incremental cost per participant re-engaged in care at $32,669 (CT), $33,807 (MA) and $14,169 (PHL). CONCLUSIONS: The costs of the CoRECT intervention that identified newly out-of-care patients and re-engaged them in HIV care are comparable with other similar interventions, suggesting a potential for its cost-effectiveness in the US context.

Comparison of methods for estimating the cost of human immunodeficiency virus-testing interventions.

CONTEXT: The Centers for Disease Control and Prevention (CDC), Division of HIV/AIDS Prevention, spends approximately 50% of its $325 million annual human immunodeficiency virus (HIV) prevention funds for HIV-testing services. An accurate estimate of the costs of HIV testing in various settings is essential for efficient allocation of HIV prevention resources. OBJECTIVES: To assess the costs of HIV-testing interventions using different costing methods. DESIGN, SETTINGS, AND PARTICIPANTS: We used the microcosting-direct measurement method to assess the costs of HIV-testing interventions in nonclinical settings, and we compared these results with those from 3 other costing methods: microcosting-staff allocation, where the labor cost was derived from the proportion of each staff person's time allocated to HIV testing interventions; gross costing, where the New York State Medicaid payment for HIV testing was used to estimate program costs, and program budget, where the program cost was assumed to be the total funding provided by Centers for Disease Control and Prevention. MAIN OUTCOME MEASURES: Total program cost, cost per person tested, and cost per person notified of new HIV diagnosis. RESULTS: The median costs per person notified of a new HIV diagnosis were $12 475, $15 018, $2697, and $20 144 based on microcosting-direct measurement, microcosting-staff allocation, gross costing, and program budget methods, respectively. Compared with the microcosting-direct measurement method, the cost was 78% lower with gross costing, and 20% and 61% higher using the microcosting-staff allocation and program budget methods, respectively. CONCLUSIONS: Our analysis showed that HIV-testing program cost estimates vary widely by costing methods. However, the choice of a particular costing method may depend on the research question being addressed. Although program budget and gross-costing methods may be attractive because of their simplicity, only the microcosting-direct measurement method can identify important determinants of the program costs and provide guidance to improve efficiency.

Cost-effectiveness of using social networks to identify undiagnosed HIV infection among minority populations.

CONTEXT: In 2003, the Centers for Disease Control and Prevention launched the Advancing HIV Prevention project to implement new strategies for diagnosing human immunodeficiency virus (HIV) infections outside medical settings and prevent new infections by working with HIV-infected persons and their partners. OBJECTIVES: : To assess the cost and effectiveness of a social network strategy to identify new HIV diagnoses among minority populations. DESIGN, SETTINGS, AND PARTICIPANTS: Four community-based organizations (CBOs) in Boston, Philadelphia, and Washington, District of Columbia, implemented a social network strategy for HIV counseling and testing from October 2003 to December 2005. We used standardized cost collection forms to collect program costs attributable to staff time, travel, incentives, test kits, testing supplies, office space, equipment, and utilities. The CBOs used the networks of high-risk and HIV-infected persons (recruiters) who referred their partners and associates for HIV counseling and testing. We obtained HIV-testing outcomes from project databases. MAIN OUTCOME MEASURES: Number of HIV tests, number of new HIV-diagnoses notified, total program cost, cost per person tested, cost per person notified of new HIV diagnosis. RESULTS: Two CBOs, both based in Philadelphia, identified 25 and 17 recruiters on average annually and tested 136 and 330 network associates, respectively. Among those tested, 12 and 13 associates were notified of new HIV diagnoses (seropositivity: 9.8%, 4.4%). CBOs in Boston, Massachusetts, and Washington, District of Columbia, identified 26 and 24 recruiters per year on average and tested 228 and 123 network associates. Among those tested, 12 and 11 associates were notified of new HIV diagnoses (seropositivity: 5.1%, 8.7%). The cost per associate notified of a new HIV diagnosis was $11 578 and $12 135 in Philadelphia, and $16 437 and $16 101 in Boston, Massachusetts, and Washington, District of Columbia. CONCLUSIONS: The cost of notifying someone with a new HIV diagnosis using social networks varied across sites. Our analysis provides useful information for program planning and evaluation.

Estimating the costs and cost-effectiveness of HIV self-testing among men who have sex with men, United States.

INTRODUCTION: HIV testing is an essential prerequisite for accessing treatment with antiretroviral therapy or prevention using pre-exposure prophylaxis. Internet distribution of HIV self-tests is a novel approach, and data on the programmatic cost of this approach are limited. We analyse the costs and cost-effectiveness of a self-testing programme. METHODS: Men who have sex with men (MSM) reporting unknown or negative HIV status were enrolled from March to August 2015 into a 12-month trial of HIV self-testing in the United States. Participants were randomly assigned either to the self-testing arm or the control arm. All participants received information on HIV testing services and locations in their community. Self-testing participants received up to four self-tests each quarter, which they could use themselves or distribute to their social network associates. Quarterly follow-up surveys collected testing outcomes, including number of tests used and new HIV diagnoses. Using trial expenditure data, we estimated the cost of implementing a self-testing programme. Primary outcomes of this analysis included total programme implementation costs, cost per self-test completed, cost per person tested, cost per new HIV diagnosis among those self-tested and cost per quality adjusted life year (QALY) saved. RESULTS: A total of 2665 men were assigned either to the self-testing arm (n = 1325) or the control arm (n = 1340). HIV testing was reported by 971 self-testing participants who completed a total of 5368 tests. In the control arm, 619 participants completed 1463 HIV tests. The self-testing participants additionally distributed 2864 self-tests to 2152 social network associates. Testing during the trial identified 59 participants and social network associates with newly diagnosed HIV infection in the self-testing arm; 11 control participants were newly diagnosed with HIV. The implementation cost of the HIV self-testing programme was $449,510. The cost per self-test completed, cost per person tested at least once, and incremental cost per new HIV diagnosis was $61, $145 and $9365 respectively. We estimated that self-testing programme potentially averted 3.34 transmissions, saved 14.86 QALYs and nearly $1.6 million lifetime HIV treatment costs. CONCLUSIONS: The HIV self-testing programme identified persons with newly diagnosed HIV infection at low cost, and the programme is cost saving.